Repeated pulses of serotonin required for long-term facilitation activate mitogen-activated protein kinase in sensory neurons of Aplysia

Science.gov (United States)

Michael, Dan; Martin, Kelsey C.; Seger, Rony; Ning, Ming-Ming; Baston, Rene; Kandel, Eric R.

1998-01-01

Long-term facilitation of the connections between the sensory and motor neurons of the gill-withdrawal reflex in Aplysia requires five repeated pulses of serotonin (5-HT). The repeated pulses of 5-HT initiate a cascade of gene activation that leads ultimately to the growth of new synaptic connections. Several genes in this process have been identified, including the transcriptional regulators apCREB-1, apCREB-2, apC/EBP, and the cell adhesion molecule apCAM, which is thought to be involved in the formation of new synaptic connections. Here we report that the transcriptional regulators apCREB-2 and apC/EBP, as well as a peptide derived from the cytoplasmic domain of apCAM, are phosphorylated in vitro by Aplysia mitogen-activated protein kinase (apMAPK). We have cloned the cDNA encoding apMAPK and show that apMAPK activity is increased in sensory neurons treated with repeated pulses of 5-HT and by the cAMP pathway. These results suggest that apMAPK may participate with cAMP-dependent protein kinase during long-term facilitation in sensory cells by modifying some of the key elements involved in the consolidation of short- to long-lasting changes in synaptic strength. PMID:9465108

Long-term repeatability of the skin prick test is high when supported by history or allergen-sensitivity tests

DEFF Research Database (Denmark)

Bødtger, Uffe; Jacobsen, C R; Poulsen, L K

2003-01-01

subjects. An SPT was positive when > or =3 mm, and repeatable if either persistently positive or negative. Clinical sensitivity to birch pollen was used as model for inhalation allergy, and was investigated at inclusion and at study termination by challenge tests, intradermal test, titrated SPT and Ig......E measurements. Birch pollen symptoms were confirmed in diaries. RESULTS: The repeatability of a positive SPT was 67%, increasing significantly to 100% when supported by the history. When not supported by history, the presence of specific IgE was significantly associated with a repeatable SPT. Allergen....... CONCLUSION: SPT changes are clinically relevant. Further studies using other allergens are needed. Long-term repeatability of SPT is high in the presence of a supportive history....

Characterization of long-term dose stability of N-isopropylacrylamide polymer gel dosimetry

International Nuclear Information System (INIS)

Chang, Y.J.; Central Taiwan University of Science and Technology, Taichung City, Taiwan, ROC; Chen, C.H.; Hsieh, B.T.

2014-01-01

In this study, the detailed characteristics, including spatial uniformity, dose distributions, inter-batch variability, reproducibility, and long-term temporal stability, of N-isopropylacrylamide (NIPAM) polymer gel dosimeter were investigated. A commercial 10x fast optical computed tomography scanner (OCTOPUS TM -10×, MGS Research, Inc., Madison, CT, USA) was used to measure NIPAM polymer gel dosimeter. A cylindrical NIPAM gel phantom that measured 10 cm × 10 cm was irradiated via a single-field treatment plan with a field size of 4 cm × 4 cm. The maximum standard deviation of spatial uniformity for NIPAM gel was less than 0.29 %. The average standard deviation among the three batches of gel dosimeters was less than 1 %. The gamma pass rate could reach as high as 96.76 % when a 3 % dose difference and a 3 mm dose-to-agreement criteria were used. The long-term measurement of irradiated NIPAM gel dosimeter indicated that the dose maps attained a gradually stable value 15 h post-irradiation and remained stable until 72 h post-irradiation. The gamma pass rate could achieve a maximum value between 24 and 72 h post-irradiation. The edge enhancement effect that occurred around the irradiated region was observed 72 h post-irradiation. Thus, the results from this study suggest that NIPAM gel dosimeter should be measured approximately 24 h post-irradiation to reduce the occurrence of the edge enhancement effect. (author)

Reaction of the hematopoietic system under long-term emotional stress developed after preliminary gamma-irradiation with low doses

International Nuclear Information System (INIS)

Moroz, B.B.; Deshevoj, Yu.B.; Lebedev, V.G.; Lyrshchikova, A.V.; Vorotnikova, T.V.

1997-01-01

In experiments on rats and mice it was shown that the preliminary protected gamma-irradiation with cumulative dose of 0.9 Gy (dose rate - 0.03 Gy/day) or single short-term gamma-irradiation with dose of 0.9 Gy (dose rate - 1.61 Gy/min) inhibited development of adaptive reactions and compensatory abilities of the hematopoietic system under long-term emotional stress

Effects of Long-Term Ayahuasca Administration on Memory and Anxiety in Rats.

Science.gov (United States)

Favaro, Vanessa Manchim; Yonamine, Maurício; Soares, Juliana Carlota Kramer; Oliveira, Maria Gabriela Menezes

2015-01-01

Ayahuasca is a hallucinogenic beverage that combines the action of the 5-HT2A/2C agonist N,N-dimethyltryptamine (DMT) from Psychotria viridis with the monoamine oxidase inhibitors (MAOIs) induced by beta-carbonyls from Banisteriopsis caapi. Previous investigations have highlighted the involvement of ayahuasca with the activation of brain regions known to be involved with episodic memory, contextual associations and emotional processing after ayahuasca ingestion. Moreover long term users show better performance in neuropsychological tests when tested in off-drug condition. This study evaluated the effects of long-term administration of ayahuasca on Morris water maze (MWM), fear conditioning and elevated plus maze (EPM) performance in rats. Behavior tests started 48h after the end of treatment. Freeze-dried ayahuasca doses of 120, 240 and 480 mg/kg were used, with water as the control. Long-term administration consisted of a daily oral dose for 30 days by gavage. The behavioral data indicated that long-term ayahuasca administration did not affect the performance of animals in MWM and EPM tasks. However the dose of 120 mg/kg increased the contextual conditioned fear response for both background and foreground fear conditioning. The tone conditioned response was not affected after long-term administration. In addition, the increase in the contextual fear response was maintained during the repeated sessions several weeks after training. Taken together, these data showed that long-term ayahuasca administration in rats can interfere with the contextual association of emotional events, which is in agreement with the fact that the beverage activates brain areas related to these processes.

Effects of Long-Term Ayahuasca Administration on Memory and Anxiety in Rats.

Directory of Open Access Journals (Sweden)

Vanessa Manchim Favaro

Full Text Available Ayahuasca is a hallucinogenic beverage that combines the action of the 5-HT2A/2C agonist N,N-dimethyltryptamine (DMT from Psychotria viridis with the monoamine oxidase inhibitors (MAOIs induced by beta-carbonyls from Banisteriopsis caapi. Previous investigations have highlighted the involvement of ayahuasca with the activation of brain regions known to be involved with episodic memory, contextual associations and emotional processing after ayahuasca ingestion. Moreover long term users show better performance in neuropsychological tests when tested in off-drug condition. This study evaluated the effects of long-term administration of ayahuasca on Morris water maze (MWM, fear conditioning and elevated plus maze (EPM performance in rats. Behavior tests started 48h after the end of treatment. Freeze-dried ayahuasca doses of 120, 240 and 480 mg/kg were used, with water as the control. Long-term administration consisted of a daily oral dose for 30 days by gavage. The behavioral data indicated that long-term ayahuasca administration did not affect the performance of animals in MWM and EPM tasks. However the dose of 120 mg/kg increased the contextual conditioned fear response for both background and foreground fear conditioning. The tone conditioned response was not affected after long-term administration. In addition, the increase in the contextual fear response was maintained during the repeated sessions several weeks after training. Taken together, these data showed that long-term ayahuasca administration in rats can interfere with the contextual association of emotional events, which is in agreement with the fact that the beverage activates brain areas related to these processes.

Linezolid-resistant Staphylococcus epidermidis associated with long-term, repeated linezolid use in a pediatric patient.

Science.gov (United States)

Ishiwada, Naruhiko; Takaya, Akiko; Kimura, Asahi; Watanabe, Masaharu; Hino, Moeko; Ochiai, Hidemasa; Matsui, Mari; Shibayama, Keigo; Yamamoto, Tomoko

2016-03-01

We report an 8-year-old patient with catheter-related bacteremia caused by linezolid-resistant Staphylococcus epidermidis that was isolated after the long-term, repeated use of linezolid. Three S. epidermidis strains isolated from this patient were bacteriologically analyzed. While the strain isolated prior to linezolid initiation was susceptible to linezolid, two strains after linezolid therapy displayed low-level linezolid susceptibility (MIC, 4 mg/L) and linezolid resistance (MIC, 16 mg/L). T2500A mutation in two copies and G2575T mutations in three copies of 23S rRNA were detected in the low-susceptible strain and the resistant strain, respectively. Linezolid-resistant S. epidermidis infection is rare, but may occur with the long-term administration of linezolid. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Immunomodulatory Effects of Macrolide Antibiotics - Part 2 : Advantages and Disadvantages of Long-Term, Low-Dose Macrolide Therapy

NARCIS (Netherlands)

Altenburg, J.; de Graaff, C. S.; van der Werf, T. S.; Boersma, W. G.

2011-01-01

The available evidence for long-term, low-dose treatment with 14- and 15-membered ring macrolides in non-cystic fibrosis (CF) bronchiectasis, COPD, chronic sinusitis, and asthma is reviewed with special attention to possible adverse effects and the emergence of resistance during long-term macrolide

Neural Plasticity Associated with Hippocampal PKA-CREB and NMDA Signaling Is Involved in the Antidepressant Effect of Repeated Low Dose of Yueju Pill on Chronic Mouse Model of Learned Helplessness.

Science.gov (United States)

Zou, Zhilu; Chen, Yin; Shen, Qinqin; Guo, Xiaoyan; Zhang, Yuxuan; Chen, Gang

2017-01-01

Yueju pill is a traditional Chinese medicine formulated to treat syndromes of mood disorders. Here, we investigated the therapeutic effect of repeated low dose of Yueju in the animal model mimicking clinical long-term depression condition and the role of neural plasticity associated with PKA- (protein kinase A-) CREB (cAMP response element binding protein) and NMDA (N-methyl-D-aspartate) signaling. We showed that a single low dose of Yueju demonstrated antidepressant effects in tests of tail suspension, forced swim, and novelty-suppressed feeding. A chronic learned helplessness (LH) protocol resulted in a long-term depressive-like condition. Repeated administration of Yueju following chronic LH remarkably alleviated all of depressive-like symptoms measured, whereas conventional antidepressant fluoxetine only showed a minor improvement. In the hippocampus, Yueju and fluoxetine both normalized brain-derived neurotrophic factor (BDNF) and PKA level. Only Yueju, not fluoxetine, rescued the deficits in CREB signaling. The chronic LH upregulated the expression of NMDA receptor subunits NR1, NR2A, and NR2B, which were all attenuated by Yueju. Furthermore, intracerebraventricular administration of NMDA blunted the antidepressant effect of Yueju. These findings supported the antidepressant efficacy of repeated routine low dose of Yueju in a long-term depression model and the critical role of CREB and NMDA signaling.

Long term repeated prescribed burning increases evenness in the basidiomycete laccase gene pool in forest soils.

Science.gov (United States)

Artz, Rebekka R E; Reid, Eileen; Anderson, Ian C; Campbell, Colin D; Cairney, John W G

2009-03-01

Repeated prescribed burning alters the biologically labile fraction of nutrients and carbon of soil organic matter (SOM). Using a long-term (30 years) repeated burning experiment where burning has been carried out at a 2- or 4-year frequency, we analysed the effect of prescribed burning on gross potential C turnover rates and phenol oxidase activity in relation to shifts in SOM composition as observed using Fourier-transform infrared spectroscopy. In tandem, we assessed the genetic diversity of basidiomycete laccases. While the overall effect of burning was a decline in phenol oxidase activity, Shannon diversity and evenness of laccases was significantly higher in burned sites. Co-correspondence analysis of SOM composition and laccase operational taxonomic unit frequency data also suggested a strong correlation. While this correlation could indicate that the observed increase in laccase genetic diversity due to burning is due to increased resource diversity, a temporal replacement of the most abundant members of the assembly by an otherwise dormant pool of fungi cannot be excluded. As such, our results fit the intermediate disturbance hypothesis. Effects were stronger in plots burned in 2-year rotations, suggesting that the 4-year burn frequency may be a more sustainable practice to ensure the long-term stability of C cycling in such ecosystems.

Long-term biodosimetry Redux

International Nuclear Information System (INIS)

Simon, Steven L.; Bouville, Andre

2016-01-01

This paper revisits and reiterates the needs, purposes and requirements of bio-dosimetric assays for long-term dose and health risk assessments. While the most crucial need for bio-dosimetric assays is to guide medical response for radiation accidents, the value of such techniques for improving our understanding of radiation health risk by supporting epidemiological (long-term health risk) studies is significant. As new cohorts of exposed persons are identified and new health risk studies are undertaken with the hopes that studying the exposed will result in a deeper understanding of radiation risk, the value of reliable dose reconstruction is underscored. The ultimate application of biodosimetry in long-term health risk studies would be to completely replace model-based dose reconstruction-a complex suite of methods for retrospectively estimating dose that is commonly fraught with large uncertainties due to the absence of important exposure-related information, as well as imperfect models. While biodosimetry could potentially supplant model-based doses, there are numerous limitations of presently available techniques that constrain their widespread application in health risk research, including limited ability to assess doses received far in the past, high cost, great inter-individual variability, invasiveness, higher than preferred detection limits and the inability to assess internal dose (for the most part). These limitations prevent the extensive application of biodosimetry to large cohorts and should be considered a challenge to researchers to develop new and more flexible techniques that meet the demands of long-term health risk research. Events in recent years, e.g. the Fukushima reactor accident and the increased threat of nuclear terrorism, underscore that any event that results in significant radiation exposures of a group of people will also produce a much larger population, exposed at lower levels, but that likewise needs (or demands) an exposure

A long-acting integrase inhibitor protects female macaques from repeated high-dose intravaginal SHIV challenge.

Science.gov (United States)

Andrews, Chasity D; Yueh, Yun Lan; Spreen, William R; St Bernard, Leslie; Boente-Carrera, Mar; Rodriguez, Kristina; Gettie, Agegnehu; Russell-Lodrigue, Kasi; Blanchard, James; Ford, Susan; Mohri, Hiroshi; Cheng-Mayer, Cecilia; Hong, Zhi; Ho, David D; Markowitz, Martin

2015-01-14

Long-acting GSK1265744 (GSK744 LA) is a strand transfer inhibitor of the HIV/SIV (simian immunodeficiency virus) integrase and was shown to be an effective preexposure prophylaxis (PrEP) agent in a low-dose intrarectal SHIV (simian-human immunodeficiency virus) rhesus macaque challenge model. We examined the pharmacokinetics and efficacy of GSK744 LA as PrEP against repeat high-dose intravaginal SHIV challenge in female rhesus macaques treated with Depo-Provera (depot medroxyprogesterone acetate), which promotes viral transmission vaginally. When Depo-Provera-treated female rhesus macaques were dosed with GSK744 LA (50 mg/kg) monthly, systemic and tissue drug concentrations were lower than previously observed in male rhesus macaques. GSK744 concentrations were fivefold lower on average in cervical tissues than in rectal tissues. Eight female rhesus macaques were treated with GSK744 LA at week 0, and four female rhesus macaques served as controls. All animals received a high-dose challenge of SHIV162P3 at week 1. No infection was detected in GSK744 LA-treated rhesus macaques, whereas viremia was detected 1 to 2 weeks after SHIV challenge in all control animals. The GSK744 LA-treated rhesus macaques were given a second administration of drug at week 4 and further challenged at weeks 5 and 7. GSK744 LA treatment protected six of eight female rhesus macaques against three high-dose SHIV challenges, whereas all control animals became infected after the first challenge (P = 0.0003, log-rank test). These results support further clinical development of GSK744 LA for PrEP. Copyright © 2015, American Association for the Advancement of Science.

Chemical protection against long term effects in mice exposed to supralethal doses of X rays

International Nuclear Information System (INIS)

Maisin, J.R.

1982-01-01

Our results demonstrate that mixtures of radioprotectors increase the degree of protection against the short and the long term effects compared with that obtained with each substance given separately. The most potent mixtures of radioprotectors (AET, MEA, Cyst, GSH, 5-HT) yield for the long term survival a dose reduction factor of 2.1. Pulmonary lesions are most often the cause of death in protected mice irradiated with 13.5 Gy or more. At the time of death signs of sclerosis and atrophy in several tissues are associated with these lung lesions in most mice and increase with dose and time after exposure. The tissues most affected are the kidney, the alimentary tract, the liver and the lymphoid tissues [fr

Neural Plasticity Associated with Hippocampal PKA-CREB and NMDA Signaling Is Involved in the Antidepressant Effect of Repeated Low Dose of Yueju Pill on Chronic Mouse Model of Learned Helplessness

Directory of Open Access Journals (Sweden)

Zhilu Zou

2017-01-01

Full Text Available Yueju pill is a traditional Chinese medicine formulated to treat syndromes of mood disorders. Here, we investigated the therapeutic effect of repeated low dose of Yueju in the animal model mimicking clinical long-term depression condition and the role of neural plasticity associated with PKA- (protein kinase A- CREB (cAMP response element binding protein and NMDA (N-methyl-D-aspartate signaling. We showed that a single low dose of Yueju demonstrated antidepressant effects in tests of tail suspension, forced swim, and novelty-suppressed feeding. A chronic learned helplessness (LH protocol resulted in a long-term depressive-like condition. Repeated administration of Yueju following chronic LH remarkably alleviated all of depressive-like symptoms measured, whereas conventional antidepressant fluoxetine only showed a minor improvement. In the hippocampus, Yueju and fluoxetine both normalized brain-derived neurotrophic factor (BDNF and PKA level. Only Yueju, not fluoxetine, rescued the deficits in CREB signaling. The chronic LH upregulated the expression of NMDA receptor subunits NR1, NR2A, and NR2B, which were all attenuated by Yueju. Furthermore, intracerebraventricular administration of NMDA blunted the antidepressant effect of Yueju. These findings supported the antidepressant efficacy of repeated routine low dose of Yueju in a long-term depression model and the critical role of CREB and NMDA signaling.

Are long-term bisphosphonate users a reality?

DEFF Research Database (Denmark)

Abrahamsen, B

2012-01-01

The prevalence of long-term bisphosphonate use may be low due to low refill compliance and gaps in treatment. An analysis of the prescription history of 58,674 bisphosphonate users in Denmark found that only 2.8 % had received ten dose years of treatment or above. INTRODUCTION: This study aims...... to describe the demographics of present bisphosphonate (BP) users, to determine the prevalence of long-term BP use, and to establish if long-term use (a 10-year history of osteoporosis treatment) translated to ten dose years of bisphosphonate prescriptions filled, given the propensity for treatment gaps...... more than ten dose years of a BP. For any osteoporosis drug, 3.0 % had received ten dose years or more, while 23.2 % had received between 5 and 10 years of treatment. CONCLUSION: Long-term users with ten dose years or more of a BP are rare due to periods of low compliance and gaps, with a discrepancy...

Preoperative High-Dose Steroid Has Long-Term Beneficial Effects for Myasthenia Gravis

Directory of Open Access Journals (Sweden)

Syuichi Tetsuka

2013-01-01

Full Text Available Previous studies addressing preoperative steroid treatment have revealed that control of myasthenia gravis (MG with steroids prior to surgery appeared to stabilize postoperative status. The purpose of our study was to clarify the clinical benefits of the preoperative programmed high-dose steroid treatment on the long-term outcomes of MG patients. We retrospectively reviewed the records of 171 MG patients who were followed up after undergoing thymectomy in our hospital between 1988 and 2006. One hundred and thirteen patients in the programmed treatment group had received preoperative steroid treatment, while 58 patients received no steroid treatment during the preoperative period. Clinical remission, which was defined as the achievement of the modified pharmacologic remission (PR for at least 1 year, and clinical benefits were compared between the two groups. With regard to the remission after thymectomy, Kaplan-Meier life-table curves for patients in the preoperative steroid treatment group versus those for patients in the no steroid preoperative treatment group revealed a significantly higher probability of the PR in the preoperative steroid treatment group (log-rank test, P<0.01. This study might be the first, as per our knowledge, to indicate that preoperative programmed high-dose steroid treatment has long-term beneficial effects for MG patients.

Effect of repeated oral therapeutic doses of methylphenidate on food intake and growth rate in rats.

Science.gov (United States)

Alam, Nausheen; Najam, Rahila

2015-01-01

Central nervous system stimulants are known to produce anorexia. Previous data suggest that methylphenidate can have variable effects on caloric intake and growth rate. A dose-response study was performed to monitor caloric intake, liquid intake and growth rate in rats following repeated administration of human oral therapeutic doses 2 mg/kg/day, 5mg/kg/day and 8mg/kg/day of methylphenidate. We found that food intake and water intake, increased in all weeks and at all doses used in the study. Growth rate increased more at higher dose (8mg/kg/day) and at low dose (2mg/kg/day) of methylphenidate in 1(st) and 2(nd) week whereas more decreased by the above doses in 3(rd) week, suggesting that food stimulation leads to initial increase in growth rate but long term administration of methylphenidate attenuate growth rate that is not due to modulation of appetite but may be due to anxiety and increased activity produce by stimulants. A possible role of DA, 5HT receptors in modulation of appetite and anxiety is discussed.

Long-term prognostic performance of low-dose coronary computed tomography angiography with prospective electrocardiogram triggering

Energy Technology Data Exchange (ETDEWEB)

Clerc, Olivier F.; Kaufmann, Basil P.; Possner, Mathias; Liga, Riccardo; Vontobel, Jan; Mikulicic, Fran; Graeni, Christoph; Benz, Dominik C.; Fuchs, Tobias A.; Stehli, Julia; Pazhenkottil, Aju P.; Gaemperli, Oliver; Kaufmann, Philipp A.; Buechel, Ronny R. [University Hospital Zurich, Cardiac Imaging, Department of Nuclear Medicine, Zurich (Switzerland)

2017-11-15

To assess long-term prognosis after low-dose 64-slice coronary computed tomography angiography (CCTA) using prospective electrocardiogram-triggering. We included 434 consecutive patients with suspected or known coronary artery disease referred for low-dose CCTA. Patients were classified as normal, with non-obstructive or obstructive lesions, or previously revascularized. Coronary artery calcium score (CACS) was assessed in 223 patients. Follow-up was obtained regarding major adverse cardiac events (MACE): cardiac death, myocardial infarction and elective revascularization. We performed Kaplan-Meier analysis and Cox regressions. Mean effective radiation dose was 1.7 ± 0.6 mSv. At baseline, 38% of patients had normal arteries, 21% non-obstructive lesions, 32% obstructive stenosis and 8% were revascularized. Twenty-nine patients (7%) were lost to follow-up. After a median follow-up of 6.1 ± 0.6 years, MACE occurred in 0% of patients with normal arteries, 6% with non-obstructive lesions, 30% with obstructive stenosis and 39% of those revascularized. MACE occurrence increased with increasing CACS (P < 0.001), but 4% of patients with CACS = 0 experienced MACE. Multivariate Cox regression identified obstructive stenosis, lesion burden in CCTA and CACS as independent MACE predictors (P ≤ 0.001). Low-dose CCTA with prospective electrocardiogram-triggering has an excellent long-term prognostic performance with a warranty period >6 years for patients with normal coronary arteries. (orig.)

Long-term prognostic performance of low-dose coronary computed tomography angiography with prospective electrocardiogram triggering

International Nuclear Information System (INIS)

Clerc, Olivier F.; Kaufmann, Basil P.; Possner, Mathias; Liga, Riccardo; Vontobel, Jan; Mikulicic, Fran; Graeni, Christoph; Benz, Dominik C.; Fuchs, Tobias A.; Stehli, Julia; Pazhenkottil, Aju P.; Gaemperli, Oliver; Kaufmann, Philipp A.; Buechel, Ronny R.

2017-01-01

To assess long-term prognosis after low-dose 64-slice coronary computed tomography angiography (CCTA) using prospective electrocardiogram-triggering. We included 434 consecutive patients with suspected or known coronary artery disease referred for low-dose CCTA. Patients were classified as normal, with non-obstructive or obstructive lesions, or previously revascularized. Coronary artery calcium score (CACS) was assessed in 223 patients. Follow-up was obtained regarding major adverse cardiac events (MACE): cardiac death, myocardial infarction and elective revascularization. We performed Kaplan-Meier analysis and Cox regressions. Mean effective radiation dose was 1.7 ± 0.6 mSv. At baseline, 38% of patients had normal arteries, 21% non-obstructive lesions, 32% obstructive stenosis and 8% were revascularized. Twenty-nine patients (7%) were lost to follow-up. After a median follow-up of 6.1 ± 0.6 years, MACE occurred in 0% of patients with normal arteries, 6% with non-obstructive lesions, 30% with obstructive stenosis and 39% of those revascularized. MACE occurrence increased with increasing CACS (P < 0.001), but 4% of patients with CACS = 0 experienced MACE. Multivariate Cox regression identified obstructive stenosis, lesion burden in CCTA and CACS as independent MACE predictors (P ≤ 0.001). Low-dose CCTA with prospective electrocardiogram-triggering has an excellent long-term prognostic performance with a warranty period >6 years for patients with normal coronary arteries. (orig.)

Low-dose penicillin in early life induces long-term changes in murine gut microbiota, brain cytokines and behavior

Science.gov (United States)

Leclercq, Sophie; Mian, Firoz M.; Stanisz, Andrew M.; Bindels, Laure B.; Cambier, Emmanuel; Ben-Amram, Hila; Koren, Omry; Forsythe, Paul; Bienenstock, John

2017-01-01

There is increasing concern about potential long-term effects of antibiotics on children's health. Epidemiological studies have revealed that early-life antibiotic exposure can increase the risk of developing immune and metabolic diseases, and rodent studies have shown that administration of high doses of antibiotics has long-term effects on brain neurochemistry and behaviour. Here we investigate whether low-dose penicillin in late pregnancy and early postnatal life induces long-term effects in the offspring of mice. We find that penicillin has lasting effects in both sexes on gut microbiota, increases cytokine expression in frontal cortex, modifies blood–brain barrier integrity and alters behaviour. The antibiotic-treated mice exhibit impaired anxiety-like and social behaviours, and display aggression. Concurrent supplementation with Lactobacillus rhamnosus JB-1 prevents some of these alterations. These results warrant further studies on the potential role of early-life antibiotic use in the development of neuropsychiatric disorders, and the possible attenuation of these by beneficial bacteria. PMID:28375200

Long term population dose due to radon (Rn-222) released from uranium mill tailings

International Nuclear Information System (INIS)

Chambers, D.B.; Lower, L.M.; Stager, R.H.

2001-01-01

The results of a study undertaken by the European Commission on the external costs (environmental and social) of various energy production systems is likely to be influential in determining how the European Union will develop its energy supply systems. The estimated costs for nuclear power from the study will be based on the findings of the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR), with the costs being dominated by the estimated long term (10,000 y) population doses due to radon (Rn-222) released from mill tailings. UNSCEAR developed a central estimate of 150 person-Sv per GW y and a range of 1 to 1,000 person-Sv per GW y. However, the generic data available to and being used by UNSCEAR are dated and are not appropriate for the current and planned future conditions in the uranium production industry, with the result that the estimated external costs of nuclear power (specifically, the doses due to radon emitted from mill tailings) are overestimated. The Uranium Institute sponsored a study to estimate long term population doses based on the most recent 1993 UNSCEAR methodology, but using data that would be more appropriate to the current major uranium production facilities. Site-specific information obtained from the owners/operators and the Uranium Institute included: present and proposed tailings management plans; tailings volumes and areas; ore grades and reserves; measurements and estimates of radon emission rates; and population densities. Tailings at closed facilities that no longer contribute to uranium production were not evaluated since it was assumed that these radon sources need not be considered in evaluating the external costs of current and future nuclear power production. Based on the same approach as UNSCEAR, but using a more sophisticated air dispersion model, and more site-specific data relative to existing sites and proposed tailings management practices, radon emission rates and population densities (that

Short-term and long-term sick-leave in Sweden

DEFF Research Database (Denmark)

Blank, N; Diderichsen, Finn

1995-01-01

The primary aim of the study was to analyse similarities and differences between repeated spells of short-term sick-leave (more than 3 spells of less than 7 days' duration in a 12-month period) and long-term absence through sickness (at least 1 spell of more than 59 days' duration in a 12-month p...

Long-term effect of inoculum pretreatment on fermentative hydrogen production by repeated batch cultivations: homoacetogenesis and methanogenesis as competitors to hydrogen production

DEFF Research Database (Denmark)

Luo, Gang; Karakashev, Dimitar Borisov; Xie, Li

2011-01-01

Long-term effects of inoculum pretreatments(heat, acid, loading-shock) on hydrogen production from glucose under different temperatures (378C, 558C) and initial pH (7 and 5.5) were studied by repeated batch cultivations. Results obtained showed that it was necessary to investigate the long......-term effect of inoculum pretreatment on hydrogen production since pretreatments may just temporarily inhibit the hydrogen consuming processes. After long-term cultivation, pretreated inocula did not enhance hydrogen production compared to untreated inocula under mesophilic conditions (initial pH 7 and pH 5.......5) and thermophilic conditions (initial pH 7). However, pretreatment could inhibit lactate production and lead to higher hydrogen yield under thermophilic conditions at initial pH 5.5. The results further demonstrated that inoculum pretreatment could not permanently inhibit either methanogenesis or homoacetogenesis...

Radiobiological restrictions and tolerance doses of repeated single-fraction hdr-irradiation of intersecting small liver volumes for recurrent hepatic metastases

Directory of Open Access Journals (Sweden)

Wust Peter

2010-05-01

Full Text Available Abstract Background To assess radiobiological restrictions and tolerance doses as well as other toxic effects derived from repeated applications of single-fraction high dose rate irradiation of small liver volumes in clinical practice. Methods Twenty patients with liver metastases were treated repeatedly (2 - 4 times at identical or intersecting locations by CT-guided interstitial brachytherapy with varying time intervals. Magnetic resonance imaging using the hepatocyte selective contrast media Gd-BOPTA was performed before and after treatment to determine the volume of hepatocyte function loss (called pseudolesion, and the last acquired MRI data set was merged with the dose distributions of all administered brachytherapies. We calculated the BED (biologically equivalent dose for a single dose d = 2 Gy for different α/β values (2, 3, 10, 20, 100 based on the linear-quadratic model and estimated the tolerance dose for liver parenchyma D90 as the BED exposing 90% of the pseudolesion in MRI. Results The tolerance doses D90 after repeated brachytherapy sessions were found between 22 - 24 Gy and proved only slightly dependent on α/β in the clinically relevant range of α/β = 2 - 10 Gy. Variance analysis showed a significant dependency of D90 with respect to the intervals between the first irradiation and the MRI control (p 90 and the pseudolesion's volume. No symptoms of liver dysfunction or other toxic effects such as abscess formation occurred during the follow-up time, neither acute nor on the long-term. Conclusions Inactivation of liver parenchyma occurs at a BED of approx. 22 - 24 Gy corresponding to a single dose of ~10 Gy (α/β ~ 5 Gy. This tolerance dose is consistent with the large potential to treat oligotopic and/or recurrent liver metastases by CT-guided HDR brachytherapy without radiation-induced liver disease (RILD. Repeated small volume irradiation may be applied safely within the limits of this study.

Long-term follow-up of low-dose external pituitary irradiation for Cushing's disease

International Nuclear Information System (INIS)

Littley, M.D.; Shalet, S.M.; Beardwell, C.G.; Ahmed, S.R.; Sutton, M.L.

1990-01-01

Twenty-four patients (three male) with Cushing's disease, aged between 11 and 67 years, were treated with low-dose external pituitary irradiation (20 Gy in eight fractions over 10-12 days) and followed for between 13 and 171 months (median 93 months). Eleven patients (46%) went into remission 4-36 months after irradiation, but five subsequently relapsed. In this series, the low incidence of radiation-induced hypopituitarism and absence of other complications attributable to radiotherapy suggest that low-dose pituitary irradiation may be a useful treatment option in selected patients. However, long-term follow-up has demonstrated a high relapse rate and failure to prevent Nelson's syndrome in adrenalectomized patients, indicating that it should not be used as primary treatment in preference to selective adenomectomy. (author)

Multidetector CT radiation dose optimisation in adults: short- and long-term effects of a clinical audit

International Nuclear Information System (INIS)

Tack, Denis; Jahnen, Andreas; Kohler, Sarah; Harpes, Nico; Back, Carlo; Maertelaer, Viviane de; Gevenois, Pierre Alain

2014-01-01

To report short- and long-term effects of an audit process intended to optimise the radiation dose from multidetector row computed tomography (MDCT). A survey of radiation dose from all eight MDCT departments in the state of Luxembourg performed in 2007 served as baseline, and involved the most frequently imaged regions (head, sinus, cervical spine, thorax, abdomen, and lumbar spine). CT dose index volume (CTDIvol), dose-length product per acquisition (DLP/acq), and DLP per examination (DLP/exa) were recorded, and their mean, median, 25th and 75th percentiles compared. In 2008, an audit conducted in each department helped to optimise doses. In 2009 and 2010, two further surveys evaluated the audit's impact on the dose delivered. Between 2007 and 2009, DLP/exa significantly decreased by 32-69 % for all regions (P < 0.001) except the lumbar spine (5 %, P = 0.455). Between 2009 and 2010, DLP/exa significantly decreased by 13-18 % for sinus, cervical and lumbar spine (P ranging from 0.016 to less than 0.001). Between 2007 and 2010, DLP/exa significantly decreased for all regions (18-75 %, P < 0.001). Collective dose decreased by 30 % and the 75th percentile (diagnostic reference level, DRL) by 20-78 %. The audit process resulted in long-lasting dose reduction, with DRLs reduced by 20-78 %, mean DLP/examination by 18-75 %, and collective dose by 30 %. (orig.)

Effects of long-term, low dose rate fission neutron irradiation on the peripheral hematological cells in rats

International Nuclear Information System (INIS)

Jiang Dingwen; Lei Chengxiang; Shen Xianrong; Ma Li; Yang Xufang; Peng Wulin; Dai Shourong

2008-01-01

Objective: To evaluate the effects of long-term, low dose rate fission neutron irradiation on the peripheral hematological cells in rats. Methods: 96 rats were randomly divided into the control group and the irradiation group with low dose rate fission neutron ( 252 Cf, 0.35 mGy/h) irradiation 20.5 h every day. 8 rats of each group were killed at 14 d, 28 d, 42d, 56d, 70d after irradiation and 35d after the irradiation, and their peripheral hematological cells were tested respectively. Results: Compared with the control group, peripheral blood WBC was reduced significantly at the dose of 0.3Gy and 0.4Gy (P < 0.05), and was reduced remarkably at dose of 0.5Gy (P<0.01) and 35d after stopping irradiation(P<0.01). At dose of 0.2Gy, Peripheral blood RBC was abnormally higher comparing with the control group (P<0.01), accompanying with higher HCT and HGB, which suggests condensed blood. At the other point, RBC tend to become lower, but only at dose 0.5Gy, and the difference is significant comparing with control group(P <0.05). At dose of 0.3Gy, 0.4Gy and 0.5Gy, HCT were significantly lower comparing with control group. Comparing with control group, MCV was higher at 35d after stopping irradiation, and PLT was significantly lower in dose of 0.2Gy. Conclusion: Long-term irradiation with low dose rate fission neutron could significantly reduce peripheral blood WBC, with less effects on RBC and PLT. The reduced WBC could not recover at 35d after stopping irradiation. (authors)

Effects of long-term low dose radiation. Epstein-Barr virus-specific antibodies in radiological technologists

Energy Technology Data Exchange (ETDEWEB)

Kumagai, Etsuko; Higashida, Yoshiharu; Onomichi, Mitsukazu; Nakamura, Ikuo; Tanoue, Shozo; Tanaka, Ryuji; Kumagai, Takashi; Katsuki, Takato; Sawada, Shozo.

1988-09-01

To clarify the long-term effects of occupational exposure to low doses of radiation, Epstein-Barr virus (EBV)-specific antibody titers in sera from 104 radiological technologists (R.T.) and 118 controls in Kumamoto prefecture were measured by the immunofluorescence method. Antibody titers to viral capsid antigen (VCA)-IgG increased with the years of experience as R.T., and the prevalence of abnormal antibody titers to both VCA-IgG and early antigen (EA)-IgG were significantly higher in R.T. with over 15 years of experience or 30 rads of cumulative radiation dose than in the controls. However, there was no correlation between exposure and the frequency of abnormal EBV-associated nuclear antigen (EBNA) antibody titers. The EBV-specific antibody titers of 24 Hiroshima atomic-bomb survivors were also measured. They were similar to those of the R.T. with over 30 years of experience. The EBV-specific antibody titers of R.T. suggest that there may be an impairment of immunologic competence after continuous long-term exposure to low doses of radiation. Also, the correlation of EBV-specific antibody titers and frequency of cells with chromosome aberrations in 53 R.T. was studied. Some correlations were found between the antibody titers to both of the VCA-IgG and EBNA and the frequency of cells with chromosome aberrations.

Long Term assessment of the dose registered by the Sanitary workers of a mutual

International Nuclear Information System (INIS)

Anies Escartin, J.; Perramon Llado, A.

2004-01-01

The analysis of a long time period of time (about 17 years) of the professional exposure to ionising radiation of the workers of an accidents Mutual, that has its own personal Dosimetry Service, allows to establish a relation between the showed global reduction of the registered doses of the people exposed and the circumstances and actions that did it possible. The fact to carry out a dosimetric control is an essential factor directed to accomplish the objective of holding the doses as low as achievable, joined with the fact of passing more strict law. Those factors that fixed a reduction of the doses inherited by the sanitary exposed workers whose relation are demonstrated in this study. The collective dose inherited by the bunch of people exposed is the parameter suitable to measure and assess the time history at medium and long term of the exposure conditions of the workers, and identify the more relevant characteristics of the risk by ionising radiation at workplace. The conclusion of the time history analysis of the quantity shows that the total collective dose for more than a thousand people group, are strongly affected by the doses corresponding to less than a 1,5 % of the users. The number of people that have a value dose higher that the average, and the high value of the dose in some periods because of their activity lead to changes of the value of the collective doses that can be higher than 100%. This great uncertainty in the measured value needs more than ten months of control to guarantee the lowering of doses received. The decreasing doses observed are strongly related with the reduction of this relative short number of cases with incidences in the doses registered. An important part of the work is related to identifying the incidences registered, noticing the evolution and checking the most suitable actions to lower it. (Author) 4 refs

Long-term effects of radiation

International Nuclear Information System (INIS)

Smith, J.; Smith, T.

1981-01-01

It is pointed out that sources of long-term damage from radiation are two-fold. People who have been exposed to doses of radiation from initial early fallout but have recovered from the acute effects may still suffer long-term damage from their exposure. Those who have not been exposed to early fallout may be exposed to delayed fallout, the hazards from which are almost exclusively from ingesting strontium, caesium and carbon isotopes present in food; the damage caused is relatively unimportant compared with that caused by the brief doses from initial radiation and early fallout. A brief discussion is presented of the distribution of delayed long-lived isotope fallout, and an outline is sketched of late biological effects, such as malignant disease, cataracts, retarded development, infertility and genetic effects. (U.K.)

Long-term dose-response studies of inhaled or injected radionuclides

International Nuclear Information System (INIS)

Boecker, B.B.; Muggenburg, B.A.; Miller, S.C.; Bradley, P.L.

1994-01-01

This report describes the scientific progress in, and current status of, life-span studies of the long-term health risks in Beagle dogs of chronic irradiation from internally deposited radionuclides or from an external source. The reporting period for this document is the 2-year period from October 1, 1991 through September 30, 1993. Studies that were initiated at three different laboratories (Inhalation Toxicology Research Institute, ITRI, University of Utah, and Argonne National Laboratory, ANL) are presented here because they are being completed at ITRI. All living dogs in the Utah-initiated studies were transferred to the ITRI facility for the remainder of their life-span observations and measurements in September 1987. This report is the fourth in a series of reports dealing with the current status and progress of both the Utah and ITRI studies. Other life-span studies involving dogs exposed to gamma radiation from an external source were initiated and conducted for many years at ANL. In 1991, the decision was made to discontinue the chronic irradiation of the remaining living dogs and to transfer all remaining dogs to ITRI for care, clinical observations, and pathological observations at death or euthanasia. This report provides the current status of these dogs. Status reports on the Utah and ITRI studies comprise most of this report. The ITRI-related section presents brief statements of project objectives, the general procedures used in these studies, and some study-specific features for each of the 19 studies being conducted with either beta- or alpha-emitting radionuclides. Dose- and effect-modifying factors being addressed in these studies include total dose, dose rate, LET, solubility, nonuniformity of dose, species, age, sex, health status, and mode of exposure. Recent additions to experimental protocols for studies in which dogs are still alive involve the collection and analysis of tumor tissues using currently available molecular biology techniques

Radiotherapy for benign achillodynia. Long-term results of the Erlangen Dose Optimization Trial

Energy Technology Data Exchange (ETDEWEB)

Ott, Oliver J.; Jeremias, Carolin; Gaipl, Udo S.; Frey, Benjamin; Schmidt, Manfred; Fietkau, Rainer [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany)

2015-12-15

The aim of this study was to evaluate the long-term efficacy of two dose-fractionation schedules for radiotherapy of achillodynia. Between February 2006 and February 2010, 112 evaluable patients were recruited for this prospective trial. All patients received orthovoltage radiotherapy. One course consisted of 6 fractions/3 weeks. In the case of insufficient remission of pain after 6 weeks, a second series was performed. Patients were randomly assigned to receive either single doses of 0.5 or 1.0 Gy. The endpoint was pain reduction. Pain was measured before, right after (early response), 6 weeks after (delayed response), and approximately 2 years after radiotherapy (long-term response) with a questionnaire-based visual analogue scale (VAS) and a comprehensive pain score (CPS). The median follow-up was 24 months (range, 11-56). The overall early, delayed, and long-term response rates for all patients were 84 %, 88 %, and 95 %, respectively. The mean VAS values before treatment for early, delayed, and long-term responses for the 0.5-Gy and 1.0-Gy groups were 55.7 ± 21.0 and 58.2 ± 23.5 (p = 0.53), 38.0 ± 23.2 and 30.4 ± 22.6 (p = 0.08), 35.5 ± 25.9 and 30.9 ± 25.4 (p = 0.52), and 11.2 ± 16.4 and 15.3 ± 18.9 (p = 0.16), respectively. The mean CPS values before treatment for early, delayed, and long-term responses were 8.2 ± 3.0 and 8.9 ± 3.3 (p = 0.24), 5.6 ± 3.1 and 5.4 ± 3.3 (p = 0.76), 4.4 ± 2.6 and 5.3 ± 3.8 (p = 0.58), and 2.2 ± 2.9 and 2.8 ± 3.3 (p = 0.51), respectively. No significant differences in long-term response quality between the two arms was found (p = 0.73). Radiotherapy is a very effective treatment for the management of benign achillodynia. For radiation protection, the dose for a radiotherapy series should not exceed 3.0 Gy. (orig.) [German] Ziel war die Untersuchung der Langzeiteffektivitaet zweier Dosisfraktionierungskonzepte bei der Strahlentherapie von Patienten mit Achillodynie. Zwischen 2006 und 2010 wurden 112 auswertbare

Short-horizon regulation for long-term investors

NARCIS (Netherlands)

Shi, Z.; Werker, B.J.M.

2012-01-01

We study the effects of imposing repeated short-horizon regulatory constraints on long-term investors. We show that Value-at-Risk and Expected Shortfall constraints, when imposed dynamically, lead to similar optimal portfolios and wealth distributions. We also show that, in utility terms, the costs

Immunomodulatory effects of macrolide antibiotics - part 2: advantages and disadvantages of long-term, low-dose macrolide therapy.

Science.gov (United States)

Altenburg, J; de Graaff, C S; van der Werf, T S; Boersma, W G

2011-01-01

The available evidence for long-term, low-dose treatment with 14- and 15-membered ring macrolides in non-cystic fibrosis (CF) bronchiectasis, COPD, chronic sinusitis, and asthma is reviewed with special attention to possible adverse effects and the emergence of resistance during long-term macrolide treatment. Macrolide maintenance therapy has been proven to be of benefit in diffuse panbronchiolitis and CF, presumably due to an anti-inflammatory mechanism of action in addition to its direct antimicrobial effect. Solid evidence to justify this treatment regimen for non-CF bronchiectasis, asthma, or sinusitis is still lacking, although a beneficial effect of long-term macrolide therapy has been found in small clinical trials on these subjects. Data from randomized trials of long-term macrolide treatment in COPD are conflicting. A sufficiently long duration of treatment and the careful selection of patients appears to be crucial. Aside from its beneficial effects, possible side effects of macrolide treatment should be taken into account, the most important of these being gastrointestinal upset and cardiac arrhythmias. Development of macrolide resistance among respiratory pathogens is very common during long-term macrolide treatment. Whether this finding is clinically significant is a matter of debate. Copyright © 2010 S. Karger AG, Basel.

Population pharmacokinetic model of THC integrates oral, intravenous, and pulmonary dosing and characterizes short- and long-term pharmacokinetics.

Science.gov (United States)

Heuberger, Jules A A C; Guan, Zheng; Oyetayo, Olubukayo-Opeyemi; Klumpers, Linda; Morrison, Paul D; Beumer, Tim L; van Gerven, Joop M A; Cohen, Adam F; Freijer, Jan

2015-02-01

Δ(9)-Tetrahydrocannobinol (THC), the main psychoactive compound of Cannabis, is known to have a long terminal half-life. However, this characteristic is often ignored in pharmacokinetic (PK) studies of THC, which may affect the accuracy of predictions in different pharmacologic areas. For therapeutic use for example, it is important to accurately describe the terminal phase of THC to describe accumulation of the drug. In early clinical research, the THC challenge test can be optimized through more accurate predictions of the dosing sequence and the wash-out between occasions in a crossover setting, which is mainly determined by the terminal half-life of the compound. The purpose of this study is to better quantify the long-term pharmacokinetics of THC. A population-based PK model for THC was developed describing the profile up to 48 h after an oral, intravenous, and pulmonary dose of THC in humans. In contrast to earlier models, the current model integrates all three major administration routes and covers the long terminal phase of THC. Results show that THC has a fast initial and intermediate half-life, while the apparent terminal half-life is long (21.5 h), with a clearance of 38.8 L/h. Because the current model characterizes the long-term pharmacokinetics, it can be used to assess the accumulation of THC in a multiple-dose setting and to forecast concentration profiles of the drug under many different dosing regimens or administration routes. Additionally, this model could provide helpful insights into the THC challenge test used for the development of (novel) compounds targeting the cannabinoid system for different therapeutic applications and could improve decision making in future clinical trials.

Combined management of retroperitoneal sarcoma with dose intensification radiotherapy and resection: Long-term results of a prospective trial.

LENUS (Irish Health Repository)

Smith, Myles J F

2014-01-07

Late failure is a challenging problem following resection of retroperitoneal sarcoma (RPS). We investigated the effects of preoperative XRT plus dose escalation with early postoperative brachytherapy (BT) on long-term survival and recurrence in RPS.

Long-Term Quality of Life Outcome After Proton Beam Monotherapy for Localized Prostate Cancer

Energy Technology Data Exchange (ETDEWEB)

Coen, John J., E-mail: jcoen@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States); Paly, Jonathan J.; Niemierko, Andrzej; Weyman, Elizabeth [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States); Rodrigues, Anita [Department of Medical Oncology, Massachusetts General Hospital, Boston, MA (United States); Shipley, William U.; Zietman, Anthony L. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States); Talcott, James A. [Department of Medical Oncology, Massachusetts General Hospital, Boston, MA (United States)

2012-02-01

Objectives: High-dose external radiation for localized prostate cancer results in favorable clinical outcomes and low toxicity rates. Here, we report long-term quality of life (QOL) outcome for men treated with conformal protons. Methods: QOL questionnaires were sent at specified intervals to 95 men who received proton radiation. Of these, 87 men reported 3- and/or 12-month outcomes, whereas 73 also reported long-term outcomes (minimum 2 years). Symptom scores were calculated at baseline, 3 months, 12 months, and long-term follow-up. Generalized estimating equation models were constructed to assess longitudinal outcomes while accounting for correlation among repeated measures in an individual patient. Men were stratified into functional groups from their baseline questionnaires (normal, intermediate, or poor function) for each symptom domain. Long-term QOL changes were assessed overall and within functional groups using the Wilcoxon signed-rank test. Results: Statistically significant changes in all four symptom scores were observed in the longitudinal analysis. For the 73 men reporting long-term outcomes, there were significant change scores for incontinence (ID), bowel (BD) and sexual dysfunction (SD), but not obstructive/irritative voiding dysfunction (OID). When stratified by baseline functional category, only men with normal function had increased scores for ID and BD. For SD, there were significant changes in men with both normal and intermediate function, but not poor function. Conclusions: Patient reported outcomes are sensitive indicators of treatment-related morbidity. These results quantitate the long-term consequences of proton monotherapy for prostate cancer. Analysis by baseline functional category provides an individualized prediction of long-term QOL scores. High dose proton radiation was associated with small increases in bowel dysfunction and incontinence, with more pronounced changes in sexual dysfunction.

Multidetector CT radiation dose optimisation in adults: short- and long-term effects of a clinical audit

Energy Technology Data Exchange (ETDEWEB)

Tack, Denis [EpiCURA Hospital, Clinique Louis Caty, Department of Radiology, Baudour (Belgium); Jahnen, Andreas; Kohler, Sarah [CRP Henri Tudor, Luxembourg (Luxembourg); Harpes, Nico; Back, Carlo [Ministry of Health, Department of Radiation Protection, Luxembourg (Luxembourg); Maertelaer, Viviane de [Universite libre de Bruxelles, Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire and SBIM, Statistical Unit, Brussels (Belgium); Gevenois, Pierre Alain [Hopital Erasme, Department of Radiology, Brussels (Belgium)

2014-01-15

To report short- and long-term effects of an audit process intended to optimise the radiation dose from multidetector row computed tomography (MDCT). A survey of radiation dose from all eight MDCT departments in the state of Luxembourg performed in 2007 served as baseline, and involved the most frequently imaged regions (head, sinus, cervical spine, thorax, abdomen, and lumbar spine). CT dose index volume (CTDIvol), dose-length product per acquisition (DLP/acq), and DLP per examination (DLP/exa) were recorded, and their mean, median, 25th and 75th percentiles compared. In 2008, an audit conducted in each department helped to optimise doses. In 2009 and 2010, two further surveys evaluated the audit's impact on the dose delivered. Between 2007 and 2009, DLP/exa significantly decreased by 32-69 % for all regions (P < 0.001) except the lumbar spine (5 %, P = 0.455). Between 2009 and 2010, DLP/exa significantly decreased by 13-18 % for sinus, cervical and lumbar spine (P ranging from 0.016 to less than 0.001). Between 2007 and 2010, DLP/exa significantly decreased for all regions (18-75 %, P < 0.001). Collective dose decreased by 30 % and the 75th percentile (diagnostic reference level, DRL) by 20-78 %. The audit process resulted in long-lasting dose reduction, with DRLs reduced by 20-78 %, mean DLP/examination by 18-75 %, and collective dose by 30 %. (orig.)

Radioimmunotherapy for liver micrometastases in mice. Pharmacokinetics, dose estimation, and long-term effect

International Nuclear Information System (INIS)

Saga, Tsuneo; Sakahara, Harumi; Nakamoto, Yuji; Sato, Noriko; Zhao, Songji; Iida, Yasuhiko; Konishi, Junji; Kuroki, Masahide; Endo, Keigo

1999-01-01

The pharmacokinetics of a therapeutic dose of 131 I-labeled antibody and the absorbed dose in liver micrometastases of human colon cancer LS174T in female BALB/c nu/nu mice were investigated, along with the long-term therapeutic effect. Mice with liver micrometastases were given an intravenous injection of 131 I-labeled anti-carcinoembryonic antigen (CEA) antibody F33-104 (8.88 MBq/40 μg). The biodistribution of the antibody was determined 1, 2, 4, 6, and 10 days later. The absorbed dose was estimated for three hypothetical tumor diameters; 1,000, 500, and 300 μm. Autoradiography showed a homogeneous distribution of radioactivity in the micrometastases, and a high uptake was maintained until day 6 (24.0% injected dose (ID)/g on day 1 to 17.8% ID/g on day 6), but decreased thereafter. The absorbed doses in the 1,000-, 500-, and 300-μm tumors were calculated to be 19.1, 12.0, and 8.2 Gy, respectively. The intravenous injection of the 131 I-labeled antibody also showed a dose-dependent therapeutic effect (all mice of the nontreated group died, with a mean survival period of 4 weeks; 3 of the 8 mice that received 9.25 MBq survived up to 120 days with no sign of liver metastasis). These data give further evidence that micrometastasis is a good target of radioimmunotherapy, and that an absorbed dose of less than 20 Gy can effectively control small metastatic lesions. (author)

Long term neurocognitive impact of low dose prenatal methylmercury exposure in Hong Kong.

Science.gov (United States)

Lam, Hugh Simon; Kwok, Ka Ming; Chan, Peggy Hiu Ying; So, Hung Kwan; Li, Albert Martin; Ng, Pak Cheung; Fok, Tai Fai

2013-04-01

International studies suggest that low dose prenatal methylmercury exposure (>29 nmol/L) has long-term adverse neurocognitive effects. There is evidence that the majority of children in Hong Kong exceed this level as a result of high fish consumption of mothers during pregnancy. To study whether there are any associations between low-dose prenatal methylmercury exposure and neurocognitive outcomes in Hong Kong children. All 1057 children from the original birth cohort were eligible for entry into the study, except children with conditions that would affect neurocognitive development, but were unrelated to methylmercury exposure. Subjects were assessed by a wide panel of tests covering a broad range of neurocognitive functions: Hong Kong Wechsler Intelligence Scale for Children (HK-WISC), Hong Kong List Learning Test (HKLLT), Tests of Everyday Attention for Children (TEACH), Boston Naming Test, and Grooved Pegboard Test. 608 subjects were recruited (median age 8.2 years, IQR 7.3, 8.8; 53.9% boys). After correction by confounders including child age and sex, multivariate analysis showed that cord blood mercury concentration was significantly associated with three subtests: Picture Arrangement of HK-WISC (coefficient -0.944, P=0.049) and Short and Long Delay Recall Difference of the HKLLT (coefficient -1.087, P=0.007 and coefficient -1.161, P=0.005, respectively), i.e., performance worsened with increasing prenatal methylmercury exposure in these subtests. Small, but statistically significant adverse associations between prenatal methylmercury exposure and long-term neurocognitive effects (a visual sequencing task and retention ability of verbal memory) were found in our study. These effects are compatible with findings of studies with higher prenatal methylmercury exposure levels and suggest that safe strategies to further reduce exposure levels in Hong Kong are desirable. Copyright © 2013 Elsevier Ltd. All rights reserved.

Long-term effects of repeated social stress on the conditioned place preference induced by MDMA in mice.

Science.gov (United States)

García-Pardo, M P; Blanco-Gandía, M C; Valiente-Lluch, M; Rodríguez-Arias, M; Miñarro, J; Aguilar, M A

2015-12-03

Previous studies have demonstrated that social defeat stress increases the rewarding effects of psychostimulant drugs such as cocaine and amphetamine. In the present study we evaluated the long-term effects of repeated social defeat (RSD) on the rewarding effects of ±3,4-methylenedioxymethamphetamine (MDMA) hydrochloride in the conditioned place preference (CPP) paradigm. Adolescent and young adult mice were exposed to four episodes of social defeat (on PND 29-40 and PND 47-56, respectively) and were conditioned three weeks later with 1.25 or 10mg/kg i.p. of MDMA (experiment 1). The long-term effects of RSD on anxiety, social behavior and cognitive processes were also evaluated in adult mice (experiment 2). RSD during adolescence enhanced vulnerability to priming-induced reinstatement in animals conditioned with 1.25mg/kg of MDMA and increased the duration of the CPP induced by the 10mg/kg of MDMA. The latter effect was also observed after RSD in young adult mice, as well as an increase in anxiety-like behavior, an alteration in social interaction (reduction in attack and increase in avoidance/flee and defensive/submissive behaviors) and an impairment of maze learning. These results support the idea that RSD stress increases the rewarding effects of MDMA and induces long-term alterations in anxiety, learning and social behavior in adult mice. Thus, exposure to stress may increase the vulnerability of individuals to developing MDMA dependence, which is a factor to be taken into account in relation to the prevention and treatment of this disorder. Copyright © 2015 Elsevier Inc. All rights reserved.

Impact of heavy repeated long term pesticide applications on soil properties in a cotton agroecosystem

International Nuclear Information System (INIS)

Hussain, Altaf; Asi, Muhammad Rafique; Iqbal, Zafar; Chaudhry, Jamil Anwar

2001-01-01

A study was conducted under field conditions to investigate the effects of heavy repeated long term pesticide applications, at their recommended doses, on some biological properties in relation to the cotton agroecosystem at NIAB, Faisalabad, Pakistan. Control, test and treated soils before (BPA) and after pesticide applications (APA) were collected and analyzed at different stages of pesticide applications. The selective tests were measurements of microbial numbers, basal as well as substrate-induced respiration, nitrification, Fe-III reduction and the activities, of dehydrogenase and arginine deaminase. Endosulfan, profenophos + alphamethrin and methamidophos inhibited while monocrotophos and bifenthrin + acetamiprid enhanced the bacterial population numbers. The fungal population was depressed with endosulfan while monocrotophos, profenophos and methamidophos stimulated it. All other applied pesticides did not cause any appreciable change in total bacterial and fungal populations throughout the study period. Monocrotophos, propargite, endosulfan alone or with dimethoate and profenophos with cypermethrin or with ethion inhibited the respiration and hence affected the biomass. All other pesticides had no effect in test and treated soils compared to control soil. No pronounced inhibition or stimulation was seen in respiration after several weeks following the applications of pesticide. Endosulfan, endosulfan with dimethoate, methamidophos stimulated while profenophos + cypermethrin and bifenthrin + endosulfan inhibited the nitrification. All other pesticide applications showed similar nitrification rates in test and treated soils compared to control soil. Iron reduction capacity was stimulated by dimethoate + endosulfan and propenophos + cypermethrin and profenphos, methamidophos, propargite and diafenthiuron + profenophos reduced it. Soil dehydrogenase activity was inhibited by methamidophos, fenpropathrin, endosulfan + dimethoate and bifenthrin + ethion

Prospective memory deficits in illicit polydrug users are associated with the average long-term typical dose of ecstasy typically consumed in a single session.

Science.gov (United States)

Gallagher, Denis T; Hadjiefthyvoulou, Florentia; Fisk, John E; Montgomery, Catharine; Robinson, Sarita J; Judge, Jeannie

2014-01-01

Neuroimaging evidence suggests that ecstasy-related reductions in SERT densities relate more closely to the number of tablets typically consumed per session rather than estimated total lifetime use. To better understand the basis of drug related deficits in prospective memory (p.m.) we explored the association between p.m. and average long-term typical dose and long-term frequency of use. Study 1: Sixty-five ecstasy/polydrug users and 85 nonecstasy users completed an event-based, a short-term and a long-term time-based p.m. task. Study 2: Study 1 data were merged with outcomes on the same p.m. measures from a previous study creating a combined sample of 103 ecstasy/polydrug users, 38 cannabis-only users, and 65 nonusers of illicit drugs. Study 1: Ecstasy/polydrug users had significant impairments on all p.m. outcomes compared with nonecstasy users. Study 2: Ecstasy/polydrug users were impaired in event-based p.m. compared with both other groups and in long-term time-based p.m. compared with nonillicit drug users. Both drug using groups did worse on the short-term time-based p.m. task compared with nonusers. Higher long-term average typical dose of ecstasy was associated with poorer performance on the event and short-term time-based p.m. tasks and accounted for unique variance in the two p.m. measures over and above the variance associated with cannabis and cocaine use. The typical ecstasy dose consumed in a single session is an important predictor of p.m. impairments with higher doses reflecting increasing tolerance giving rise to greater p.m. impairment.

Core features of repeated suicidal behaviour: a long-term follow-up after suicide attempts in a low-suicide-incidence population

DEFF Research Database (Denmark)

Wang, August G; Mortensen, Gudrun

2006-01-01

BACKGROUND: The aim of this article was to study repeated suicidal behaviour in a low-incidence population to elucidate robust risk factors. METHODS: A cohort of first-ever suicide attempters from 1960 to 1982 on the Faroe Islands was followed up for a minimum of 20 years. The cohort was initiall...... and the level of determination behind the suicide attempt emerge as targets for prevention. Alcohol intoxication at the initial episode seems to be a strong long-term as well as short-term risk factor.......BACKGROUND: The aim of this article was to study repeated suicidal behaviour in a low-incidence population to elucidate robust risk factors. METHODS: A cohort of first-ever suicide attempters from 1960 to 1982 on the Faroe Islands was followed up for a minimum of 20 years. The cohort was initially...... characterized in psychiatric and social terms. RESULTS: The incidence of suicidal behaviour for the cohort years (age 15 years and older) was 37.9 per 100,000 per year (95% confidence interval 31.5-45.1). It was associated, as expected, with gender, age, residence, marital status, occupation, diagnosis...

Medical and Psychiatric Effects of Long-Term Dependence on High Dose of tramadol.

Science.gov (United States)

El-Hadidy, Mohmed Adel; Helaly, Ahmed Mohamed Nabil

2015-04-01

Tramadol dependence has been studied recently after large-scale exposure. Although tramadol dependence has increased rapidly in Egypt since 2004, no studies have evaluated the effect of high dose long-term tramadol dependence. To address the chronic sequel of tramadol dependence over at least 5 years duration with a large dose (more than 675 mg/day, three tablets or more, each tablet of 225 mg). The study was aimed to check the physical and psychiatric status during tramadol dependence and 3 months after complete treatment. The present study was applied on 79 patients with single tramadol-dependence dose of 675 mg or more for 5 years or more. We examined the physical and psychological impact of tramadol abuse before and after 3 months of stoppage of the drug. The blood chemistry was nearly within normal parameters, although slight nonsignificant rise in liver enzymes was reported in some cases. Patients during tramadol dependence period were angry, hostile, and aggressive. On the other hand, after treatment the main problem observed was the significant increase in comorbid anxiety, depressive, and obsessive-compulsive symptoms, but no increase was found in psychotic symptoms. Tramadol-dependence dose was more important than duration of use in psychiatric illness. Tramadol dependence on high dose could be physically safe to some limit, but psychiatrically it has many side effects.

A long-term risk-benefit analysis of low-dose aspirin in primary prevention.

Science.gov (United States)

Wu, I-Chen; Hsieh, Hui-Min; Yu, Fang-Jung; Wu, Meng-Chieh; Wu, Tzung-Shiun; Wu, Ming-Tsang

2016-02-01

The long-term risk-benefit effect of occasional and regular use of low-dose aspirin (≤ 100 mg per day) in primary prevention of vascular diseases and cancers was calculated. One representative database of 1 000 000 participants from Taiwan's National Health Insurance scheme in 1997-2000 was used. The potential study subjects were those aged 30-95 years, were found not to have been prescribed aspirin before 1 January 2000, but to have first been prescribed low-dose aspirin (≤ 100 mg per day) after that date and were followed up to 31 December 2009. Participants prescribed low-dose aspirin risk. A total of 1720 pairs were analysed. During the study period, haemorrhage and ischaemia occurred in 25 (1·45%) and 67 participants (3·90%) in occasional users and 69 (4·01%) and 100 participants (5·81%) in regular users, whereas cancer occurred in 32 participants (1·86%) in occasional users and 26 participants (1·51%) in regular users. The crude and adjusted net clinical risks of low-dose aspirin use between the two frequency of users (≥ 80% vs. prevention against major vascular diseases and cancer. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

Stress responses of adolescent male and female rats exposed repeatedly to cat odor stimuli, and long-term enhancement of adult defensive behaviors.

Science.gov (United States)

Wright, Lisa D; Muir, Katherine E; Perrot, Tara S

2013-07-01

In order to characterize the short- and long-term effects of repeated stressor exposure during adolescence, and to compare the effects of using two sources of cat odor as stressor stimuli, male and female adolescent rats (postnatal day (PND) ∼ 38-46) were exposed on five occasions to either a control stimulus, a cloth stimulus containing cat hair/dander, or a section of cat collar previously worn by a cat. Relative to control stimulus exposure, activity was suppressed and defensive behavior enhanced during exposure to either cat odor stimulus (most pervasively in rats exposed to the collar). Only cloth-exposed rats showed elevated levels of corticosterone (CORT), and only after repeated stressor exposure, but interestingly, rats exposed to the collar stimulus during adolescence continued to show increased behavioral indices of anxiety in adulthood. In this group, the time an individual spent in physical contact with a cagemate during the final adolescent exposure was negatively related to stress-induced CORT output in adulthood, which suggests that greater use of social support during adolescent stress may facilitate adult behavioral coping, without necessitating increased CORT release. These findings demonstrate that adolescent male and female rats respond defensively to cat odor stimuli across repeated exposures and that exposure to such stressors during adolescence can augment adult anxiety-like behavior in similar stressful conditions. These findings also suggest a potential role for social behavior during adolescent stressor exposure in mediating long-term outcomes. Copyright © 2012 Wiley Periodicals, Inc.

Metabolic interactions between low doses of benzo[a]pyrene and tributyltin in arctic charr (salvelinus alpinus): a long-term in vivo study

International Nuclear Information System (INIS)

Padros, Jaime; Pelletier, Emilien; Ribeiro, Ciro Oliveira

2003-01-01

We have previously reported that short-term, single exposure to a high dose of tributyltin (TBT), a widely used antifouling biocide, inhibited both the in vivo metabolism and metabolic activation of the carcinogenic polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP) in fish; (BaP), in turn, stimulated TBT metabolism. Here, we provide further mechanistic evidence of mutual metabolic interactions between BaP and TBT in response to long-term, repeated exposures to low doses. Juvenile Arctic charr (Salvelinus alpinus) received 10 separate ip injections (a single injection every 6 days) of BaP (3 mg/kg), TBT (0.3 mg/kg), or both in combination; control fish received corn oil vehicle only. Two days after the 2nd (Day 8), 6 th (Day 32), and 10th dose (Day 56), blood, bile, and liver samples were collected and analyzed for a suite of biomarkers. HPLC/fluorescence analysis indicated that TBT cotreatment inhibited the formation of (+)-anti-BaP diol-epoxide adducts with plasma albumin (53%, Day 8), hepatic DNA (27%, Day 32), or both albumin and globin (50 and 58%, Day 56) compared to BaP alone. This antagonistic interaction was associated with a time-dependent modulation (inhibition at Day 8, enhancement at Day 32) of both cytochrome P450 (P450)1A-mediated ethoxyresorufin O-deethylase (EROD) activity and biliary BaP metabolite formation. TBT cotreatment also inhibited (39%) the BaP-mediated induction of hepatic glutathione S-transferase (GST) activity observed at Day 8. Treatment with TBT alone increased EROD activity (60%) at Day 32, but decreased both GST activity (70 and 37%) and glutathione content (24% and 16%) at Days 32 and 56, respectively. GC/MS analysis revealed that, at Day 56, BaP cotreatment increased (200%) the levels of biliary butyltin compounds, including mono- and dibutyltin metabolites. This potentiative interaction was associated with a protective effect of BaP cotreatment against the TBT-mediated decreases in GST activity and glutathione content. The

Independence of long-term contextual memory and short-term perceptual hypotheses: Evidence from contextual cueing of interrupted search.

Science.gov (United States)

Schlagbauer, Bernhard; Mink, Maurice; Müller, Hermann J; Geyer, Thomas

2017-02-01

Observers are able to resume an interrupted search trial faster relative to responding to a new, unseen display. This finding of rapid resumption is attributed to short-term perceptual hypotheses generated on the current look and confirmed upon subsequent looks at the same display. It has been suggested that the contents of perceptual hypotheses are similar to those of other forms of memory acquired long-term through repeated exposure to the same search displays over the course of several trials, that is, the memory supporting "contextual cueing." In three experiments, we investigated the relationship between short-term perceptual hypotheses and long-term contextual memory. The results indicated that long-term, contextual memory of repeated displays neither affected the generation nor the confirmation of short-term perceptual hypotheses for these displays. Furthermore, the analysis of eye movements suggests that long-term memory provides an initial benefit in guiding attention to the target, whereas in subsequent looks guidance is entirely based on short-term perceptual hypotheses. Overall, the results reveal a picture of both long- and short-term memory contributing to reliable performance gains in interrupted search, while exerting their effects in an independent manner.

Impact of repeated long term application of atrazine on soil properties and bound residues formation

International Nuclear Information System (INIS)

Behki, R.; Khan, S.U.

2001-01-01

The effect of repeated long term application of the herbicide atrazine on the activities of microorganisms, enzymes, as well as on the bound residues formation, was investigated. Bacteria, fungi and soil respiration were in general inhibited in the first year of application. However, in the second and third year no such trend was observed. Similarly, a decreasing trend in the Fe(III)-reduction, nitrification and arginine deamination was observed in the first year whereas in the subsequent two years no such trend was prominent. The dehydrogenase and arylsulfatase activities showed an increasing trend after the application of the herbicide. Column studies showed that extractable residues of atrazine and carbofuran gradually decreased after the application of the pesticides. Amendments of the soil containing 14 C-bound residues did not increase 14 CO 2 evolution. Unextractable 14 C was higher and mineralization of 14 C-2,4-D was lower in previously untreated soil than in soils with histories of atrazine and carbofuran application. (author)

Long-term Conventionally Dosed Vancomycin Therapy In Patients With Orthopaedic Implant-related Infections Seems As Effective And Safe As Long-term Penicillin Or Clindamycin Therapy. A Retrospective Cohort Study Of 103 Patients.

Science.gov (United States)

Aleman, Jacomien; Moojen, Dirk Jan F; van Ogtrop, Marc L; Poolman, Rudolf W; Franssen, Eric J F

2018-01-01

Objectives : Antimicrobial therapy is one of the cornerstones of orthopaedic implant-related infections (OIRI) treatment. Infections with Gram-positive bacteria are often treated with vancomycin, penicillin or clindamycin. A recent IDSA guideline suggests increasing the dose of vancomycin to increase the trough vancomycin target serum concentrations. This is deemed necessary because of an observed decrease in vancomycin susceptibility among Gram-positive bacteria. However, elevated vancomycin concentrations are correlated with the risk of nephrotoxicity, especially with prolonged therapy. Compared to most countries, rates of resistance against antibiotics among bacteria in the Netherlands are lower for currently available antibiotics, therefore lower target concentrations of vancomycin are probably efficacious for the treatment of infections. In this study we evaluated the efficacy and safety of long-term conventionally dosed vancomycin therapy, as an initial therapy for OIRI, and compared this with long-term penicillin and clindamycin therapy, as initial therapy, in patients with Gram-positive orthopaedic implant-related infections. Methods : A retrospective, observational study was conducted in 103 adult patients treated for OIRI, with vancomycin, penicillin or clindamycin for at least 10 days. The target trough serum concentration of vancomycin was 10-15 mg/l. Results : 74% of our patients were treated successfully with vancomycin, as initial therapy, (no reinfection within 1 year) versus 55% of our patients treated with either an antibiotic of the penicillin class (mostly flucloxacillin) or clindamycin (p=0.08), as initial therapy. For patients treated with vancomycin we observed a serum creatinine increase of 6 μmol/l, for patients treated with either an antibiotic of the penicillin class or clindamycin the serum creatinine increase was 4 μmol/l (p=0.395). Conclusions : In our population of patients with OIRI long-term treatment with conventionally dosed

Efficacy of modest dose irradiation in combination with long-term endocrinal treatment for high-risk prostate cancer. A preliminary report

International Nuclear Information System (INIS)

Sasaki, Tomonari; Nakamura, Katsumasa; Shioyama, Yoshiyuki

2004-01-01

Although radiotherapy in combination with endocrinal manipulation has been identified as an effective treatment for patients with high-risk prostate cancer, the optimal dose for locoregional control of prostate cancer in combination with hormonal therapy has not yet been determined. The efficacy of modest doses of irradiation (60-62 Gy) combined with long-term endocrinal treatment for patients with high-risk prostate cancer (defined as a pretreatment prostate-specific antigen (PSA) level greater than 20 ng/ml or a Gleason's score of 8-10 or T3-T4 disease) was analyzed in 60 Japanese patients. The patients included in this study had received radical radiotherapy with long-term endocrinal manipulation in the period between 1993 and 2000. The median age of the patients was 70 years (range, 56-83). Neoadjuvant hormonal therapy with a median duration of 3.9 months was performed prior to radiotherapy, and hormonal therapy was continued until recurrence. A median dose of 61.4 Gy (range, 44-71.4) was delivered to the prostate. Pelvic node irradiation was performed in 49 patients (81.6%). After a median follow-up period of 28.5 months, the overall survival, cause-specific survival and biochemical relapse-free survival at 3 years were 94.4%, 96% and 89.8%, respectively. Local failure was observed in one patient, distant metastases were observed in three patients and a late toxic effect greater than Grade 2 was not observed in any patients. This study, though preliminary due to a short-term follow-up period, reveals the possibility that modest doses of irradiation combined with long-term endocrinal treatment could be an effective means of achieving excellent local control of high-risk prostate cancer. (author)

Semantic and phonological contributions to short-term repetition and long-term cued sentence recall.

Science.gov (United States)

Meltzer, Jed A; Rose, Nathan S; Deschamps, Tiffany; Leigh, Rosie C; Panamsky, Lilia; Silberberg, Alexandra; Madani, Noushin; Links, Kira A

2016-02-01

The function of verbal short-term memory is supported not only by the phonological loop, but also by semantic resources that may operate on both short and long time scales. Elucidation of the neural underpinnings of these mechanisms requires effective behavioral manipulations that can selectively engage them. We developed a novel cued sentence recall paradigm to assess the effects of two factors on sentence recall accuracy at short-term and long-term stages. Participants initially repeated auditory sentences immediately following a 14-s retention period. After this task was complete, long-term memory for each sentence was probed by a two-word recall cue. The sentences were either concrete (high imageability) or abstract (low imageability), and the initial 14-s retention period was filled with either an undemanding finger-tapping task or a more engaging articulatory suppression task (Exp. 1, counting backward by threes; Exp. 2, repeating a four-syllable nonword). Recall was always better for the concrete sentences. Articulatory suppression reduced accuracy in short-term recall, especially for abstract sentences, but the sentences initially recalled following articulatory suppression were retained better at the subsequent cued-recall test, suggesting that the engagement of semantic mechanisms for short-term retention promoted encoding of the sentence meaning into long-term memory. These results provide a basis for using sentence imageability and subsequent memory performance as probes of semantic engagement in short-term memory for sentences.

The six year report: Acidification of surface water in Europe and North America. Dose/response relationships and long-term trends

Energy Technology Data Exchange (ETDEWEB)

Skjelkvaale, B L; Newell, A D; Raddum, G; Johannessen, M; Hovind, H; Tjomsland, T; Wathne, B M

1994-12-31

This report discusses The International Cooperative Programme on Assessment and Monitoring of Acidification of Rivers and Lakes, which is designed to (1) establish degree and extent of acidification of surface waters, (2) evaluate dose/response relationships and (3) define long-term trends and variations in aquatic chemistry and biota attributable to atmospheric pollution. Data from 200 sites in 14 countries of Europe and North America are available. Dose/response relationships show that the fauna is adapted to different water qualities in different regions, and that critical limits for the fauna must be calculated according to data for the specific region. Long-term trends of water chemistry show decreases in SO{sub 4}{sup 2-} and Ca{sup 2+} at many sites. Nitrate shows no consistent trends. 66 refs., 26 figs., 16 tabs.

Antimicrobial use in long-term-care facilities

NARCIS (Netherlands)

Nicolle, LE; Bentley, DW; Garibaldi, R; Neuhaus, EG; Smith, PW

There is intense antimicrobial use in long-term-care facilities (LTCFs), and studies repeatedly document that much of this use is inappropriate. The current crisis in antimicrobial resistance, which encompasses the LTCF, heightens concerns of antimicrobial use. Attempts to improve antimicrobial use

Long-Term Follow-up of Acoustic Schwannoma Radiosurgery With Marginal Tumor Doses of 12 to 13 Gy

International Nuclear Information System (INIS)

Chopra, Rahul; Kondziolka, Douglas; Niranjan, Ajay; Lunsford, L. Dade; Flickinger, John C.

2007-01-01

Purpose: To define long-term tumor control and clinical outcomes of radiosurgery with marginal tumor doses of 12 to 13 Gy for unilateral acoustic schwannoma. Methods and Materials: A total of 216 patients with previously untreated unilateral acoustic schwannoma underwent Gamma Knife radiosurgery between 1992 and 2000 with marginal tumor doses of 12 to 13 Gy (median, 13 Gy). Median follow-up was 5.7 years (maximum, 12 years; 41 patients with >8 years). Treatment volumes were 0.08-37.5 cm 3 (median, 1.3 cm 3 ). Results: The 10-year actuarial resection-free control rate was 98.3% ± 1.0%. Three patients required tumor resection: 2 for tumor growth and 1 partial resection for an enlarging adjacent subarachnoid cyst. Among 121 hearing patients with >3 years of follow-up, crude hearing preservation rates were 71% for keeping the same Gardner-Robertson hearing level, 74% for serviceable hearing, and 95% for any testable hearing. For 25 of these patients with intracanalicular tumors, the respective rates for preserving the same Gardner-Robertson level, serviceable hearing, and testable hearing were 80%, 88%, and 96%. Ten-year actuarial rates for preserving the same Gardner-Robertson hearing levels, serviceable hearing, any testable hearing, and unchanged facial and trigeminal nerve function were 44.0% ± 11.7%, 44.5% ± 10.5%, 85.3% ± 6.2%, 100%, and 94.9% ± 1.8%, respectively. Conclusions: Acoustic schwannoma radiosurgery with 12 to 13 Gy provides high rates of long-term tumor control and cranial nerve preservation after long-term follow-up

Effect of zinc supplementation of pregnant rats on short-term and long-term memory of their offspring

International Nuclear Information System (INIS)

Ali, M.A.; Ghotbeddin, Z.; Parham, G.H.

2007-01-01

To see the dose dependent effects of zinc chloride on the short-term and long-term memory in a shuttle box (rats). Six pair adult wistar rats were taken for this experiment. One group of pregnant rats received a daily oral dose of 20 mg/kg Zn as zinc chloride and the remaining groups received a daily oral dose of (30, 50, 70,100 mg/kg) zinc chloride for two weeks by gavage. One month after birth, a shuttle box was used to test short-term and long-term memory. Two criteria were considered to behavioral test, including latency in entering dark chamber and time spent in the dark chamber. This experiment showed that oral administration of ZnCl/sub 2/ with (20, 30, 50 mg/kg/day) doses after 2 weeks at the stage of pregnancy, can improve the working memory of their offspring (p<0.05). Where as ZnCl/sub 2/ with 30 mg/kg/day dose has been more effective than other doses (p<0.001). But rat which received ZnCl/sub 2/ with 100 mg/kg/day at the stage of pregnancy, has shown significant impairment in working (short-term) memory of their offspring (p<0.05) and there was no significant difference in reference (long-term) memory 3 for any of groups. This study has demonstrated that zinc chloride consumption with 30 mg/kg/day dose for two weeks at the stage of pregnancy in rats, has positive effect on short-term memory on their offspring. But consumption of enhanced zinc 100 mg/kg/day in pregnant rats can cause short-term memory impairment. On the other hand, zinc supplementation such as zinc chloride has no effect on long-term memory. (author)

Repeated dose 90-day oral toxicity test of G-7% NANA in rats: An application of new criterion for toxicity determination to test article-induced changes.

Science.gov (United States)

Heo, Hye Seon; An, MinJi; Lee, Ji Sun; Kim, Hee Kyong; Park, Yeong-Chul

2018-06-01

G-7% NANA is N-acetylneuraminic acid(NANA) containing 7% sialic acid isolated from glycomacropeptide (GMP), a compound of milk. Since NANA is likely to have immunotoxicity, the need to ensure safety for long-term administration has been raised. In this study, a 90-day repeated oral dose toxicity test was performed in rats using G-7% NANA in the dosages of 0, 1250, 2500 and 5000 mg/kg/day.A toxicity determination criterion based on the significant change caused by the administration of the substancewas developed for estimating NOEL, NOAEL and LOAELapplied to this study. When analyzing the immunological markers, no significant changes were observed, even if other significant changes were observed in the high dose group. In accordance with the toxicity determination criterion developed, the NOEL in male and female has been determined as 2500 mg/kg/day, and the NOAEL in females has been determined as 5000 mg/kg/day. The toxicity determination criterion, applied for the first time in the repeated dose toxicity tests, could provide a basis for distinguishing NOEL and NOAEL more clearly; nevertheless, the toxicity determination criterion needs to be supplemented by adding differentiating adverse effects and non-adverse effects based on more experiences of the repeated dose toxicity tests. Copyright © 2018 Elsevier Inc. All rights reserved.

Chip-based human liver-intestine and liver-skin co-cultures--A first step toward systemic repeated dose substance testing in vitro.

Science.gov (United States)

Maschmeyer, Ilka; Hasenberg, Tobias; Jaenicke, Annika; Lindner, Marcus; Lorenz, Alexandra Katharina; Zech, Julie; Garbe, Leif-Alexander; Sonntag, Frank; Hayden, Patrick; Ayehunie, Seyoum; Lauster, Roland; Marx, Uwe; Materne, Eva-Maria

2015-09-01

Systemic repeated dose safety assessment and systemic efficacy evaluation of substances are currently carried out on laboratory animals and in humans due to the lack of predictive alternatives. Relevant international regulations, such as OECD and ICH guidelines, demand long-term testing and oral, dermal, inhalation, and systemic exposure routes for such evaluations. So-called "human-on-a-chip" concepts are aiming to replace respective animals and humans in substance evaluation with miniaturized functional human organisms. The major technical hurdle toward success in this field is the life-like combination of human barrier organ models, such as intestine, lung or skin, with parenchymal organ equivalents, such as liver, at the smallest biologically acceptable scale. Here, we report on a reproducible homeostatic long-term co-culture of human liver equivalents with either a reconstructed human intestinal barrier model or a human skin biopsy applying a microphysiological system. We used a multi-organ chip (MOC) platform, which provides pulsatile fluid flow within physiological ranges at low media-to-tissue ratios. The MOC supports submerse cultivation of an intact intestinal barrier model and an air-liquid interface for the skin model during their co-culture with the liver equivalents respectively at (1)/100.000 the scale of their human counterparts in vivo. To increase the degree of organismal emulation, microfluidic channels of the liver-skin co-culture could be successfully covered with human endothelial cells, thus mimicking human vasculature, for the first time. Finally, exposure routes emulating oral and systemic administration in humans have been qualified by applying a repeated dose administration of a model substance - troglitazone - to the chip-based co-cultures. Copyright © 2015. Published by Elsevier B.V.

Long-term follow-up study of compensated low-dose 131I therapy for Graves' disease

International Nuclear Information System (INIS)

Sridama, V.; McCormick, M.; Kaplan, E.L.; Fauchet, R.; DeGroot, L.J.

1984-01-01

We treated 187 patients who had Graves' disease with low-dose radioactive iodide ( 131 I), using a protocol that included a compensation for thyroid size. The incidence of early hypothyroidism (12 per cent) was acceptably low in the first year after 131 I treatment, but we found a cumulative high incidence (up to 76 per cent) at the end of the 11th year. In contrast, the incidence of permanent hypothyroidism was relatively stable in 166 surgically treated patients, increasing from 19 to 27 per cent at the end of 11 years. Among 122 medically treated patients, only 40 per cent entered remission, and hypothyroidism developed in 2 per cent during the same period of follow-up. The long-term incidence of hypothyroidism in our patients treated with low-dose 131 I therapy was much higher than that found in earlier studies using a comparable dose. Our study suggests that it will be difficult to modify therapy with 131 I alone to produce both early control of thyrotoxicosis and a low incidence of hypothyroidism

Long-Term Results After High-Dose Radiotherapy and Adjuvant Hormones in Prostate Cancer: How Curable Is High-Risk Disease?

Energy Technology Data Exchange (ETDEWEB)

Zapatero, Almudena, E-mail: azapatero.hlpr@salud.madrid.org [Department of Radiation Oncology, Hospital Universitario de la Princesa, Madrid (Spain); Garcia-Vicente, Feliciano [Department of Medical Physics, Hospital Universitario de la Princesa, Madrid (Spain); Martin de Vidales, Carmen; Cruz Conde, Alfonso; Ibanez, Yamile [Department of Radiation Oncology, Hospital Universitario de la Princesa, Madrid (Spain); Fernandez, Inmaculada; Rabadan, Mariano [Department of Urology, Hospital Universitario de la Princesa, Madrid (Spain)

2011-12-01

Purpose: To analyze long-term outcome and prognostic factors for high-risk prostate cancer defined by National Comprehensive Cancer Network criteria treated with high-dose radiotherapy and androgen deprivation in a single institution. Methods and Materials: A total of 306 patients treated between 1995 and 2007 in a radiation dose-escalation program fulfilled the National Comprehensive Cancer Network high-risk criteria. Median International Commission on Radiation Units and Measurements radiation dose was 78 Gy (range, 66.0-84.1 Gy). Long-term androgen deprivation (LTAD) was administered in 231 patients, short-term androgen deprivation (STAD) in 59 patients, and no hormones in 16 patients. The Phoenix (nadir plus 2 ng/mL) consensus definition was used for biochemical control. Multivariate analysis was performed to determine the independent prognostic impact of clinical and treatment factors. Median follow-up time was 64 months (range, 24-171 months). Results: The actuarial overall survival at 5 and 10 years was 95.7% and 89.8%, respectively, and the corresponding biochemical disease-free survival (bDFS) was 89.5% and 67.2%, respectively. Fourteen patients (4.6%) developed distant metastasis. Multivariate analysis showed that Gleason score >7 (p = 0.001), pretreatment prostate-specific antigen (PSA) level >20 ng/mL (p = 0.037), higher radiation dose (p = 0.005), and the use of adjuvant LTAD vs. STAD (p = 0.011) were independent prognostic factors affecting bDFS in high-risk disease. The 5-year bDFS for patients treated with LTAD plus radiotherapy dose >78 Gy was 97%. Conclusions: For high-risk patients the present series showed that the use of LTAD in conjunction with higher doses (>78 Gy) of radiotherapy was associated with improved biochemical tumor control. We observed that the presence of Gleason sum >7 and pretreatment PSA level >20 ng/mL in the same patient represents a 6.8 times higher risk of PSA failure. These men could be considered for clinical trials with

Cystic fibrosis in adults. Short-term and long-term reproducibility of the Brody score for lung morphology in low-dose MDCT scans

Energy Technology Data Exchange (ETDEWEB)

Weber, K.; Paolini, M.; Schmitz, M.; Coppenrath, E.; Reiser, M.; Mueller-Lisse, U.G. [Ludwig-Maximilians-Univ. Muenchen (Germany). Inst. fuer Klinische Radiologie; Fischer, R.; Huber, R. [Ludwig-Maximilians-Univ. Muenchen (Germany). Medical Hospital V

2014-01-15

Purpose: The semi-quantitative Brody score measures the severity of cystic fibrosis (CF)-related lung disease. We investigated the short-term (28 - 60 days) and long-term (2 - 7 years) intra- and inter-observer reproducibility of the Brody score in low-dose multidetector row computed tomography examinations performed in inspiration (LDCTs) of adult CF patients. Materials and Methods: Composite Brody scores and respective underlying bronchiectasis, mucus plugging, peribronchial thickening, parenchymal opacity, and hyperinflation subscores were evaluated twice (time interval, 1 - 84 months) by each of 3 independent radiologists (1 - 20 years of professional diagnostic radiology experience) in LDCTs (4 - 64 rows, 120 KVp, 10 - 15 mAs/slice, CTDIw approx. 1.0 mGy, effective dose approx. 0.5 mSv) of 15 adult patients with CF-related lung disease (8 female, 7 male, age, 18 - 50 years, mean, 33 years). Results: The average reproducibility of the Brody score was within +/-7 % (range, 2 - 30 %) between radiologists, and +/-6 % (3 - 12 %) within radiologists (short-term, 28 - 60 days, 4 %, 0 - 12 %, long-term, 2 - 7 years, 12 %, 1 - 36 %). For the different subscores, the reproducibility was within +/-25 % (15 - 41 %) between radiologists and +/-23 % (12 - 46 %) within radiologists. Conclusion: The Brody score shows high average inter-observer reproducibility in LDCTs of adult CF patients. The Brody score also demonstrates high average intra-observer reproducibility if subsequent assessments are made within 28 - 61 days. With time intervals of 2 - 7 years between subsequent evaluations, however, intra-observer reproducibility decreases. Respective subscores each demonstrate lower intra- and inter-observer reproducibility than does the composite Brody score. (orig.)

Metronomic Treatment with Low-Dose Trofosfamide Leads to a Long-Term Remission in a Patient with Docetaxel-Refractory Advanced Metastatic Prostate Cancer

Directory of Open Access Journals (Sweden)

Jochen Greiner

2010-01-01

Full Text Available The treatment of metastatic prostate cancer patients refractory to androgen withdrawal and docetaxel therapy is currently discouraging and new therapeutic approaches are vastly needed. Here, we report a long-term remission over one year in a 68-year-old patient with metastatic docetaxel-refractory prostate cancer employing low-dose trofosfamide. The patient suffered from distant failure with several bone lesions and lymph node metastases depicted by a (11 C-Choline positron emission tomography/computerized tomography (PET/CT. After initiation of trofosfamide 100 mg taken orally once a day we observed a steadily decreasing PSA value from initial 46.6 down to 2.1 g/l. The Choline-PET/CT was repeated after 10 months of continuous therapy and demonstrated a partial remission of the bone lesions and a regression of all involved lymph nodes but one. Taken together we found an astonishing and durable activity of the alkylating agent trofosfamide given in a metronomic fashion. We rate the side effects as low and state an excellent therapeutic ratio of this drug in our patient.

Effects of dose, sex, and long-term abstention from use on toxic effects of MDMA (ecstasy) on brain serotonin neurons

NARCIS (Netherlands)

Reneman, L.; Booij, J.; de Bruin, K.; Reitsma, J. B.; de Wolff, F. A.; Gunning, W. B.; den Heeten, G. J.; van den Brink, W.

2001-01-01

BACKGROUND: 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) is a popular recreational drug that has been shown to damage brain serotonin neurons in high doses. However, effects of moderate MDMA use on serotonin neurons have not been studied, and sex differences and the long-term effects of MDMA

Radiation dose exposure in patients affected by lymphoma undergoing repeat CT examinations: how to manage the radiation dose variability.

Science.gov (United States)

Paolicchi, Fabio; Bastiani, Luca; Guido, Davide; Dore, Antonio; Aringhieri, Giacomo; Caramella, Davide

2018-03-01

To assess the variability of radiation dose exposure in patients affected by lymphoma undergoing repeat CT (computed tomography) examinations and to evaluate the influence of different scan parameters on the overall radiation dose. A series of 34 patients (12 men and 22 women with a median age of 34.4 years) with lymphoma, after the initial staging CT underwent repeat follow-up CT examinations. For each patient and each repeat examination, age, sex, use of AEC system (Automated Exposure Control, i.e. current modulation), scan length, kV value, number of acquired scans (i.e. number of phases), abdominal size diameter and dose length product (DLP) were recorded. The radiation dose of just one venous phase was singled out from the DLP of the entire examination. All scan data were retrieved by our PACS (Picture Archiving and Communication System) by means of a dose monitoring software. Among the variables we considered, no significant difference of radiation dose was observed among patients of different ages nor concerning tube voltage. On the contrary the dose delivered to the patients varied depending on sex, scan length and usage of AEC. No significant difference was observed depending on the behaviour of technologists, while radiologists' choices had indirectly an impact on the radiation dose due to the different number of scans requested by each of them. Our results demonstrate that patients affected by lymphoma who undergo repeat whole body CT scanning may receive unnecessary overexposure. We quantified and analyzed the most relevant variables in order to provide a useful tool to manage properly CT dose variability, estimating the amount of additional radiation dose for every single significant variable. Additional scans, incorrect scan length and incorrect usage of AEC system are the most relevant cause of patient radiation exposure.

Long-term potentiation and olfactory memory formation in the carp (Cyprinus carpio L.) olfactory bulb.

Science.gov (United States)

Satou, M; Anzai, S; Huruno, M

2005-05-01

Long-term potentiation of synaptic transmission is considered to be an elementary process underlying the cellular mechanism of memory formation. In the present study we aimed to examine whether or not the dendrodendritic mitral-to-granule cell synapses in the carp olfactory bulb show plastic changes after their repeated activation. It was found that: (1) the dendrodendritic mitral-to-granule cell synapses showed three types of plasticity after tetanic electrical stimulation applied to the olfactory tract-long-term potentiation (potentiation lasting >1 h), short-term potentiation (potentiation lasting 1 h) of the odor-evoked bulbar response accompanied the electrically-induced LTP, and; (4) repeated olfactory stimulation enhanced dendrodendritic mitral-to-granule cell transmission. Based on these results, it was proposed that long-term potentiation (as well as olfactory memory) occurs at the dendrodendritic mitral-to-granule cell synapses after strong and long-lasting depolarization of granule cells, which follows repeated and simultaneous synaptic activation of both the peripheral and deep dendrites (or somata).

Bleeding Risk with Long-Term Low-Dose Aspirin: A Systematic Review of Observational Studies

Science.gov (United States)

García Rodríguez, Luis A.; Martín-Pérez, Mar; Hennekens, Charles H.; Rothwell, Peter M.; Lanas, Angel

2016-01-01

Background Low-dose aspirin has proven effectiveness in secondary and primary prevention of cardiovascular events, but is also associated with an increased risk of major bleeding events. For primary prevention, this absolute risk must be carefully weighed against the benefits of aspirin; such assessments are currently limited by a lack of data from general populations. Methods Systematic searches of Medline and Embase were conducted to identify observational studies published between 1946 and 4 March 2015 that reported the risks of gastrointestinal (GI) bleeding or intracranial hemorrhage (ICH) with long-term, low-dose aspirin (75–325 mg/day). Pooled estimates of the relative risk (RR) for bleeding events with aspirin versus non-use were calculated using random-effects models, based on reported estimates of RR (including odds ratios, hazard ratios, incidence rate ratios and standardized incidence ratios) in 39 articles. Findings The incidence of GI bleeding with low-dose aspirin was 0.48–3.64 cases per 1000 person-years, and the overall pooled estimate of the RR with low-dose aspirin was 1.4 (95% confidence interval [CI]: 1.2–1.7). For upper and lower GI bleeding, the RRs with low-dose aspirin were 2.3 (2.0–2.6) and 1.8 (1.1–3.0), respectively. Neither aspirin dose nor duration of use had consistent effects on RRs for upper GI bleeding. The estimated RR for ICH with low-dose aspirin was 1.4 (1.2–1.7) overall. Aspirin was associated with increased bleeding risks when combined with non-steroidal anti-inflammatory drugs, clopidogrel and selective serotonin reuptake inhibitors compared with monotherapy. By contrast, concomitant use of proton pump inhibitors decreased upper GI bleeding risks relative to aspirin monotherapy. Conclusions The risks of major bleeding with low-dose aspirin in real-world settings are of a similar magnitude to those reported in randomized trials. These data will help inform clinical judgements regarding the use of low-dose aspirin

Toxicological Effects of Caco-2 Cells Following Short-Term and Long-Term Exposure to Ag Nanoparticles

Directory of Open Access Journals (Sweden)

Ni Chen

2016-06-01

Full Text Available Extensive utilization increases the exposure of humans to Ag nanoparticles (NPs via the oral pathway. To comprehensively address the action of Ag NPs to the gastrointestinal systems in real situations, i.e., the long-term low-dose exposure, we evaluated and compared the toxicity of three Ag NPs (20–30 nm with different surface coatings to the human intestine cell Caco-2 after 1-day and 21-day exposures, using various biological assays. In both the short- and long-term exposures, the variety of surface coating predominated the toxicity of Ag NPs in a descending order of citrate-coated Ag NP (Ag-CIT, bare Ag NP (Ag-B, and poly (N-vinyl-2-pyrrolidone-coated Ag NP (Ag-PVP. The short-term exposure induced cell growth inhibition and death. The cell viability loss appeared after cells were exposed to 0.7 μg/mL Ag-CIT, 0.9 μg/mL Ag-B or >1.0 μg/mL Ag-PVP for 24 h. The short-term and higher-dose exposure also induced reactive oxygen species (ROS generation, mitochondrial damage, cell membrane leakage, apoptosis, and inflammation (IL-8 level. The long-term exposure only inhibited the cell proliferation. After 21-day exposure to 0.4 μg/mL Ag-CIT, the cell viability dropped to less than 50%, while cells exposed to 0.5 μg/mL Ag-PVP remained normal as the control. Generally, 0.3 μg/mL is the non-toxic dose for the long-term exposure of Caco-2 cells to Ag NPs in this study. However, cells presented inflammation after exposure to Ag NPs with the non-toxic dose in the long-term exposure.

Utility of repeated praziquantel dosing in the treatment of schistosomiasis in high-risk communities in Africa: a systematic review.

Directory of Open Access Journals (Sweden)

Charles H King

2011-09-01

Full Text Available Controversy persists about the optimal approach to drug-based control of schistosomiasis in high-risk communities. In a systematic review of published studies, we examined evidence for incremental benefits from repeated praziquantel dosing, given 2 to 8 weeks after an initial dose, in Schistosoma-endemic areas of Africa.We performed systematic searches of electronic databases PubMed and EMBASE for relevant data using search terms 'schistosomiasis', 'dosing' and 'praziquantel' and hand searches of personal collections and bibliographies of recovered articles. In 10 reports meeting study criteria, improvements in parasitological treatment outcomes after two doses of praziquantel were greater for S. mansoni infection than for S. haematobium infection. Observed cure rates (positive to negative conversion in egg detection assays were, for S. mansoni, 69-91% cure after two doses vs. 42-79% after one dose and, for S. haematobium, 46-99% cure after two doses vs. 37-93% after a single dose. Treatment benefits in terms of reduction in intensity (mean egg count were also different for the two species-for S. mansoni, the 2-dose regimen yielded an weighted average 89% reduction in standardized egg counts compared to a 83% reduction after one dose; for S. haematobium, two doses gave a 93% reduction compared to a 94% reduction with a single dose. Cost-effectiveness analysis was performed based on Markov life path modeling.Although schedules for repeated treatment with praziquantel require greater inputs in terms of direct costs and community participation, there are incremental benefits to this approach at an estimated cost of $153 (S. mansoni-$211 (S. haematobium per additional lifetime QALY gained by double treatment in school-based programs. More rapid reduction of infection-related disease may improve program adherence, and if, as an externality of the program, transmission can be reduced through more effective coverage, significant additional benefits are

Dose measurements and LET-determination in space station MIR during the Russian long term flight RLF

International Nuclear Information System (INIS)

Vana, N.; Schoener, N.; Fugger, M.; Akatov, Y.; Shurshakov, V.

1996-01-01

For determination of the absorbed dose and the dose equivalent in complex mixed radiation fields, new methods were developed in the frame of the Austrian-Soviet space mission AUSTROMIR in October 1991. The method utilizes the changes of peak height ratios in thermoluminescence glowcurves. Peak height ratios depend on the linear energy transfer (LET) of absorbed radiation. This effect was calibrated in different radiation fields (alpha-, beta-, gamma-, neutron fields and heavy charged particle beams). The method was approached for dose measurements during several space programs (DOSIMIR, BION-10, PHOTONS). During the Russian long term flight RLF six dosemeter packets were exposed in three different periods. Two positions with different shielding (the working area and the cabin of the board engineer) were chosen for the exposition of the dosemeters during each period in order to measure the variation of absorbed dose as well as the variation of average LET of absorbed radiation within the habitable part of space station MIR. These results will be compared with the results during two former periods of measurements on space station MIR (AUSTROMIR/DOSIMIR) and results obtained inside of biosatellite BION-10 and during the space shuttle mission STS-60. (author)

Long-term tolerance and outcomes for dose escalation in early salvage post-prostatectomy radiation therapy

International Nuclear Information System (INIS)

Safdieh, Joseph; Schwartz, David; Weiner, Joseph; Weiss, Jeffrey P.; Madeb, Isaac; Rotman, Marvin; Schreiber, David; Rineer, Justin

2014-01-01

To study the long-term outcomes and tolerance in our patients who received dose escalated radiotherapy in the early salvage post-prostatectomy setting. The medical records of 54 consecutive patients who underwent radical prostatectomy subsequently followed by salvage radiation therapy (SRT) to the prostate bed between 2003-2010 were analyzed. Patients included were required to have a pre-radiation prostate specific antigen level (PSA) of 2 ng/mL or less. The median SRT dose was 70.2 Gy. Biochemical failure after salvage radiation was defined as a PSA level >0.2 ng/mL. Biochemical control and survival endpoints were analyzed using the Kaplan-Meier method. Univariate and multivariate Cox regression analysis were used to identify the potential impact of confounding factors on outcomes. The median pre-SRT PSA was 0.45 ng/mL and the median follow-up time was 71 months. The 4- and 7-year actuarial biochemical control rates were 75.7% and 63.2%, respectively. The actuarial 4- and 7-year distant metastasis-free survival was 93.7% and 87.0%, respectively, and the actuarial 7-year prostate cancer specific survival was 94.9%. Grade 3 late genitourinary toxicity developed in 14 patients (25.9%), while grade 4 late genitourinary toxicity developed in 2 patients (3.7%). Grade 3 late gastrointestinal toxicity developed in 1 patient (1.9%), and grade 4 late gastrointestinal toxicity developed in 1 patient (1.9%). In this series with long-term follow-up, early SRT provided outcomes and toxicity profiles similar to those reported from the three major randomized trials studying adjuvant radiation therapy.

Corticosterone stress response shows long-term repeatability and links to personality in free-living Nazca boobies.

Science.gov (United States)

Grace, Jacquelyn K; Anderson, David J

2014-11-01

The concept of "coping styles", or consistently different responses to stressors, is of broad interest in behavioral ecology and biomedicine. Two critical predictions of this concept are individual consistency of neurophysiological and behavioral responses (relative to population variability) and a negative relationship between aggression/proactivity and hypothalamic-pituitary-adrenal axis reactivity. Recent studies failed to provide strong support for these predictions, especially outside of strictly controlled conditions, and long-term measures to test the first prediction are rare. Here, we demonstrate individual repeatability across 2-3years of maximum circulating corticosterone concentration [CORT] and area under the [CORT] response curve (AUCI) during a standard capture-restraint test in wild, free-living adult Nazca boobies (Sula granti). We also show that the stress response predicts the personality traits aggression and anxiety in these birds (measured in the wild); however, the strength of these results was weak. Maximum [CORT] and AUCI showed higher repeatability between years than baseline [CORT]. After controlling breeding status, sex, mass, date sampled, and their interactions, baseline [CORT] was most closely related to personality traits, followed by AUCI, and then maximum [CORT]. The direction of these relationships depended on whether the testing context was social or non-social. [CORT] parameters had little to no relationship with cross-context plasticity in personality traits. Our results generally affirm two critical predictions of coping styles, but match the emerging trend that these relationships are weak in the wild, and may depend on testing context. Copyright © 2014 Elsevier Inc. All rights reserved.

Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study.

Science.gov (United States)

Marincek, Nicolas; Jörg, Ann-Catherine; Brunner, Philippe; Schindler, Christian; Koller, Michael T; Rochlitz, Christoph; Müller-Brand, Jan; Maecke, Helmut R; Briel, Matthias; Walter, Martin A

2013-01-15

We describe the long-term outcome after clinical introduction and dose escalation of somatostatin receptor targeted therapy with [90Y-DOTA]-TOC in patients with metastasized neuroendocrine tumors. In a clinical phase I dose escalation study we treated patients with increasing [90Y-DOTA]-TOC activities. Multivariable Cox regression and competing risk regression were used to compare efficacy and toxicities of the different dosage protocols. Overall, 359 patients were recruited; 60 patients were enrolled for low dose (median: 2.4 GBq/cycle, range 0.9-7.8 GBq/cycle), 77 patients were enrolled for intermediate dose (median: 3.3 GBq/cycle, range: 2.0-7.4 GBq/cycle) and 222 patients were enrolled for high dose (median: 6.7 GBq/cycle, range: 3.7-8.1 GBq/cycle) [90Y-DOTA]-TOC treatment. The incidences of hematotoxicities grade 1-4 were 65.0%, 64.9% and 74.8%; the incidences of grade 4/5 kidney toxicities were 8.4%, 6.5% and 14.0%, and the median survival was 39 (range: 1-158) months, 34 (range: 1-118) months and 29 (range: 1-113) months. The high dose protocol was associated with an increased risk of kidney toxicity (Hazard Ratio: 3.12 (1.13-8.59) vs. intermediate dose, p = 0.03) and a shorter overall survival (Hazard Ratio: 2.50 (1.08-5.79) vs. low dose, p = 0.03). Increasing [90Y-DOTA]-TOC activities may be associated with increasing hematological toxicities. The dose related hematotoxicity profile of [90Y-DOTA]-TOC could facilitate tailoring [90Y-DOTA]-TOC in patients with preexisting hematotoxicities. The results of the long-term outcome suggest that fractionated [90Y-DOTA]-TOC treatment might allow to reduce renal toxicity and to improve overall survival. (ClinicalTrials.gov number NCT00978211).

Introduction of long term cycle of reactor operation

International Nuclear Information System (INIS)

Aoyati, M.; Tanaka, T.

2004-01-01

Introduction of long term cycle of LWR reactor operation at NPP in Japan is considered, and problems of technical, legislative and economical character, increase of power coefficient are discussed. More long term operation period provides decreasing frequency of periodic inspections and reduction of personnel radiation doses. Reliability of fuel, energetic equipment, mechanisms and devices must be taken into account for the decision of technical problems. Consumptions for electric power generation are studied [ru

The Effect of Dose Rate on Composite Durability When Exposed to a Simulated Long-Term Lunar Radiation Environment

Science.gov (United States)

Rojdev, Kristina; O'Rourke, Mary Jane; Hill, Charles; Nutt, Steven; Atwell, William

2011-01-01

Human exploration of space beyond low Earth orbit (LEO) requires a safe living and working environment for crew. Composite materials are one type of material being investigated by NASA as a multi-functional structural approach to habitats for long-term use in space or on planetary surfaces with limited magnetic fields and atmosphere. These materials provide high strength with the potential for decreased weight and increased radiation protection of crew and electronics when compared with conventional aluminum structures. However, these materials have not been evaluated in a harsh radiation environment, as would be experienced outside of LEO or on a planetary surface. Thus, NASA has been investigating the durability of select composite materials in a long-term radiation environment. Previously, NASA exposed composite samples to a simulated, accelerated 30-year radiation treatment and tensile stresses similar to those of a habitat pressure vessel. The results showed evidence of potential surface oxidation and enhanced cross-linking of the matrix. As a follow-on study, we performed the same accelerated exposure alongside an exposure with a decreased dose rate. The slower dose ]rate is comparable to a realistic scenario, although still accelerated. Strain measurements were collected during exposure and showed that with a fastdose rate, the strain decreased with time, but with a slow ]dose rate, the strain increased with time. After the radiation exposures, samples were characterized via tensile tests, flexure tests, Fourier Transform Infrared Spectroscopy (FTIR), and Differential Scanning Calorimetry (DSC). The results of these tests will be discussed.

Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium elegans Extract Administration to Rats.

Science.gov (United States)

Choi, Jia; Ryu, Su-Jung; Kim, Kui-Jin; Kim, Hyung-Min; Chung, Hee-Chul; Lee, Boo-Yong

2018-01-20

Gelidium elegans extract (GEE) is derived from a red alga from the Asia-Pacific region, which has antioxidant, anti-adipogenic, and anti-hyperglycemic effects. However, detailed studies of the toxicology of GEE have not been performed. We evaluated the single oral dose toxicity of GEE in male and female Sprague-Dawley (CD) rats. GEE did not cause deaths or have toxic effects at dosages of 5000 mg/kg/day, although compound-colored stools and diarrhea were observed in both sexes, which lasted 5000 mg/kg. We next evaluated the repeated oral dose toxicity of GEE in CD rats over 14 days and 13 weeks. GEE did not induce any significant toxicological changes in either sex at 2000 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects, in terms of clinical signs, mortality, body mass, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy, organ masses, or histopathology, at dosages of 500, 1000, or 2000 mg/kg/day. The no observed adverse effect level (NOAEL) for GEE is thus likely to be >2000 mg/kg/day, and no pathology was identified in potential target organs. Therefore, this study indicates that repeated oral dosing with GEE is safe in CD rats.

Short- and long-term reproducibility of radioisotopic examination of gastric emptying

Energy Technology Data Exchange (ETDEWEB)

Jonderko, K. (Silesian School of Medicine, Katowice (Poland). Dept. of Gastroenterology)

1990-01-01

Reproducibility of gastric emptying (GE) of a radiolabelled solid meal was assessed. The short-term reproducibility was evaluated on the basis of 12 paired GE examinations performed 1-3 days apart. Twelve paired GE examinations taken 3-8 months apart enabled long-term reproducibility assessment. Reproducibility of GE parameters was expressed in terms of the coefficient of variation, CV. No significant between-day variation of solid GE was found either regarding the short-term or the long-term reproducibility. Although slightly higher CV values characterized the long-term reproducibility of the GE parameters considered, the variations of the differences between repeated GE examinations did not differ significantly between short- and long-term GE reproducibility. The results obtained justify the use of radioisotopic GE measurement for the assessment of early and late results of pharmacologic or surgical management. (author).

An Improved Methodology of Monetary Values of the Unit Collective Dose for Intervention Against Long-Term Exposure Following a Nuclear Accident

International Nuclear Information System (INIS)

Hwang, Won Tae; Kim, Eun Han; Suh, Kyung Suk; Choi, Young Gil; Han, Moon Hee

2002-01-01

A more practice approach for the determination of monetary values of the unit collective dose for intervention against long-term exposure following a nuclear accident was proposed. In addition, the monetary values of the unit collective dose estimated from the proposed approach were compared with those estimated from the previous model, which are derived from assumptions of routine exposure and the same values are applied in a nuclear accident without modification, using Korea economic data. The monetary values based on the proposed approach showed a distinct difference depending on inequity in the distribution of individual doses. The discounting rate was also an important factor in determination of monetary values of the unit collective dose

An Improved Methodology of Monetary Values of the Unit Collective Dose for Intervention Against Long-Term Exposure Following a Nuclear Accident

Energy Technology Data Exchange (ETDEWEB)

Hwang, Won Tae; Kim, Eun Han; Suh, Kyung Suk; Choi, Young Gil; Han, Moon Hee [KAERI, Daejeon (Korea, Republic of)

2002-06-15

A more practice approach for the determination of monetary values of the unit collective dose for intervention against long-term exposure following a nuclear accident was proposed. In addition, the monetary values of the unit collective dose estimated from the proposed approach were compared with those estimated from the previous model, which are derived from assumptions of routine exposure and the same values are applied in a nuclear accident without modification, using Korea economic data. The monetary values based on the proposed approach showed a distinct difference depending on inequity in the distribution of individual doses. The discounting rate was also an important factor in determination of monetary values of the unit collective dose.

Interactions between cannabidiol and Δ9-THC following acute and repeated dosing: Rebound hyperactivity, sensorimotor gating and epigenetic and neuroadaptive changes in the mesolimbic pathway.

Science.gov (United States)

Todd, Stephanie M; Zhou, Cilla; Clarke, David J; Chohan, Tariq W; Bahceci, Dilara; Arnold, Jonathon C

2017-02-01

The evidence base for the use of medical cannabis preparations containing specific ratios of cannabidiol (CBD) and Δ 9 -tetrahydrocannabinol (THC) is limited. While there is abundant data on acute interactions between CBD and THC, few studies have assessed the impact of their repeated co-administration. We previously reported that CBD inhibited or potentiated the acute effects of THC dependent on the measure being examined at a 1:1 CBD:THC dose ratio. Further, CBD decreased THC effects on brain regions involved in memory, anxiety and body temperature regulation. Here we extend on these finding by examining over 15 days of treatment whether CBD modulated the repeated effects of THC on behaviour and neuroadaption markers in the mesolimbic dopamine pathway. After acute locomotor suppression, repeated THC caused rebound locomotor hyperactivity that was modestly inhibited by CBD. CBD also slightly reduced the acute effects of THC on sensorimotor gating. These subtle effects were found at a 1:1 CBD:THC dose ratio but were not accentuated by a 5:1 dose ratio. CBD did not alter the trajectory of enduring THC-induced anxiety nor tolerance to the pharmacological effects of THC. There was no evidence of CBD potentiating the behavioural effects of THC. However we demonstrated for the first time that repeated co-administration of CBD and THC increased histone 3 acetylation (H3K9/14ac) in the VTA and ΔFosB expression in the nucleus accumbens. These changes suggest that while CBD may have protective effects acutely, its long-term molecular actions on the brain are more complex and may be supradditive. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Patient Outcomes in Dose Reduction or Discontinuation of Long-Term Opioid Therapy: A Systematic Review.

Science.gov (United States)

Frank, Joseph W; Lovejoy, Travis I; Becker, William C; Morasco, Benjamin J; Koenig, Christopher J; Hoffecker, Lilian; Dischinger, Hannah R; Dobscha, Steven K; Krebs, Erin E

2017-08-01

Expert guidelines recommend reducing or discontinuing long-term opioid therapy (LTOT) when risks outweigh benefits, but evidence on the effect of dose reduction on patient outcomes has not been systematically reviewed. To synthesize studies of the effectiveness of strategies to reduce or discontinue LTOT and patient outcomes after dose reduction among adults prescribed LTOT for chronic pain. MEDLINE, EMBASE, PsycINFO, CINAHL, and the Cochrane Library from inception through April 2017; reference lists; and expert contacts. Original research published in English that addressed dose reduction or discontinuation of LTOT for chronic pain. Two independent reviewers extracted data and assessed study quality using the U.S. Preventive Services Task Force quality rating criteria. All authors assessed evidence quality using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Prespecified patient outcomes were pain severity, function, quality of life, opioid withdrawal symptoms, substance use, and adverse events. Sixty-seven studies (11 randomized trials and 56 observational studies) examining 8 intervention categories, including interdisciplinary pain programs, buprenorphine-assisted dose reduction, and behavioral interventions, were found. Study quality was good for 3 studies, fair for 13 studies, and poor for 51 studies. Many studies reported dose reduction, but rates of opioid discontinuation ranged widely across interventions and the overall quality of evidence was very low. Among 40 studies examining patient outcomes after dose reduction (very low overall quality of evidence), improvement was reported in pain severity (8 of 8 fair-quality studies), function (5 of 5 fair-quality studies), and quality of life (3 of 3 fair-quality studies). Heterogeneous interventions and outcome measures; poor-quality studies with uncontrolled designs. Very low quality evidence suggests that several types of interventions may be effective to reduce or

Long-term heart function after adjuvant epirubicin chemotherapy for breast cancer

DEFF Research Database (Denmark)

Appel, Jon M; Zerahn, Bo; Møller, Susanne

2012-01-01

Newer studies raise concern that adjuvant anthracycline treatment for breast cancer (BC) causes long-term heart damage. We aimed to examine whether heart failure or impairment could be demonstrated several years after low-dose epirubicin-based adjuvant treatment.......Newer studies raise concern that adjuvant anthracycline treatment for breast cancer (BC) causes long-term heart damage. We aimed to examine whether heart failure or impairment could be demonstrated several years after low-dose epirubicin-based adjuvant treatment....

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.

Long-term psychosocial consequences of surgical congenital malformations.

Science.gov (United States)

Diseth, Trond H; Emblem, Ragnhild

2017-10-01

Surgical congenital malformations often represent years of treatment, large number of hospital stays, treatment procedures, and long-term functional sequels affecting patients' psychosocial functioning. Both functional defects and psychosocial difficulties that occur commonly in childhood may pass through adolescence on to adulthood. This overview presents reports published over the past 3 decades to elucidate the long-term psychosocial consequences of surgical congenital malformations. Literature searches conducted on PubMed database revealed that less than 1% of all the records of surgical congenital malformations described long-term psychosocial consequences, but with diverse findings. This inconsistency may be due to methodological differences or deficiencies; especially in study design, patient sampling, and methods. Most of the studies revealed that the functional deficits may have great impact on patients' mental health, psychosocial functioning, and QoL; both short- and long-term negative consequences. Factors other than functional problems, e.g., repeated anesthesia, multiple hospitalization, traumatic treatment procedures, and parental dysfunctioning, may also predict long-term mental health and psychosocial functioning. Through multidisciplinary approach, pediatric surgeons should also be aware of deficits in emotional and psychosocial functioning. To achieve overall optimal psychosocial functioning, the challenge is to find a compromise between physically optimal treatment procedures and procedures that are not psychologically detrimental. Copyright © 2017. Published by Elsevier Inc.

Conditioning radium needles for long term storage : Sri Lankan experience

International Nuclear Information System (INIS)

Ranjith, H.L.A.; Shantha, T.H.S.; Gunaratne, M.G.J.; De Silva, U.W.K.H.; Perera, H.P.H.

2000-01-01

Radium the first radioisotope invented by Madame Curie was used for cancer therapy for the intracavitory treatment of cervical cancers and as oral implants etc. Radium needles and other geometries were made in standard strengths and Radium therapy enjoyed a heyday during the 1st half of the 20th century. Radium-226 is a long-lived radioactive material with a half-life of 1600 years. The use of radium was abandoned in the world in 1980s with the invention of short lived radioactive materials offering remote after loading systems which minimise radiation protection and waste disposal problems associated with long lived radioactive materials. This paper reports the conditioning procedure of the spent radium sources for long term storage (less than 20 years) and transport to national/ international stores if needed. The dose received by those involved in this exercise is also discussed in terms of radiation protection. The Ra was contained for long term storage according to international radiation safety regulations with a surface dose of less than 2 mSv per hour in a conditioned package having 17.5 GBq activity and can be transported to national/international stores if needed. The highest dose received during the exercise is well within the recommended dose limits for occupational exposures (20 and 500 mSv per year) for whole body and extremities respectively

In vitro chondrocyte toxicity following long-term, high-dose exposure to Gd-DTPA and a novel cartilage-targeted MR contrast agent

Energy Technology Data Exchange (ETDEWEB)

Midura, Sharon; Midura, Ronald J. [Cleveland Clinic, Biomedical Engineering, Lerner Research Institute, Cleveland, OH (United States); Schneider, Erika [Cleveland Clinic, Imaging Institute, A21, Cleveland, OH (United States); NitroSci Pharmaceuticals, New Berlin, WI (United States); Rosen, Gerald M. [University of Maryland School of Pharmacy, Department of Pharmaceutical Sciences, Baltimore, MD (United States); NitroSci Pharmaceuticals, New Berlin, WI (United States); Winalski, Carl S. [Cleveland Clinic, Biomedical Engineering, Lerner Research Institute, Cleveland, OH (United States); Cleveland Clinic, Imaging Institute, A21, Cleveland, OH (United States)

2017-01-15

To determine the concentrations exhibiting toxicity of a cartilage-targeted magnetic resonance imaging contrast agent compared with gadopentetate dimeglumine (Gd-DT-PA) in chondrocyte cultures. A long-term Swarm rat chondrosarcoma chondrocyte-like cell line was exposed for 48 h to 1.0-20 mM concentrations of diaminobutyl-linked nitroxide (DAB4-DLN) citrate, 1.0-20 mM Gd-DTPA, 1.0 μM staurosporine (positive control), or left untreated. Cell appearance, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays of metabolic activity, quantitative PicoGreen assays of DNA content, and calcein-AM viability assays were compared. At 1.0-7.5 mM, minimal decrease in cell proliferation was found for both agents. At all doses of both agents, cell culture appearances were similar after 24 h of treatment. At the higher doses, differences in cell culture appearance were found after 48 h of treatment, with dose-dependent declines in chondrocyte populations for both agents. Concentration-dependent declines in DNA content and calcein fluorescence were found after 48 h of treatment, but beginning at a lower dose of DAB4-DLN citrate than Gd-DTPA. Dose-dependent decreases in MTT staining (cell metabolism) were apparent for both agents, but larger effects were evident at a lower dose for DAB-DLN citrate. Poor MTT staining of cells exposed for 48 h to 20 mM DAB4-DLN citrate probably indicates dead or dying cells. The minimal effect of the long-term exposure of model chondrocyte cell cultures to DAB4-DLN citrate and Gd-DTPA concentrations up to 7.5 mM (3x typical arthrographic administration) is supporting evidence that these doses are acceptable for MR arthrography. The findings are reassuring given that the experimental exposure to the contrast agents at sustained concentrations was much longer than when used clinically. (orig.)

In vitro chondrocyte toxicity following long-term, high-dose exposure to Gd-DTPA and a novel cartilage-targeted MR contrast agent

International Nuclear Information System (INIS)

Midura, Sharon; Midura, Ronald J.; Schneider, Erika; Rosen, Gerald M.; Winalski, Carl S.

2017-01-01

To determine the concentrations exhibiting toxicity of a cartilage-targeted magnetic resonance imaging contrast agent compared with gadopentetate dimeglumine (Gd-DT-PA) in chondrocyte cultures. A long-term Swarm rat chondrosarcoma chondrocyte-like cell line was exposed for 48 h to 1.0-20 mM concentrations of diaminobutyl-linked nitroxide (DAB4-DLN) citrate, 1.0-20 mM Gd-DTPA, 1.0 μM staurosporine (positive control), or left untreated. Cell appearance, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays of metabolic activity, quantitative PicoGreen assays of DNA content, and calcein-AM viability assays were compared. At 1.0-7.5 mM, minimal decrease in cell proliferation was found for both agents. At all doses of both agents, cell culture appearances were similar after 24 h of treatment. At the higher doses, differences in cell culture appearance were found after 48 h of treatment, with dose-dependent declines in chondrocyte populations for both agents. Concentration-dependent declines in DNA content and calcein fluorescence were found after 48 h of treatment, but beginning at a lower dose of DAB4-DLN citrate than Gd-DTPA. Dose-dependent decreases in MTT staining (cell metabolism) were apparent for both agents, but larger effects were evident at a lower dose for DAB-DLN citrate. Poor MTT staining of cells exposed for 48 h to 20 mM DAB4-DLN citrate probably indicates dead or dying cells. The minimal effect of the long-term exposure of model chondrocyte cell cultures to DAB4-DLN citrate and Gd-DTPA concentrations up to 7.5 mM (3x typical arthrographic administration) is supporting evidence that these doses are acceptable for MR arthrography. The findings are reassuring given that the experimental exposure to the contrast agents at sustained concentrations was much longer than when used clinically. (orig.)

Whole-Body Exposure to 28Si-Radiation Dose-Dependently Disrupts Dentate Gyrus Neurogenesis and Proliferation in the Short Term and New Neuron Survival and Contextual Fear Conditioning in the Long Term.

Science.gov (United States)

Whoolery, Cody W; Walker, Angela K; Richardson, Devon R; Lucero, Melanie J; Reynolds, Ryan P; Beddow, David H; Clark, K Lyles; Shih, Hung-Ying; LeBlanc, Junie A; Cole, Mara G; Amaral, Wellington Z; Mukherjee, Shibani; Zhang, Shichuan; Ahn, Francisca; Bulin, Sarah E; DeCarolis, Nathan A; Rivera, Phillip D; Chen, Benjamin P C; Yun, Sanghee; Eisch, Amelia J

2017-11-01

Astronauts traveling to Mars will be exposed to chronic low doses of galactic cosmic space radiation, which contains highly charged, high-energy (HZE) particles. 56 Fe-HZE-particle exposure decreases hippocampal dentate gyrus (DG) neurogenesis and disrupts hippocampal function in young adult rodents, raising the possibility of impaired astronaut cognition and risk of mission failure. However, far less is known about how exposure to other HZE particles, such as 28 Si, influences hippocampal neurogenesis and function. To compare the influence of 28 Si exposure on indices of neurogenesis and hippocampal function with previous studies on 56 Fe exposure, 9-week-old C57BL/6J and Nestin-GFP mice (NGFP; made and maintained for 10 or more generations on a C57BL/6J background) received whole-body 28 Si-particle-radiation exposure (0, 0.2 and 1 Gy, 300 MeV/n, LET 67 KeV/μ, dose rate 1 Gy/min). For neurogenesis assessment, the NGFP mice were injected with the mitotic marker BrdU at 22 h postirradiation and brains were examined for indices of hippocampal proliferation and neurogenesis, including Ki67 + , BrdU + , BrdU + NeuN + and DCX + cell numbers at short- and long-term time points (24 h and 3 months postirradiation, respectively). In the short-term group, stereology revealed fewer Ki67 + , BrdU + and DCX + cells in 1-Gy-irradiated group relative to nonirradiated control mice, fewer Ki67 + and DCX + cells in 0.2 Gy group relative to control group and fewer BrdU + and DCX + cells in 1 Gy group relative to 0.2 Gy group. In contrast to the clearly observed radiation-induced, dose-dependent reductions in the short-term group across all markers, only a few neurogenesis indices were changed in the long-term irradiated groups. Notably, there were fewer surviving BrdU + cells in the 1 Gy group relative to 0- and 0.2-Gy-irradiated mice in the long-term group. When the short- and long-term groups were analyzed by sex, exposure to radiation had a similar effect on neurogenesis indices

Repeated dose titration versus age-based method in electroconvulsive therapy: a pilot study

NARCIS (Netherlands)

Aten, J.J.; Oudega, M.L.; van Exel, E.; Stek, M.L.; van Waarde, J.A.

2015-01-01

In electroconvulsive therapy (ECT), a dose titration method (DTM) was suggested to be more individualized and therefore more accurate than formula-based dosing methods. A repeated DTM (every sixth session and dose adjustment accordingly) was compared to an age-based method (ABM) regarding treatment

Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study

Directory of Open Access Journals (Sweden)

Marincek Nicolas

2013-01-01

Full Text Available Abstract Background We describe the long-term outcome after clinical introduction and dose escalation of somatostatin receptor targeted therapy with [90Y-DOTA]-TOC in patients with metastasized neuroendocrine tumors. Methods In a clinical phase I dose escalation study we treated patients with increasing [90Y-DOTA]-TOC activities. Multivariable Cox regression and competing risk regression were used to compare efficacy and toxicities of the different dosage protocols. Results Overall, 359 patients were recruited; 60 patients were enrolled for low dose (median: 2.4 GBq/cycle, range 0.9-7.8 GBq/cycle, 77 patients were enrolled for intermediate dose (median: 3.3 GBq/cycle, range: 2.0-7.4 GBq/cycle and 222 patients were enrolled for high dose (median: 6.7 GBq/cycle, range: 3.7-8.1 GBq/cycle [90Y-DOTA]-TOC treatment. The incidences of hematotoxicities grade 1–4 were 65.0%, 64.9% and 74.8%; the incidences of grade 4/5 kidney toxicities were 8.4%, 6.5% and 14.0%, and the median survival was 39 (range: 1–158 months, 34 (range: 1–118 months and 29 (range: 1–113 months. The high dose protocol was associated with an increased risk of kidney toxicity (Hazard Ratio: 3.12 (1.13-8.59 vs. intermediate dose, p = 0.03 and a shorter overall survival (Hazard Ratio: 2.50 (1.08-5.79 vs. low dose, p = 0.03. Conclusions Increasing [90Y-DOTA]-TOC activities may be associated with increasing hematological toxicities. The dose related hematotoxicity profile of [90Y-DOTA]-TOC could facilitate tailoring [90Y-DOTA]-TOC in patients with preexisting hematotoxicities. The results of the long-term outcome suggest that fractionated [90Y-DOTA]-TOC treatment might allow to reduce renal toxicity and to improve overall survival. (ClinicalTrials.gov number NCT00978211.

Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study

Science.gov (United States)

2013-01-01

Background We describe the long-term outcome after clinical introduction and dose escalation of somatostatin receptor targeted therapy with [90Y-DOTA]-TOC in patients with metastasized neuroendocrine tumors. Methods In a clinical phase I dose escalation study we treated patients with increasing [90Y-DOTA]-TOC activities. Multivariable Cox regression and competing risk regression were used to compare efficacy and toxicities of the different dosage protocols. Results Overall, 359 patients were recruited; 60 patients were enrolled for low dose (median: 2.4 GBq/cycle, range 0.9-7.8 GBq/cycle), 77 patients were enrolled for intermediate dose (median: 3.3 GBq/cycle, range: 2.0-7.4 GBq/cycle) and 222 patients were enrolled for high dose (median: 6.7 GBq/cycle, range: 3.7-8.1 GBq/cycle) [90Y-DOTA]-TOC treatment. The incidences of hematotoxicities grade 1–4 were 65.0%, 64.9% and 74.8%; the incidences of grade 4/5 kidney toxicities were 8.4%, 6.5% and 14.0%, and the median survival was 39 (range: 1–158) months, 34 (range: 1–118) months and 29 (range: 1–113) months. The high dose protocol was associated with an increased risk of kidney toxicity (Hazard Ratio: 3.12 (1.13-8.59) vs. intermediate dose, p = 0.03) and a shorter overall survival (Hazard Ratio: 2.50 (1.08-5.79) vs. low dose, p = 0.03). Conclusions Increasing [90Y-DOTA]-TOC activities may be associated with increasing hematological toxicities. The dose related hematotoxicity profile of [90Y-DOTA]-TOC could facilitate tailoring [90Y-DOTA]-TOC in patients with preexisting hematotoxicities. The results of the long-term outcome suggest that fractionated [90Y-DOTA]-TOC treatment might allow to reduce renal toxicity and to improve overall survival. Trial registration ClinicalTrials.gov number:NCT00978211 PMID:23320604

Osteomalacia and Fanconi's syndrome caused by long-term low-dose adefovir dipivoxil.

Science.gov (United States)

Wang, B-F; Wang, Y; Wang, B-Y; Sun, F-R; Zhang, D; Chen, Y-S

2015-06-01

Adefovir dipivoxil (ADV) is recommended for patients infected with lamivudine-refractory hepatitis B virus (HBV). We report a case of low-dose ADV-induced hypophosphatemic osteomalacia that initially presented as diffuse musculoskeletal pain. A 59-year-old Chinese man reported an 18-month history of severe chest wall pain and multiple bone pain during the previous 4 months with no antecedent trauma. There was no clinical evidence of an infectious, inflammatory or malignant process. Medical history showed that the patient had a history of chronic hepatitis B infection, and receiving lamivudine at a daily dose of 100 mg for 70 months. Lamivudine was changed to adefovir (10 mg/day) for the past 42 months. His serum inorganic phosphorus concentration was significantly low (0·4 mmol/l; 0·81-1·5 mmol/L), and the result of a urine routine test was abnormal. Combined with unbearable bone pain, spontaneous fractures, changes in laboratory markers and the result of ECT and other radiographic findings, the diagnosis of Fanconi's syndrome with osteomalacia was established. Dramatic clinical, laboratory and imaging improvement was observed after ADV discontinuation. This case indicates that Fanconi's syndrome with osteomalacia can be acquired by a chronic hepatitis B patient taking ADV at a conventional dosage of 10 mg/day. Therefore, patients with HBV treated with long-term ADV should be regularly monitored for renal function, serum calcium and serum phosphate. Urine testing for ion concentration should also be undertaken. © 2015 John Wiley & Sons Ltd.

Factors impacting short and long-term kidney graft survival: modification by single intra-operative -high-dose induction with ATG-Fresenius.

Science.gov (United States)

Kaden, Jürgen; May, Gottfried; Völp, Andreas; Wesslau, Claus

2011-01-01

A majority of recipients benefited from the intra-operative single high-dose induction (HDI) with ATG-Fresenius (ATG-F) still leaving a group of recipients who did not profit from this kind of induction. Therefore the aim of this retrospective analysis was 1st to identify the risk factors impacting short and long-term graft survival, and 2nd to assess the efficacy of this type of induction in kidney graft recipients with or without these risk factors. A total of 606 recipients receiving two different immunosuppressive treatment regimens (1st: Triple drug therapy [TDT, n=196] consisting mainly of steroids, azathioprine and cyclosporine; 2nd: TDT + 9 mg/kg ATG-F intra-operatively [HDI, n=410]) were included in this analysis and grouped according to their kidney graft survival time (short GST: ≤1 yr, n=100 and long GST: >5 yrs, n=506). The main risk factors associated with a shortened graft survival were pre-transplant sensitization, re-transplantation, rejections (in particular vascular or mixed ones) and the necessity of a long-term anti-rejection therapy. Adding ATG-F single high dose induction to TDT was more efficient in prolonging kidney graft survival than TDT alone not only in recipients without any risk factors (p<0.005) but also in recipients with at least one risk factor (p<0.021). Only in 4.6% of recipients having two or more risk factors this effect could not be demonstrated. The intra-operative single high-dose induction with ATG-F significantly improves the kidney graft survival in recipients with or without risk factors and can therefore be recommended.

Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium elegans Extract Administration to Rats

Directory of Open Access Journals (Sweden)

Jia Choi

2018-01-01

Full Text Available Gelidium elegans extract (GEE is derived from a red alga from the Asia–Pacific region, which has antioxidant, anti-adipogenic, and anti-hyperglycemic effects. However, detailed studies of the toxicology of GEE have not been performed. We evaluated the single oral dose toxicity of GEE in male and female Sprague-Dawley (CD rats. GEE did not cause deaths or have toxic effects at dosages of 5000 mg/kg/day, although compound-colored stools and diarrhea were observed in both sexes, which lasted <2 days. Therefore, the LD50 of GEE is likely to be >5000 mg/kg. We next evaluated the repeated oral dose toxicity of GEE in CD rats over 14 days and 13 weeks. GEE did not induce any significant toxicological changes in either sex at 2000 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects, in terms of clinical signs, mortality, body mass, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy, organ masses, or histopathology, at dosages of 500, 1000, or 2000 mg/kg/day. The no observed adverse effect level (NOAEL for GEE is thus likely to be >2000 mg/kg/day, and no pathology was identified in potential target organs. Therefore, this study indicates that repeated oral dosing with GEE is safe in CD rats.

Long-term Outcomes With Planned Multistage Reduced Dose Repeat Stereotactic Radiosurgery for Treatment of Inoperable High-Grade Arteriovenous Malformations: An Observational Retrospective Cohort Study.

Science.gov (United States)

Marciscano, Ariel E; Huang, Judy; Tamargo, Rafael J; Hu, Chen; Khattab, Mohamed H; Aggarwal, Sameer; Lim, Michael; Redmond, Kristin J; Rigamonti, Daniele; Kleinberg, Lawrence R

2017-07-01

There is no consensus regarding the optimal management of inoperable high-grade arteriovenous malformations (AVMs). This long-term study of 42 patients with high-grade AVMs reports obliteration and adverse event (AE) rates using planned multistage repeat stereotactic radiosurgery (SRS). To evaluate the efficacy and safety of multistage SRS with treatment of the entire AVM nidus at each treatment session to achieve complete obliteration of high-grade AVMs. Patients with high-grade Spetzler-Martin (S-M) III-V AVMs treated with at least 2 multistage SRS treatments from 1989 to 2013. Clinical outcomes of obliteration rate, minor/major AEs, and treatment characteristics were collected. Forty-two patients met inclusion criteria (n = 26, S-M III; n = 13, S-M IV; n = 3, S-M V) with a median follow-up was 9.5 yr after first SRS. Median number of SRS treatment stages was 2, and median interval between stages was 3.5 yr. Twenty-two patients underwent pre-SRS embolization. Complete AVM obliteration rate was 38%, and the median time to obliteration was 9.7 yr. On multivariate analysis, higher S-M grade was significantly associated ( P = .04) failure to achieve obliteration. Twenty-seven post-SRS AEs were observed, and the post-SRS intracranial hemorrhage rate was 0.027 events per patient year. Treatment of high-grade AVMs with multistage SRS achieves AVM obliteration in a meaningful proportion of patients with acceptable AE rates. Lower obliteration rates were associated with higher S-M grade and pre-SRS embolization. This approach should be considered with caution, as partial obliteration does not protect from hemorrhage. Copyright © 2017 by the Congress of Neurological Surgeons

Long-term effects of ionizing radiation on gene expression in a zebrafish model.

Directory of Open Access Journals (Sweden)

Lahcen Jaafar

Full Text Available Understanding how initial radiation injury translates into long-term effects is an important problem in radiation biology. Here, we define a set of changes in the transcription profile that are associated with the long-term response to radiation exposure. The study was performed in vivo using zebrafish, an established radiobiological model organism. To study the long-term response, 24 hour post-fertilization embryos were exposed to 0.1 Gy (low dose or 1.0 Gy (moderate dose of whole-body gamma radiation and allowed to develop for 16 weeks. Liver mRNA profiles were then analyzed using the Affymetrix microarray platform, with validation by quantitative PCR. As a basis for comparison, 16-week old adults were exposed at the same doses and analyzed after 4 hours. Statistical analysis was performed in a way to minimize the effects of multiple comparisons. The responses to these two treatment regimes differed greatly: 360 probe sets were associated primarily with the long-term response, whereas a different 2062 probe sets were associated primarily with the response when adults of the same age were irradiated 4 hours before exposure. Surprisingly, a ten-fold difference in radiation dose (0.1 versus 1.0 Gy had little effect. Analysis at the gene and pathway level indicated that the long-term response includes the induction of cytokine and inflammatory regulators and transcription and growth factors. The acute response includes the induction of p53 target genes and modulation of the hypoxia-induced transcription factor-C/EBP axis. Results help define genes and pathways affected in the long-term, low and moderate dose radiation response and differentiate them from those affected in an acute response in the same tissue.

A GPU implementation of a track-repeating algorithm for proton radiotherapy dose calculations

International Nuclear Information System (INIS)

Yepes, Pablo P; Mirkovic, Dragan; Taddei, Phillip J

2010-01-01

An essential component in proton radiotherapy is the algorithm to calculate the radiation dose to be delivered to the patient. The most common dose algorithms are fast but they are approximate analytical approaches. However their level of accuracy is not always satisfactory, especially for heterogeneous anatomical areas, like the thorax. Monte Carlo techniques provide superior accuracy; however, they often require large computation resources, which render them impractical for routine clinical use. Track-repeating algorithms, for example the fast dose calculator, have shown promise for achieving the accuracy of Monte Carlo simulations for proton radiotherapy dose calculations in a fraction of the computation time. We report on the implementation of the fast dose calculator for proton radiotherapy on a card equipped with graphics processor units (GPUs) rather than on a central processing unit architecture. This implementation reproduces the full Monte Carlo and CPU-based track-repeating dose calculations within 2%, while achieving a statistical uncertainty of 2% in less than 1 min utilizing one single GPU card, which should allow real-time accurate dose calculations.

Preclinical assessment of HIV vaccines and microbicides by repeated low-dose virus challenges.

Directory of Open Access Journals (Sweden)

Roland R Regoes

2005-08-01

Full Text Available Trials in macaque models play an essential role in the evaluation of biomedical interventions that aim to prevent HIV infection, such as vaccines, microbicides, and systemic chemoprophylaxis. These trials are usually conducted with very high virus challenge doses that result in infection with certainty. However, these high challenge doses do not realistically reflect the low probability of HIV transmission in humans, and thus may rule out preventive interventions that could protect against "real life" exposures. The belief that experiments involving realistically low challenge doses require large numbers of animals has so far prevented the development of alternatives to using high challenge doses.Using statistical power analysis, we investigate how many animals would be needed to conduct preclinical trials using low virus challenge doses. We show that experimental designs in which animals are repeatedly challenged with low doses do not require unfeasibly large numbers of animals to assess vaccine or microbicide success.Preclinical trials using repeated low-dose challenges represent a promising alternative approach to identify potential preventive interventions.

Long-term results of hysteroscopic myomectomy for abnormal uterine bleeding

NARCIS (Netherlands)

Emanuel, M. H.; Wamsteker, K.; Hart, A. A.; Metz, G.; Lammes, F. B.

1999-01-01

To analyze the efficacy of transcervical resection of submucous myomas and to identify prognostic factors for long-term results. Two-hundred eighty-five women were treated with transcervical resection of submucous myomas without endometrial ablation. In case of incomplete resection a repeat

Repeated CT scans in trauma transfers: An analysis of indications, radiation dose exposure, and costs

International Nuclear Information System (INIS)

Hinzpeter, Ricarda; Sprengel, Kai; Wanner, Guido A.; Mildenberger, Peter; Alkadhi, Hatem

2017-01-01

Highlights: • Repetition of CT in trauma patients occurs relatively often. • Repetition of CT is mainly caused by inadequate image data transfer. • Potentially preventable CT examinations add radiation dose to patients. • Repeated CT is associated with excess costs to the health care system. - Abstract: Objectives: To identify the number of CT scans repeated in acute trauma patients receiving imaging before being referred to a trauma center, to define indications, and to assess radiation doses and costs of repeated CT. Methods: This retrospective study included all adult trauma patients transferred from other hospitals to a Level-I trauma center during 2014. Indications for repeated CT scans were categorized into: inadequate CT image data transfer, poor image quality, repetition of head CT after head injury together with completion to whole-body CT (WBCT), and follow-up of injury known from previous CT. Radiation doses from repeated CT were determined; costs were calculated using a nation-wide fee schedule. Results: Within one year, 85/298 (28.5%) trauma patients were transferred from another hospital because of severe head injury (n = 45,53%) and major body trauma (n = 23;27%) not manageable in the referring hospital, repatriation from a foreign country (n = 14;16.5%), and no ICU-capacity (n = 3;3.5%). Of these 85 patients, 74 (87%) had repeated CT in our center because of inadequate CT data transfer (n = 29;39%), repetition of head CT with completion to WBCT (n = 24;32.5%), and follow-up of known injury (n = 21;28.5%). None occurred because of poor image quality. Cumulative dose length product (DLP) and annual costs of potential preventable, repeated CT (inadequate data transfer) was 631mSv (81′304mGy*cm) and 35′233€, respectively. Conclusion: A considerable number of transferred trauma patients undergo potentially preventable, repeated CT, adding radiation dose to patients and costs to the health care system.

Repeated CT scans in trauma transfers: An analysis of indications, radiation dose exposure, and costs

Energy Technology Data Exchange (ETDEWEB)

Hinzpeter, Ricarda, E-mail: Ricarda.Hinzpeter@usz.ch [Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, University of Zurich, Raemistr. 100, Zurich CH-8091 (Switzerland); Sprengel, Kai, E-mail: Kai.Sprengel@usz.ch [Division of Trauma Surgery, Department of Surgery, University Hospital Zurich, University of Zurich, Raemistr. 100, CH-8091 Zurich (Switzerland); Wanner, Guido A., E-mail: Guido.Wanner@sbk-vs.de [Division of Trauma Surgery, Department of Surgery, University Hospital Zurich, University of Zurich, Raemistr. 100, CH-8091 Zurich (Switzerland); Department of General Surgery, Schwarzwald-Baar Klinikum, University of Freiburg, Klinikstr. 11, D-78052 Villingen-Schwenningen (Germany); Mildenberger, Peter, E-mail: peter.mildenberger@unimedizin-mainz.de [Department of Diagnostic and Interventional Radiology, University Hospital of Mainz, Langenbeckstr. 1, D-55131 Mainz (Germany); Alkadhi, Hatem, E-mail: hatem.alkadhi@usz.ch [Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, University of Zurich, Raemistr. 100, Zurich CH-8091 (Switzerland)

2017-03-15

Highlights: • Repetition of CT in trauma patients occurs relatively often. • Repetition of CT is mainly caused by inadequate image data transfer. • Potentially preventable CT examinations add radiation dose to patients. • Repeated CT is associated with excess costs to the health care system. - Abstract: Objectives: To identify the number of CT scans repeated in acute trauma patients receiving imaging before being referred to a trauma center, to define indications, and to assess radiation doses and costs of repeated CT. Methods: This retrospective study included all adult trauma patients transferred from other hospitals to a Level-I trauma center during 2014. Indications for repeated CT scans were categorized into: inadequate CT image data transfer, poor image quality, repetition of head CT after head injury together with completion to whole-body CT (WBCT), and follow-up of injury known from previous CT. Radiation doses from repeated CT were determined; costs were calculated using a nation-wide fee schedule. Results: Within one year, 85/298 (28.5%) trauma patients were transferred from another hospital because of severe head injury (n = 45,53%) and major body trauma (n = 23;27%) not manageable in the referring hospital, repatriation from a foreign country (n = 14;16.5%), and no ICU-capacity (n = 3;3.5%). Of these 85 patients, 74 (87%) had repeated CT in our center because of inadequate CT data transfer (n = 29;39%), repetition of head CT with completion to WBCT (n = 24;32.5%), and follow-up of known injury (n = 21;28.5%). None occurred because of poor image quality. Cumulative dose length product (DLP) and annual costs of potential preventable, repeated CT (inadequate data transfer) was 631mSv (81′304mGy*cm) and 35′233€, respectively. Conclusion: A considerable number of transferred trauma patients undergo potentially preventable, repeated CT, adding radiation dose to patients and costs to the health care system.

Long-term radiation effects on commercial cable-insulating materials irradiated at CERN

International Nuclear Information System (INIS)

Maier, P.; Stolarz, A.

1983-01-01

Long-term irradiation damage tests have been carried out on a variety of flexible cable-insulating materials offered to CERN by different European cable manufacturers. Tensile test specimens were exposed for a maximum of three years in high-level radiation areas of the Super Proton Synchrotron (SPS) and for comparison at high dose rates in a nuclear reactor. The degradation of mechanical properties after irradiation in air depends not only on the total absorbed dose, but also on the dose rate for most of these polymer compounds. These dose-rate effects vary between material types and for different compounds. The results presented here illustrate the difference in radiation damage between short-term and long-term irradiation conditions in a typical service application for the various materials tested. They also allow safety factors to be estimated for the extrapolation of the limiting exposure in service from accelerated material tests in the range of dose rates covered. A discussion of the available models of the dose-rate effects results in a conservative estimate for extrapolation to low dose rates from measured values at intermediate dose rates of the order of 0.1 Gy/s. Based on short-term irradiation tests only, the safety factors to be applied depend on the end-point criterion used, and may vary between 1 and 10 for the range of dose rates and materials considered here. (orig.)

Long-term use of metformin and colorectal cancer risk in type II diabetics

DEFF Research Database (Denmark)

Cardel, Majken; Jensen, S. M.; Pottegård, Anton

2014-01-01

of prescriptions for a cumulative dose of 2000 g within 5 years prior to the index date. To control for potential confounders, we used unconditional logistic regression. We generated adjusted odds ratios (OR) for the association between metformin and CRC and performed subanalyses for selected subgroups...... and for the dose-response relation. We identified 2088 cases and 9060 controls during the study period. The association between long-term metformin use and CRC gave an adjusted OR at 0.83 (95% CI 0.68-1.00). A protective effect on CRC with long-term use of metformin was only evident for women (OR 0.66 vs. 0.......99 for men). There was a significant dose-response association of metformin use > 250 defined daily dose (DDD) and for the duration of metformin use > 1 year. We found an indication of a protective effect of long-term metformin use against CRC in type II diabetics, although this effect was only seen in women....

How much radiation dose, to whom? Long-term storage, surveillance, retrieval and long processes cause additional dose to employees; Wie viel Strahlendosis fuer wen? Lange Lagerung, Offenhaltung und ein langer Entsorgungsprozess bedeuten zusaetzliche Dosis fuer Beschaeftigte

Energy Technology Data Exchange (ETDEWEB)

Walther, Clemens [Hannover Univ. (Germany). Inst. fuer Radiooekologie und Strahlenschutz; Riemann, Moritz [Kiel Univ. (Germany). Lehrstuhl fuer Philosophie und Ethik der Umwelt

2017-09-01

In the case of final nuclear waste disposal there are concurrent interests with respect to radiation protection: The realization of a disposal option with minimum required follow-up care needs time causing additional radiation exposure for the employees, also the option of long-term storage, surveillance and retrieval possibilities cause additional dose to employees. The contribution discusses possible consideration of requests for the different options.

The long-term effectiveness of generic adult fixed-dose combination ...

African Journals Online (AJOL)

Background: Access to pediatric antiretroviral formulations is increasing in resource-limited countries, however adult FDCs are still commonly used by antiretroviral therapy (ART) programs. Objective: To describe long-term effectiveness of using adult FDC of d4T+3TC+NVP (Triomune) in children for HIV treatment. Methods: ...

Long-term, repeated measurements of mouse cortical microflow at the same region of interest with high spatial resolution.

Science.gov (United States)

Tomita, Yutaka; Pinard, Elisabeth; Tran-Dinh, Alexy; Schiszler, Istvan; Kubis, Nathalie; Tomita, Minoru; Suzuki, Norihiro; Seylaz, Jacques

2011-02-04

A method for long-term, repeated, semi-quantitative measurements of cerebral microflow at the same region of interest (ROI) with high spatial resolution was developed and applied to mice subjected to focal arterial occlusion. A closed cranial window was chronically implanted over the left parieto-occipital cortex. The anesthetized mouse was placed several times, e.g., weekly, under a dynamic confocal microscope, and Rhodamine B-isothiocyanate-dextran was each time intravenously injected as a bolus, while microflow images were video recorded. Left and right tail veins were sequentially catheterized in a mouse three times at maximum over a 1.5 months' observation period. Smearing of the input function resulting from the use of intravenous injection was shown to be sufficiently small. The distal middle cerebral artery (MCA) was thermocoagulated through the cranial window in six mice, and five sham-operated mice were studied in parallel. Dye injection and video recording were conducted four times in this series, i.e., before and at 10 min, 7 and 30 days after sham operation or MCA occlusion. Pixelar microflow values (1/MTT) in a matrix of approximately 50×50 pixels were displayed on a two-dimensional (2-D) map, and the frequency distribution of the flow values was also calculated. No significant changes in microflow values over time were detected in sham-operated mice, while the time course of flow changes in the ischemic penumbral area in operated mice was similar to those reported in the literature. This method provides a powerful tool to investigate long-term changes in mouse cortical microflow under physiological and pathological conditions. Copyright © 2010 Elsevier B.V. All rights reserved.

Short- and Long-Term Effects of Prenatal Exposure to Iron Oxide Nanoparticles: Influence of Surface Charge and Dose on Developmental and Reproductive Toxicity

Directory of Open Access Journals (Sweden)

Kristin R. Di Bona

2015-12-01

Full Text Available Iron oxide nanoparticles (NPs are commonly utilized for biomedical, industrial, and commercial applications due to their unique properties and potential biocompatibility. However, little is known about how exposure to iron oxide NPs may affect susceptible populations such as pregnant women and developing fetuses. To examine the influence of NP surface-charge and dose on the developmental toxicity of iron oxide NPs, Crl:CD1(ICR (CD-1 mice were exposed to a single, low (10 mg/kg or high (100 mg/kg dose of positively-charged polyethyleneimine-Fe2O3-NPs (PEI-NPs, or negatively-charged poly(acrylic acid-Fe2O3-NPs (PAA-NPs during critical windows of organogenesis (gestation day (GD 8, 9, or 10. A low dose of NPs, regardless of charge, did not induce toxicity. However, a high exposure led to charge-dependent fetal loss as well as morphological alterations of the uteri (both charges and testes (positive only of surviving offspring. Positively-charged PEI-NPs given later in organogenesis resulted in a combination of short-term fetal loss (42% and long-term alterations in reproduction, including increased fetal loss for second generation matings (mice exposed in utero. Alternatively, negatively-charged PAA-NPs induced fetal loss (22% earlier in organogenesis to a lesser degree than PEI-NPs with only mild alterations in offspring uterine histology observed in the long-term.

Impact of Diabetes on Long-Term Outcome After Primary Angioplasty

DEFF Research Database (Denmark)

De Luca, Giuseppe; Dirksen, Maurits T; Spaulding, Christian

2012-01-01

Diabetes has been shown to be associated with worse survival and repeat target vessel revascularization (TVR) after primary angioplasty. The aim of the current study was to evaluate the impact of diabetes on long-term outcome in patients undergoing primary angioplasty treated with bare metal sten...

A single low dose of Fe ions can cause long-term biological responses in NL20 human bronchial epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Cao, Qianlin; Wang, Jingdong; Cao, Jianping; Yang, Hongying [Medical College of Soochow University/Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, School of Radiation Medicine and Protection, Suzhou, Jiangsu (China); Liu, Wei [Soochow University, Department of Radiotherapy and Oncology, Second Affiliated Hospital, Suzhou, Jiangsu (China)

2018-03-15

Space radiation cancer risk may be a potential obstacle for long-duration spaceflight. Among all types of cancer space radiation may induce, lung cancer has been estimated to be the largest potential risk. Although previous animal study has shown that Fe ions, the most important contributor to the total dose equivalent of space radiation, induced a higher incidence of lung tumorigenesis per dose than X-rays, the underlying mechanisms at cellular level remained unclear. Therefore, in the present study, we investigated long-term biological changes in NL20 human bronchial epithelial cells after exposure to Fe ion or X-ray irradiation. We found that compared with sham control, the progeny of NL20 cells irradiated with 0.1 Gy of Fe ions showed slightly increased micronucleus formation, significantly decreased cell proliferation, disturbed cell cycle distribution, and obviously elevated intracellular ROS levels accompanied by reduced SOD1 and SOD2 expression, but the progeny of NL20 cells irradiated with 0.9 Gy of X-rays did not show any significant changes. More importantly, Fe ion exposure caused much greater soft-agar colony formation than X-rays did in the progeny of irradiated NL20 cells, clearly suggesting higher cell transformation potential of Fe ions compared with X-rays. These data may shed the light on the potential lung tumorigenesis risk from Fe ion exposure. In addition, ATM inhibition by Ku55933 reversed some of the changes in the progeny of Fe ion-irradiated cells but not others such as soft-agar colony formation, suggesting complex processes from DNA damage to carcinogenesis. These data indicate that even a single low dose of Fe ions can induce long-term biological responses such as cell transformation, etc., suggesting unignorable health risk from space radiation to astronauts. (orig.)

High-dose total-body irradiation and autologous marrow reconstitution in dogs: dose-rate-related acute toxicity and fractionation-dependent long-term survival

International Nuclear Information System (INIS)

Deeg, H.J.; Storb, R.; Weiden, P.L.; Schumacher, D.; Shulman, H.; Graham, T.; Thomas, E.D.

1981-01-01

Beagle dogs treated by total-body irradiation (TBI) were given autologous marrow grafts in order to avoid death from marrow toxicity. Acute and delayed non-marrow toxicities of high single-dose (27 dogs) and fractionated TBI (20 dogs) delivered at 0.05 or 0.1 Gy/min were compared. Fractionated TBI was given in increments of 2 Gy every 6 hr for three increments per day. Acute toxicity and early mortality (<1 month) at identical total irradiation doses were comparable for dogs given fractionated or single-dose TBI. With single-dose TBI, 14, 16, and 18 Gy, respectively, given at 0.05 Gy/min, 0/5, 5/5, and 2/2 dogs died from acute toxicity; with 10, 12, and 14 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 5/5 dogs died acutely. With fractionated TBI, 14 and 16 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 2/2 dogs died auctely. Early deaths were due to radiation enteritis with or without associated septicemia (29 dogs; less than or equal to Day 10). Three dogs given 10 Gy of TBI at 0.1 Gy/min died from bacterial pneumonia; one (Day 18) had been given fractionated and two (Days 14, 22) single-dose TBI. Fifteen dogs survived beyond 1 month; eight of these had single-dose TBI (10-14 Gy) and all died within 7 months of irradiation from a syndrome consisting of hepatic damage, pancreatic fibrosis, malnutrition, wasting, and anemia. Seven of the 15 had fractionated TBI, and only one (14 Gy) died on Day 33 from hepatic failure, whereas 6 (10-14 Gy) are alive and well 250 to 500 days after irradiation. In conclusion, fractionated TBI did not offer advantages over single-dose TBI with regard to acute toxicity and early mortality; rather, these were dependent upon the total dose of TBI. The total acutely tolerated dose was dependent upon the exposure rate; however, only dogs given fractionated TBI became healthy long-term survivors

Pharmacology of ayahuasca administered in two repeated doses.

Science.gov (United States)

Dos Santos, Rafael G; Grasa, Eva; Valle, Marta; Ballester, Maria Rosa; Bouso, José Carlos; Nomdedéu, Josep F; Homs, Rosa; Barbanoj, Manel J; Riba, Jordi

2012-02-01

Ayahuasca is an Amazonian tea containing the natural psychedelic 5-HT(2A/2C/1A) agonist N,N-dimethyltryptamine (DMT). It is used in ceremonial contexts for its visionary properties. The human pharmacology of ayahuasca has been well characterized following its administration in single doses. To evaluate the human pharmacology of ayahuasca in repeated doses and assess the potential occurrence of acute tolerance or sensitization. In a double-blind, crossover, placebo-controlled clinical trial, nine experienced psychedelic drug users received PO the two following treatment combinations at least 1 week apart: (a) a lactose placebo and then, 4 h later, an ayahuasca dose; and (b) two ayahuasca doses 4 h apart. All ayahuasca doses were freeze-dried Amazonian-sourced tea encapsulated to a standardized 0.75 mg DMT/kg bodyweight. Subjective, neurophysiological, cardiovascular, autonomic, neuroendocrine, and cell immunity measures were obtained before and at regular time intervals until 12 h after first dose administration. DMT plasma concentrations, scores in subjective and neurophysiological variables, and serum prolactin and cortisol were significantly higher after two consecutive doses. When effects were standardized by plasma DMT concentrations, no differences were observed for subjective, neurophysiological, autonomic, or immunological effects. However, we observed a trend to reduced systolic blood pressure and heart rate, and a significant decrease for growth hormone (GH) after the second ayahuasca dose. Whereas there was no clear-cut tolerance or sensitization in the psychological sphere or most physiological variables, a trend to lower cardiovascular activation was observed, together with significant tolerance to GH secretion.

Long-Term Safety of Repeated Blood-Brain Barrier Opening via Focused Ultrasound with Microbubbles in Non-Human Primates Performing a Cognitive Task.

Science.gov (United States)

Downs, Matthew E; Buch, Amanda; Sierra, Carlos; Karakatsani, Maria Eleni; Teichert, Tobias; Chen, Shangshang; Konofagou, Elisa E; Ferrera, Vincent P

2015-01-01

Focused Ultrasound (FUS) coupled with intravenous administration of microbubbles (MB) is a non-invasive technique that has been shown to reliably open (increase the permeability of) the blood-brain barrier (BBB) in multiple in vivo models including non-human primates (NHP). This procedure has shown promise for clinical and basic science applications, yet the safety and potential neurological effects of long term application in NHP requires further investigation under parameters shown to be efficacious in that species (500 kHz, 200-400 kPa, 4-5 μm MB, 2 minute sonication). In this study, we repeatedly opened the BBB in the caudate and putamen regions of the basal ganglia of 4 NHP using FUS with systemically-administered MB over 4-20 months. We assessed the safety of the FUS with MB procedure using MRI to detect edema or hemorrhaging in the brain. Contrast enhanced T1-weighted MRI sequences showed a 98% success rate for openings in the targeted regions. T2-weighted and SWI sequences indicated a lack edema in the majority of the cases. We investigated potential neurological effects of the FUS with MB procedure through quantitative cognitive testing of' visual, cognitive, motivational, and motor function using a random dot motion task with reward magnitude bias presented on a touchpanel display. Reaction times during the task significantly increased on the day of the FUS with MB procedure. This increase returned to baseline within 4-5 days after the procedure. Visual motion discrimination thresholds were unaffected. Our results indicate FUS with MB can be a safe method for repeated opening of the BBB at the basal ganglia in NHP for up to 20 months without any long-term negative physiological or neurological effects with the parameters used.

Conversion of short-term to long-term memory in the novel object recognition paradigm.

Science.gov (United States)

Moore, Shannon J; Deshpande, Kaivalya; Stinnett, Gwen S; Seasholtz, Audrey F; Murphy, Geoffrey G

2013-10-01

It is well-known that stress can significantly impact learning; however, whether this effect facilitates or impairs the resultant memory depends on the characteristics of the stressor. Investigation of these dynamics can be confounded by the role of the stressor in motivating performance in a task. Positing a cohesive model of the effect of stress on learning and memory necessitates elucidating the consequences of stressful stimuli independently from task-specific functions. Therefore, the goal of this study was to examine the effect of manipulating a task-independent stressor (elevated light level) on short-term and long-term memory in the novel object recognition paradigm. Short-term memory was elicited in both low light and high light conditions, but long-term memory specifically required high light conditions during the acquisition phase (familiarization trial) and was independent of the light level during retrieval (test trial). Additionally, long-term memory appeared to be independent of stress-mediated glucocorticoid release, as both low and high light produced similar levels of plasma corticosterone, which further did not correlate with subsequent memory performance. Finally, both short-term and long-term memory showed no savings between repeated experiments suggesting that this novel object recognition paradigm may be useful for longitudinal studies, particularly when investigating treatments to stabilize or enhance weak memories in neurodegenerative diseases or during age-related cognitive decline. Copyright © 2013 Elsevier Inc. All rights reserved.

Optimal low-dose radiosurgery combined with and without intervention for unruptured arteriovenous malformations. A long-term follow-up study

International Nuclear Information System (INIS)

Inoue, Hiroshi K.; Naitou, Isao

2006-01-01

Treatment indication for unruptured arteriovenous malformations (AVMs) of the brain was investigated based on long-term results of low-dose Gamma Knife (GK) surgery. Thirty-nine patients with unruptured AVMs treated with GK surgery were followed more than 7 years. These AVMs were found due to seizure and steal symptoms in 22 and 4 patients, respectively, and incidentally in 13. Embolization was performed in 6 patients before GK surgery. Total obliteration was obtained in 83.3% after initial treatment and 95.8% after additional treatment. Bleeding before total obliteration occurred in 2 patients and adverse effect on the internal capsule in 1. It is concluded that low-dose GK surgery is safe and effective for the treatment of unruptured AVMs, especially symptomatic AVMs in functional areas. (author)

Conformal irradiation of the prostate: estimating long-term rectal bleeding risk using dose-volume histograms

International Nuclear Information System (INIS)

Hartford, Alan C.; Niemierko, Andrzej; Adams, Judith A.; Urie, Marcia M.; Shipley, William U.

1996-01-01

Purpose: Dose-volume histograms (DVHs) may be very useful tools for estimating probability of normal tissue complications (NTCP), but there is not yet an agreed upon method for their analysis. This study introduces a statistical method of aggregating and analyzing primary data from DVHs and associated outcomes. It explores the dose-volume relationship for NTCP of the rectum, using long-term data on rectal wall bleeding following prostatic irradiation. Methods and Materials: Previously published data were reviewed and updated on 41 patients with Stages T3 and T4 prostatic carcinoma treated with photons followed by perineal proton boost, including dose-volume histograms (DVHs) of each patient's anterior rectal wall and data on the occurrence of postirradiation rectal bleeding (minimum FU > 4 years). Logistic regression was used to test whether some individual combination of dose and volume irradiated might best separate the DVHs into categories of high or low risk for rectal bleeding. Further analysis explored whether a group of such dose-volume combinations might be superior in predicting complication risk. These results were compared with results of the 'critical volume model', a mathematical model based on assumptions of underlying radiobiological interactions. Results: Ten of the 128 tested dose-volume combinations proved to be 'statistically significant combinations' (SSCs) distinguishing between bleeders (14 out of 41) and nonbleeders (27 out of 41), ranging contiguously between 60 CGE (Cobalt Gray Equivalent) to 70% of the anterior rectal wall and 75 CGE to 30%. Calculated odds ratios for each SSC were not significantly different across the individual SSCs; however, analysis combining SSCs allowed segregation of DVHs into three risk groups: low, moderate, and high. Estimates of probabilities of normal tissue complications (NTCPs) based on these risk groups correlated strongly with observed data (p = 0.003) and with biomathematical model-generated NTCPs

Memory effect in expressed emotions during long term group interactions

NARCIS (Netherlands)

Gorbunov, R.; Barakova, E.I.; Rauterberg, M.; Ferrández Vicente, J.M.; Álvarez-Sánchez, J.R.; de la Paz López, F.; Toledo Moreo, J.; Adeli, H.

2017-01-01

Long-term interactions in groups can be monitored through games in which the participants need to show their social preferences by making choice to help or to use egoistic game strategy. In this paper we analyse the facial expressions of a group of isolated individuals (astronauts) during repeated

Preclinical rodent toxicity studies for long term use of ceftriaxone

Directory of Open Access Journals (Sweden)

Elena Ratti

2015-01-01

Ceftriaxone showed rapid absorption with half-life values ranging between 1 and 1.5 h. Additionally, there was no evidence of accumulation and a virtually complete elimination by 16 h after the last dose. Overall there were no toxicologically meaningful drug-related animal findings associated with the long-term administration (6 months of ceftriaxone. These results support safety of long-term use of ceftriaxone in human clinical trials.

Adult height after long-term, continuous growth hormone (GH) treatment in short children born small for gestational age: results of a randomized, double-blind, dose-response GH trial

NARCIS (Netherlands)

Y. van Pareren; M. Houdijk; M. Jansen (Maarten); M. Reeser; P.G.H. Mulder (Paul); A.C.S. Hokken-Koelega (Anita)

2003-01-01

textabstractThe GH dose-response effect of long-term continuous GH treatment on adult height (AH) was evaluated in 54 short children born small for gestational age (SGA) who were participating in a randomized, double-blind, dose-response trial. Patients were randomly and blindly

The effects of multiple UV exposures on HIV-LTR (long terminal repeat) expression

International Nuclear Information System (INIS)

Schreck, S.; Milton, J.; Panozzo, J.; Libertin, C.R.; Woloschak, G.E.; Loyola Univ., Maywood, IL

1995-01-01

Previous studies have shown that cellular stress agents such as UV radiation induce transcription from the long terminal repeat (LTR) of the human immunodeficiency virus (HIV). Using HeLa cells stably transfected with the HIV-LTR sequence, which transcriptionally drives the chloramphenicol acetyl transferase (CAT) reporter gene, we examined the effects of multiple exposures to UVC (254 nm) on HIV-LTR-CAT expression. Low doses (≤ 5 J m -2 ) had no effect on CAT expression, but up to 29-fold induction was observed with 10 J m -2 when cells were harvested 48 h after completion of the exposure. Little difference was noted in induction levels when cells were exposed to one 25 J m -2 dose, viable cells were harvested at 24 h, 48 h or 72 h, and cell lysates were assayed for CAT expression. Two sequential 12.5 J m -2 exposures, given 24 h apart, resulted in an additive effect on CAT expression; these two exposures produced CAT activity equivalent to that induced following a single 25 J m -2 dose. Our data suggest that HIV-LTR requires a specific threshold UV dose in order to elicit induction; a maximal induction dose is also evident; exposures higher than this maximal dose contribute no more to HIV-LTR induction in viable cells. (author)

Radiation Dose and Subsequent Risk for Stomach Cancer in Long-term Survivors of Cervical Cancer

Energy Technology Data Exchange (ETDEWEB)

Kleinerman, Ruth A., E-mail: kleinerr@mail.nih.gov [Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services, Rockville, Maryland (United States); Smith, Susan A. [Department of Radiation Physics, University of Texas M D Anderson Cancer Center, Houston, Texas (United States); Holowaty, Eric [Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario (Canada); Hall, Per [Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm (Sweden); Pukkala, Eero [Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki (Finland); Vaalavirta, Leila [Department of Oncology, Helsinki University Central Hospital, Helsinki (Finland); Stovall, Marilyn; Weathers, Rita [Department of Radiation Physics, University of Texas M D Anderson Cancer Center, Houston, Texas (United States); Gilbert, Ethel [Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services, Rockville, Maryland (United States); Aleman, Berthe M.P. [Department of Radiotherapy, The Netherlands Cancer Institute, Amsterdam (Netherlands); Kaijser, Magnus [Clinical Epidemiology Unit, Department of Medicine, Karolinska Institute, Stockholm (Sweden); Andersson, Michael [Department of Oncology, Copenhagen University Hospital, Copenhagen (Denmark); Storm, Hans [Cancer Prevention and Documentation, Danish Cancer Society, Copenhagen (Denmark); Joensuu, Heikki [Department of Oncology, Helsinki University Central Hospital, Helsinki (Finland); Lynch, Charles F. [Department of Epidemiology, University of Iowa, Iowa City, Iowa (United States); and others

2013-08-01

Purpose: To assess the dose–response relationship for stomach cancer after radiation therapy for cervical cancer. Methods and Materials: We conducted a nested, matched case–control study of 201 cases and 378 controls among 53,547 5-year survivors of cervical cancer diagnosed from 1943 to 1995, from 5 international, population-based cancer registries. We estimated individual radiation doses to the site of the stomach cancer for all cases and to corresponding sites for the matched controls (overall mean stomach tumor dose, 2.56 Gy, range 0.03-46.1 and after parallel opposed pelvic fields, 1.63 Gy, range 0.12-6.3). Results: More than 90% of women received radiation therapy, mostly with external beam therapy in combination with brachytherapy. Stomach cancer risk was nonsignificantly increased (odds ratio 1.27-2.28) for women receiving between 0.5 and 4.9 Gy to the stomach cancer site and significantly increased at doses ≥5 Gy (odds ratio 4.20, 95% confidence interval 1.41-13.4, P{sub trend}=.047) compared with nonirradiated women. A highly significant radiation dose–response relationship was evident when analyses were restricted to the 131 cases (251 controls) whose stomach cancer was located in the middle and lower portions of the stomach (P{sub trend}=.003), whereas there was no indication of increasing risk with increasing dose for 30 cases (57 controls) whose cancer was located in the upper stomach (P{sub trend}=.23). Conclusions: Our findings show for the first time a significant linear dose–response relationship for risk of stomach cancer in long-term survivors of cervical cancer.

Radiation Dose and Subsequent Risk for Stomach Cancer in Long-term Survivors of Cervical Cancer

International Nuclear Information System (INIS)

Kleinerman, Ruth A.; Smith, Susan A.; Holowaty, Eric; Hall, Per; Pukkala, Eero; Vaalavirta, Leila; Stovall, Marilyn; Weathers, Rita; Gilbert, Ethel; Aleman, Berthe M.P.; Kaijser, Magnus; Andersson, Michael; Storm, Hans; Joensuu, Heikki; Lynch, Charles F.

2013-01-01

Purpose: To assess the dose–response relationship for stomach cancer after radiation therapy for cervical cancer. Methods and Materials: We conducted a nested, matched case–control study of 201 cases and 378 controls among 53,547 5-year survivors of cervical cancer diagnosed from 1943 to 1995, from 5 international, population-based cancer registries. We estimated individual radiation doses to the site of the stomach cancer for all cases and to corresponding sites for the matched controls (overall mean stomach tumor dose, 2.56 Gy, range 0.03-46.1 and after parallel opposed pelvic fields, 1.63 Gy, range 0.12-6.3). Results: More than 90% of women received radiation therapy, mostly with external beam therapy in combination with brachytherapy. Stomach cancer risk was nonsignificantly increased (odds ratio 1.27-2.28) for women receiving between 0.5 and 4.9 Gy to the stomach cancer site and significantly increased at doses ≥5 Gy (odds ratio 4.20, 95% confidence interval 1.41-13.4, P trend =.047) compared with nonirradiated women. A highly significant radiation dose–response relationship was evident when analyses were restricted to the 131 cases (251 controls) whose stomach cancer was located in the middle and lower portions of the stomach (P trend =.003), whereas there was no indication of increasing risk with increasing dose for 30 cases (57 controls) whose cancer was located in the upper stomach (P trend =.23). Conclusions: Our findings show for the first time a significant linear dose–response relationship for risk of stomach cancer in long-term survivors of cervical cancer

Spatial structure of food contamination with 137Cs and estimation of long-term internal dose loads on population of Belarus

International Nuclear Information System (INIS)

Krivoruchko, K.

1997-01-01

An analysis of 53,207 records of 137 Cs contents in 83 types of food products obtained in 1993 in Belarus was carried out. Internal exposure by eight selected food components has been estimated. To map the non-uniformly distributed data, different types of geostatical approaches are used. The results of spatial analysis of long term internal dose loads on populations under high radiation risk could be used in decision making. (author)

Antithrombotic effect of repeated doses of the ethanolic extract of ...

African Journals Online (AJOL)

Antithrombotic effect of repeated doses of the ethanolic extract of local olive ( Olea europaea L.) leaves in rabbits. ... The incidence of thromboembolic diseases is increasing, and they are a major cause of mortality and morbidity worldwide. Mediterranean diet is known for its high content of olive products, especially olive oil, ...

Self-assembling siloxane bilayer directly on SiO2 surface of micro-cantilevers for long-term highly repeatable sensing to trace explosives.

Science.gov (United States)

Chen, Ying; Xu, Pengcheng; Li, Xinxin

2010-07-02

This paper presents a novel sensing layer modification technique for static micro-cantilever sensors that detect trace explosives by measuring specific adsorption-induced surface stress. For the first time, a method of directly modifying a siloxane sensing bilayer on an SiO(2) surface is proposed to replace the conventional self-assembled monolayers (SAMs) of thiols on Au to avoid the trouble from long-term unstable Au-S bonds. For modifying the long-term reliable sensing bilayer on the piezoresistor-integrated micro-cantilevers, a siloxane-head bottom layer is self-assembled directly on the SiO(2) cantilever surface, which is followed by grafting another explosive-sensing-group functionalized molecule layer on top of the siloxane layer. The siloxane-modified sensor has experimentally exhibited a highly resoluble response to 0.1 ppb TNT vapor. More importantly, the repeated detection results after 140 days show no obvious attenuation in sensing signal. Also observed experimentally, the specific adsorption of the siloxane sensing bilayer to TNT molecules causes a tensile surface stress on the cantilever. Herein the measured tensile surface stress is in contrast to the compressive surface stress normally measured from conventional cantilever sensors where the sensitive thiol-SAMs are modified on an Au surface. The reason for this newly observed phenomenon is discussed and preliminarily analyzed.

Self-assembling siloxane bilayer directly on SiO2 surface of micro-cantilevers for long-term highly repeatable sensing to trace explosives

International Nuclear Information System (INIS)

Chen Ying; Xu Pengcheng; Li Xinxin

2010-01-01

This paper presents a novel sensing layer modification technique for static micro-cantilever sensors that detect trace explosives by measuring specific adsorption-induced surface stress. For the first time, a method of directly modifying a siloxane sensing bilayer on an SiO 2 surface is proposed to replace the conventional self-assembled monolayers (SAMs) of thiols on Au to avoid the trouble from long-term unstable Au-S bonds. For modifying the long-term reliable sensing bilayer on the piezoresistor-integrated micro-cantilevers, a siloxane-head bottom layer is self-assembled directly on the SiO 2 cantilever surface, which is followed by grafting another explosive-sensing-group functionalized molecule layer on top of the siloxane layer. The siloxane-modified sensor has experimentally exhibited a highly resoluble response to 0.1 ppb TNT vapor. More importantly, the repeated detection results after 140 days show no obvious attenuation in sensing signal. Also observed experimentally, the specific adsorption of the siloxane sensing bilayer to TNT molecules causes a tensile surface stress on the cantilever. Herein the measured tensile surface stress is in contrast to the compressive surface stress normally measured from conventional cantilever sensors where the sensitive thiol-SAMs are modified on an Au surface. The reason for this newly observed phenomenon is discussed and preliminarily analyzed.

Short-term treatment with flumazenil restores long-term object memory in a mouse model of Down syndrome.

Science.gov (United States)

Colas, Damien; Chuluun, Bayarsaikhan; Garner, Craig C; Heller, H Craig

2017-04-01

Down syndrome (DS) is a common genetic cause of intellectual disability yet no pro-cognitive drug therapies are approved for human use. Mechanistic studies in a mouse model of DS (Ts65Dn mice) demonstrate that impaired cognitive function is due to excessive neuronal inhibitory tone. These deficits are normalized by chronic, short-term low doses of GABA A receptor (GABA A R) antagonists in adult animals, but none of the compounds investigated are approved for human use. We explored the therapeutic potential of flumazenil (FLUM), a GABA A R antagonist working at the benzodiazepine binding site that has FDA approval. Long-term memory was assessed by the Novel Object Recognition (NOR) testing in Ts65Dn mice after acute or short-term chronic treatment with FLUM. Short-term, low, chronic dose regimens of FLUM elicit long-lasting (>1week) normalization of cognitive function in both young and aged mice. FLUM at low dosages produces long lasting cognitive improvements and has the potential of fulfilling an unmet therapeutic need in DS. Copyright © 2017. Published by Elsevier Inc.

Long-term outcomes from dose-escalated image-guided intensity-modulated radiotherapy with androgen deprivation: encouraging results for intermediate- and high-risk prostate cancer.

Science.gov (United States)

Wilcox, Shea W; Aherne, Noel J; Benjamin, Linus C; Wu, Bosco; de Campos Silva, Thomaz; McLachlan, Craig S; McKay, Michael J; Last, Andrew J; Shakespeare, Thomas P

2014-01-01

Dose-escalated (DE) radiotherapy in the setting of localized prostate cancer has been shown to improve biochemical disease-free survival (bDFS) in several studies. In the same group of patients, androgen deprivation therapy (ADT) has been shown to confer a survival benefit when combined with radiotherapy doses of up to 70 Gy; however, there is currently little long-term data on patients who have received high-dose intensity-modulated radiotherapy (IMRT) with ADT. We report the long-term outcomes in a large cohort of patients treated with the combination of DE image-guided IMRT (IG-IMRT) and ADT. Patients with localized prostate cancer were identified from a centralized database across an integrated cancer center. All patients received DE IG-IMRT, combined with ADT, and had a minimum follow up of 12 months post-radiotherapy. All relapse and toxicity data were collected prospectively. Actuarial bDFS, metastasis-free survival, prostate cancer-specific survival, and multivariate analyses were calculated using the SPSS v20.0 statistical package. Seven hundred and eighty-two eligible patients were identified with a median follow up of 46 months. Overall, 4.3% of patients relapsed, 2.0% developed distant metastases, and 0.6% died from metastatic prostate cancer. At 5-years, bDFS was 88%, metastasis-free survival was 95%, and prostate cancer-specific survival was 98%. Five-year grade 2 genitourinary and gastrointestinal toxicity was 2.1% and 3.4%, respectively. No grade 3 or 4 late toxicities were reported. Pretreatment prostate specific antigen (P=0.001) and Gleason score (P=0.03) were significant in predicting biochemical failure on multivariate analysis. There is a high probability of tumor control with DE IG-IMRT combined with androgen deprivation, and this is a technique with a low probability of significant late toxicity. Our long term results corroborate the safety and efficacy of treating with IG-IMRT to high doses and compares favorably with published series for

The effects of refreshing and elaboration on working memory performance, and their contributions to long-term memory formation.

Science.gov (United States)

Bartsch, Lea M; Singmann, Henrik; Oberauer, Klaus

2018-03-19

Refreshing and elaboration are cognitive processes assumed to underlie verbal working-memory maintenance and assumed to support long-term memory formation. Whereas refreshing refers to the attentional focussing on representations, elaboration refers to linking representations in working memory into existing semantic networks. We measured the impact of instructed refreshing and elaboration on working and long-term memory separately, and investigated to what extent both processes are distinct in their contributions to working as well as long-term memory. Compared with a no-processing baseline, immediate memory was improved by repeating the items, but not by refreshing them. There was no credible effect of elaboration on working memory, except when items were repeated at the same time. Long-term memory benefited from elaboration, but not from refreshing the words. The results replicate the long-term memory benefit for elaboration, but do not support its beneficial role for working memory. Further, refreshing preserves immediate memory, but does not improve it beyond the level achieved without any processing.

Long-Term Anabolic Androgenic Steroid Use Is Associated with Increased Atrial Electromechanical Delay in Male Bodybuilders

Directory of Open Access Journals (Sweden)

Mustafa Akçakoyun

2014-01-01

Full Text Available We investigated the effect of long-term supraphysiologic doses of anabolic androgenic steroids (AAS on atrial electromechanical delay (AEMD in male bodybuilders. We clearly demonstrated that long-term consumption of supraphysiologic doses of AAS is associated with higher values of inter- and intra-AEMD in healthy young bodybuilders.

What we have learned about scheduling elective repeat cesarean delivery at term.

Science.gov (United States)

Tita, Alan T N

2016-08-01

The optimal timing of delivery in the setting of various clinical conditions and scenarios remains one of the most common questions for obstetric providers. Over the past 5-10 years, the optimal timing of delivery at term, particularly for elective repeat cesareans, has been the subject of considerable investigation and discussion. There is an increasing consensus that when women opt for an elective repeat cesarean delivery, it should be performed at term rather than preterm. The recent redefinition of the "term" period into early term (37-38 weeks), full-term (39-40 weeks), late term (41 weeks), and post term designations (≥42 weeks) underscores observed heterogeneity in outcomes following delivery at term. The American College of Obstetricians and Gynecologists currently recommends that elective repeat cesarean delivery be performed at full-term. Herein, the available data to support this recommendation regarding timing of elective repeat cesarean delivery are reviewed, including contributions from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network. Copyright © 2016. Published by Elsevier Inc.

Target-Dependent Structural Changes Accompanying Long-Term Synaptic Facilitation in Aplysia Neurons

Science.gov (United States)

Glanzman, David L.; Kandel, Eric R.; Schacher, Samuel

1990-08-01

The mechanisms underlying structural changes that accompany learning and memory have been difficult to investigate in the intact nervous system. In order to make these changes more accessible for experimental analysis, dissociated cell culture and low-light-level video microscopy were used to examine Aplysia sensory neurons in the presence or absence of their target cells. Repeated applications of serotonin, a facilitating transmitter important in behavioral dishabituation and sensitization, produced growth of the sensory neurons that paralleled the long-term enhancement of synaptic strength. This growth required the presence of the postsynaptic motor neuron. Thus, both the structural changes and the synaptic facilitation of Aplysia sensorimotor synapses accompanying long-term behavioral sensitization can be produced in vitro by applying a single facilitating transmitter repeatedly. These structural changes depend on an interaction of the presynaptic neuron with an appropriate postsynaptic target.

Effect of repeated small-dose γ-ray irradiation on atopic dermatitis in NC/Nga mice

International Nuclear Information System (INIS)

Fang, Su-Ping; Muto, Yasuko; Tago, Fumitoshi; Simura, Noriko; Kojima, Shuji

2006-01-01

We previously showed that several small-dose 0.5 Gy whole-body γ-ray irradiation inhibits tumor growth in mice via elevation of the interferon (IFN)-γ/interleukin 4 (IL-4) ratio concomitantly with a decrease in the percentage of B cells. Here, we examined whether repeated small-dose (0.5 Gy, 10 times) γ-ray irradiation influences atopic dermatitis in an NC/Nga mouse model. It was found that repeated γ-ray irradiation increased total IgE in comparison with the disease-control group. Levels of IL-4 and IL-5 were increased versus the disease-control group, while IFN-γ was slightly decreased, resulting in a further decrease of the IFN-γ/IL-4 ratio compared with the disease-control group. These results indicate that repeated small-dose γ-ray irradiation may exacerbate atopic dermatitis. This may be because the irradiation induces not helper T lymphocyte 1 (Th1), but Th2 polarization in this atopic mouse model, i.e., the effects of small-dose irradiation may be different in conditions involving immune hypersensitivity and impaired immunity. (author)

Transformative art: art as means for long-term neurocognitive change.

Science.gov (United States)

Preminger, Son

2012-01-01

Every artwork leads to a unique experience by the observer or participant, may it be sensory, emotional, cognitive, interactive, or spiritual experience. At the neurobiological level, such experiences are manifested as activation of the corresponding neural networks. Neuroscience has demonstrated that experience, in particular repeated experience, can cause a long-term change in the involved brain circuits (experience-dependent plasticity). This review will discuss the molding and transformative aspect of arts, examining how repeated and on-going experience of arts may alter cognitive, emotional, and behavioral patterns as well as their underlying neural circuits. The application of this approach to cognitive training and neuropsychological rehabilitation methods will be addressed as well. In addition, it will be suggested that this approach to art, as a long-term transformative medium, may lead to a novel viewpoint on art and a different approach to its creation. Artists can design artworks that aspire to form, in addition to one-shot influencing experience, on-going experiences which gradually create a lasting change, possibly improving audiences' neuropsychological functions.

Transformative Art:Art as Means for Long-term Neurocognitive Change

Directory of Open Access Journals (Sweden)

Son ePreminger

2012-04-01

Full Text Available Every artwork leads to a unique experience by the observer or participant, may it be sensory, emotional, cognitive, interactive or spiritual experience. At the neurobiological level, such experiences are manifested as activation of the corresponding neural networks. Neuroscience has demonstrated that experience, in particular repeated experience, can cause a long-term change in the involved brain circuits (experience-dependent plasticity. This review will discuss the molding and transformative aspect of arts, examining how repeated and on-going experience of arts may alter cognitive, emotional and behavioral patterns as well as their underlying neural circuits. The application of this approach to cognitive training and neuropsychological rehabilitation methods will be addressed as well. In addition, it will be suggested that this approach to art, as long-term transformative, may lead to a novel viewpoint on art and a different approach to its creation. Artists can design artworks that aspire to form, in addition to one-shot influencing experience, on-going experiences which gradually create a lasting change, possibly improving audiences' neuropsychological functions.

Visual long-term memory for spatial frequency?

Science.gov (United States)

Lages, Martin; Paul, Aileen

2006-06-01

It has been suggested that a visual long-term memory based on a sensory representation of the stimulus accounts for discrimination performance when the reference and the test stimuli are separated in time. Decision processes involved in setting response criteria, however, may also contribute to discrimination performance. In the present study, it is shown that under proper control, spatial frequency discrimination thresholds from a group of observers, each performing on a single trial, are significantly higher for a 2-h than for a 5-sec retention interval, whereas thresholds from individual observers performing in repeated trials with a 2-h retention interval are considerably lower. The results suggest that discrimination performance may depend on the retention of task-relevant information, such as a response criterion, rather than on visual memory of the stimulus. It is concluded that it is risky to postulate a high-fidelity long-term visual memory for spatial frequency on the basis of psychophysical group discrimination thresholds.

Effectiveness and tolerance of long-term malaria prophylaxis with mefloquine. Need for a better dosing regimen.

Science.gov (United States)

Lobel, H O; Bernard, K W; Williams, S L; Hightower, A W; Patchen, L C; Campbell, C C

1991-01-16

To measure the effectiveness and tolerance of long-term malaria prophylaxis with mefloquine, the incidence of Plasmodium falciparum malaria and of adverse reactions was compared in Peace Corps volunteers in West Africa who took mefloquine every 2 weeks and in volunteers who took chloroquine phosphate weekly. Mefloquine was only 63% more effective than chloroquine; the monthly incidence of P falciparum infections was one case per 100 volunteers who took mefloquine and 2.7 cases per 100 volunteers who took chloroquine. Using daily proguanil (chloroguanide) hydrochloride in addition to chloroquine did not provide additional protection. All mefloquine prophylaxis failures occurred during the second week of the every-2-weeks dosing regimen in volunteers who had used mefloquine for more than 2 months. Blood concentrations of mefloquine were lower during the second week of the alternate-week regimen than during the first week, suggesting that blood levels are too low during the second week to suppress parasitemia. No serious adverse reactions were observed. The results indicate that a dosing regimen of 250 mg of mefloquine weekly should be considered for travelers to areas with chloroquine-resistant P falciparum malaria.

Repeated dose titration versus age-based method in electroconvulsive therapy: a pilot study.

Science.gov (United States)

Aten, Jan Jaap; Oudega, Mardien; van Exel, Eric; Stek, Max L; van Waarde, Jeroen A

2015-06-01

In electroconvulsive therapy (ECT), a dose titration method (DTM) was suggested to be more individualized and therefore more accurate than formula-based dosing methods. A repeated DTM (every sixth session and dose adjustment accordingly) was compared to an age-based method (ABM) regarding treatment characteristics, clinical outcome, and cognitive functioning after ECT. Thirty-nine unipolar depressed patients dosed using repeated DTM and 40 matched patients treated with ABM were compared. Montgomery-Åsberg Depression Rating Scale (MADRS) and Mini-Mental State Examination (MMSE) were assessed at baseline and at the end of the index course, as well as the total number of ECT sessions. Both groups were similar regarding age, sex, psychotic features, mean baseline MADRS, and median baseline MMSE. At the end of the index course, the two methods showed equal outcome (mean end MADRS, 11.6 ± 8.3 in DTM and 9.5 ± 7.6 in ABM (P = 0.26); median end MMSE, 28 (25-29) and 28 (25-29.8), respectively (P = 0.81). However, the median number of all ECT sessions differed 16 (11-22) in DTM versus 12 (10-14.8) in ABM; P = 0.02]. Using regression analysis, dosing method and age were independently associated with the total number of ECT sessions, with less sessions needed in ABM (P = 0.02) and in older patients (P = 0.001). In this comparative cohort study, ABM and DTM showed equal outcome for depression and cognition. However, the median ECT course duration in repeated DTM appeared longer. Additionally, higher age was associated with shorter ECT courses regardless of the dosing method. Further prospective studies are needed to confirm these findings.

Human pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) after repeated doses taken 4 h apart Human pharmacology of MDMA after repeated doses taken 4 h apart.

Science.gov (United States)

Farré, Magí; Tomillero, Angels; Pérez-Mañá, Clara; Yubero, Samanta; Papaseit, Esther; Roset, Pere-Nolasc; Pujadas, Mitona; Torrens, Marta; Camí, Jordi; de la Torre, Rafael

2015-10-01

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a popular psychostimulant, frequently associated with multiple administrations over a short period of time. Repeated administration of MDMA in experimental settings induces tolerance and metabolic inhibition. The aim is to determine the acute pharmacological effects and pharmacokinetics resulting from two consecutive 100mg doses of MDMA separated by 4h. Ten male volunteers participated in a randomized, double-blind, crossover, placebo-controlled trial. The four conditions were placebo plus placebo, placebo plus MDMA, MDMA plus placebo, and MDMA plus MDMA. Outcome variables included pharmacological effects and pharmacokinetic parameters. After a second dose of MDMA, most effects were similar to those after a single dose, despite a doubling of MDMA concentrations (except for systolic blood pressure and reaction time). After repeated MDMA administration, a 2-fold increase was observed in MDMA plasma concentrations. For a simple dose accumulation MDMA and MDA concentrations were higher (+23.1% Cmax and +17.1% AUC for MDMA and +14.2% Cmax and +10.3% AUC for MDA) and HMMA and HMA concentrations lower (-43.3% Cmax and -39.9% AUC for HMMA and -33.2% Cmax and -35.1% AUC for HMA) than expected, probably related to MDMA metabolic autoinhibition. Although MDMA concentrations doubled after the second dose, most pharmacological effects were similar or slightly higher in comparison to the single administration, except for systolic blood pressure and reaction time which were greater than predicted. The pharmacokinetic-effects relationship suggests that when MDMA is administered at a 4h interval there exists a phenomenon of acute tolerance to its effects. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Optogenetic long-term manipulation of behavior and animal development.

Directory of Open Access Journals (Sweden)

Christian Schultheis

Full Text Available Channelrhodopsin-2 (ChR2 is widely used for rapid photodepolarization of neurons, yet, as it requires high-intensity blue light for activation, it is not suited for long-term in vivo applications, e.g. for manipulations of behavior, or photoactivation of neurons during development. We used "slow" ChR2 variants with mutations in the C128 residue, that exhibit delayed off-kinetics and increased light sensitivity in Caenorhabditis elegans. Following a 1 s light pulse, we could photodepolarize neurons and muscles for minutes (and with repeated brief stimulation, up to days with low-intensity light. Photoactivation of ChR2(C128S in command interneurons elicited long-lasting alterations in locomotion. Finally, we could optically induce profound changes in animal development: Long-term photoactivation of ASJ neurons, which regulate larval growth, bypassed the constitutive entry into the "dauer" larval state in daf-11 mutants. These lack a guanylyl cyclase, which possibly renders ASJ neurons hyperpolarized. Furthermore, photostimulated ASJ neurons could acutely trigger dauer-exit. Thus, slow ChR2s can be employed to long-term photoactivate behavior and to trigger alternative animal development.

The Fukushima nuclear accident and the pale grass blue butterfly: evaluating biological effects of long-term low-dose exposures.

Science.gov (United States)

Hiyama, Atsuki; Nohara, Chiyo; Taira, Wataru; Kinjo, Seira; Iwata, Masaki; Otaki, Joji M

2013-08-12

On August 9th 2012, we published an original research article in Scientific Reports, concluding that artificial radionuclides released from the Fukushima Dai-ichi Nuclear Power Plant exerted genetically and physiologically adverse effects on the pale grass blue butterfly Zizeeria maha in the Fukushima area. Immediately following publication, many questions and comments were generated from all over the world. Here, we have clarified points made in the original paper and answered questions posed by the readers. The following points were clarified. (1) There are many advantages to using the pale grass blue butterfly as an indicator species. (2) The forewings of the individuals collected in Fukushima were significantly smaller than in the northern and southern localities. (3) We observed growth retardation in the butterflies from the Fukushima area. (4) The aberrant colour patterns in the butterflies obtained in the Fukushima area were different from the colour patterns induced by temperature and sibling crosses but similar to those induced by external and internal exposures to the artificial radionuclides and by a chemical mutagen, suggesting that genetic mutations caused the aberrations. (5) This species of butterfly has been plentiful in Fukushima area for at least half a century. We here present specimens collected from Fukushima Prefecture before the accident. (6) Mutation accumulation was detected by the increase in the abnormality rates from May 2011 to September 2011. (7) The abnormal traits were heritable. (8) Our sampling localities were not affected by the tsunami. (9) We used a high enough number of samples to obtain statistically significant results. (10) The standard rearing method was followed, producing normal adults in the control groups. (11) The exposure experiments successfully reproduced the results of the field work. This species of butterfly is vulnerable to long-term low-dose internal and external exposures; however, insect cells are known to be

Long-Term Prediction of Severe Hypoglycemia in Type 1 Diabetes

DEFF Research Database (Denmark)

Henriksen, Marie Moth; Færch, Louise; Thorsteinsson, Birger

2016-01-01

BACKGROUND: Prediction of risk of severe hypoglycemia (SH) in patients with type 1 diabetes is important to prevent future episodes, but it is unknown if it is possible to predict the long-term risk of SH. The aim of the study is to assess if long-term prediction of SH is possible in type 1...... diabetes. METHODS: A follow-up study was performed with 98 patients with type 1 diabetes. At baseline and at follow-up, the patients filled in a questionnaire about diabetes history and complications, number of SH in the preceding year and state of awareness, and HbA1c and C-peptide levels were measured......-up. CONCLUSIONS: Long-term prediction of severe hypoglycemia in type 1 diabetes was not possible, although baseline hypoglycemia unawareness tended to remain a predictor for risk of SH at follow-up. Therefore, it is important repeatedly to assess the different risk factors of SH to determine the actual risk....

Subliminal messages exert long-term effects on decision making

OpenAIRE

Ruch, Simon; Züst, Marc; Henke, Katharina

2016-01-01

Subliminal manipulation is often considered harmless because its effects typically decay within a second. So far, subliminal long-term effects on behavior were only observed in studies which repeatedly presented highly familiar information such as single words. These studies suggest that subliminal messages are only slowly stored and might not be stored at all if they provide novel, unfamiliar information. We speculated that subliminal messages might affect delayed decision making especially ...

Long term results of anterior corpectomy and fusion for cervical spondylotic myelopathy.

Directory of Open Access Journals (Sweden)

Rui Gao

Full Text Available BACKGROUND: Results showed good clinical outcomes of anterior corpectomy and fusion (ACCF for patients with cervical spondylotic myelopathy (CSM during a short term follow-up; however, studies assessing long term results are relatively scarce. In this study we intended to assess the long term clinical and radiographic outcomes, find out the factors that may affect the long term clinical outcome and evaluate the incidence of adjacent segment disease (ASD. METHODS: This is a retrospective study of 145 consecutive CSM patients on ACCF treatment with a minimum follow-up of 5 years. Clinical data were collected from medical and operative records. Patients were evaluated by using the Japanese Orthopedic Association (JOA scoring system preoperatively and during the follow-up. X-rays results of cervical spine were obtained from all patients. Correlations between the long term clinical outcome and various factors were also analyzed. FINDINGS: Ninety-three males and fifty-two females completed the follow-up. The mean age at operation was 51.0 years, and the mean follow-up period was 102.1 months. Both postoperative sagittal segmental alignment (SSA and the sagittal alignment of the whole cervical spine (SACS increased significantly in terms of cervical lordosis. The mean increase of JOA was 3.8 ± 1.3 postoperatively, and the overall recovery rate was 62.5%. Logistic regression analysis showed that preoperative duration of symptoms >12 months, high-intensity signal in spinal cord and preoperative JOA score ≤ 9 were important predictors of the fair recovery rate (≤ 50%. Repeated surgery due to ASD was performed in 7 (4.8% cases. CONCLUSIONS: ACCF with anterior plate fixation is a reliable and effective method for treating CSM in terms of JOA score and the recovery rate. The correction of cervical alignment and the repeated surgery rate for ASD are also considered to be satisfactory.

Long-term TLD measurements of environmental background radiation in the New York City Area

International Nuclear Information System (INIS)

Maiello, M.

1994-11-01

The results of month-long TLD measurements at seven locations within 150 km of New York City are reported for 12 years at a few locations and for up to 18 years at others. At some locations, multiple dosimeters were deployed to acquire concurrent indoor and outdoor measurements. The sites were varied and include an urban high-rise residence, three suburban backyards, a rural hillside, and the wooded outskirts of a nuclear power plant (nonoperational). Long-term mean dose rates in air ranged from 50.8 to 123.1 nGy h -1 (5.8 to 14.1 μR h -1 ) across the area. The typical seasonal dose rate in air variations are presented for two of the sites and are briefly discussed in terms of soil conditions. The data indicate that it is possible to achieve monthly variations from the long-term mean as high as 20 to 40%. One of these locations was monitored for indoor (2 floors) and outdoor air dose rates. This allowed for a time series comparison to be performed illustrating the changing contribution of terrestrial radiation to the total dose rate relative to the steady building material-derived radioactivity. This site also permitted the calculation of indoor/outdoor ratios for two floors. Another suburban location yielded an indoor/outdoor ratio using ground floor dose-rate-in-air measurements. Also presented are mean annual dose rates in air showing a long-term decrease at some locations. A statistical Kendall test was performed to quantify the magnitude of the decrease. A definitive explanation of this trend requires further study

Long-term BPA infusions. Evaluation in the rat brain tumor and rat spinal cord models

International Nuclear Information System (INIS)

Coderre, J.A.; Micca, P.L.; Nawrocky, M.M.; Joel, D.D.; Morris, G.M.

2000-01-01

In the BPA-based dose escalation clinical trial, the observations of tumor recurrence in areas of extremely high calculated tumor doses suggest that the BPA distribution is non-uniform. Longer (6-hour) i.v. infusions of BPA are evaluated in the rat brain tumor and spinal cord models to address the questions of whether long-term infusions are more effective against the tumor and whether long-term infusions are detrimental in the central nervous system. In the rat spinal cord, the 50% effective doses (ED 50 ) for myeloparesis were not significantly different after a single i.p. injection of BPA-fructose or a 6 hour i.v. infusion. In the rat 9L gliosarcoma brain tumor model, BNCT following 2-hr or 6-hr infusions of BPA-F produced similar levels of long term survival. (author)

Long-term effect of urethral dilatation and internal urethrotomy for urethral strictures.

Science.gov (United States)

Veeratterapillay, Rajan; Pickard, Rob S

2012-11-01

Urethral dilatation and direct visual internal urethrotomy (DVIU) are widely used minimally invasive options to manage men with urethral strictures. Advances in open urethroplasty with better long-term cure rates have fuelled the continuing debate as to which treatment is best for primary and recurrent urethral strictures. We reviewed recent literature to identify contemporary practice of urethral dilatation and DVIU and the long-term outcome of these procedures. Systematic literature search for the period January 2010 to December 2011 showed that urethral dilatation and DVIU remain frequently used treatment options as confirmed by surveys of urologists in the USA and the Netherlands. Multiple reports of laser DVIU confirm the safety of this approach but long-term data were lacking. Stricture free rates from urethra dilatation and DVIU vary from 10 to 90% at 12 months, although adjunctive intermittent self-dilatation can reduce time to recurrence. Although quality-of-life benefit appears good in the short term, repeated procedures may harm sexual function in the long-term. Urethral dilatation and DVIU remain widely used in urethral stricture management but high-level comparative evidence of benefit and harms against urethroplasty in the short and long-term is still lacking.

Repeated, long-distance migrations by a philopatric predator targeting highly contrasting ecosystems.

Science.gov (United States)

Lea, James S E; Wetherbee, Bradley M; Queiroz, Nuno; Burnie, Neil; Aming, Choy; Sousa, Lara L; Mucientes, Gonzalo R; Humphries, Nicolas E; Harvey, Guy M; Sims, David W; Shivji, Mahmood S

2015-06-09

Long-distance movements of animals are an important driver of population spatial dynamics and determine the extent of overlap with area-focused human activities, such as fishing. Despite global concerns of declining shark populations, a major limitation in assessments of population trends or spatial management options is the lack of information on their long-term migratory behaviour. For a large marine predator, the tiger shark Galeocerdo cuvier, we show from individuals satellite-tracked for multiple years (up to 1101 days) that adult males undertake annually repeated, round-trip migrations of over 7,500 km in the northwest Atlantic. Notably, these migrations occurred between the highly disparate ecosystems of Caribbean coral reef regions in winter and high latitude oceanic areas in summer, with strong, repeated philopatry to specific overwintering insular habitat. Partial migration also occurred, with smaller, immature individuals displaying reduced migration propensity. Foraging may be a putative motivation for these oceanic migrations, with summer behaviour showing higher path tortuosity at the oceanic range extremes. The predictable migratory patterns and use of highly divergent ecosystems shown by male tiger sharks appear broadly similar to migrations seen in birds, reptiles and mammals, and highlight opportunities for dynamic spatial management and conservation measures of highly mobile sharks.

Repeated, long-distance migrations by a philopatric predator targeting highly contrasting ecosystems

Science.gov (United States)

Lea, James S. E.; Wetherbee, Bradley M.; Queiroz, Nuno; Burnie, Neil; Aming, Choy; Sousa, Lara L.; Mucientes, Gonzalo R.; Humphries, Nicolas E.; Harvey, Guy M.; Sims, David W.; Shivji, Mahmood S.

2015-06-01

Long-distance movements of animals are an important driver of population spatial dynamics and determine the extent of overlap with area-focused human activities, such as fishing. Despite global concerns of declining shark populations, a major limitation in assessments of population trends or spatial management options is the lack of information on their long-term migratory behaviour. For a large marine predator, the tiger shark Galeocerdo cuvier, we show from individuals satellite-tracked for multiple years (up to 1101 days) that adult males undertake annually repeated, round-trip migrations of over 7,500 km in the northwest Atlantic. Notably, these migrations occurred between the highly disparate ecosystems of Caribbean coral reef regions in winter and high latitude oceanic areas in summer, with strong, repeated philopatry to specific overwintering insular habitat. Partial migration also occurred, with smaller, immature individuals displaying reduced migration propensity. Foraging may be a putative motivation for these oceanic migrations, with summer behaviour showing higher path tortuosity at the oceanic range extremes. The predictable migratory patterns and use of highly divergent ecosystems shown by male tiger sharks appear broadly similar to migrations seen in birds, reptiles and mammals, and highlight opportunities for dynamic spatial management and conservation measures of highly mobile sharks.

Leksell Gamma Knife radiosurgery of the jugulotympanic glomus tumor: long-term results.

Science.gov (United States)

Liscak, Roman; Urgosik, Dusan; Chytka, Tomas; Simonova, Gabriela; Novotny, Josef; Vymazal, Josef; Guseynova, Khumar; Vladyka, Vilibald

2014-12-01

Glomus tumors usually display indolent behavior, and the effectiveness of radiation in stopping their growth can be assessed after long-term follow-up. Currently only midterm results of radiosurgery are available, so the authors included patients treated by Gamma Knife at least 10 years ago in this study to obtain a perspective of long-term results. During the period from 1992 to 2003, the Gamma Knife was used to treat 46 patients with glomus tumors. The age of the patients ranged from 21 to 79 years (median 56 years). Gamma Knife radiosurgery was the primary treatment in 17 patients (37%). Open surgery preceded radiosurgery in 46% of cases, embolization in 17%, and fractionated radiotherapy in 4%. The volume of the tumor ranged from 0.2 to 24.3 cm(3) (median 3.6 cm(3)). The minimal dose to the tumor margin ranged between 10 and 30 Gy (median 20 Gy). One patient was lost for follow-up after radiosurgery. Clinical follow-up was available in 45 patients and 44 patients were followed with MRI in a follow-up period that ranged from 12 to 217 months (median 118 months). Neurological deficits improved in 19 (42%) of 45 patients and deteriorated in 2 patients (4%). Tumor size decreased in 34 (77%) of 44 patients with imaging follow-up, while an increase in volume was observed in 1 patient (2%) 182 months after radiosurgery and Gamma Knife treatment was repeated. One patient underwent another Gamma Knife treatment for secondary induced meningioma close to the glomus tumor 98 months after initial radiosurgical treatment. Seven patients died 22-96 months after radiosurgery (median 48 months), all for unrelated reasons. Radiosurgery has proved to be a safe treatment with a low morbidity rate and a reliable long-term antiproliferative effect.

Radiation dose and long term risk of cardiac pathology following radiotherapy and anthracyclin for a childhood cancer

International Nuclear Information System (INIS)

Guldner, Laurence; Haddy, Nadia; Pein, Francois; Diallo, Ibrahima; Shamsaldin, Akthar; Dahan, Michel; Lebidois, Jerome; Merlet, Pascal; Villain, Elisabeth; Sidi, Daniel; Sakiroglu, Olivia; Hartmann, Olivier; Leftakopoulos, Dimitri; Vathaire, Florent de

2006-01-01

Purpose: To determine the cardiac status in children 15 years (yrs) or more after a solid tumour treatment. Patients and Methods: Of the 447 patients, 229 were fully studied and 218 were not. The following cardiac evaluation was proposed to all the 447 consecutive patients: (1) cardiac Doppler US by one of two expert cardiologists; (2) cardiac rhythm and conduction abnormalities including 24-h holter ECG; (3) 131 I-mIBG myocardial scintigraphy; (4) serum brain natriuretic peptide levels at rest; (5) an exercise test with VO 2 max measurement. The radiation dose delivered to 7 points in the heart was estimated for all patients who had received radiotherapy. Results: Cardiac disorder was diagnosed in 89 evaluated patients (39%) including 24 heart failures and 65 other asymptomatic cardiac diseases. When adjusting on potential confounders, cardiac disorder and cardiac failure risks were respectively linear (ERR at 1 Gy: 26%) and linear-quadratic (ERR at 1 Gy: 19%) functions of the average radiation dose received to the heart. No interaction between cumulative dose of adriamycin and average radiation dose was evidenced for cardiac disorders, but the ERR/Gy of cardiac failure was higher for patients receiving less than 350 mg/m 2 of Adriamycin. Conclusion: Long term heart pathologies are probably one of the major iatrogenic risks encored by patients who survived a childhood cancer. This study strongly emphasizes the need to limit the heart irradiation during radiotherapy, particularly, for patients who also received or were susceptible to later received adriamycin

Long-term experience of plasmapheresis in antibody-mediated rejection in renal transplantation.

LENUS (Irish Health Repository)

Brown, C M

2009-11-01

Antibody-mediated rejection (AMR) continues to pose a serious challenge in renal transplantation with potentially devastating consequences. Treatment options for this condition include plasmapheresis, high-dose intravenous immunoglobulin (IVIG), plasmapheresis with low-dose IVIG, and the use of rituximab (anti-CD20 chimeric antibody). We previously reported on the short-term outcome of plasmapheresis as a rescue therapy for AMR in our centre. We now report on the long-term follow up.

Long-Term Coffee Consumption Is Associated with Decreased Incidence of New-Onset Hypertension: A Dose-Response Meta-Analysis.

Science.gov (United States)

Grosso, Giuseppe; Micek, Agnieszka; Godos, Justyna; Pajak, Andrzej; Sciacca, Salvatore; Bes-Rastrollo, Maira; Galvano, Fabio; Martinez-Gonzalez, Miguel A

2017-08-17

To perform a dose-response meta-analysis of prospective cohort studies investigating the association between long-term coffee intake and risk of hypertension. An online systematic search of studies published up to November 2016 was performed. Linear and non-linear dose-response meta-analyses were conducted; potential evidence of heterogeneity, publication bias, and confounding effect of selected variables were investigated through sensitivity and meta-regression analyses. Seven cohorts including 205,349 individuals and 44,120 cases of hypertension were included. In the non-linear analysis, there was a 9% significant decreased risk of hypertension per seven cups of coffee a day, while, in the linear dose-response association, there was a 1% decreased risk of hypertension for each additional cup of coffee per day. Among subgroups, there were significant inverse associations for females, caffeinated coffee, and studies conducted in the US with longer follow-up. Analysis of potential confounders revealed that smoking-related variables weakened the strength of association between coffee consumption and risk of hypertension. Increased coffee consumption is associated with a modest decrease in risk of hypertension in prospective cohort studies. Smoking status is a potential effect modifier on the association between coffee consumption and risk of hypertension.

Immunomodulatory effect of ganoderma lucidum polysaccharides (GLP) on long-term heavy-load exercising mice.

Science.gov (United States)

Shi, Yali; Cai, Dehua; Wang, Xiaojie; Liu, Xinshen

2012-12-01

Long-term heavy-load exercise can lead to a decrease in the organism's immune response. In this study, we used 100 Kunming (KM) mice to investigate the immune-regulatory effects of Ganoderma lucidum polysaccharides (GLP) on long-term heavy-load exercising mice. Peripheral white blood cells (WBC), the absolute value of neutrophils (NEUT), the phagocytic function of macrophages, serum agglutination valence, and the number of plaque-forming cells (PFC) were evaluated 4 weeks after gavaging long-term heavy-load exercising mice with GLP. After exercise, the WBC count in peripheral blood, absolute neutrophil count, macrophage phagocytic index, serum agglutination valence, and the number of plaque-forming cells were significantly reduced in the mice not fed GLP. Both medium and high doses of GLP drastically increased peripheral WBC, absolute neutrophil count, macrophage phagocytic index, serum agglutination valence, and the number of plaque-forming cells in long-term heavy-load exercising mice. High doses of GLP increased peritoneal macrophage phagocytic rate considerably. With this study, we demonstrate that 4 weeks of heavy-load exercise can lead to exercise-induced immunosuppression in mice. A supplement of GLP fed to these mice improves both non-specific and specific immune responses among these mice. The effect for the high-dose GLP treatment is especially significant.

Thallium Intoxication Treated with Long-Term Hemodialysis, Forced Diuresis and Prussian Blue

DEFF Research Database (Denmark)

Larsen, Elfinn; Solgaard, Per Bent; Freund, L. Gade

1978-01-01

A 56 yr old woman, who ingested 2 g of thallium sulfate, was successfully treated with long-term hemodialysis for 200 h during 10 days, combined with forced diuresis and Prussian blue. The effect of the artificial kidney dialysis was determined by repeated analysis of the Tl concentration...

On the long-term development of population dose in radioactively contaminated parts of Korma County (Belarus)

International Nuclear Information System (INIS)

Dederichs, H.; Pillath, J.; Heuel-Fabianek, B.; Hill, P.; Lennartz, R.

2009-01-01

Radiological long-term measurements were performed between 1998 and 2007 in a region in Belarus that was affected by the Chernobyl accident. The internal radiation exposure of the inhabitants in the village of Volincy (Korma County) - caused by the existing contamination and an increasing lack of precaution over time with regard to eating home-grown food - has experienced a significant decrease from a very high level. The external exposure, however, reveals a different picture. Although an overall decrease was observed, the organic constituents of the soil show an increase in contamination. This increase was not observed in soils from cultivated land or gardens. In addition to the measurements, a relationship based on mutual trust allowed us to offer the inhabitants individual advice on how to reduce internal contamination. As a result of this advice and the decreasing environmental contamination (topsoil and crops), the internal dose was reduced significantly. Today, the internal exposure has only increased slightly and has no significant negative influence on the health of the people. The internal dose will decrease to less than 0.2 mSv/a in 2011 and to below 0.1 mSv/a in 2020. Despite this, the cumulative dose will remain significantly higher than normal background values due to external exposure. If internal exposure is checked on a regular basis and advice is offered on an individual basis, there should be no specific danger for the people in the region in the near future. Resettlement may even be possible in former prohibited areas provided that people comply with appropriate dietary rules. (orig.)

Age and Chronicity of Administration Dramatically Influenced the Impact of Low Dose Paraquat Exposure on Behavior and Hypothalamic-Pituitary-Adrenal Activity

Directory of Open Access Journals (Sweden)

Chris A. Rudyk

2017-07-01

Full Text Available Little is known of the age-dependent and long-term consequences of low exposure levels of the herbicide and dopaminergic toxicant, paraquat. Thus, we assessed the dose-dependent effects of paraquat using a typical short-term (3 week exposure procedure, followed by an assessment of the effects of chronic (16 weeks exposure to a very low dose (1/10th of what previously induced dopaminergic neuronal damage. Short term paraquat treatment dose-dependently induced deficits in locomotion, sucrose preference and Y-maze performance. Chronic low dose paraquat treatment had a very different pattern of effects that were also dependent upon the age of the animal: in direct contrast to the short-term effects, chronic low dose paraquat increased sucrose consumption and reduced forced swim test (FST immobility. Yet these effects were age-dependent, only emerging in mice older than 13 months. Likewise, Y-maze spontaneous alternations and home cage activity were dramatically altered as a function of age and paraquat chronicity. In both the short and long-term exposure studies, increased corticosterone and altered hippocampal glucocorticoid receptor (GR levels were induced by paraquat, but surprisingly these effects were blunted in the older mice. Thus, paraquat clearly acts as a systemic stressor in terms of corticoid signaling and behavioral outcomes, but that paradoxical effects may occur with: (a repeated exposure at; (b very low doses; and (c older age. Collectively, these data raise the possibility that repeated “hits” with low doses of paraquat in combination with aging processes might have promoted compensatory outcomes.

Long-term effects of acoustic reafference training (ART).

Science.gov (United States)

Pizzera, Alexandra; Hohmann, Tanja; Streese, Lukas; Habbig, Anja; Raab, Markus

2017-11-01

In sport visual feedback is often used to enhance performance, mostly neglecting the auditory modality. However, athletes produce natural sounds when they move (acoustic reafferences) which they perceive and use to control their movements. We examined the short- and long-term effects of a training intervention on a complex movement by using acoustic reafferences. Natural step sounds produced during hurdling were recorded and played back to the participants immediately before each trial, with an increase (fast group), decrease (slow group), or no manipulation (control group) in the tempo. All groups increased their hurdling performance regarding overall running time, with the slow group showing the best performance development. After a 10-week retention, the fast and slow group further increased performance, whereas the control group declined. The repeated experience with acoustic information associated with the rhythmic pattern of hurdling may have helped developing a cognitive representation of that movement, especially regarding long-term effects.

Self-assembling siloxane bilayer directly on SiO{sub 2} surface of micro-cantilevers for long-term highly repeatable sensing to trace explosives

Energy Technology Data Exchange (ETDEWEB)

Chen Ying; Xu Pengcheng; Li Xinxin, E-mail: xxli@mail.sim.ac.cn [State Key Lab of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050 (China)

2010-07-02

This paper presents a novel sensing layer modification technique for static micro-cantilever sensors that detect trace explosives by measuring specific adsorption-induced surface stress. For the first time, a method of directly modifying a siloxane sensing bilayer on an SiO{sub 2} surface is proposed to replace the conventional self-assembled monolayers (SAMs) of thiols on Au to avoid the trouble from long-term unstable Au-S bonds. For modifying the long-term reliable sensing bilayer on the piezoresistor-integrated micro-cantilevers, a siloxane-head bottom layer is self-assembled directly on the SiO{sub 2} cantilever surface, which is followed by grafting another explosive-sensing-group functionalized molecule layer on top of the siloxane layer. The siloxane-modified sensor has experimentally exhibited a highly resoluble response to 0.1 ppb TNT vapor. More importantly, the repeated detection results after 140 days show no obvious attenuation in sensing signal. Also observed experimentally, the specific adsorption of the siloxane sensing bilayer to TNT molecules causes a tensile surface stress on the cantilever. Herein the measured tensile surface stress is in contrast to the compressive surface stress normally measured from conventional cantilever sensors where the sensitive thiol-SAMs are modified on an Au surface. The reason for this newly observed phenomenon is discussed and preliminarily analyzed.

Long-term modeling on HPV vaccination: do we really need any more?

Science.gov (United States)

Garattini, Livio; Curto, Alessandro; van de Vooren, Katelijne

2015-04-01

The human papillomavirus (HPV) is closely related to cervical cancer. In 2007, the EMA approved two vaccines, a bivalent and a quadrivalent one, launched at three-dose schedules and very high prices worldwide. We describe what happened in the EU and what might change in the near future from an economic perspective. HPV vaccination is now established in most EU countries. The main target group of the programs is girls aged 10-14 years. Many western countries used competitive tendering to purchase the two vaccines, achieving considerable savings. The extension to males has been a hotly debated issue. The sex limitation implies that this vaccination cannot by definition achieve a 'herd immunity' effect. EMA recently approved a two-dose schedule for both vaccines that should lead to savings, although it is hard to predict how the forthcoming nonavalent vaccine will affect the market situation. Several economic evaluations based on long-term models have been published on the HPV vaccination in the recent years, using official list prices as a baseline. Most of these models can be considered mere exercises in long-term forecasting. Recently, further long-term models have been published with two- and three-dose schedules as alternatives, and the nonavalent vaccine. We wonder what added value they give for public policy purposes.

Long-term outcome of urethroplasty after failed urethrotomy versus primary repair.

Science.gov (United States)

Barbagli, G; Palminteri, E; Lazzeri, M; Guazzoni, G; Turini, D

2001-06-01

A urethral stricture recurring after repeat urethrotomy challenges even a skilled urologist. To address the question of whether to repeat urethrotomy or perform open reconstructive surgery, we retrospectively review a series of 93 patients comparing those who underwent primary repair versus those who had undergone urethrotomy and underwent secondary treatment. From 1975 to 1998, 93 males between age 13 and 78 years (mean 39) underwent surgical treatment for bulbar urethral stricture. In 46 (49%) of the patients urethroplasty was performed as primary repair, and in 47 (51%) after previously failed urethrotomy. The strictures were localized in the bulbous urethra without involvement of penile or membranous tracts. The etiology was ischemic in 37 patients, traumatic in 23, unknown in 17 and inflammatory in 16. To simplify evaluation of the results, the clinical outcome was considered either a success or a failure at the time any postoperative procedure was needed, including dilation. In our 93 patients primary urethroplasty had a final success rate of 85%, and after failed urethrotomy 87%. Previously failed urethrotomy did not influence the long-term outcome of urethroplasty. The long-term results of different urethroplasty techniques had a final success rate ranging from 77% to 96%. We conclude that failed urethrotomy does not condition the long-term result of surgical repair. With extended followup, the success rate of urethroplasty decreases with time but it is in fact still higher than that of urethrotomy.

Dose of jogging and long-term mortality

DEFF Research Database (Denmark)

Schnohr, Peter; O'Keefe, James H; Marott, Jacob L

2015-01-01

BACKGROUND: People who are physically active have at least a 30% lower risk of death during follow-up compared with those who are inactive. However, the ideal dose of exercise for improving longevity is uncertain. OBJECTIVES: The aim of this study was to investigate the association between joggin...

Evaluation of the repeated-dose liver micronucleus assay using 2,4-dinitrotoluene: a report of a collaborative study by CSGMT/JEMS.MMS.

Science.gov (United States)

Maeda, Akihisa; Tsuchiyama, Hiromi; Asaoka, Yoshiji; Hirakata, Mikito; Miyoshi, Tomoya; Oshida, Keiyu; Miyamoto, Yohei

2015-03-01

The liver micronucleus assay using young adult rats has the potential to detect liver carcinogens by repeated dosing, and could be expected to be integrated into repeated-dose toxicity studies using a hepatocyte isolation method without the traditional in situ collagenase perfusion. In this study, to assess the performance of the repeated-dose liver micronucleus assay, 2,4-dinitrotoluene (DNT), which is a rodent liver carcinogen, was administered orally to male rats at doses of 50, 100 and 200 mg/kg/day once daily for 14 or 28 consecutive days, and the frequencies of micronucleated hepatocytes (MNHEPs) and micronucleated immature erythrocytes (MNIMEs) were examined. Significant increases in the MNHEPs were observed at 50 mg/kg/day or more in the 14-day treatment, and 50 and 100 mg/kg/day in the 28-day treatment. These increases were dependent on both the dose and the number of administrations, which indicates the possibility that the MNHEPs accumulate as a result of repeated dosing. In contrast, no increase in the MNIMEs was observed. In conclusion, the repeated-dose liver micronucleus assay using young adult rats is sufficiently sensitive to detect the genotoxicity of 2,4-DNT at a low dose.

Cannabinoid Hyperemesis Syndrome: A Case Report of Cyclic Severe Hyperemesis and Abdominal Pain with Long-Term Cannabis Use

Directory of Open Access Journals (Sweden)

Julia Hermes-Laufer

2016-01-01

Full Text Available Introduction. Cannabinoid Hyperemesis Syndrome (CHS is a rare condition that includes cyclic severe vomiting in subjects who have been consuming large doses of cannabis for several years. One of the major diagnostic criteria is the alleviation of symptoms by hot showers. The syndrome was first described in 2004 and is so far neither completely understood nor well known. The latter leads to continued morbidity in concerned subjects and unnecessary expenses for futile investigations. Standard treatments of vomiting as 5-HT3 or D2-receptor antagonists have been shown to be ineffective in alleviating the symptoms. The only long-term satisfying treatment option is the complete abstinence from cannabis consumption. Case Summary. In this case report we describe a 26-year-old male Caucasian long-term cannabis consumer who repeatedly presented in our emergency room with cyclic severe nausea and vomiting ceased by hot showers and resistant to all other treatments. The final diagnosis was not established until his third visit to the ER. Conclusion. CHS is an important differential diagnosis in patients who present with cyclic vomiting and abdominal pain with a history of long-term cannabis use. Recognition of this syndrome is important in order to avoid unnecessary clinical testing and to help the patients break the cycle of drug use.

Audit of long-term and short-term liabilities

Directory of Open Access Journals (Sweden)

Korinko M.D.

2017-03-01

Full Text Available The article determines the importance of long-term and short-term liabilities for the management of financial and material resources of an enterprise. It reviews the aim, objects and information generators for realization of audit of short-term and long-term obligations. The organizing and methodical providing of audit of long-term and short-term liabilities of an enterprise are generalized. The authors distinguish the stages of realization of audit of long-term and short-term liabilities, the aim of audit on each of the presented stages, and recommend methodical techniques. It is fixed that it is necessary to conduct the estimation of the systems of internal control and record-keeping of an enterprise by implementation of public accountant procedures for determination of volume and maintenance of selection realization. After estimating the indicated systems, a public accountant determines the methodology for realization of public accountant verification of long-term and short-term liabilities. The analytical procedures that public accountants are expedient to use for realization of audit of short-term and long-term obligations are determined. The authors suggest the classification of the educed defects on the results of the conducted public accountant verification of short-term and long-term obligations.

TREND: a program using cumulative sum methods to detect long-term trends in data

International Nuclear Information System (INIS)

Cranston, R.J.; Dunbar, R.M.; Jarvis, R.G.

1976-01-01

TREND is a computer program, in FORTRAN, to investigate data for long-term trends that are masked by short-term statistical fluctuations. To do this, it calculates and plots the cumulative sum of deviations from a chosen mean. As a further aid to diagnosis, the procedure can be repeated with a summation of the cumulative sum itself. (author)

Low-dose-rate brachytherapy for patients with transurethral resection before implantation in prostate cancer: long-term results

International Nuclear Information System (INIS)

Prada, Pedro J.; Anchuelo, Javier; Blanco, Ana Garcia; Paya, Gema; Cardenal, Juan; Acuña, Enrique; Ferri, Maria; Vazquez, Andres; Pacheco, Maite; Sanchez, Jesica

2016-01-01

Objectives: We analyzed the long-term oncologic outcome for patients with prostate cancer and transurethral resection who were treated using low-dose-rate (LDR) prostate brachytherapy. Methods and Materials: From January 2001 to December 2005, 57 consecutive patients were treated with clinically localized prostate cancer. No patients received external beam radiation. All of them underwent LDR prostate brachytherapy. Biochemical failure was defined according to the 'Phoenix consensus'. Patients were stratified as low and intermediate risk based on The Memorial Sloan Kettering group definition. Results: The median follow-up time for these 57 patients was 104 months. The overall survival according to Kaplan-Meier estimates was 88% (±6%) at 5 years and 77% (±6%) at 12 years. The 5 and 10 years for failure in tumour-free survival (TFS) was 96% and respectively (±2%), whereas for biochemical control was 94% and respectively (±3%) at 5 and 10 years, 98% (±1%) of patients being free of local recurrence. A patient reported incontinence after treatment (1.7%). The chronic genitourinary complains grade I were 7% and grade II, 10%. At six months 94% of patients reported no change in bowel function. Conclusions: The excellent long-term results and low morbidity presented, as well as the many advantages of prostate brachytherapy over other treatments, demonstrates that brachytherapy is an effective treatment for patients with transurethral resection and clinical organ-confined prostate cancer. (author)

Low-dose-rate brachytherapy for patients with transurethral resection before implantation in prostate cancer: long-term results

Energy Technology Data Exchange (ETDEWEB)

Prada, Pedro J.; Anchuelo, Javier; Blanco, Ana Garcia; Paya, Gema; Cardenal, Juan; Acuña, Enrique; Ferri, Maria [Department of Radiation Oncology, Hospital Universitario Marqués de Valdecilla, Santander, Cantabria (Spain); Vazquez, Andres; Pacheco, Maite; Sanchez, Jesica [Department of Radiation Physics, Hospital Universitario Marqués de Valdecilla, Santander, Cantabria (Spain)

2016-01-15

Objectives: We analyzed the long-term oncologic outcome for patients with prostate cancer and transurethral resection who were treated using low-dose-rate (LDR) prostate brachytherapy. Methods and Materials: From January 2001 to December 2005, 57 consecutive patients were treated with clinically localized prostate cancer. No patients received external beam radiation. All of them underwent LDR prostate brachytherapy. Biochemical failure was defined according to the 'Phoenix consensus'. Patients were stratified as low and intermediate risk based on The Memorial Sloan Kettering group definition. Results: The median follow-up time for these 57 patients was 104 months. The overall survival according to Kaplan-Meier estimates was 88% (±6%) at 5 years and 77% (±6%) at 12 years. The 5 and 10 years for failure in tumour-free survival (TFS) was 96% and respectively (±2%), whereas for biochemical control was 94% and respectively (±3%) at 5 and 10 years, 98% (±1%) of patients being free of local recurrence. A patient reported incontinence after treatment (1.7%). The chronic genitourinary complains grade I were 7% and grade II, 10%. At six months 94% of patients reported no change in bowel function. Conclusions: The excellent long-term results and low morbidity presented, as well as the many advantages of prostate brachytherapy over other treatments, demonstrates that brachytherapy is an effective treatment for patients with transurethral resection and clinical organ-confined prostate cancer. (author)

Long-term outcomes from dose-escalated image-guided intensity-modulated radiotherapy with androgen deprivation: encouraging results for intermediate- and high-risk prostate cancer

Directory of Open Access Journals (Sweden)

Wilcox SW

2014-08-01

Full Text Available Shea W Wilcox,1,4 Noel J Aherne,2,4 Linus C Benjamin,1 Bosco Wu,1 Thomaz de Campos Silva,3 Craig S McLachlan,4 Michael J McKay,3,5 Andrew J Last,1 Thomas P Shakespeare1–4 1North Coast Cancer Institute, Port Macquarie, NSW, Australia; 2North Coast Cancer Institute, Coffs Harbour, NSW, Australia; 3North Coast Cancer Institute, Lismore, NSW, Australia; 4The University of New South Wales, Rural Clinical School, Sydney, NSW, Australia; 5The University of Sydney, Sydney, NSW, Australia Purpose: Dose-escalated (DE radiotherapy in the setting of localized prostate cancer has been shown to improve biochemical disease-free survival (bDFS in several studies. In the same group of patients, androgen deprivation therapy (ADT has been shown to confer a survival benefit when combined with radiotherapy doses of up to 70 Gy; however, there is currently little long-term data on patients who have received high-dose intensity-modulated radiotherapy (IMRT with ADT. We report the long-term outcomes in a large cohort of patients treated with the combination of DE image-guided IMRT (IG-IMRT and ADT. Methods and materials: Patients with localized prostate cancer were identified from a centralized database across an integrated cancer center. All patients received DE IG-IMRT, combined with ADT, and had a minimum follow up of 12 months post-radiotherapy. All relapse and toxicity data were collected prospectively. Actuarial bDFS, metastasis-free survival, prostate cancer-specific survival, and multivariate analyses were calculated using the SPSS v20.0 statistical package. Results: Seven hundred and eighty-two eligible patients were identified with a median follow up of 46 months. Overall, 4.3% of patients relapsed, 2.0% developed distant metastases, and 0.6% died from metastatic prostate cancer. At 5-years, bDFS was 88%, metastasis-free survival was 95%, and prostate cancer-specific survival was 98%. Five-year grade 2 genitourinary and gastrointestinal toxicity was 2

Using electrophysiology to demonstrate that cueing affects long-term memory storage over the short term.

Science.gov (United States)

Maxcey, Ashleigh M; Fukuda, Keisuke; Song, Won S; Woodman, Geoffrey F

2015-10-01

As researchers who study working memory, we often assume that participants keep a representation of an object in working memory when we present a cue that indicates that the object will be tested in a couple of seconds. This intuitively accounts for how well people can remember a cued object, relative to their memory for that same object presented without a cue. However, it is possible that this superior memory does not purely reflect storage of the cued object in working memory. We tested the hypothesis that cues presented during a stream of objects, followed by a short retention interval and immediate memory test, can change how information is handled by long-term memory. We tested this hypothesis by using a family of frontal event-related potentials believed to reflect long-term memory storage. We found that these frontal indices of long-term memory were sensitive to the task relevance of objects signaled by auditory cues, even when the objects repeated frequently, such that proactive interference was high. Our findings indicate the problematic nature of assuming process purity in the study of working memory, and demonstrate that frequent stimulus repetitions fail to isolate the role of working memory mechanisms.

Dopamine transporter down-regulation following repeated cocaine: implications for 3,4-methylenedioxymethamphetamine-induced acute effects and long-term neurotoxicity in mice.

Science.gov (United States)

Peraile, I; Torres, E; Mayado, A; Izco, M; Lopez-Jimenez, A; Lopez-Moreno, J A; Colado, M I; O'Shea, E

2010-01-01

3,4-Methylenedioxymethamphetamine (MDMA) and cocaine are two widely abused psychostimulant drugs targeting the dopamine transporter (DAT). DAT availability regulates dopamine neurotransmission and uptake of MDMA-derived neurotoxic metabolites. We aimed to determine the effect of cocaine pre-exposure on the acute and long-term effects of MDMA in mice. Mice received a course of cocaine (20 mg*kg(-1), x2 for 3 days) followed by MDMA (20 mg*kg(-1), x2, 3 h apart). Locomotor activity, extracellular dopamine levels and dopaminergic neurotoxicity were determined. Furthermore, following the course of cocaine, DAT density in striatal plasma membrane and endosome fractions was measured. Four days after the course of cocaine, challenge with MDMA attenuated the MDMA-induced striatal dopaminergic neurotoxicity. Co-administration of the protein kinase C (PKC) inhibitor NPC 15437 prevented cocaine protection. At the same time, after the course of cocaine, DAT density was reduced in the plasma membrane and increased in the endosome fraction, and this effect was prevented by NPC 15437. The course of cocaine potentiated the MDMA-induced increase in extracellular dopamine and locomotor activity, following challenge 4 days later, compared with those pretreated with saline. Repeated cocaine treatment followed by withdrawal protected against MDMA-induced dopaminergic neurotoxicity by internalizing DAT via a mechanism which may involve PKC. Furthermore, repeated cocaine followed by withdrawal induced behavioural and neurochemical sensitization to MDMA, measures which could be indicative of increased rewarding effects of MDMA.

Independence of long-term contextual memory and short-term perceptual hypotheses: evidence from contextual cueing of interrupted search

OpenAIRE

Schlagbauer, B.; Mink, M.; Muller, Hermann J.; Geyer, T.

2017-01-01

Observers are able to resume an interrupted search trial faster relative to responding to a new, unseen display. This finding of rapid resumption is attributed to short-term perceptual hypotheses generated on the current look and confirmed upon subsequent looks at the same display. It has been suggested that the contents of perceptual hypotheses are similar to those of other forms of memory acquired long-term through repeated exposure to the same search displays over the course of several tri...

Long-term health outcomes after exposure to repeated concussion in elite level: rugby union players.

Science.gov (United States)

McMillan, T M; McSkimming, P; Wainman-Lefley, J; Maclean, L M; Hay, J; McConnachie, A; Stewart, W

2017-06-01

There is continuing concern about effects of concussion in athletes, including risk of the neurodegenerative disease chronic traumatic encephalopathy. However, information on long-term health and wellbeing in former athletes is limited. Outcome after exposure to repeated brain injury was investigated in 52 retired male Scottish international rugby players (RIRP) and 29 male controls who were similar in age and social deprivation. Assessment included history of playing rugby and traumatic brain injury, general and mental health, life stress, concussion symptoms, cognitive function, disability and markers of chronic stress (allostatic load). The estimated number of concussions in RIRP averaged 14 (median=7; IQR 5-40). Performance was poorer in RIRP than controls on a test of verbal learning (p=0.022) and of fine co-ordination of the dominant hand (p=0.038) and not significantly different on other cognitive tests (p>0.05). There were no significant associations between number of concussions and performance on cognitive tests. Other than a higher incidence of cardiovascular disease in controls, no group differences were detected in general or mental health or estimates of allostatic load. In RIRP, persisting symptoms attributed to concussion were more common if reporting more than nine concussions (p=0.028), although these symptoms were not perceived to affect social or work functioning. Despite a high number of concussions in RIRP, differences in mental health, social or work functioning were not found late after injury. Subtle group differences were detected on two cognitive tests, the cause of which is uncertain. Prospective group comparison studies on representative cohorts are required. 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/.

Short-term memory to long-term memory transition in a nanoscale memristor.

Science.gov (United States)

Chang, Ting; Jo, Sung-Hyun; Lu, Wei

2011-09-27

"Memory" is an essential building block in learning and decision-making in biological systems. Unlike modern semiconductor memory devices, needless to say, human memory is by no means eternal. Yet, forgetfulness is not always a disadvantage since it releases memory storage for more important or more frequently accessed pieces of information and is thought to be necessary for individuals to adapt to new environments. Eventually, only memories that are of significance are transformed from short-term memory into long-term memory through repeated stimulation. In this study, we show experimentally that the retention loss in a nanoscale memristor device bears striking resemblance to memory loss in biological systems. By stimulating the memristor with repeated voltage pulses, we observe an effect analogous to memory transition in biological systems with much improved retention time accompanied by additional structural changes in the memristor. We verify that not only the shape or the total number of stimuli is influential, but also the time interval between stimulation pulses (i.e., the stimulation rate) plays a crucial role in determining the effectiveness of the transition. The memory enhancement and transition of the memristor device was explained from the microscopic picture of impurity redistribution and can be qualitatively described by the same equations governing biological memories. © 2011 American Chemical Society

Accelerated long-term forgetting in children with idiopathic generalized epilepsy.

Science.gov (United States)

Gascoigne, Michael B; Barton, Belinda; Webster, Richard; Gill, Deepak; Antony, Jayne; Lah, Suncica Sunny

2012-12-01

The rapid forgetting of information over long (but not short) delays (accelerated long-term forgetting [ALF]) has been associated with temporal lobe epilepsy but not idiopathic generalized epilepsy (IGE). Long-term memory formation (consolidation) is thought to demand an interaction between medial temporal and neocortical networks, which could be disrupted by epilepsy/seizures themselves. The present study investigates whether ALF is present in children with IGE and whether it relates to epilepsy severity. Sixty-one children (20 with IGE and 41 healthy controls [HC]) of comparable age, sex, and parental socioeconomic status completed neuropsychological tests, including a measure of verbal learning and recall after, short (30-min) and long (7-day) delays, and recognition. Epilepsy severity was rated by treating neurologists. A two-way repeated measures analysis of covariance (ANCOVA) found a significant Group x Delay interaction; the children with IGE recalled (and recognized) significantly fewer words after a long, but not short (2- and 30-min) delay relative to the HC children. Moreover, greater epilepsy severity was associated with poorer recognition. This study demonstrates, to our knowledge for the first time, that children with IGE present with ALF, which is related to epilepsy severity. These findings support the notion that epilepsy/seizures themselves may disrupt long-term memory consolidation, which interferes with day-to-day functioning of children with IGE. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

Long-term follow-up study and long-term care of childhood cancer survivors

Directory of Open Access Journals (Sweden)

Hyeon Jin Park

2010-04-01

Full Text Available The number of long-term survivors is increasing in the western countries due to remarkable improvements in the treatment of childhood cancer. The long-term complications of childhood cancer survivors in these countries were brought to light by the childhood cancer survivor studies. In Korea, the 5-year survival rate of childhood cancer patients is approaching 70%; therefore, it is extremely important to undertake similar long-term follow-up studies and comprehensive long-term care for our population. On the basis of the experiences of childhood cancer survivorship care of the western countries and the current Korean status of childhood cancer survivors, long-term follow-up study and long-term care systems need to be established in Korea in the near future. This system might contribute to the improvement of the quality of life of childhood cancer survivors through effective intervention strategies.

Long-term environmental behaviour of radionuclides

Energy Technology Data Exchange (ETDEWEB)

Brechignac, F.; Moberg, L.; Suomela, M

2000-04-01

The radioactive pollution of the environment results from the atmospheric nuclear weapons testing (during the mid-years of twentieth century), from the development of the civilian nuclear industry and from accidents such as Chernobyl. Assessing the resulting radiation that humans might receive requires a good understanding of the long-term behaviour of radionuclides in the environment. This document reports on a joint European effort to advance this understanding, 3 multinational projects have been coordinated: PEACE, EPORA and LANDSCAPE. This report proposes an overview of the results obtained and they are presented in 6 different themes: (i) redistribution in the soil-plant system, (ii) modelling, (iii) countermeasures, (iv) runoff (v) spatial variations, and (vi) dose assessment. The long term behaviour of the radionuclides {sup 137}Cs, {sup 90}Sr and {sup 239-240}Pu is studied through various approaches, these approaches range from in-situ experiments designed to exploit past contamination events to laboratory simulations. A broad scope of different ecosystems ranging from arctic and boreal regions down to mediterranean ones has been considered. (A.C.)

Long-term environmental behaviour of radionuclides

International Nuclear Information System (INIS)

Brechignac, F.; Moberg, L.; Suomela, M.

2000-04-01

The radioactive pollution of the environment results from the atmospheric nuclear weapons testing (during the mid-years of twentieth century), from the development of the civilian nuclear industry and from accidents such as Chernobyl. Assessing the resulting radiation that humans might receive requires a good understanding of the long-term behaviour of radionuclides in the environment. This document reports on a joint European effort to advance this understanding, 3 multinational projects have been coordinated: PEACE, EPORA and LANDSCAPE. This report proposes an overview of the results obtained and they are presented in 6 different themes: i) redistribution in the soil-plant system, ii) modelling, iii) countermeasures, iv) runoff v) spatial variations, and vi) dose assessment. The long term behaviour of the radionuclides 137 Cs, 90 Sr and 239-240 Pu is studied through various approaches, these approaches range from in-situ experiments designed to exploit past contamination events to laboratory simulations. A broad scope of different ecosystems ranging from arctic and boreal regions down to mediterranean ones has been considered. (A.C.)

Long-Term Effects of Neonatal Pain and Stress on Reactivity of the Nociceptive System.

Science.gov (United States)

Butkevich, I P; Mikhailenko, V A

2016-10-01

The influence of inflammatory pain and/or weaning stress at different terms of neonatal development on functional activity of the nociceptive system during adulthood was studied in rats. Repeated stress in 1-2-day-old rat pups (a premature baby model) enhanced pain sensitivity to peripheral inflammation in both males and females. Repeated inflammatory pain experienced by male pups aged 1-2 or 7-8 days (models of preterm and full-term baby), even in presence of mother, enhanced pain behavior under conditions of repeated inflammatory pain in adulthood. Pain sensitivity in adult animals before (hot plate test) and after formation of the inflammatory focus (formalin test) depended on the age when the animals were subjected to the injury, type of exposure, and on animal sex. The priority data obtained by us will help to understand the mechanisms of long-term effects of early injuries and are important for pediatricians and neonatologists.

Long-Term Studies of Prescribed Burning in Loblolly Pine Forests of the Southeastern Coastal Plain

Science.gov (United States)

Thomas A. Waldrop; David H. van Lear; F. Thomas Lloyd; William R. Harms

1987-01-01

Prescribed fire provides many benefits in southern pine A study begun in 1946 provides a unique opportunity stands. to observe long-term changes in understory vegetation, soil properties, and overstory tree growth caused by repeated burning.

Radiolytic gas production during long-term storage of nuclear wastes

International Nuclear Information System (INIS)

Bibler, N.E.

1976-01-01

Gases produced by in situ radiolysis of sealed solidified nuclear wastes during long-term storage could conceivably breach containment. Therefore, candidate waste forms (matrices containing simulated nuclear wastes) were irradiated with 60 Co-γ and 244 Cm-α radiation. These forms were: cement containing simulated fission product sludges, vermiculite containing organic liquids, and cellulosics contaminated with α-emitting transuranic isotopes. For cement waste forms exposed to γ-radiolysis, an equilibrium hydrogen pressure was reached that was dose rate dependent. For α-radiolysis, equilibrium was not reached. With organic wastes (n-octane on vermiculite), H 2 and traces of CO 2 and CH 4 were produced, and O 2 was consumed with both radiations. Only energy absorbed by the organic material was effective in producing H 2 . At low dose rates with both α- and γ-irradiations, G(H 2 ) was 4.5 and G(-O 2 ) was 5.0. Also, equilibrium was not obtained. For cellulosic material, H 2 , CO 2 , and CO were produced in the ratio of 1.0:0.7:0.3, and O 2 was consumed. With α-radiolysis, G(gas) was dose dependent; measured values ranged from 2.2 to 0.6 as the dose increased. Implications of all these results on long-term storage of radioactive waste are discussed. Some data from an actual nuclear wasteform are also presented

Long-term prophylaxis in severe factor VII deficiency.

Science.gov (United States)

Siboni, S M; Biguzzi, E; Mistretta, C; Garagiola, I; Peyvandi, F

2015-11-01

The spectrum of bleeding problems in FVII deficiency is highly variable and FVII levels and causative genetic mutations correlate poorly with the bleeding risk. Long-term prophylaxis is generally initiated in order to prevent subsequent CNS bleeding after a first event or in patients with other major/ life threatening/ frequent bleeding symptoms as gastrointestinal bleeding or hemarthrosis. However few data are available in the literature regarding FVII prophylaxis and clinical decisions cannot be based on evidence. We report the data available in the literature on FVII prophylaxis and our personal experience regarding three patients affected by severe FVII deficiency. Specific papers on long-term prophylaxis in severe FVII deficiency were identified using the database, PUBMED. The most frequent indications for long-term prophylaxis were CNS bleeding (58%), hemartrosis (15%) and GI bleeding (9%). Patients were treated with various dosages and frequency. Prophylactic treatment with 10-30U/kg (pdFVII) or 20-30mcg/kg (rFVIIa) twice or three times/weeks was described to be effective. In the literature and in our experience, prophylaxis can be considered in patients with severe FVII deficiency and severe bleeding phenotype. A dose of 10-30U/kg (pdFVII) or 20-30 microg/kg (rFVIIa) twice or three times/week is usually administrated, but dose and frequency can be tailored based on the clinical follow-up of the patients. Since hemarthrosis is a frequent manifestation, a suggestion to improve the outcomes of patients with severe FVII deficiency is to monitor joint condition in order to identify early arthropathy that could be another indication to start secondary prophylaxis. © 2015 John Wiley & Sons Ltd.

Long-term carbimazole pretreatment reduces the efficacy of radioiodine therapy

Directory of Open Access Journals (Sweden)

C Shivaprasad

2015-01-01

Full Text Available Introduction: Data from several studies suggest that pretreatment with antithyroid drugs (ATD before 131 I increases the risk of treatment failure. This effect has been demonstrated more consistently with propylthiouracil than with carbimazole (CMZ or methimazole (MMI. Men with Graves′ disease (GD have a lower rate of remission with 131 I compared to women and the impact of long-term ATD pretreatment on the success of 131 I is unknown. The objective of our study was to compare the efficacy of fixed doses of radioiodine between patients with and without long-term CMZ pretreatment. Materials and Methods: We performed a retrospective study on 335 male patients with GD treated with 131 I from 1998 to 2008. 148 patients had been pretreated with CMZ, and the remaining 187 patients received 131 I without pretreatment. We compared the success rate of a single dose of 131 I, between patients with and without long-term CMZ pretreatment. Results: The success rate of a single dose of 131 I was significantly higher in patients without pretreatment than in patients who were pretreated with CMZ (91.4% vs. 82.3%, P = 0.01. The rate of hypothyroidism in the first 6 months after 131 I therapy was significantly higher in patients without pretreatment (55.1% vs. 44.6%, P = 0.05. There was also a trend for higher cumulative rate of hypothyroidism at last follow-up in nonpretreated patients (78.1% vs. 69.7%. Conclusion: Male patients with Graves′ hyperthyroidism pretreated with CMZ have lower efficacy with 131I therapy compared to nonpretreated patients. CMZ pretreatment given for a prolonged period reduces the efficacy of 131 I therapy.

Life-long diseases need life-long treatment: long-term safety of ciclosporin in canine atopic dermatitis

Science.gov (United States)

Nuttall, Tim; Reece, Douglas; Roberts, Elizabeth

2014-01-01

Ciclosporin (Atopica; Novartis Animal Health) has been licensed for canine atopic dermatitis (AD) since 2002. Adverse events (AEs) have been reported in 55 per cent of 759 dogs in 15 clinical trials, but are rare in pharmacovigilance data (71.81 AEs/million capsules sold). Gastrointestinal reactions were most common, but were mild and rarely required intervention. Other AEs were rare (≤1 per cent in clinical trials; metabolism is not clinically significant for normal dogs. Concomitant treatment with most drugs is safe. Effects on cytochrome P450 and MDR1 P-glycoprotein activity may elevate plasma ciclosporin concentrations, but short-term changes are not clinically significant. Monitoring of complete blood counts, urinalysis or ciclosporin levels is not justified except with higher than recommended doses and/or long-term concurrent immunosuppressive drugs. Ciclosporin is not a contraindication for killed (including rabies) vaccines, but the licensed recommendation is that live vaccination is avoided during treatment. In conclusion, ciclosporin has a positive risk-benefit profile for the long-term management of canine AD. PMID:24682696

Long-Term Musical Group Interaction Has a Positive Influence on Empathy in Children

Science.gov (United States)

Rabinowitch, Tal-Chen; Cross, Ian; Burnard, Pamela

2013-01-01

Musical group interaction (MGI) is a complex social setting requiring certain cognitive skills that may also elicit shared psychological states. We argue that many MGI-specific features may also be important for emotional empathy, the ability to experience another person's emotional state. We thus hypothesized that long-term repeated participation…

Mild erythrocytopenia is the most frequent long-term sequel after peptide receptor radionuclide Therapy: Results of long-term follow-up in more than 500 Patients from a single centre

International Nuclear Information System (INIS)

Schmidt, J.; Kulkami, H.R.; Baum, R.P.; Menghui, Y.

2015-01-01

Full text of publication follows. Aim: Peptide receptor radionuclide therapy (PRRT) is highly effective in well differentiated neuroendocrine neoplasms (NENs) and lends a benefit in overall survival of several years. Renal toxicity is a well-known adverse effect of PRRNT. Hematological toxicity as possible long-term sequel has been hardly examined. Therefore we investigated the effect of PRRT on the hematological status (erythrocytes, leukocytes, thrombocytes) of patients who received individualized therapy at our centre. Materials and Methods: Out of over 500 patients, 59 chemotherapy naive patients with well-differentiated NENs who were treated with at least 3 cycles of PRRT with 177 Lu- and/or 90 Y- labeled DOTATATE/DOTATOC and long-term follow-up were selected for this analysis. Blood counts were documented before the first cycle and repeated at monthly intervals between further cycles and during re-staging examinations after PRRT for many years. Comparisons were done between the hematological status before the first cycle and the one 3 years after the last cycle of PRRT. Results: All 3 cell lines were significantly decreased 3 years after the last radionuclide therapy (erythrocytes, leukocytes: p=0,000; thrombocytes: p=0,002; confidence interval 95%). But only erythrocytes showed a significant decrement, i.e., below the reference level of our in-house laboratory (mean value ± standard deviation: (4.07 ± 0.69)/l; reference level: 4.1-5.4/l). Conclusions: Mild erythrocytopenia is the most frequent long-term sequel after PRRT. Although it has to be considered that repeated cycles probably cause impoverishment in bone marrow reserve (or red cell precursors), PRRT achieves both significant improvement in clinical symptoms and excellent palliation. Thus it remains a safe procedure if performed at specialized centres with interdisciplinary and long-term care. (authors)

EVALUATION OF RADIONUCLIDE ACCUMULATION IN SOIL DUE TO LONG-TERM IRRIGATION

International Nuclear Information System (INIS)

De Wesley Wu

2006-01-01

Radionuclide accumulation in soil due to long-term irrigation is an important part of the model for predicting radiation dose in a long period of time. The model usually assumes an equilibrium condition in soil with a constant irrigation rate, so that radionuclide concentration in soil does not change with time and can be analytically solved. This method is currently being used for the dose assessment in the Yucca Mountain project, which requires evaluating radiation dose for a period of 10,000 years. There are several issues associated with the method: (1) time required for the equilibrium condition, (2) validity of constant irrigation rate, (3) agricultural land use for a long period of time, and (4) variation of a radionuclide concentration in water. These issues are evaluated using a numerical method with a simple model built in the GoldSim software. Some key radionuclides, Tc-99, Np-237, Pu-239, and Am-241 are selected as representative radionuclides. The results indicate that the equilibrium model is acceptable except for a radionuclide that requires long time to accumulate in soil and that its concentration in water changes dramatically with time (i.e. a sharp peak). Then the calculated dose for that radionuclide could be overestimated using the current equilibrium method

Experimental study on the long-term effect of cadmium in mice fed cadmium-polluted rice with special reference to the effect of repeated reproductive cycles

International Nuclear Information System (INIS)

Watanabe, M.; Shiroishi, K.; Nishino, H.; Shinmura, T.; Murase, H.; Shoji, T.; Naruse, Y.; Kagamimori, S.

1986-01-01

Long-term biological effects of cadmium-polluted rice and effect of repeated reproductive cycles on them were examined. Female SLC-B6D2F mice (female C57BL/6, male DBA/2) were fed a rice diet containing 65% unpolished rice for about 2 years from 7 weeks of age. The unpolished rice preparations used were commercially available rice (non-Cd-polluted) and Cd-polluted rice (over 1.0 ppm). Average Cd contents in each diet class were 0.12, 0.48, 1.78, 1.75, and 47.1 ppm (50 ppm Cd as CdCl 2 added). Some experimental mice were subjected to repeated reproductive cycles (parity group). Hematological, biochemical, and pathological examinations of urine, blood, and tissues, including Cd measurement, were carried out. Results after statistical analysis indicate Cd toxicities such as anemia and disturbances of Ca metabolism. These Cd effects were found to be enhanced by the reproductive cycles. Soft X-ray radiograms showed osteoporosis in the parity groups, especially in the groups with diets of higher Cd content. However, we could not find any sign of disturbance of renal function under our experimental conditions

Impact peculiarities of long-term gamma-irradiation with low-dose rate on the development of laboratory rats and their sperm production

International Nuclear Information System (INIS)

Klepko, A.V.; Motrina, O.A.; Vatlyitsova, O.S.; And Others

2015-01-01

The experiments were performed on laboratory white rats of 2.5 months in age. Animals were irradiated in gamma-field of 'Ethalon' device in a dose range 0.1-1.0 Gy. Testicles, epididymices, ventral prostate were retrieved from decapitated animal, each organ weight being determined for every exposure dose. Sperm quantities in testicles and epididymices were identified with aid of phase-contrast microscopy after tissue homogenization in saline containing Triton X-100 and NaN_3. Kinetic characteristics of spermatozoa were analyzed by video recording at 37 C. The longterm gamma-irradiation with low dose rate was shown to cause no effect on the dynamics of animal weight and weight of epididymices changes. However the testes weight was noticed to diminish at doses 0.1, 0.3, 0.6 and 1.0 Gy, the latter dose being stimulative for the ventral prostate growth and weight accumulation. Total sperm quantities in testicles and epididymices along with daily sperm production declined in gamma-irradiated rats compared to control. However curvilinear and straight line spermatozoid velocity as well as the frequency of tail oscillations tended to increase. Long-term gamma-irradiation of the rat whole body with low dose rate just insignificantly affects the development of testes and ventral prostate. Apart from this, radiation effects showed up in sperm production slight suppression, from the on hand, and sperm velocity along with tail oscillations intensification, from the other hand

Long-term survival in advanced melanoma patients using repeated therapies: successive immunomodulation improving the odds?

International Nuclear Information System (INIS)

Coventry, Brendon J; Baume, Dominique; Lilly, Carrie

2015-01-01

Patients with advanced metastatic melanoma are often confronted with little prospect of medium- to longer-term survival by any currently available therapeutic means. However, most clinicians are aware of exceptional cases where survival defies the notion of futility. Prolonged survival from immunotherapies, including interleukin-2, vaccines and antibodies to cytotoxic lymphocyte antigen-4, and programmed death-1 receptor inhibitory monoclonal antibody, implies a role for immune system modulation. We aimed to identify cases where exceptional survival from advanced melanoma occurred prior to recent novel therapies to facilitate better understanding of this phenomenon. Cases of long-term survival of ≥3 years’ duration (from diagnosis of metastatic disease) were identified from the database of one clinician; these cases were treated before the availability of newer immunotherapies, and they were documented and examined. A literature search for reported outcome measures from published studies using older and recent therapies for advanced melanoma was conducted to enable the comparison of data. Eighteen cases were identified that identified survival of ≥3 years’ duration from metastatic disease (12 American Joint Committee on Cancer [AJCC] Stage IV cases; six AJCC III cases) diagnosis. These were assessed and reported to detail the clinical course. Standard clinical prognostication methods predicted high risk of early mortality in those patients. No identifiable differences could be detected between these and other patients with similar patterns of disease. At evaluation, 17 patients (94%) had survived ≥5 years, and eleven patients (61%) had survived ≥10 years (range: 3–15 years). The median survival duration with metastatic disease was 11 years; 15 remained alive and three had died. Published studies of melanoma therapies were tabled for comparison. The fact that 18 cases of exceptional survival in advanced melanoma were identified is remarkable in itself

Long-term dietary supplementation with low-dose nobiletin ameliorates hepatic steatosis, insulin resistance, and inflammation without altering fat mass in diet-induced obesity.

Science.gov (United States)

Kim, Young-Je; Choi, Myung-Sook; Woo, Je Tae; Jeong, Mi Ji; Kim, Sang Ryong; Jung, Un Ju

2017-08-01

We evaluated the long-term effect of low-dose nobiletin (NOB), a polymethoxylated flavone, on diet-induced obesity and related metabolic disturbances. C57BL/6J mice were fed a high-fat diet (HFD, 45 kcal% fat) with or without NOB (0.02%, w/w) for 16 weeks. NOB did not alter food intake or body weight. Despite increases in fatty acid oxidation-related genes expression and enzymes activity in adipose tissue, NOB did not affect adipose tissue weight due to simultaneous increases in lipogenic genes expression and fatty acid synthase activity. However, NOB significantly decreased not only pro-inflammatory genes expression in adipose tissue but also proinflammatory cytokine levels in plasma. NOB-supplemented mice also showed improved glucose tolerance and insulin resistance, along with decreased levels of plasma insulin, free fatty acids, total cholesterol, non-HDL-cholesterol, and apolipoprotein B. In addition, NOB caused significant decreases in hepatic lipid droplet accumulation and triglyceride content by activating hepatic fatty acid oxidation-related enzymes. Hepatic proinflammatory TNF-α mRNA expression, collagen accumulation, and plasma levels of aminotransferases, liver damage indicators, were also significantly lower in NOB-supplemented mice. These findings suggest that long-term supplementation with low-dose NOB can protect against HFD-induced inflammation, insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease, without ameliorating adiposity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Single and 2-week repeated intravenous dose toxicity studies of disodium mercaptoundecahydro-closo-dodecaborate in rats

Energy Technology Data Exchange (ETDEWEB)

Itoh, Fumio; Yabuuchi, Kazuya; Ohno, Kouji; Muraoka, Yoshihiro [Shionogi and Co. Ltd., Toyonaka, Osaka (Japan). Developmental Research Lab.; Ikeuchi, Isao

1998-10-01

Disodium mercaptoundecahydro-closo-dodecaborate (BSH) is a boron compound used in Boron Neutron Capture Therapy for malignant brain tumors. Intravenous single and 2-week repeated dose toxicity studies of BSH were performed in Sprague-Dawley rats. In the single-dose study, BSH was administered at doses of 100, 300 or 600 mg/kg. Death occurred within 10 min (acute type) or from 5 hr to 2 days (delayed type) after dosing in the 600 mg/kg group. No differences in mortality by sex and dosing speed were observed. Major causes of death were considered to be circulatory disorder in acute death and renal injury in delayed death. The renal injury was observed in the 300 and 600 mg/kg groups. In the 2-week repeated dose study, BSH was administered at doses of 30, 100 or 300 mg/kg/day for 14 days. Body weight gain was suppressed in the 100 and 300 mg/kg groups. One male in the 300 mg/kg group died due to renal and pulmonary lesions at day 8. Slight anemia was observed in the 300 mg/kg group. Pathologically, the kidney showed tubular regeneration with increase of weight in the 300 mg/kg. From these results, the NOAEL of BSH is 30 mg/kg/day. (author)

[Long-term psychiatric hospitalizations].

Science.gov (United States)

Plancke, L; Amariei, A

2017-02-01

Long-term hospitalizations in psychiatry raise the question of desocialisation of the patients and the inherent costs. Individual indicators were extracted from a medical administrative database containing full-time psychiatric hospitalizations for the period 2011-2013 of people over 16 years old living in the French region of Nord-Pas-de-Calais. We calculated the proportion of people who had experienced a hospitalization with a duration of 292 days or more during the study period. A bivariate analysis was conducted, then ecological data (level of health-care offer, the deprivation index and the size of the municipalities of residence) were included into a multilevel regression model in order to identify the factors significantly related to variability of long-term hospitalization rates. Among hospitalized individuals in psychiatry, 2.6% had had at least one hospitalization of 292 days or more during the observation period; the number of days in long-term hospitalization represented 22.5% of the total of days of full-time hospitalization in psychiatry. The bivariate analysis revealed that seniority in the psychiatric system was strongly correlated with long hospitalization rates. In the multivariate analysis, the individual indicators the most related to an increased risk of long-term hospitalization were: total lack of autonomy (OR=9.0; 95% CI: 6.7-12.2; P<001); diagnoses of psychological development disorders (OR=9.7; CI95%: 4.5-20.6; P<.001); mental retardation (OR=4.5; CI95%: 2.5-8.2; P<.001): schizophrenia (OR=3.0; CI95%: 1.7-5.2; P<.001); compulsory hospitalization (OR=1.7; CI95%: 1.4-2.1; P<.001); having experienced therapeutic isolation (OR=1.8; CI95%: 1.5-2.1; P<.001). Variations of long-term hospitalization rates depending on the type of establishment were very high, but the density of hospital beds or intensity of ambulatory activity services were not significantly linked to long-term hospitalization. The inhabitants of small urban units had

Long-term consumption of aspartame and brain antioxidant defense status.

Science.gov (United States)

Abhilash, M; Sauganth Paul, M V; Varghese, Mathews V; Nair, R Harikumaran

2013-04-01

The present study investigated the effect of long-term intake of aspartame, a widely used artificial sweetener, on antioxidant defense status in the rat brain. Male Wistar rats weighing 150-175 g were randomly divided into three groups as follows: The first group was given aspartame at a dose of 500 mg/kg body weight (b.w.); the second group was given aspartame at dose of 1,000 mg/kg b.w., respectively, in a total volume of 3 mL of water; and the control rats received 3 mL of distilled water. Oral intubations were done in the morning, daily for 180 days. The concentration of reduced glutathione (GSH) and the activity of glutathione reductase (GR) were significantly reduced in the brain of rats that had received the dose of 1,000 mg/kg b.w. of aspartame, whereas only a significant reduction in GSH concentration was observed in the 500-mg/kg b.w. aspartame-treated group. Histopathological examination revealed mild vascular congestion in the 1,000 mg/kg b.w. group of aspartame-treated rats. The results of this experiment indicate that long-term consumption of aspartame leads to an imbalance in the antioxidant/pro-oxidant status in the brain, mainly through the mechanism involving the glutathione-dependent system.

Unusual structures are present in DNA fragments containing super-long Huntingtin CAG repeats.

Directory of Open Access Journals (Sweden)

Daniel Duzdevich

2011-02-01

Full Text Available In the R6/2 mouse model of Huntington's disease (HD, expansion of the CAG trinucleotide repeat length beyond about 300 repeats induces a novel phenotype associated with a reduction in transcription of the transgene.We analysed the structure of polymerase chain reaction (PCR-generated DNA containing up to 585 CAG repeats using atomic force microscopy (AFM. As the number of CAG repeats increased, an increasing proportion of the DNA molecules exhibited unusual structural features, including convolutions and multiple protrusions. At least some of these features are hairpin loops, as judged by cross-sectional analysis and sensitivity to cleavage by mung bean nuclease. Single-molecule force measurements showed that the convoluted DNA was very resistant to untangling. In vitro replication by PCR was markedly reduced, and TseI restriction enzyme digestion was also hindered by the abnormal DNA structures. However, significantly, the DNA gained sensitivity to cleavage by the Type III restriction-modification enzyme, EcoP15I."Super-long" CAG repeats are found in a number of neurological diseases and may also appear through CAG repeat instability. We suggest that unusual DNA structures associated with super-long CAG repeats decrease transcriptional efficiency in vitro. We also raise the possibility that if these structures occur in vivo, they may play a role in the aetiology of CAG repeat diseases such as HD.

Radiosurgery of craniopharyngiomas. Results of long-term follow-up

International Nuclear Information System (INIS)

Kida, Yoshihisa; Hasegawa, Toshinori; Yoshimoto, Masayuki; Koike, Johzi; Kobayashi, Tatsuya

2007-01-01

Long-term follow-up results of craniopharyngiomas after radiosurgery are reported. Among 125 cases of craniopharyngioma, long-term follow-up more than 6 months is obtained in 108 cases. Majority of the cases have had surgical excision before radiosurgery. The tumors, 19 mm in mean diameter were treated with the mean maximum dose of 22.1 Gy and with the marginal dose of 11.6 Gy. The final radiological outcomes during 63 months of mean follow-up showed 9 complete responses (CRs), 61 partial responses (PRs), 1 minor response (MR), 19 no changes (NCs) and 18 PGs, indicating the response rate of 65% and the control rate of 83% respectively. Neurological and endocrinological signs were improved in 18%, unchanged in 53% and worsened in 15% of cases, meanwhile 8% of the patients were dead. Small and solid tumors were the best indication for radiosurgery due to excellent tumor control as well as no adverse effects. They may have a good chance for complete remission. In conclusion a sufficient tumor resection with microsurgery is required and subsequent radiosurgery is most adequate for treating craniopharyngiomas. (author)

Long-Term Effectiveness and Safety of Dexmethylphenidate Extended-Release Capsules in Adult ADHD

Science.gov (United States)

Adler, Lenard A.; Spencer, Thomas; McGough, James J.; Jiang, Hai; Muniz, Rafael

2009-01-01

Objective: This study evaluates dexmethylphenidate extended release (d-MPH-ER) in adults with ADHD. Method: Following a 5-week, randomized, controlled, fixed-dose study of d-MPH-ER 20 to 40 mg/d, 170 adults entered a 6-month open-label extension (OLE) to assess long-term safety, with flexible dosing of 20 to 40 mg/d. Exploratory effectiveness…

Long-term potentiation and long-term depression: a clinical perspective

Directory of Open Access Journals (Sweden)

Timothy V.P. Bliss

2011-01-01

Full Text Available Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke.

Long-term follow-up of psilocybin-facilitated smoking cessation.

Science.gov (United States)

Johnson, Matthew W; Garcia-Romeu, Albert; Griffiths, Roland R

2017-01-01

A recent open-label pilot study (N = 15) found that two to three moderate to high doses (20 and 30 mg/70 kg) of the serotonin 2A receptor agonist, psilocybin, in combination with cognitive behavioral therapy (CBT) for smoking cessation, resulted in substantially higher 6-month smoking abstinence rates than are typically observed with other medications or CBT alone. To assess long-term effects of a psilocybin-facilitated smoking cessation program at ≥12 months after psilocybin administration. The present report describes biologically verified smoking abstinence outcomes of the previous pilot study at ≥12 months, and related data on subjective effects of psilocybin. All 15 participants completed a 12-month follow-up, and 12 (80%) returned for a long-term (≥16 months) follow-up, with a mean interval of 30 months (range = 16-57 months) between target-quit date (i.e., first psilocybin session) and long-term follow-up. At 12-month follow-up, 10 participants (67%) were confirmed as smoking abstinent. At long-term follow-up, nine participants (60%) were confirmed as smoking abstinent. At 12-month follow-up 13 participants (86.7%) rated their psilocybin experiences among the five most personally meaningful and spiritually significant experiences of their lives. These results suggest that in the context of a structured treatment program, psilocybin holds considerable promise in promoting long-term smoking abstinence. The present study adds to recent and historical evidence suggesting high success rates when using classic psychedelics in the treatment of addiction. Further research investigating psilocybin-facilitated treatment of substance use disorders is warranted.

Long-term variation of outdoor radon equilibrium equivalent concentration

Energy Technology Data Exchange (ETDEWEB)

Hoetzl, H. [GSF-Forschungszentrum fuer Umwelt und Gesundheit, Inst. fuer Strahlenschutz, Oberschleissheim (Germany); Winkler, R. [GSF-Forschungszentrum fuer Umwelt und Gesundheit, Inst. fuer Strahlenschutz, Oberschleissheim (Germany)

1994-10-01

Long-term variation of outdoor radon equilibrium equivalent concentration was investigated from 1982 to 1992 at a semi-natural location 10 km north of Munich, southern Germany. For this period the continuous measurement yielded a long-term average of 8.6 Bq.m{sup -3} (arithmetic mean) and 6.9 Bq.m{sup -3} (geometric mean), from which an average annual effective dose of 0.14 mSv due to outdoor radon can be derived. A long-term trend of the radon concentration was not detectable over the whole period of observation. However, by time series analysis, a long-term cyclic pattern was identified with two maxima (1984-1986, 1989-1991) and two minima (1982-1983, 1987-1988). The seasonal pattern is characterized by an autumn maximum and an early summer minimum. On average, the seasonal maximum in October was found to be higher by a factor of 2 than the June minimum. The diurnal variation of the radon concentration shows a maximum in the early morning and a minimum in the afternoon. On average, this maximum is a factor of 2 higher than the minimum. In the long term a seasonal pattern was observed for diurnal variation, with an average diurnal maximum to minimum ratio of 1.5 in winter compared with 3.5 in the summer months. The radon concentration is correlated with a meteorological parameter (stagnation index) which takes into account horizontal and vertical exchange processes and the wash-out of aerosols in the lower atmosphere. (orig.)

Long-term variation of outdoor radon equilibrium equivalent concentration

International Nuclear Information System (INIS)

Hoetzl, H.; Winkler, R.

1994-01-01

Long-term variation of outdoor radon equilibrium equivalent concentration was investigated from 1982 to 1992 at a semi-natural location 10 km north of Munich, southern Germany. For this period the continuous measurement yielded a long-term average of 8.6 Bq.m -3 (arithmetic mean) and 6.9 Bq.m -3 (geometric mean), from which an average annual effective dose of 0.14 mSv due to outdoor radon can be derived. A long-term trend of the radon concentration was not detectable over the whole period of observation. However, by time series analysis, a long-term cyclic pattern was identified with two maxima (1984-1986, 1989-1991) and two minima (1982-1983, 1987-1988). The seasonal pattern is characterized by an autumn maximum and an early summer minimum. On average, the seasonal maximum in October was found to be higher by a factor of 2 than the June minimum. The diurnal variation of the radon concentration shows a maximum in the early morning and a minimum in the afternoon. On average, this maximum is a factor of 2 higher than the minimum. In the long term a seasonal pattern was observed for diurnal variation, with an average diurnal maximum to minimum ratio of 1.5 in winter compared with 3.5 in the summer months. The radon concentration is correlated with a meteorological parameter (stagnation index) which takes into account horizontal and vertical exchange processes and the wash-out of aerosols in the lower atmosphere. (orig.)

Transcriptional regulation of long-term memory in the marine snail Aplysia

Directory of Open Access Journals (Sweden)

Lee Yong-Seok

2008-06-01

Full Text Available Abstract Whereas the induction of short-term memory involves only covalent modifications of constitutively expressed preexisting proteins, the formation of long-term memory requires gene expression, new RNA, and new protein synthesis. On the cellular level, transcriptional regulation is thought to be the starting point for a series of molecular steps necessary for both the initiation and maintenance of long-term synaptic facilitation (LTF. The core molecular features of transcriptional regulation involved in the long-term process are evolutionally conserved in Aplysia, Drosophila, and mouse, and indicate that gene regulation by the cyclic AMP response element binding protein (CREB acting in conjunction with different combinations of transcriptional factors is critical for the expression of many forms of long-term memory. In the marine snail Aplysia, the molecular mechanisms that underlie the storage of long-term memory have been extensively studied in the monosynaptic connections between identified sensory neuron and motor neurons of the gill-withdrawal reflex. One tail shock or one pulse of serotonin (5-HT, a modulatory transmitter released by tail shocks, produces a transient facilitation mediated by the cAMP-dependent protein kinase leading to covalent modifications in the sensory neurons that results in an enhancement of transmitter release and a strengthening of synaptic connections lasting minutes. By contrast, repeated pulses of 5-hydroxytryptamine (5-HT induce a transcription- and translation-dependent long-term facilitation (LTF lasting more than 24 h and trigger the activation of a family of transcription factors in the presynaptic sensory neurons including ApCREB1, ApCREB2 and ApC/EBP. In addition, we have recently identified novel transcription factors that modulate the expression of ApC/EBP and also are critically involved in LTF. In this review, we examine the roles of these transcription factors during consolidation of LTF induced

Transcriptional regulation of long-term memory in the marine snail Aplysia.

Science.gov (United States)

Lee, Yong-Seok; Bailey, Craig H; Kandel, Eric R; Kaang, Bong-Kiun

2008-06-17

Whereas the induction of short-term memory involves only covalent modifications of constitutively expressed preexisting proteins, the formation of long-term memory requires gene expression, new RNA, and new protein synthesis. On the cellular level, transcriptional regulation is thought to be the starting point for a series of molecular steps necessary for both the initiation and maintenance of long-term synaptic facilitation (LTF). The core molecular features of transcriptional regulation involved in the long-term process are evolutionally conserved in Aplysia, Drosophila, and mouse, and indicate that gene regulation by the cyclic AMP response element binding protein (CREB) acting in conjunction with different combinations of transcriptional factors is critical for the expression of many forms of long-term memory. In the marine snail Aplysia, the molecular mechanisms that underlie the storage of long-term memory have been extensively studied in the monosynaptic connections between identified sensory neuron and motor neurons of the gill-withdrawal reflex. One tail shock or one pulse of serotonin (5-HT), a modulatory transmitter released by tail shocks, produces a transient facilitation mediated by the cAMP-dependent protein kinase leading to covalent modifications in the sensory neurons that results in an enhancement of transmitter release and a strengthening of synaptic connections lasting minutes. By contrast, repeated pulses of 5-hydroxytryptamine (5-HT) induce a transcription- and translation-dependent long-term facilitation (LTF) lasting more than 24 h and trigger the activation of a family of transcription factors in the presynaptic sensory neurons including ApCREB1, ApCREB2 and ApC/EBP. In addition, we have recently identified novel transcription factors that modulate the expression of ApC/EBP and also are critically involved in LTF. In this review, we examine the roles of these transcription factors during consolidation of LTF induced by different

Trastuzumab use during pregnancy: long-term survival after locally advanced breast cancer and long-term infant follow-up.

Science.gov (United States)

Andrade, Jurandyr M de; Brito, Luiz G O; Moises, Elaine C D; Amorim, Andréa C; Rapatoni, Liane; Carrara, Hélio H A; Tiezzi, Daniel G

2016-04-01

Here, we describe the case of a patient diagnosed with locally advanced breast cancer 8 years ago. Her treatment course was neoadjuvant chemotherapy, followed by mastectomy and then adjuvant radiotherapy and trastuzumab (TTZ). During the use of adjuvant targeted therapy, an incidental pregnancy was diagnosed. Four years later, she developed bone and cerebral metastases, and since then, she has received courses of TTZ, capecitabine, lapatinib, and radiotherapy with intermittent control of the disease. Her 7-year-old son presents a normal physical and long-term neurological developmental curve according to specialized evaluation. This case is unique for several reasons: the patient received the highest dose of TTZ yet described during pregnancy (4400 mg); there has been a long period of disease-free survival after treatment for locally advanced breast cancer and long overall survival despite successive disease progressions during the metastatic phase of the disease (97 months), and there was a monitored pediatric follow-up period (7 years).

Review of European research trends of low dose radiation risk

International Nuclear Information System (INIS)

Iwasaki, Toshiyasu; Yoshida, Kazuo

2010-01-01

Large research projects on low dose radiation effects in Europe and US over the past decade have provided limited scientific knowledge which could underpin the validation of radiation protection systems. Recently in Europe, there have been repeated discussions and dialogues to improve the situation, and as the consequence, the circumstances surrounding low dose radiation risks are changing. In 2009, Multidisciplinary European Low Dose Initiative (MELODI) was established as a trans-national organization capable of ensuring appropriate governance of research in the pursuit of a long term shared vision, and Low Dose Research towards Multidisciplinary Integration (DoReMi) network was launched in 2010 to achieve fairly short term results in order to prove the validity of the MELODI approach. It is expected to be very effective and powerful activities to facilitate the reduction of uncertainties in the understanding of low dose risks, but the regulatory requests rushing the reinforcement of radiological protection regulations based on the precautional principles are more increasing. To develop reasonable radiological protection systems based on scientific evidences, we need to accelerate to collect scientific evidences which could directly underpin more appropriate radiation protection systems even in Japan. For the purpose, we Japan need to develop from an independent standpoint and share as a multidisciplinary vision a long term and holistic research strategy which enables to enhance Japanese advantages such as low dose rate facilities and animal facilities, as soon as possible. (author)

Long-term microwaving of denture base materials: effects on dimensional, color and translucency stability

Directory of Open Access Journals (Sweden)

Nick POLYCHRONAKIS

2018-06-01

Full Text Available Abstract While the combined effect of microwave irradiation with cleansing solutions on denture base materials has been investigated, the effects of only using microwave irradiation and, more importantly, in a long-term basis, was not studied yet. Objective The purpose of this study was to evaluate the effect of a long-term repeated microwaving on the dimensional, color and translucency stability of acrylic and polyamide denture base materials. Material and Methods Thirty two specimens (32 mm x 10 mm x 2.5 mm from polyamide (Valplast and PMMA (Vertex Rapid Simplified denture base materials were made. Eight specimens from each material were immersed in distilled water (control and 8 were subjected to microwave exposure at 450 W for 3 minutes for a period simulating 224 days of daily disinfection. Linear dimension, color change (ΔE* and translucency parameter (TP were measured at baseline and after certain intervals up to 224 cycles of immersion, using a digital calliper and a portable colorimeter. The results were analysed using two-way repeated measures ANOVA to estimate possible differences among predetermined cycles and material type. Regression analysis was also performed to estimate the trend of changes with time. Statistical evaluations performed at a significance level of 5%. Results Data analysis showed significant changes in length at baseline with an increasing number of cycles (p0.05. TP decreased similarly in both materials following microwave action but in a significantly higher level for Valplast (p<0.001. Conclusions The results indicated that long-term repeated microwaving affects linear dimensional, color and translucency changes of both materials. Differences between PMMA and polyamide material were noted only in dimension and translucency changes.

The effects of repeated low-dose sarin exposure

International Nuclear Information System (INIS)

Shih, T.-M.; Hulet, S.W.; McDonough, J.H.

2006-01-01

This project assessed the effects of repeated low-dose exposure of guinea pigs to the organophosphorus nerve agent sarin. Animals were injected once a day, 5 days per week (Monday-Friday), for 2 weeks with fractions (0.3x, 0.4x, 0.5x, or 0.6x) of the established LD 5 dose of sarin (42 μg/kg, s.c.). The animals were assessed for changes in body weight, red blood cell (RBC) acetylcholinesterase (AChE) levels, neurobehavioral reactions to a functional observational battery (FOB), cortical electroencephalographic (EEG) power spectrum, and intrinsic acetylcholine (ACh) neurotransmitter (NT) regulation over the 2 weeks of sarin exposure and for up to 12 days postinjection. No guinea pig receiving 0.3, 0.4 or 0.5 x LD 5 of sarin showed signs of cortical EEG seizures despite decreases in RBC AChE levels to as low as 10% of baseline, while seizures were evident in animals receiving 0.6 x LD 5 of sarin as early as the second day; subsequent injections led to incapacitation and death. Animals receiving 0.5 x LD 5 sarin showed obvious signs of cholinergic toxicity; overall, 2 of 13 animals receiving 0.5 x LD 5 sarin died before all 10 injections were given, and there was a significant increase in the angle of gait in the animals that lived. By the 10th day of injection, the animals receiving saline were significantly easier to remove from their cages and handle and significantly less responsive to an approaching pencil and touch on the rump in comparison with the first day of testing. In contrast, the animals receiving 0.4 x LD 5 sarin failed to show any significant reductions in their responses to an approaching pencil and a touch on the rump as compared with the first day. The 0.5 x LD 5 sarin animals also failed to show any significant changes to the approach and touch responses and did not adjust to handling or removal from the cage from the first day of injections to the last day of handling. Thus, the guinea pigs receiving the 0.4 and 0.5 x LD 5 doses of sarin failed to

Effect of repeated ultraviolet irradiation on skin of hairless mice

International Nuclear Information System (INIS)

Alpermann, H.; Vogel, H.G.

1978-01-01

The effect of repeated UV-irradiation on mechanical and biochemical parameters was studied in skin of hairless mice. uV-A irradiation for a period of 1 h daily over 8 weeks caused only a slight increase in skin thickness and a decrease in ultimate strain. The changes induced by UV-B and C, however, were quite remarkable. Skin thickness was increased depending on the daily dose exposure time (15-90 s at an irradiation rate of 20mW/cm 2 UV-B and A and of 14mW/cm 2 UV-C) and the duration of treatment (1-6 weeks). Ultimate load, tensile strength and modulus of elasticity showed an increase following medium dosages after 1 and 2 weeks, however, a decrease after high dosages and longterm treatment. Ultimate strain was found to be the most sensitive parameter being decreased depending on exposure time and duration of treatment. Insoluble collagen and total collagen were decreased after long-term treatment thus being correlated with the mechanical parameters. The elastin content was only barely influenced and not correlated with the mechanical data, e.g. the modulus of elasticity. Thus, a favourable effect of short-treatment with low doses of UV-irradiation of mechanical parameters of skin could be demonstrated. Long-term treatment with relatively high doses of UV-B, however, resulted in unfavourable effects, whereby first ultimate strain, then ultimate load, modulus of elasticity and tensile strength were decreased. (orig.) [de

Long-Term Safety and Immunogenicity of a Tetravalent Live-Attenuated Dengue Vaccine and Evaluation of a Booster Dose Administered to Healthy Thai Children.

Science.gov (United States)

Watanaveeradej, Veerachai; Simasathien, Sriluck; Mammen, Mammen P; Nisalak, Ananda; Tournay, Elodie; Kerdpanich, Phirangkul; Samakoses, Rudiwilai; Putnak, Robert J; Gibbons, Robert V; Yoon, In-Kyu; Jarman, Richard G; De La Barrera, Rafael; Moris, Philippe; Eckels, Kenneth H; Thomas, Stephen J; Innis, Bruce L

2016-06-01

We evaluated the safety and immunogenicity of two doses of a live-attenuated, tetravalent dengue virus vaccine (F17/Pre formulation) and a booster dose in a dengue endemic setting in two studies. Seven children (7- to 8-year-olds) were followed for 1 year after dose 2 and then given a booster dose (F17/Pre formulation), and followed for four more years (Child study). In the Infant study, 49 2-year-olds, vaccinated as infants, were followed for approximately 3.5 years after dose 2 and then given a booster dose (F17) and followed for one additional year. Two clinically notable events were observed, both in dengue vaccine recipients in the Infant study: 1 case of dengue approximately 2.7 years after dose 2 and 1 case of suspected dengue after booster vaccinations. The booster vaccinations had a favorable safety profile in terms of reactogenicity and adverse events reported during the 1-month follow-up periods. No vaccine-related serious adverse events were reported during the studies. Neutralizing antibodies against dengue viruses 1-4 waned during the 1-3 years before boosting, which elicited a short-lived booster response but did not provide a long-lived, multivalent antibody response in most subjects. Overall, this candidate vaccine did not elicit a durable humoral immune response. © The American Society of Tropical Medicine and Hygiene.

Radiation Doses to Structures Within and Adjacent to the Larynx are Correlated With Long-Term Diet- and Speech-Related Quality of Life

International Nuclear Information System (INIS)

Dornfeld, Ken; Simmons, Joel R.; Karnell, Lucy; Karnell, Michael; Funk, Gerry; Yao Min; Wacha, Judith; Zimmerman, Bridget; Buatti, John M.

2007-01-01

Purpose: To test the hypothesis that radiation dose to key sites in the upper aerodigestive tract is associated with long-term functional outcome after (chemo)radiotherapy for head-and-neck cancers. Methods and Materials: This study examined the outcome for 27 patients treated with intensity-modulated radiotherapy for definitive management of their head-and-neck cancer who were disease free for at least 1 year after treatment. Head-and-neck cancer-specific quality of life (QoL) was assessed before treatment and at 1 year after treatment. Type of diet tolerated, presence of a feeding tube, and degree of weight loss 1 year after treatment were also used as outcome measures. Radiation doses delivered to various points along the upper aerodigestive tract, including base of tongue, lateral pharyngeal walls, and laryngeal structures, were determined from each treatment plan. Radiation doses for each of these points were tested for correlation with outcome measures. Results: Higher doses delivered to the aryepiglottic folds, false vocal cords, and lateral pharyngeal walls near the false cords correlated with a more restrictive diet, and higher doses to the aryepiglottic folds correlated with greater weight loss (p < 0.05) 1 year after therapy. Better posttreatment speech QoL scores were associated with lower doses delivered to structures within and surrounding the larynx. Conclusion: Our data show an inverse relationship between radiation dose delivered to laryngeal structures and speech and diet and QoL outcomes after definitive (chemo)radiation treatment. These findings suggest that efforts to deliver lower doses to laryngeal structures may improve outcomes after definitive (chemo)radiation therapy

Long-Term Symbolic Learning

National Research Council Canada - National Science Library

Kennedy, William G; Trafton, J. G

2007-01-01

What are the characteristics of long-term learning? We investigated the characteristics of long-term, symbolic learning using the Soar and ACT-R cognitive architectures running cognitive models of two simple tasks...

Pediatric polytrauma : Short-term and long-term outcomes

NARCIS (Netherlands)

vanderSluis, CK; Kingma, J; Eisma, WH; tenDuis, HJ

Objective: To assess the short-term and long-term outcomes of pediatric polytrauma patients and to analyze the extent to which short-term outcomes can predict long-term outcomes. Materials and Methods: Ail pediatric polytrauma patients (Injury Severity Score of greater than or equal to 16, less than

Long-term opioid therapy in Denmark

DEFF Research Database (Denmark)

Birke, H; Ekholm, Ola; Sjøgren, P

2017-01-01

significantly associated with initiation of L-TOT in individuals with CNCP at baseline. During follow-up, L-TOT in CNCP patients increased the likelihood of negative changes in pain interference with work (OR 9.2; 95% CI 1.9-43.6) and in moderate activities (OR 3.7; 95% CI 1.1-12.6). The analysis of all......,145). A nationally representative subsample of individuals (n = 2015) completed the self-administered questionnaire in both 2000 and 2013. Collected information included chronic pain (≥6 months), health behaviour, self-rated health, pain interference with work activities and physical activities. Long-term users were...... individuals indicated a dose-response relationship between longer treatment duration and the risk of experiencing negative changes. CONCLUSIONS: Individuals on L-TOT seemed not to achieve the key goals of opioid therapy: pain relief, improved quality of life and functional capacity. SIGNIFICANCE: Long...

Impact of short‐term, repeated water fasting on the weight of mice

OpenAIRE

Zahra Mishmast; Reza Rahimzadeh Oskuee; Amirali Aryan; Kamran Ghafarzadegan; Kiarash Ghazvini

2014-01-01

Introduction: Caloric restriction is a strategy applied for weight loss. Water fasting is a popular way for obesity treatment. However, little is known about the impact of water fasting on weight. Therefore, this study was conducted to investigate the effect of short-term, repeated water fasting on the weight of mice. Methods: In this study, the physiological effect of short-term, repeated water fasting on the weight of female mice was evaluated. At 6 weeks of age, mice were randomly assigned...

Driving ability in cancer patients receiving long-term morphine analgesia.

Science.gov (United States)

Vainio, A; Ollila, J; Matikainen, E; Rosenberg, P; Kalso, E

1995-09-09

When given in single doses to healthy volunteers, opioid analgesics impair reaction time, muscle coordination, attention, and short-term memory sufficiently to affect driving and other skilled activities. Despite the increasing use of oral morphine daily, little is known about the effect of long-term opioid therapy on psychomotor performance. To examine the effects of continuous morphine medication, psychological and neurological tests originally designed for professional motor vehicle drivers were conducted in two groups of cancer patients who were similar apart from experience of pain. 24 were on continuous morphine (mean 209 mg oral morphine daily) for cancer pain; and 25 were pain-free without regular analgesics. Though the results were a little worse in the patients taking morphine, there were no significant differences between the groups in intelligence, vigilance, concentration, fluency of motor reactions, or division of attention. Of the neural function tests, reaction times (auditory, visual, associative), thermal discrimination, and body sway with eyes open were similar in the two groups; only balancing ability with closed eyes was worse in the morphine group. These results indicate that, in cancer patients receiving long-term morphine treatment with stable doses, morphine has only a slight and selective effect on functions related to driving.

The normal mouse urinary bladder reservoir function evaluated by repeated cystometries. Early and late changes after irradiation alone and irradiation combined with cis-diamine-dichloroplatinium (II) and cyclophosphamide

International Nuclear Information System (INIS)

Lundbeck, F.

1994-01-01

The main aim of the present thesis was 1) to develop and investigate the feasibility of an in vivo assay in mice using repeated cystometries in a long term study, 2) to demonstrate changes in the bladder reservoir function after radiation alone or combined with cyclophosphamide (CTX) or cis-diamine-dichloroplatinium (II) (cis-DDP), and 3) to investigate the radiation sensitivity of the bladder for changes in dose per fraction, and also to investigate whether there is an association between early and late radiation-induced change in bladder reservoir function. From the results presented the following can be concluded: Bladder fillings in anesthetized mice can be performed repeatedly in long term studies. The procedure is easy to perform and well tolerated by the animals. The level of radiation dose determines the degree of early response and the time of onset of the late response. Combinations with CTX or cis-DDP increase the early radiation response, and the late response is expressed at an earlier time compared with radiation alone. The mouse urinary bladder appears to be one of the least sensitive late responding tissues to changes in dose per fraction. 93 refs., 7 figs., 1 tab

Mood disorders and serotonin transporter density in ecstasy users - the influence of long-term abstention, dose, and gender

NARCIS (Netherlands)

de Win, Maartje M. L.; Reneman, Liesbeth; Reitsma, Johannes B.; den Heeten, Gerard J.; Booij, Jan; van den Brink, Wim

2004-01-01

Rationale. Neurotoxic effects of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") on the serotonin (5-HT) system have been described in animals and humans, but little is known about long-term effects of ecstasy use on mood. Objectives. To investigate short-term and long-term effects of ecstasy

Long-term dose-response studies of inhaled or injected radionuclides. Biennial report, 1 October 1991--30 September 1993

Energy Technology Data Exchange (ETDEWEB)

Boecker, B.B.; Muggenburg, B.A.; Miller, S.C.; Bradley, P.L. [eds.

1994-01-01

This report describes the scientific progress in, and current status of, life-span studies of the long-term health risks in Beagle dogs of chronic irradiation from internally deposited radionuclides or from an external source. The reporting period for this document is the 2-year period from October 1, 1991 through September 30, 1993. Studies that were initiated at three different laboratories (Inhalation Toxicology Research Institute, ITRI, University of Utah, and Argonne National Laboratory, ANL) are presented here because they are being completed at ITRI. All living dogs in the Utah-initiated studies were transferred to the ITRI facility for the remainder of their life-span observations and measurements in September 1987. This report is the fourth in a series of reports dealing with the current status and progress of both the Utah and ITRI studies. Other life-span studies involving dogs exposed to gamma radiation from an external source were initiated and conducted for many years at ANL. In 1991, the decision was made to discontinue the chronic irradiation of the remaining living dogs and to transfer all remaining dogs to ITRI for care, clinical observations, and pathological observations at death or euthanasia. This report provides the current status of these dogs. Status reports on the Utah and ITRI studies comprise most of this report. The ITRI-related section presents brief statements of project objectives, the general procedures used in these studies, and some study-specific features for each of the 19 studies being conducted with either beta- or alpha-emitting radionuclides. Dose- and effect-modifying factors being addressed in these studies include total dose, dose rate, LET, solubility, nonuniformity of dose, species, age, sex, health status, and mode of exposure. Recent additions to experimental protocols for studies in which dogs are still alive involve the collection and analysis of tumor tissues using currently available molecular biology techniques.

Long-term results of golimumab therapy for rheumatoid arthritis. Therapy compliance issues

Directory of Open Access Journals (Sweden)

N. V. Chichasova

2016-01-01

Full Text Available The goal of therapy for rheumatoid arthritis (RA is to suppress inflammation, to prevent or delay destructive changes in the joints, and to normalize functions during the longest monitoring of the course of RA. The data of randomized controlled trials and national registries are of great importance to a clinician. The paper reviews the literature data characterizing the long-term results of RA therapy with the tumor necrosis factor-α inhibitor golimumab (GLM and patient compliance with the therapy. Treatment with GLM at the registered subcutaneous dose of 50 mg once every 4 weeks gives rise to an effect in the vast majority of patients regardless of the type of previous ineffective therapy, the dose of concurrently administered methotrexate, the number of previous ineffective disease-modifying antirheumatic drugs, and the use and nonuse of glucocorticoids. GLM is characterized by a long-term (as long as 5 years effect with suppressed progression of destruction, functional recovery, and satisfactory tolerability with no additional risk for adverse events as the therapy is continued.

Long-term management of GERD in the elderly with pantoprazole

Directory of Open Access Journals (Sweden)

Carlo Calabrese

2007-04-01

Full Text Available Carlo Calabrese, Anna Fabbri, Giulio Di FeboDepartment of Internal Medicine and Gastroenterology, University of Bologna, ItalyAbstract: The prevalence of gastroesophageal reflux disease (GERD increases with age and elderly are more likely to develop severe disease. Older patients often complain of less severe or frequent heartburn than younger patients and they may present with atypical symptoms such as dysphagia, weight loss, or extraesophageal symptoms. Proton pump inhibitors (PPIs are central in the management of GERD and are unchallenged with regards to their efficacy. They are considered safe and more effective than histamine receptor antagonists for healing esophagitis and for preventing its recurrence using a long term maintenance treatment. PPI have minimal side effects and few slight drug interactions and are considered safe for long term treatment. Pantoprazole is significantly effective both for acute and long-term treatment with excellent control of relapse and symptoms. It is well tolerated even for long-term therapy and its tolerability is optimal. Pantoprazole shows to have minimal interactions with other drugs because of a lower affinity for cytocrome P450 than older PPIs. Although the majority of elderly has concomitant illnesses and receive other drugs, this does not adversely effect the efficacy of pantoprazole because of its pharmacokinetics, which are independent of patient age. Clinical practice suggests that a low dose maintenance of PPIs should be used in older patients with GERD.Keywords: GERD, long-term management, pantoprazole, safety, efficacy, tolerability

Case Reports Showing a Long-Term Effect of Subanesthetic Ketamine Infusion in Reducing L-DOPA-Induced Dyskinesias

Directory of Open Access Journals (Sweden)

Scott J. Sherman

2016-02-01

Full Text Available Ketamine is an FDA-approved drug with a known safety profile. Low-dose subanesthetic intravenous ketamine infusion treatment has led to long-term reduction of treatment-resistant depression and of chronic pain states. We report on low-dose subanesthetic intravenous ketamine infusion treatment in Parkinson's disease (PD patients by 5 case studies and show a long-lasting therapeutic benefit to reduce L-DOPA-induced dyskinesia (LID, improve on time, and reduce depression. Based on the literature we hypothesize that low-dose ketamine may act as a ‘chemical deep brain stimulation', by desynchronizing hypersynchronous oscillatory brain activity, including in the basal ganglia and the motor cortex. The presented PD case reports indicate tolerability, safety and long-term beneficial effects of low-dose ketamine infusion that should be further investigated in a properly controlled prospective clinical trial for treatment of LID, as well as the prevalent nonmotor features pain and depression in PD patients.

Long-term effects of recurrent intermittent hypoxia and hyperoxia on respiratory system mechanics in neonatal mice.

Science.gov (United States)

Dylag, Andrew M; Mayer, Catherine A; Raffay, Thomas M; Martin, Richard J; Jafri, Anjum; MacFarlane, Peter M

2017-04-01

Premature infants are at increased risk for wheezing disorders. Clinically, these neonates experience recurrent episodes of apnea and desaturation often treated by increasing the fraction of inspired oxygen (FIO 2 ). We developed a novel paradigm of neonatal intermittent hypoxia with subsequent hyperoxia overshoots (CIH O/E ) and hypothesized that CIH O/E elicits long-term changes on pulmonary mechanics in mice. Neonatal C57BL/6 mice received CIH O/E , which consisted of 10% O2 (1 min) followed by a transient exposure to 50% FIO 2 , on 10-min repeating cycles 24 h/d from birth to P7. Baseline respiratory mechanics, methacholine challenge, RT-PCR for pro and antioxidants, radial alveolar counts, and airway smooth muscle actin were assessed at P21 after 2-wk room air recovery. Control groups were mice exposed to normoxia, chronic intermittent hyperoxia (CIH E ), and chronic intermittent hypoxia (CIH O ). CIH O/E and CIH E increased airway resistance at higher doses of methacholine and decreased baseline compliance compared with normoxia mice. Lung mRNA for NOX2 was increased by CIH O/E . Radial alveolar counts and airway smooth muscle actin was not different between groups. Neonatal intermittent hypoxia/hyperoxia exposure results in long-term changes in respiratory mechanics. We speculate that recurrent desaturation with hyperoxia overshoot may increase oxidative stress and contribute to wheezing in former preterm infants.

Gemcitabine Plus Radiation Therapy for High-Grade Glioma: Long-Term Results of a Phase 1 Dose-Escalation Study

Energy Technology Data Exchange (ETDEWEB)

Kim, Michelle M., E-mail: michekim@med.umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Camelo-Piragua, Sandra [Department of Pathology, University of Michigan, Ann Arbor, Michigan (United States); Schipper, Matthew; Tao, Yebin [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Department of Biostatistics, University of Michigan, Ann Arbor, Michigan (United States); Normolle, Daniel [Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Junck, Larry; Mammoser, Aaron [Department of Neurology, University of Michigan, Ann Arbor, Michigan (United States); Betz, Bryan L. [Department of Pathology, University of Michigan, Ann Arbor, Michigan (United States); Cao, Yue [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan (United States); Kim, Christopher J. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Heth, Jason; Sagher, Oren [Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan (United States); Lawrence, Theodore S. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Tsien, Christina I. [Department of Radiation Oncology, Washington University, St. Louis, Missouri (United States)

2016-02-01

Purpose: To evaluate the tolerability and efficacy of gemcitabine plus radiation therapy (RT) in this phase 1 study of patients with newly diagnosed malignant glioma (HGG). Patients and Methods: Between 2004 and 2012, 29 adults with HGG were enrolled. After any extent of resection, RT (60 Gy over 6 weeks) was given concurrent with escalating doses of weekly gemcitabine. Using a time-to-event continual reassessment method, 5 dose levels were evaluated starting at 500 mg/m{sup 2} during the last 2 weeks of RT and advanced stepwise into earlier weeks. The primary objective was to determine the recommended phase 2 dose of gemcitabine plus RT. Secondary objectives included progression-free survival, overall survival (OS), and long-term toxicity. Results: Median follow-up was 38.1 months (range, 8.9-117.5 months); 24 patients were evaluable for toxicity. After 2005 when standard practice changed, patients with World Health Organization grade 4 tumors were no longer enrolled. Median progression-free survival for 22 patients with grade 3 tumors was 26.0 months (95% confidence interval [CI] 15.6-inestimable), and OS was 48.5 months (95% CI 26.8-inestimable). In 4 IDH mutated, 1p/19q codeleted patients, no failures occurred, with all but 1 alive at time of last follow-up. Seven with IDH mutated, non-codeleted tumors with ATRX loss had intermediate OS of 73.5 months (95% CI 32.8-inestimable). Six nonmutated, non-codeleted patients had a median OS of 26.5 months (95% CI 25.4-inestimable). The recommended phase 2 dose of gemcitabine plus RT was 750 mg/m{sup 2}/wk given the last 4 weeks of RT. Dose reductions were most commonly due to grade 3 neutropenia; no grade 4 or 5 toxicities were seen. Conclusions: Gemcitabine concurrent with RT is well-tolerated and yields promising outcomes, including in patients with adverse molecular features. It is a candidate for further study, particularly for poor-prognosis patient subgroups with HGG.

Colchicine triggered severe rhabdomyolysis after long-term low-dose simvastatin therapy: a case report.

Science.gov (United States)

Frydrychowicz, Clara; Pasieka, Bastian; Pierer, Matthias; Mueller, Wolf; Petros, Sirak; Weidhase, Lorenz

2017-01-04

Rhabdomyolysis is a widely recognized yet rare complication in statin use. Rhabdomyolysis might be triggered by the prescription of high doses of statins or by statin accumulation due to interactions with concomitant medication. Muscle cell destruction as evidenced by myoglobin elevation can induce potentially life-threatening acute renal failure. We report a case of a 70-year-old obese white man with sudden onset of severe rhabdomyolysis with consecutive renal failure. His medication included low-dose simvastatin, which he had taken for 6 years up until the event. The statin was withdrawn immediately. After 3 days of veno-venous hemofiltration his renal function was completely restored. Clinicians in both primary and special care might be unaware that side effects of statins do occur even after a long uneventful statin medication; they should be advised not to exclude that possibility upfront, even if a patient has tolerated the medication for years.

Repeated-dose effects of mequitazine, cetirizine and dexchlorpheniramine on driving and psychomotor performance.

Science.gov (United States)

Theunissen, Eef L; Vermeeren, Annemiek; Ramaekers, Johannes G

2006-01-01

Previous studies have demonstrated that the antihistamines mequitazine, cetirizine and dexchlorpheniramine produce mild sedation after single doses. It is unknown, however, whether acute sedation persists after repeated dosing. Therefore, this study assessed the effects of repeated dosing of these antihistamines on driving and psychomotor performance. Sixteen healthy volunteers were treated with mequitazine 10 mg q.a.m., cetirizine 10 mg q.a.m., dexchlorpheniramine Repetab 6 mg b.i.d. and placebo for four separate 8-day periods. Drug effects were assessed on days 1 and 8 using on-the-road driving tests (highway driving and car following), psychomotor tests (tracking and divided attention) and subjective questionnaires. Dexchlorpheniramine and mequitazine significantly impaired driving performance on the highway driving test on the first day; dexchlorpheniramine increased Standard Deviation of Lateral Position by 2 cm [95% confidence interval (CI) 0.5, 3.8] and mequitazine by 2.5 cm (CI 1.0, 4.3). These effects on driving performance disappeared after 8 days of treatment. No effect of treatment was found on car following, tracking and divided attention. Although subjective ratings confirmed that subjects knew their driving had been impaired in the mequitazine and dexchlorpheniramine condition after completion of the highway driving test on day 1, they did not expect their driving to be affected before the start of the test. Cetirizine did not impair performance on any of the tests. Single doses of mequitazine 10 mg and dexchlorpheniramine Repetab 6 mg cause mild driving impairment. However, when taken over several days, the impairing effect wears off, possibly as a result of tolerance.

Post-assessment of pre-stressed containment structures by evaluation of monitored long term deformation results

International Nuclear Information System (INIS)

Wienand, B.

2015-01-01

The comparison of monitored long term deformations of containment structures with calculated values achieved by using design material parameters shows occasionally considerable deviations, partly caused by conservative assumptions in the containments design phase. Systematic post-assessment and adaption of the decisive parameters attains better coincidence. In the present investigation measured long-term deformations are first of all compared to pre-calculated values based on the material parameters defined in the design phase. Afterwards, the deformations deviations are minimized by repeating the calculation with assessed material parameters. This method appears to be a suitable method to predict the future containment structure long-term behavior and to achieve a possible life-time extension. The presented investigation was performed as part of NUGENIA ACCEPPT project which researches the ageing of concrete containment structures in nuclear power plants

When palliative treatment achieves more than palliation: Instances of long-term survival after palliative radiotherapy

Directory of Open Access Journals (Sweden)

Madhup Rastogi

2012-01-01

Full Text Available Context: Palliative radiotherapy aims at symptom alleviation and improvement of quality of life. It may be effective in conferring a reasonable quantum of local control, as well as possibly prolonging survival on the short term. However, there can be rare instances where long-term survival, or even cure, results from palliative radiotherapy, which mostly uses sub-therapeutic doses. Aim: To categorize and characterize the patients with long-term survival and/or cure after palliative radiotherapy. Materials and Methods: This study is a retrospective analysis of hospital records of patients treated with palliative radiotherapy from 2001 to 2006 at the Regional Cancer Centre, Shimla. Results: Of the analyzed 963 patients who received palliative radiotherapy, 2.4% (n = 23 survived at least 5 years, with a large majority of these surviving patients (73.9%, n = 17 being free of disease. Conclusions: In addition to providing valuable symptom relief, palliative radiotherapy utilizing sub-therapeutic doses may, in a small proportion of patients, bestow long-term survival, and possibly cure. Rationally, such a favorable, but rare outcome cannot be expected with supportive care alone.

Development of QSAR models using artificial neural network analysis for risk assessment of repeated-dose, reproductive, and developmental toxicities of cosmetic ingredients.

Science.gov (United States)

Hisaki, Tomoka; Aiba Née Kaneko, Maki; Yamaguchi, Masahiko; Sasa, Hitoshi; Kouzuki, Hirokazu

2015-04-01

Use of laboratory animals for systemic toxicity testing is subject to strong ethical and regulatory constraints, but few alternatives are yet available. One possible approach to predict systemic toxicity of chemicals in the absence of experimental data is quantitative structure-activity relationship (QSAR) analysis. Here, we present QSAR models for prediction of maximum "no observed effect level" (NOEL) for repeated-dose, developmental and reproductive toxicities. NOEL values of 421 chemicals for repeated-dose toxicity, 315 for reproductive toxicity, and 156 for developmental toxicity were collected from Japan Existing Chemical Data Base (JECDB). Descriptors to predict toxicity were selected based on molecular orbital (MO) calculations, and QSAR models employing multiple independent descriptors as the input layer of an artificial neural network (ANN) were constructed to predict NOEL values. Robustness of the models was indicated by the root-mean-square (RMS) errors after 10-fold cross-validation (0.529 for repeated-dose, 0.508 for reproductive, and 0.558 for developmental toxicity). Evaluation of the models in terms of the percentages of predicted NOELs falling within factors of 2, 5 and 10 of the in-vivo-determined NOELs suggested that the model is applicable to both general chemicals and the subset of chemicals listed in International Nomenclature of Cosmetic Ingredients (INCI). Our results indicate that ANN models using in silico parameters have useful predictive performance, and should contribute to integrated risk assessment of systemic toxicity using a weight-of-evidence approach. Availability of predicted NOELs will allow calculation of the margin of safety, as recommended by the Scientific Committee on Consumer Safety (SCCS).

Long-term survival in advanced melanoma patients using repeated therapies: successive immunomodulation improving the odds?

Directory of Open Access Journals (Sweden)

Coventry BJ

2015-04-01

Full Text Available Brendon J Coventry, Dominique Baume, Carrie Lilly Discipline of Surgery, Royal Adelaide Hospital, University of Adelaide, Adelaide, SA, Australia Background: Patients with advanced metastatic melanoma are often confronted with little prospect of medium- to longer-term survival by any currently available therapeutic means. However, most clinicians are aware of exceptional cases where survival defies the notion of futility. Prolonged survival from immunotherapies, including interleukin-2, vaccines and antibodies to cytotoxic lymphocyte antigen-4, and programmed death-1 receptor inhibitory monoclonal antibody, implies a role for immune system modulation. We aimed to identify cases where exceptional survival from advanced melanoma occurred prior to recent novel therapies to facilitate better understanding of this phenomenon. Methods: Cases of long-term survival of ≥3 years' duration (from diagnosis of metastatic disease were identified from the database of one clinician; these cases were treated before the availability of newer immunotherapies, and they were documented and examined. A literature search for reported outcome measures from published studies using older and recent therapies for advanced melanoma was conducted to enable the comparison of data. Results: Eighteen cases were identified that identified survival of ≥3 years' duration from metastatic disease (12 American Joint Committee on Cancer [AJCC] Stage IV cases; six AJCC III cases diagnosis. These were assessed and reported to detail the clinical course. Standard clinical prognostication methods predicted high risk of early mortality in those patients. No identifiable differences could be detected between these and other patients with similar patterns of disease. At evaluation, 17 patients (94% had survived ≥5 years, and eleven patients (61% had survived ≥10 years (range: 3–15 years. The median survival duration with metastatic disease was 11 years; 15 remained alive and three

Long term radiological impact of thorium extraction

International Nuclear Information System (INIS)

Menard, S.; Schapira, J.P.

1995-01-01

Thorium extraction produces a certain amount of radioactive wastes. Potential long term radiological impact of these residues has been calculated using the recent ICRP-68 ingestion dose factors in connection with the computing code DECAY, developed at Orsay and described in this work. This code solves the well known Bateman's equations which govern the time dependence of a set of coupled radioactive nuclei. Monazites will be very likely the minerals to be exploited first, in case of an extensive use of thorium as nuclear fuel. Because monazites contain uranium as well, mining residues will contain not only the descendants of 232 Th and a certain proportion of non-extracted thorium (taken here to be 5%), but also this uranium, if left in the wastes for economical reasons. If no uranium would be present at all in the mineral, the potential radiotoxicity would strongly decrease in approximately 60 years, at the pace of the 5.8 years period of 228 Ra, which becomes the longest-lived radionuclide of the 4n radioactive family in the residues. Moreover, there is no risk due to radon exhalation, because of the very short period of 220 Rn. These significant differences between uranium and thorium mining have to be considered in view of some estimated long term real radiological impacts due to uranium residues, which could reach a value of the order of 1 mSv/year, the dose limit recommended for the public by the recent ICRP-60. (authors). 15 refs., 4 figs., 3 tabs., 43 appendices

Near-Term Actions to Address Long-Term Climate Risk

Science.gov (United States)

Lempert, R. J.

2014-12-01

Addressing climate change requires effective long-term policy making, which occurs when reflecting on potential events decades or more in the future causes policy makers to choose near-term actions different than those they would otherwise pursue. Contrary to some expectations, policy makers do sometimes make such long-term decisions, but not as commonly and successfully as climate change may require. In recent years however, the new capabilities of analytic decision support tools, combined with improved understanding of cognitive and organizational behaviors, has significantly improved the methods available for organizations to manage longer-term climate risks. In particular, these tools allow decision makers to understand what near-term actions consistently contribute to achieving both short- and long-term societal goals, even in the face of deep uncertainty regarding the long-term future. This talk will describe applications of these approaches for infrastructure, water, and flood risk management planning, as well as studies of how near-term choices about policy architectures can affect long-term greenhouse gas emission reduction pathways.

Long-term results after fibroid embolization; Langzeitergebnisse nach Myomembolisation

Energy Technology Data Exchange (ETDEWEB)

Mueller-Huelsbeck, S. [Medizinischer Klinikverbund Flensburg, Akademisches Lehrkrankenhaus des Universitaetsklinikums Schleswig-Holstein, Abt. Diagnostische und interventionelle Radiologie/Neuroradiologie, Ev.-Luth. Diakonissenanstalt zu Flensburg, Flensburg (Germany)

2008-07-15

Fibroids (leiomyoma) are the most frequent benign tumors of the uterus during female reproductive age. In the case of clinical symptoms, uterine artery embolization (UAE) is a well established treatment option for symptomatic fibroids, resulting in promising long-term results. In order to estimate long-term success after UAE, reduction of fibroids and uterus volume is less important than complete improvement and disappearance of fibroid-related symptoms. In addition to a high technical success rate and a low perioperative complication rate, UAE results in high short-term and long-term patient satisfaction (>87%) and improvement of symptoms (>81%). Candidates for UAE should be informed about potential reinterventions in terms of repeated UAE (up to 18% of cases) or surgical treatment options. (orig.) [German] Myome sind die haeufigsten gutartigen soliden Tumoren des weiblichen Genitaltrakts im reproduktiven Alter. Bei klinischen Beschwerden stellt die Uterusarterienembolisation (UAE) zur Therapie des symptomatischen Uterus myomatosus einen fest etabliertes Verfahren dar, das mit viel versprechenden Langzeitergebnissen aufwarten kann. Im Vordergrund der Abschaetzung eines lang andauernden Therapieerfolgs nach UAE stehen weniger die Volumenreduktion eines dominanten Myoms bzw. des gesamten Uterus nach der Behandlung, sondern vielmehr die Besserung oder das voellige Verschwinden der von der Patientin initial vor der UAE angegebenen (myombedingten) Beschwerden. Neben einer hohen technischen Erfolgsrate und geringen perioperativen Komplikationsrate fuehrt die fachkundig durchgefuehrte UAE sowohl im Kurz- als auch Langzeitverlauf zu einem hohen Mass an Patientenzufriedenheit (>87%), verbunden mit einer deutlichen Symptombesserung (>81%). Ueber eine Reintervention (in bis zu ca. 18% der Faelle) im Sinne einer erneuten UAE oder einer operativen Massnahme sollten die Patientinnen allerdings im Vorfeld aufgeklaert werden. (orig.)

Long-term effects of ayahuasca in patients with recurrent depression: a 5-year qualitative follow-up

Directory of Open Access Journals (Sweden)

Rafael G. Dos Santos

Full Text Available Abstract Background Ayahuasca is a botanical hallucinogenic preparation traditionally used by indigenous populations of Northwestern Amazonian countries for ritual and therapeutic purposes. It is rich in β-carboline alkaloids and N,N-dimethyltryptamine (DMT. Preclinical, observational, and experimental studies suggest that ayahuasca and its alkaloids have anxiolytic and antidepressive effects. We recently reported in an open-label trial that ayahuasca administration was associated with significant decreases in depression symptoms for 2-3 weeks after the experimental session in 17 patients with treatment-resistant major depressive disorder. Objectives To investigate if the experiment had any long-lasting effects on patients Methods Eight patients were interviewed 4 to 7 years after ayahuasca intake. Results Our results suggest that ayahuasca was well tolerated and that symptom reductions were limited to a few weeks. Importantly, most patients believed that the experience was among the most important of their lives, even 4-7 years later. Discussion To the best of our knowledge, this is the first long-term follow-up of a clinical sample that participated in an ayahuasca trial. Further studies with different and repeated dosing should be designed to further explore the antidepressive and anxiolytic effects of ayahuasca.

The effect of teaching method on long-term knowledge retention.

Science.gov (United States)

Beers, Geri W; Bowden, Susan

2005-11-01

Choosing a teaching strategy that results in knowledge retention on the part of learners can be challenging for educators. Studies on problem-based learning (PBL) have supported its effectiveness, compared to other, more traditional strategies. The results of a previous study comparing the effect of lecture versus PBL on objective test scores indicated there was no significant difference in scores. To measure long-term knowledge retention, the same groups were evaluated 1 year after instruction. The posttest administered in the original study was repeated, and the scores from a comprehensive adult health examination and the endocrine subsection were analyzed. At an alpha level of 0.05, a statistically significant difference was found in the scores on two of the measures. The scores of the PBL group were significantly higher on the endocrine section of the examination and the repeat posttest.

Repeated batch fermentation of immobilized E. coli expressing Vitreoscilla hemoglobin for long-term use.

Science.gov (United States)

Sar, Taner; Seker, Gamze; Erman, Ayse Gokce; Stark, Benjamin C; Yesilcimen Akbas, Meltem

2017-09-03

This study describes an efficient and reusable process for ethanol production from medium containing whey powder, using alginate immobilized ethanologenic E. coli strains either expressing (TS3) or not expressing (FBR5) Vitreoscilla hemoglobin. Reuseabilities of the FBR5 and TS3 strains were investigated regarding their ethanol production capacities over the course of 15 successive 96-h batch fermentations. The ethanol production was fairly stable over the entire duration of the experiment, with strain TS3 maintaining a substantial advantage over strain FBR5. Storage of both strains in 2 different solutions for up to 60 d resulted in only a modest loss of ethanol production, with strain TS3 consistently outperforming strain FBR5 by a substantial amount. Strains stored for 15 or 30 d maintained their abilities to produce ethanol without dimunition over the course of 8 successive batch fermentations; again strain TS3 maintained a substantial advantage over strain FBR5 throughout the entire experiment. Thus, immobilization is a useful strategy to maintain the advantage in ethanol productivity afforded by expression of Vitreoscilla hemoglobin over long periods of time and large numbers of repeated batch fermentations, including, as in this case, using media with food processing wastes as the carbon source.

Long-term survival with repeat resection for lung oligometastasis from pancreatic ductal adenocarcinoma: a case report.

Science.gov (United States)

Matsuki, Ryota; Sugiyama, Masanori; Takei, Hidefumi; Kondo, Haruhiko; Fujiwara, Masachika; Shibahara, Junji; Furuse, Junji

2018-03-27

Long-term survival after resection of metastases from pancreatic ductal adenocarcinoma is rare. A 54-year-old man underwent pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) with UICC staging pT3N1M0 followed by adjuvant chemotherapy with gemcitabine (GEM). Three years after radical resection of the primary tumor, a tiny nodule was found in the lower lobe of the left lung. Despite treatment with GEM, it increased gradually, but no other metastases were found. Eighteen months after the first indication of the nodule, wedge resection was performed. Pathological examination of the nodule indicated a metastatic tumor from PDAC. Pulmonary metastasectomy was again performed for lung oligometastases at 77 and 101 months after PD. The patient has been asymptomatic without tumor recurrence for 4 years since the last pulmonary resection. In PDAC, the treatment strategy for oligometastasis is controversial. However, a few cases of long-term survival after pulmonary metastasectomy for oligometastasis of PDAC have been reported. More such cases need to be studied to address this issue effectively.

Long Term Financing of Infrastructure

OpenAIRE

Sinha, Sidharth

2014-01-01

Infrastructure projects, given their long life, require long term financing. The main sources of long term financings are insurance and pension funds who seek long term investments with low credit risk. However, in India household financial savings are mainly invested in bank deposits. Insurance and pension funds account for only a small percentage of household financial savings. In addition most infrastructure projects do not qualify for investment by insurance and pension funds because of t...

ExStroke Pilot Trial of the effect of repeated instructions to improve physical activity after ischaemic stroke

DEFF Research Database (Denmark)

Boysen, Gudrun; Krarup, Lars-Henrik; Zeng, Xianrong

2009-01-01

To investigate if repeated verbal instructions about physical activity to patients with ischaemic stroke could increase long term physical activity.......To investigate if repeated verbal instructions about physical activity to patients with ischaemic stroke could increase long term physical activity....

Long term stability of power systems

Energy Technology Data Exchange (ETDEWEB)

Kundur, P; Gao, B [Powertech Labs. Inc., Surrey, BC (Canada)

1994-12-31

Power system long term stability is still a developing subject. In this paper we provide our perspectives and experiences related to long term stability. The paper begins with the description of the nature of the long term stability problem, followed by the discussion of issues related to the modeling and solution techniques of tools for long term stability analysis. Cases studies are presented to illustrate the voltage stability aspect and plant dynamics aspect of long term stability. (author) 20 refs., 11 figs.

Influence of the design temperature on long-term safety of a salt dome repository

International Nuclear Information System (INIS)

Buhmann, D.; Brenner, J.; Storck, R.

1993-03-01

All studies made so far within the framwork of the mixed concept system analysis proceeded from a design temperature of the mine structure of 200 C. The concept based on a design temperature of 150 C was aimed at studying whether it made sense to maintain lower temperatures, if necessary. Deterministic and probabilistic calculations were made in order to determine the influence of the lower design temperature on long-term safety. The calculations were based on concept A of Joint Borehole and Gallery Storage. Assuming reference values of the input parameters, the deterministic calculations do not produce any radionuclide release from the mine structure. If, however, one assumes a lower rate for rock convergence, radionuclides are released at maximum dose rates of about 3.10 -5 Sv/a. Even a larger volume of limited brine inclusions may lead to radionuclide releases, in that case with dose commitments of the order of magnitude of 1.10 -5 Sv/a. The probabilistic calculations show that a design temperature of 150 C for long-term safety is less favourable than a higher design temperature. The share of simulations in the probabilistic calculations with a radionuclide release, and the expected value of dose commitment, are almost double as high as in the concept based on 200 C design temperature. Thus a higher design temperature is preferable with regard to the long-term safety of a salt repository. The most important parameters concerning dose commitment are the volume of limited brine inclusions, the convergence rate, and the permeability of barriers and backfilling rock. (orig./HP) [de

Impact of short‐term, repeated water fasting on the weight of mice

Directory of Open Access Journals (Sweden)

Zahra Mishmast

2014-09-01

Full Text Available Introduction: Caloric restriction is a strategy applied for weight loss. Water fasting is a popular way for obesity treatment. However, little is known about the impact of water fasting on weight. Therefore, this study was conducted to investigate the effect of short-term, repeated water fasting on the weight of mice. Methods: In this study, the physiological effect of short-term, repeated water fasting on the weight of female mice was evaluated. At 6 weeks of age, mice were randomly assigned to either repeated-fasting or control group (fed ad libitum. Each group consisted of twenty mice. As the fasting period started, the repeated-fasting group had access to only water; animals had free access to food and water on non-fasting days. Body weight of each group before, during, and after the fasting period was recorded. Results: Body weight of the fasting group significantly decreased, unlike the control group. However, the fasting group gained weight rapidly after being re-fed and became significantly heavier than mice in the control group (P

Infection and immunity in Down syndrome: a trial of long-term low oral doses of zinc.

Science.gov (United States)

Lockitch, G; Puterman, M; Godolphin, W; Sheps, S; Tingle, A J; Quigley, G

1989-05-01

To determine whether orally administered zinc supplements could correct the abnormal humoral and cell-mediated immunity of Down syndrome, we randomly assigned 64 children with Down syndrome, aged 1 to 19 years and living at home, to receive either zinc gluconate or placebo daily for 6-month periods with crossover from one regimen to another. Control subjects were siblings and age-matched, unrelated children. Serum zinc, copper, and measures of immune system competence were tested at 3- or 6-month intervals. Parents kept daily logs of clinical symptoms such as cough and diarrhea and of physician visits. Mean serum zinc concentrations increased to about 150% of baseline during zinc supplementation, but we found no effect on serum levels of copper, immunoglobulins, or complement; on lymphocyte number or subset distribution; or on in vitro response to mitogens. Children with Down syndrome who were receiving zinc had a trend toward fewer days or episodes of cough and fever but no change in other clinical variables. Long-term, low-dose oral zinc supplementation to improve depressed immune response or to decrease infections in children with Down syndrome cannot be recommended.

Single and repeated dose pharmacokinetics of dexketoprofen trometamol in patients with impaired liver function.

Science.gov (United States)

Valles, J; Artigas, R; Bertolotti, M; Crea, A; Muller, F; Paredes, I; Capriati, A

2006-06-01

Dexketoprofen trometamol, a high water-soluble salt of the active enantiomer of rac-ketoprofen, is a nonsteroidal antiinflammatory drug (NSAID) used for pain relief. This study compared the pharmacokinetics of dexketoprofen in patients with impaired liver function and normal subjects following single and repeated oral dosing. Subjects with normal liver function (n = 6) and with Child-Pugh A (n = 7) or Child-Pugh B (n = 5) hepatic impairment scores completed this open-label and parallel study. They received 25 mg dexketoprofen (equivalent to 37 mg of its tromethamine salt) as a single (day 1) and a 3-day repeated dose (1 dose every 8 hours for a total of 10 doses). Dexketoprofen concentrations were determined in plasma and urine by reverse-phase high performance liquid chromatography (HPLC). Model-independent pharmacokinetic parameters were obtained. All subjects completed the study. No serious adverse events were recorded. Following the single dose, mean (+/- SEM) Cmax were 3027.7 +/- 429.3 ng/ml (healthy subjects), 2856.3 +/- 340.3 ng/ml (Child-Pugh A) and 1937.2 +/- 328.0 ng/ml (Child-Pugh B). Median tmax were 0.49 h (0.33-0.68) h, 0.50 h (0.33-0.67) h and 0.67 h (0.33-1.50) h. AUC0-x averaged 3778.0 +/- 439.0 ng.h/ml, 4890.4 +/- 539.1 ng.h/ml and 3985.0 +/- 712.0 ng.h/ml. Mean CL/F were 101.1 +/- 11.3 ml/h/kg, 73.3 +/- 9.9 ml/h/kg and 88.8 +/- 15.5 ml/h/kg and V/F averaged 0.192 +/- 0.018 l/kg, 0.162 +/- 0.006 l/kg and 0.214 +/- 0.044 l/kg. Following the repeated administration, similar results were obtained showing no drug accumulation. As related to the administered dose, median excretions of unchanged and conjugated dexketoprofen in urine were 2.1% and 67.1% in healthy subjects, 2.8% and 60.9% in Child-Pugh A subjects and 4.4% and 47.7% in Child-Pugh B volunteers. A trend towards a reduced urinary excretion of conjugated dexketoprofen in hepatic patients, more evident in the Child-Pugh B than in the Child-Pugh A groups, was observed when compared with healthy

Dienogest in long-term treatment of endometriosis

Directory of Open Access Journals (Sweden)

Schindler AE

2011-07-01

Full Text Available Adolf E SchindlerInstitute for Medical Research and Education, Essen, GermanyAbstract: Endometriosis is a chronic disease primarily affecting women of childbearing age, in which endometriotic lesions form outside the uterus, typically leading to painful symptoms, fatigue, and infertility. The symptoms of endometriosis may cause significant impairment in quality of life and represent a substantial economic burden to patients, families, and society. There is no cure for endometriosis; management consists of alleviating pain and other symptoms, reducing endometriotic lesions, and improving quality of life. Recurrence after surgical intervention is common, while the clinical evidence to support the efficacy and safety of many medications currently used in endometriosis is limited. Dienogest is an oral progestin that has been investigated extensively in the treatment of endometriosis in two clinical programs performed in Europe and Japan, including dose-ranging, placebo-controlled, active comparator-controlled, and long-term (up to 65 weeks studies. These studies demonstrated that dienogest 2 mg daily effectively alleviates the painful symptoms of endometriosis, reduces endometriotic lesions, and improves indices of quality of life. Dienogest showed a favorable safety and tolerability profile in these studies, with predictable adverse effects, high rates of patient compliance, and low withdrawal rates. This review article describes the clinical trial evidence that characterizes the efficacy and safety of dienogest in endometriosis, including two studies characterizing dienogest in long-term use. The relevance of these findings to the management of endometriosis in clinical practice is discussed.Keywords: dienogest, endometriosis, progestins, long-term treatment, quality of life, symptoms, pain

Repeat Gamma Knife surgery for vestibular schwannomas

Science.gov (United States)

Lonneville, Sarah; Delbrouck, Carine; Renier, Cécile; Devriendt, Daniel; Massager, Nicolas

2015-01-01

Background: Gamma Knife (GK) surgery is a recognized treatment option for the management of small to medium-sized vestibular schwannoma (VS) associated with high-tumor control and low morbidity. When a radiosurgical treatment fails to stop tumor growth, repeat GK surgery can be proposed in selected cases. Methods: A series of 27 GK retreatments was performed in 25 patients with VS; 2 patients underwent three procedures. The median time interval between GK treatments was 45 months. The median margin dose used for the first, second, and third GK treatments was 12 Gy, 12 Gy, and 14 Gy, respectively. Six patients (4 patients for the second irradiation and 2 patients for the third irradiation) with partial tumor regrowth were treated only on the growing part of the tumor using a median margin dose of 13 Gy. The median tumor volume was 0.9, 2.3, and 0.7 cc for the first, second, and third treatments, respectively. Stereotactic positron emission tomography (PET) guidance was used for dose planning in 6 cases. Results: Mean follow-up duration was 46 months (range 24–110). At the last follow-up, 85% of schwannomas were controlled. The tumor volume decreased, remained unchanged, or increased after retreatment in 15, 8, and 4 cases, respectively. Four patients had PET during follow-up, and all showed a significant metabolic decrease of the tumor. Hearing was not preserved after retreatment in any patients. New facial or trigeminal palsy did not occur after retreatment. Conclusions: Our results support the long-term efficacy and low morbidity of repeat GK treatment for selected patients with tumor growth after initial treatment. PMID:26500799

Real time source term and dose assessment

International Nuclear Information System (INIS)

Breznik, B.; Kovac, A.; Mlakar, P.

2001-01-01

The Dose Projection Programme is a tool for decision making in case of nuclear emergency. The essential input data for quick emergency evaluation in the case of hypothetical pressurised water reactor accident are following: source term, core damage assessment, fission product radioactivity, release source term and critical exposure pathways for an early phase of the release. A reduced number of radio-nuclides and simplified calculations can be used in dose calculation algorithm. Simple expert system personal computer programme has been developed for the Krsko Nuclear Power Plant for dose projection within the radius of few kilometers from the pressurised water reactor in early phase of an accident. The input data are instantaneous data of core activity, core damage indicators, release fractions, reduction factor of the release pathways, spray operation, release timing, and dispersion coefficient. Main dose projection steps are: accurate in-core radioactivity determination using reactor power input; core damage and in-containment source term assessment based on quick indications of instrumentation or on activity analysis data; user defines release pathway for typical PWR accident scenarius; dose calculation is performed only for exposure pathway critical for decision about evacuation or sheltering in early phase of an accident.(author)

Long-term outcomes after disease activity-guided dose reduction of TNF inhibition in rheumatoid arthritis: 3-year data of the DRESS study - a randomised controlled pragmatic non-inferiority strategy trial

NARCIS (Netherlands)

Bouman, Chantal Am; van Herwaarden, Noortje; van den Hoogen, Frank Hj; Fransen, Jaap; van Vollenhoven, Ronald F.; Bijlsma, Johannes Wj; Maas, Aatke van der; den Broeder, Alfons A.

2017-01-01

Tumour necrosis factor inhibitors (TNFi) are effective in rheumatoid arthritis (RA), but disadvantages include adverse events (AEs) and high costs. This can be improved by disease activity-guided dose reduction (DR). We aimed to assess long-term outcomes of TNFi DR in RA by using 3-year data from

Long-term outcomes after disease activity-guided dose reduction of TNF inhibition in rheumatoid arthritis: 3-year data of the DRESS study - a randomised controlled pragmatic non-inferiority strategy trial

NARCIS (Netherlands)

Bouman, C.A.M.; Herwaarden, N. van; Hoogen, F.H.J. van den; Fransen, J.; Vollenhoven, R.F. van; Bijlsma, J.W.; Maas, A.V.; Broeder, A.A. den

2017-01-01

OBJECTIVE: Tumour necrosis factor inhibitors (TNFi) are effective in rheumatoid arthritis (RA), but disadvantages include adverse events (AEs) and high costs. This can be improved by disease activity-guided dose reduction (DR). We aimed to assess long-term outcomes of TNFi DR in RA by using 3-year

Acute ethanol has biphasic effects on short- and long-term memory in both foreground and background contextual fear conditioning in C57BL/6 mice.

Science.gov (United States)

Gulick, Danielle; Gould, Thomas J

2007-09-01

Ethanol is a frequently abused, addictive drug that impairs cognitive function. Ethanol may disrupt cognitive processes by altering attention, short-term memory, and/or long-term memory. Interestingly, some research suggests that ethanol may enhance cognitive processes at lower doses. The current research examined the dose-dependent effects of ethanol on contextual and cued fear conditioning. In addition, the present studies assessed the importance of stimulus salience in the effects of ethanol and directly compared the effects of ethanol on short-term and long-term memory. This study employed both foreground and background fear conditioning, which differ in the salience of contextual stimuli, and tested conditioning at 4 hours, 24 hours, and 1 week in order to assess the effects of ethanol on short-term and long-term memory. Foreground conditioning consisted of 2 presentations of a foot shock unconditioned stimulus (US) (2 seconds, 0.57 mA). Background conditioning consisted of 2 auditory conditioned stimulus (30 seconds, 85 dB white noise)-foot shock (US; 2 seconds, 0.57 mA) pairings. For both foreground and background conditioning, ethanol enhanced short-term and long-term memory for contextual and cued conditioning at a low dose (0.25 g/kg) and impaired short-term and long-term memory for contextual and cued conditioning at a high dose (1.0 g/kg). These results suggest that ethanol has long-lasting, biphasic effects on short-term and long-term memory for contextual and cued conditioning. Furthermore, the effects of ethanol on contextual fear conditioning are independent of the salience of the context.

Repeat Gamma-Knife Radiosurgery for Refractory or Recurrent Trigeminal Neuralgia with Consideration About the Optimal Second Dose.

Science.gov (United States)

Park, Seong-Cheol; Kwon, Do Hoon; Lee, Do Hee; Lee, Jung Kyo

2016-02-01

To investigate adequate radiation doses for repeat Gamma Knife radiosurgery (GKS) for trigeminal neuralgia in our series and meta-analysis. Fourteen patients treated by ipsilateral repeat GKS for trigeminal neuralgia were included. Median age of patients was 65 years (range, 28-78), the median target dose, 140-180). Patients were followed a median of 10.8 months (range, 1-151) after the second gamma-knife surgery. Brainstem dose analysis and vote-counting meta-analysis of 19 studies were performed. After the second gamma-knife radiosurgeries, pain was relieved effectively in 12 patients (86%; Barrow Neurological Institute Pain Intensity Score I-III). Post-gamma-knife radiosurgery trigeminal nerve deficits were mild in 5 patients. No serious anesthesia dolorosa was occurred. The second GKS radiation dose ≤ 60 Gy was significantly associated with worse pain control outcome (P = 0.018 in our series, permutation analysis of variance, and P = 0.009 in the meta-analysis, 2-tailed Fisher's exact test). Cumulative dose ≤ 140-150 Gy was significantly associated with poor pain control outcome (P = 0.033 in our series and P = 0.013 in the meta-analysis, 2-tailed Fisher's exact test). A cumulative brainstem edge dose >12 Gy tended to be associated with trigeminal nerve deficit (P = 0.077). Our study suggests that the second GKS dose is a potentially important factor. Copyright © 2016 Elsevier Inc. All rights reserved.

Lansoprazole for secondary prevention of gastric or duodenal ulcers associated with long-term low-dose aspirin therapy: results of a prospective, multicenter, double-blind, randomized, double-dummy, active-controlled trial.

Science.gov (United States)

Sugano, Kentaro; Matsumoto, Yasushi; Itabashi, Tsukasa; Abe, Sumihisa; Sakaki, Nobuhiro; Ashida, Kiyoshi; Mizokami, Yuji; Chiba, Tsutomu; Matsui, Shigeyuki; Kanto, Tatsuya; Shimada, Kazuyuki; Uchiyama, Shinichiro; Uemura, Naomi; Hiramatsu, Naoki

2011-06-01

The efficacy of low-dose lansoprazole has not been established for the prevention of recurrent gastric or duodenal ulcers in those receiving long-term low-dose aspirin (LDA) for cardiovascular and cerebrovascular protection. This study sought to examine the efficacy of low-dose lansoprazole (15 mg once daily) for the secondary prevention of LDA-associated gastric or duodenal ulcers. Patients were randomized to receive lansoprazole 15 mg daily (n = 226) or gefarnate 50 mg twice daily (n = 235) for 12 months or longer in a prospective, multicenter, double-blind, randomized active-controlled trial, followed by a 6-month follow-up study with open-label lansoprazole treatment. The study utilized 94 sites in Japan and 461 Japanese patients with a history of gastric or duodenal ulcers who required long-term LDA therapy for cardiovascular and cerebrovascular disease. The primary endpoint was the development of gastric or duodenal ulcers. The cumulative incidence of gastric or duodenal ulcers on days 91, 181, and 361 from the start of the study was calculated by the Kaplan-Meier method as 1.5, 2.1, and 3.7%, respectively, in the lansoprazole group versus 15.2, 24.0, and 31.7%, respectively, in the gefarnate group. The risk of ulcer development was significantly (log-rank test, P lansoprazole group than in the gefarnate group, with the hazard ratio being 0.099 (95% confidence interval [CI] 0.042-0.230). Lansoprazole was superior to gefarnate in reducing the risk of gastric or duodenal ulcer recurrence in patients with a definite history of gastric or duodenal ulcers who required long-term LDA therapy.

Exposing Students to Repeat Photography: Increasing Cultural Understanding on a Short-Term Study Abroad

Science.gov (United States)

Lemmons, Kelly K.; Brannstrom, Christian; Hurd, Danielle

2014-01-01

Traditionally, repeat photography has been used to analyze land cover change. This paper describes how repeat photography may be used as a tool to enhance the short-term study abroad experience by facilitating cultural interaction and understanding. We present evidence from two cases and suggest a five-step repeat photography method for educators…

Long term strain behavior of PMMA based polymer optical fibers

DEFF Research Database (Denmark)

Bundalo, Ivan-Lazar; Nielsen, Kristian; Woyessa, Getinet

2015-01-01

We are reporting on the viscoelasticity of PMMA based Fiber Bragg Grating (FBG) strain sensors when exposed to repeated sequences of long term strain and relaxation with various duty-cycles. In terms of the FBG wavelength and how it follows the strain cycle, we have shown that in the small strain...... regime (up to 1%) an elastic-dominated fast relaxing range, which is followed by a mainly viscous relaxation, depends both on the strain level and on the strain duration. For a small ratio of the strain-relax durations, this fast relaxation range stays almost the same. However, with increasing strain...... duration, for the same relaxation time, this range will be shortened, which might influence the sensing capabilities of the fiber sensor....

Long-Term Impact of Immunosuppressants at Therapeutic Doses on Male Reproductive System in Unilateral Nephrectomized Rats: A Comparative Study

Directory of Open Access Journals (Sweden)

Yehui Chen

2013-01-01

Full Text Available Cyclosporine, tacrolimus, and sirolimus are commonly used in renal transplant recipients to prevent rejection. However, information for comparative effects of these agents on the male productive system is extremely limited and controversial. In a physiologically and clinically relevant rat model of unilateral nephrectomy, we demonstrated that long-term oral administration of both cyclosporine and sirolimus at doses equivalent to the therapeutic levels used for postrenal transplant patients significantly affects testicular development and the hypothalamic-pituitary-gonadal axis accompanied by profound histological changes of testicular structures on both light and electron microscopic examinations. Spermatogenesis was also severely impaired as indicated by low total sperm counts along with reduction of sperm motility and increase in sperm abnormality after treatment with these agents, which may lead to male infertility. On the other hand, treatment with therapeutic dose of tacrolimus only induced mild reduction of sperm count without histological evidence of testicular injury. The current study clearly demonstrates that commonly used immunosuppressants have various impacts on male reproductive system even at therapeutic levels. Our data provide useful information for the assessment of male infertility in renal transplant recipients who wish to father children. Clinical trials to address these issues should be urged.

An Automated Inpatient Split-dose Bowel Preparation System Improves Colonoscopy Quality and Reduces Repeat Procedures.

Science.gov (United States)

Yadlapati, Rena; Johnston, Elyse R; Gluskin, Adam B; Gregory, Dyanna L; Cyrus, Rachel; Werth, Lindsay; Ciolino, Jody D; Grande, David P; Keswani, Rajesh N

2017-07-19

Inpatient colonoscopy preparations are often inadequate, compromising patient safety and procedure quality, while resulting in greater hospital costs. The aims of this study were to: (1) design and implement an electronic inpatient split-dose bowel preparation order set; (2) assess the intervention's impact upon preparation adequacy, repeated colonoscopies, hospital days, and costs. We conducted a single center prospective pragmatic quasiexperimental study of hospitalized adults undergoing colonoscopy. The experimental intervention was designed using DMAIC (define, measure, analyze, improve, and control) methodology. Prospective data collected over 12 months were compared with data from a historical preintervention cohort. The primary outcome was bowel preparation quality and secondary outcomes included number of repeated procedures, hospital days, and costs. On the basis of a Delphi method and DMAIC process, we created an electronic inpatient bowel preparation order set inclusive of a split-dose bowel preparation algorithm, automated orders for rescue medications, and nursing bowel preparation checks. The analysis data set included 969 patients, 445 (46%) in the postintervention group. The adequacy of bowel preparation significantly increased following intervention (86% vs. 43%; P<0.01) and proportion of repeated procedures decreased (2.0% vs. 4.6%; P=0.03). Mean hospital days from bowel preparation initiation to discharge decreased from 8.0 to 6.9 days (P=0.02). The intervention resulted in an estimated 1-year cost-savings of $46,076 based on a reduction in excess hospital days associated with repeated and delayed procedures. Our interdisciplinary initiative targeting inpatient colonoscopy preparations significantly improved quality and reduced repeat procedures, and hospital days. Other institutions should consider utilizing this framework to improve inpatient colonoscopy value.

Long-term outcomes and cost effectiveness of high-dose dexamethasone for cardiac surgery : A randomised trial

NARCIS (Netherlands)

Dieleman, J. M.; de Wit, G. A.; Nierich, A. P.; Rosseel, P. M.; van der Maaten, J. M.; Hofland, J.; Diephuis, J. C.; de Lange, F.; Boer, C.; Neslo, R. E.; Moons, K. G.; van Herwerden, L. A.; Tijssen, J. G.; Kalkman, C. J.; van Dijk, D.

Prophylactic intra-operative administration of dexamethasone may improve short-term clinical outcomes in cardiac surgical patients. The purpose of this study was to evaluate long-term clinical outcomes and cost effectiveness of dexamethasone versus placebo. Patients included in the multicentre,

Long-term outcomes and cost effectiveness of high-dose dexamethasone for cardiac surgery: a randomised trial

NARCIS (Netherlands)

Dieleman, J. M.; de Wit, G. A.; Nierich, A. P.; Rosseel, P. M.; van der Maaten, J. M.; Hofland, J.; Diephuis, J. C.; de Lange, F.; Boer, C.; Neslo, R. E.; Moons, K. G.; van Herwerden, L. A.; Tijssen, J. G.; Kalkman, C. J.; van Dijk, D.

2017-01-01

Prophylactic intra-operative administration of dexamethasone may improve short-term clinical outcomes in cardiac surgical patients. The purpose of this study was to evaluate long-term clinical outcomes and cost effectiveness of dexamethasone versus placebo. Patients included in the multicentre,

Adenovirus serotype 11 causes less long-term intraperitoneal inflammation than serotype 5: Implications for ovarian cancer therapy

International Nuclear Information System (INIS)

Thoma, Clemens; Bachy, Veronique; Seaton, Patricia; Green, Nicola K.; Greaves, David R.; Klavinskis, Linda; Seymour, Leonard W.; Morrison, Joanne

2013-01-01

In a phase II/III clinical trial intraperitoneal (i.p.) administration of a group C adenovirus vector (Ad5) caused bowel adhesion formation, perforation and obstruction. However, we had found that i.p. group B, in contrast to group C adenoviruses, did not cause adhesions in nude BALB/c ovarian cancer models, prompting further investigation. Ex vivo, group B Ad11 caused lower inflammatory responses than Ad5 on BALB/c peritoneal macrophages. In vivo, i.p. Ad11 triggered short-term cytokine and cellular responses equal to Ad5 in both human CD46-positive and -negative mice. In contrast, in a long-term study of repeated i.p. administration, Ad11 caused no/mild, whereas Ad5 induced moderate/severe adhesions and substantial liver toxicity accompanied by elevated levels of IFNγ and VEGF and loss of i.p. macrophages, regardless of CD46 expression. It appears that, although i.p. Ad11 evokes immediate inflammation similar to Ad5, repeated administration of Ad11 is better tolerated and long-term fibrotic tissue remodelling is reduced. - Highlights: • i.p. Ad11 causes less long-term intraperitoneal inflammation than Ad5 in CD46-transgenic mice. • Ex vivo BALB/c peritoneal macrophages express less RANTES after Ad11 than Ad3 or Ad5 treatment. • In vivo, cytokine and cellular responses 6 h after i.p. Ad11 are equal to Ad5. • In contrast, after repeated i.p. application, Ad5, but not Ad11, causes severe i.p. toxicity. • The use of Ad11 instead of Ad5 might increase patient safety in future virotherapy of ovarian cancer

Adenovirus serotype 11 causes less long-term intraperitoneal inflammation than serotype 5: Implications for ovarian cancer therapy

Energy Technology Data Exchange (ETDEWEB)

Thoma, Clemens, E-mail: c.thoma@oxfordalumni.org [Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU (United Kingdom); Bachy, Veronique [Peter Gorer Department of Immunobiology, Kings College London, Guys Hospital, Great Maze Pond, London SE1 9RT (United Kingdom); Seaton, Patricia [Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU (United Kingdom); Green, Nicola K. [Clinical Biomanufacturing Facility, University of Oxford, Old Road, Oxford OX3 7JT (United Kingdom); Greaves, David R. [Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE (United Kingdom); Klavinskis, Linda [Peter Gorer Department of Immunobiology, Kings College London, Guys Hospital, Great Maze Pond, London SE1 9RT (United Kingdom); Seymour, Leonard W. [Department of Oncology, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ (United Kingdom); Morrison, Joanne [Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU (United Kingdom); Department of Obstetrics and Gynaecology, Musgrove Park Hospital, Taunton TA1 5DA (United Kingdom)

2013-12-15

In a phase II/III clinical trial intraperitoneal (i.p.) administration of a group C adenovirus vector (Ad5) caused bowel adhesion formation, perforation and obstruction. However, we had found that i.p. group B, in contrast to group C adenoviruses, did not cause adhesions in nude BALB/c ovarian cancer models, prompting further investigation. Ex vivo, group B Ad11 caused lower inflammatory responses than Ad5 on BALB/c peritoneal macrophages. In vivo, i.p. Ad11 triggered short-term cytokine and cellular responses equal to Ad5 in both human CD46-positive and -negative mice. In contrast, in a long-term study of repeated i.p. administration, Ad11 caused no/mild, whereas Ad5 induced moderate/severe adhesions and substantial liver toxicity accompanied by elevated levels of IFNγ and VEGF and loss of i.p. macrophages, regardless of CD46 expression. It appears that, although i.p. Ad11 evokes immediate inflammation similar to Ad5, repeated administration of Ad11 is better tolerated and long-term fibrotic tissue remodelling is reduced. - Highlights: • i.p. Ad11 causes less long-term intraperitoneal inflammation than Ad5 in CD46-transgenic mice. • Ex vivo BALB/c peritoneal macrophages express less RANTES after Ad11 than Ad3 or Ad5 treatment. • In vivo, cytokine and cellular responses 6 h after i.p. Ad11 are equal to Ad5. • In contrast, after repeated i.p. application, Ad5, but not Ad11, causes severe i.p. toxicity. • The use of Ad11 instead of Ad5 might increase patient safety in future virotherapy of ovarian cancer.

rhEPO Enhances Cellular Anti-oxidant Capacity to Protect Long-Term Cultured Aging Primary Nerve Cells.

Science.gov (United States)

Wang, Huqing; Fan, Jiaxin; Chen, Mengyi; Yao, Qingling; Gao, Zhen; Zhang, Guilian; Wu, Haiqin; Yu, Xiaorui

2017-08-01

Erythropoietin (EPO) may protect the nervous system of animals against aging damage, making it a potential anti-aging drug for the nervous system. However, experimental evidence from natural aging nerve cell models is lacking, and the efficacy of EPO and underlying mechanism of this effect warrant further study. Thus, the present study used long-term cultured primary nerve cells to successfully mimic the natural aging process of nerve cells. Starting on the 11th day of culture, cells were treated with different concentrations of recombinant human erythropoietin (rhEPO). Using double immunofluorescence labeling, we found that rhEPO significantly improved the morphology of long-term cultured primary nerve cells and increased the total number of long-term cultured primary cells. However, rhEPO did not improve the ratio of nerve cells. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to measure nerve cell activity and showed that rhEPO significantly improved the activity of long-term cultured primary nerve cells. Moreover, Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double immunofluorescence labeling flow cytometry revealed that rhEPO reduced the apoptotic rate of long-term cultured primary nerve cells. Senescence-associated β-galactosidase (SA-β-gal) immunohistochemistry staining showed that rhEPO significantly reduced the aging rate of long-term cultured primary nerve cells. Immunochemistry revealed that rhEPO enhanced intracellular superoxide dismutase (SOD) activity and glutathione (GSH) abundance and reduced the intracellular malondialdehyde (MDA) level. In addition, this effect depended on the dose, was maximized at a dose of 100 U/ml and was more pronounced than that of vitamin E. In summary, this study finds that rhEPO protects long-term cultured primary nerve cells from aging in a dose-dependent manner. The mechanism of this effect may be associated with the enhancement of the intracellular anti

Pulmonary function changes in long-term survivors of bone marrow transplantation

International Nuclear Information System (INIS)

Gore, Elizabeth M.; Lawton, Colleen A.; Ash, Robert C.; Lipchik, Randolph J.

1996-01-01

Purpose: This study was undertaken to evaluate long-term pulmonary function changes in patients undergoing bone marrow transplantation (BMT), to assess their clinical significance, and to identify factors influencing these changes. Methods and Materials: Pulmonary function tests (PFT) were evaluated before and after BMT in 111 adult patients undergoing BMT between 1985 and 1991. Forced expiratory volume at 1 s (FEV 1 ), forced vital capacity (FVC), diffusing capacity (DLCO), and total lung capacity (TLC) were evaluated. One hundred and three patients (92.8%) received total body irradiation (TBI) to a total dose of 14 Gy in nine equal fractions. The lung dose was restricted to 1 , FVC, and TLC were lower than pre transplant values (p 1 did not fall significantly in patients without acute or chronic GVHD and recovered earlier than in patients without post transplant pulmonary infection. Recovery of FVC, TLC, and DLCO was also delayed in patients with acute and chronic GVHD and post transplant pulmonary infection. Multiple regression analysis revealed an association between a higher radiation dose to the lungs, and decreased FVC at 2 years (p = 0.01). Progressive obstructive pulmonary disease was not observed. Conclusions: An initial decline in PFTs with subsequent recovery was observed. Factors associated with delayed recovery and incomplete recovery of PFTs were GVHD, post transplant pulmonary infection, and higher radiation dose to the lungs. The conditioning regimen used at Medical College of Wisconsin, including relatively high TBI doses with partial transmission pulmonary shielding, appears to be well tolerated by the lungs in long-term survivors. No progressive decline in PFTs or symptomatic decline in pulmonary function was observed during the time interval studied

Long-term monitoring FBG-based cable load sensor

Science.gov (United States)

Zhang, Zhichun; Zhou, Zhi; Wang, Chuan; Ou, Jinping

2006-03-01

Stay cables are the main load-bearing components of stayed-cable bridges. The cables stress status is an important factor to the stayed-cable bridge structure safety evaluation. So it's very important not only to the bridge construction, but also to the long-term safety evaluation for the bridge structure in-service. The accurate measurement for cable load depends on an effective sensor, especially to meet the long time durability and measurement demand. FBG, for its great advantage of corrosion resistance, absolute measurement, high accuracy, electro-magnetic resistance, quasi-distribution sensing, absolute measurement and so on, is the most promising sensor, which can cater for the cable force monitoring. In this paper, a load sensor has been developed, which is made up of a bushing elastic supporting body, 4 FBGs uniformly-spaced attached outside of the bushing supporting body, and a temperature compensation FBG for other four FBGs, moreover a cover for protection of FBGs. Firstly, the sensor measuring principle is analyzed, and relationship equation of FBG wavelength shifts and extrinsic load has also been gotten. And then the sensor calibration experiments of a steel cable stretching test with the FBG load sensor and a reference electric pressure sensor is finished, and the results shows excellent linearity of extrinsic load and FBG wavelength shifts, and good repeatability, which indicates that such kind of FBG-based load sensor is suitable for load measurement, especially for long-term, real time monitoring of stay-cables.

The nucleic acid metabolism in rat liver after single and long-term administration of tritium oxide

International Nuclear Information System (INIS)

Shorokhova, V.B.

1984-01-01

It was shown that after a single administration of tritiUm oxide in a dose of 22.2 MBq/g body mass the liver mass increased, the concentration of nucleic acids decreased and the biosynthesjs rate increased dUring a one-month observation. By the end of the observation period (the first year) the parameters under study were normalized. The long-term administration of tritium oxide in daily doses of 0.37, 0.925 and 1.85 MBq/g body mass caused changes in the nucleac acid metabolism which were less manifest (at early times), than in the case of a single injection. At the same time, the long-term administration of tritium oxide in the dose of 0.925 MBq/g caused a substantial disturbance of the nucleic acid metabolism at later times (after 2-9 months)

Long-term accumulation and microdistribution of uranium in the bone and marrow of beagle dog.

Science.gov (United States)

Arruda-Neto, J D T; Manso Guevara, M V; Nogueira, G P; Taricano, I D; Saiki, M; Zamboni, C B; Bonamin, L V; Camargo, S P; Cestari, A C; Deppman, A; Garcia, F; Gouveia, A N; Guzman, F; Helene, O A M; Jorge, S A C; Likhachev, V P; Martins, M N; Mesa, J; Rodriguez, O; Vanin, V R

2004-08-01

The accumulation and microdistribution of uranium in the bone and marrow of Beagle dogs were determined by both neutron activation and neutron-fission analysis. The experiment started immediately after the weaning period, lasting till maturity. Two animal groups were fed daily with uranyl nitrate at concentrations of 20 and 100 microg g(-1) food. Of the two measuring techniques, uranium accumulated along the marrow as much as in the bone, contrary to the results obtained with single, acute doses. The role played by this finding for the evaluation of radiobiological long-term risks is discussed. It was demonstrated, by means of a biokinetical approach, that the long-term accumulation of uranium in bone and marrow could be described by a piling up of single dose daily incorporation.

Nucleic acid metabolism in hemopoietic tissues of polycythemic rats during long-term fractionated irradiation

International Nuclear Information System (INIS)

Mushkacheva, G.S.; Murzina, L.D.

1980-01-01

A study was made of the effect of long-term fractionated exposure with a daily dose of 50 R on the nucleic acid metabolism in hemopoietic tissues (bone marrow and spleen) of rats with erythropoiesis selectively inhibited by posttransfusion polycythemia. The comparison of present and previously obtained results enables us to conclude that the pathways of changes in the nucleic acid metabolism, which is responsible for hemopoiesis compensation during long-term exposure, are, in the main, similar for both white and red compartments of hemopoiesis

Long-term effects of 239Pu injection in adult, weanling, newborn and fetal rats

International Nuclear Information System (INIS)

Sikov, M.R.; Mahlum, D.D.; Hess, J.O.; Carr, D.B.

1979-01-01

We have completed biological evaluations comparing long-term effects in rats exposed to 239 Pu citrate as adults, weanlings, newborns, or late fetuses, and statistical analyses have been initiated. In rats exposed postnatally, statistically significant alterations in terminal body weight and in weights of several organs were found at higher doses. Survivorship decreased with increasing dose in the postnatal groups, but not in rats exposed prenatally

Long-term urethral catheterisation.

Science.gov (United States)

Turner, Bruce; Dickens, Nicola

This article discusses long-term urethral catheterisation, focusing on the relevant anatomy and physiology, indications for the procedure, catheter selection and catheter care. It is important that nurses have a good working knowledge of long-term catheterisation as the need for this intervention will increase with the rise in chronic health conditions and the ageing population.

Long-term outcomes of percutaneous lumbar facet synovial cyst rupture

Energy Technology Data Exchange (ETDEWEB)

Huang, Ambrose J.; Bos, Stijn A.; Torriani, Martin; Simeone, F.J.; Chang, Connie Y.; Pomerantz, Stuart R.; Bredella, Miriam A. [Massachusetts General Hospital and Harvard Medical School, Department of Radiology, Boston, MA (United States)

2017-01-15

To evaluate the therapeutic value, safety, and long-term clinical outcomes of percutaneous lumbar facet synovial cyst (LFSC) rupture. Our study was institutional review board (IRB)-approved and Health Insurance Portability and Accountability Act (HIPAA)-compliant. The study group comprised 71 patients (44 women, mean age: 65 ± 17 years) who underwent CT- or fluoroscopy-guided percutaneous LFSC rupture. The technical success of LFSC rupture, the long-term clinical outcome, including repeat procedures or surgery, and imaging findings on MRI and CT were recorded. Seventy-nine LFSC ruptures were performed in 71 patients. CT guidance was used in 57 cases and fluoroscopy guidance in 22 cases. LFSC rupture was technically successful in 58 out of 79 cases (73 %). Mean injection volume for cyst rupture was 3.6 ± 2.2 mL and a combination of steroid and anesthetic was injected in all cases. Over a mean follow-up time of 44 months, 12 % of patients underwent repeat cyst rupture, and 46 % eventually underwent surgery, whereas the majority of patients (55 %) experienced symptomatic relief and did not undergo surgery. There was no significant association between a successful outcome and age, sex, level, or size of LFSC (p > 0.1). LFSCs with T2 hypointensity were more likely to require surgery (p = 0.02). There was one complication, a bacterial skin infection that completely resolved following antibiotic therapy. Percutaneous LFSC rupture is an effective and safe nonsurgical treatment option for LFSC. More than half of treated patients were able to avoid subsequent surgery. Therefore, percutaneous LFSC rupture should be considered before surgical intervention. (orig.)

Decreasing Trend in the Use and Long-Term Use of Benzodiazepines Among Young Adults.

Science.gov (United States)

Tähkäpää, Sanna-Mari; Saastamoinen, Leena; Airaksinen, Marja; Tuulio-Henriksson, Annamari; Aalto-Setälä, Terhi; Kurko, Terhi

2018-03-14

Patterns of benzodiazepine (BZD) use and long-term use among young adults are not well known. Our aim was to study trends in BZD use and long-term use among 18-25-year-old young adults by gender and active substance in a nationwide retrospective longitudinal register-based setting. All Finns aged 18-25 years with reimbursed purchases of BZDs in 2006-2014 recorded to the Finnish Prescription Register were included. Annual prevalence rates of BZD use and long-term use among young adults were reported overall, according to gender, drug group (anxiolytic or hypnotic), and active substance. Long-term use of BZDs was defined as purchasing ≥180 Defined Daily Doses (DDDs) in at least two drug purchases during a calendar year. Overall prevalence of BZD use among young adults decreased from 24.0 to 18.8 users per 1000 inhabitants in 2006-2014. Prevalence of long-term use decreased from 5.5 to 3.3 users per 1000 inhabitants. Overall BZD use was higher among females, whereas long-term use was more common among males. Use of anxiolytics was more common than use of hypnotics. Oxazepam, alprazolam, zopiclone, and zolpidem were the most used BZDs, whereas alprazolam and clonazepam were the substances with most long-term use. The use and long-term use of BZDs have decreased annually since 2008 among Finnish young adults. Further research is needed to investigate the reasons behind the decline.

Long-term visual changes following pituitary irradiation

International Nuclear Information System (INIS)

Movsas, Benjamin; Movsas, Tammy Z.; Steinberg, Seth M.; Okunieff, Paul

1995-01-01

Purpose: To analyze possible long-term effects of pituitary irradiation on visual fields and acuity. Methods and Materials: Eighty-six patients were treated with radiotherapy for pituitary tumors at the National Cancer Institute between 1980 and 1991. Twenty-one patients had baseline preradiation and long-term follow-up visual fields. Eyes were followed with serial Goldmann or Humphrey visual field testing. Neuroradiologic correlation was made with the available brain scans. There were 12 females and 9 males with an median age of 44. Eighteen patients had hormone-secreting tumors and three had chromophobe adenomas. All but one patient with an inoperable invasive macroadenoma were irradiated after one or more transphenoidal resections or a craniotomy. The indications for radiation in the operable patients were: nine patients, partial tumor resection; nine patients, tumor recurrence; and two patients, persistent hormonal elevation after surgery. The median dose delivered was 50 Gy (45-59.4 Gy). The average field size was 6 x 6 cm (5 x 5 cm to 10 x 12.5 cm). Results: With a median follow-up of 48 months (14-128) after radiotherapy, 1 out of 21 patients has recurred (at 8 months) and all patients are alive. Of the 38 sighted eyes, 27 had normal visual fields before and after radiation, 7 eyes showed improvement, and 4 eyes had a stable defect, mostly in the superior temporal region. There were no cases of radiation-induced visual field or acuity deterioration. Six out of 21 patients (29%) had neurologic symptoms in follow-up, most of which appeared vascular in nature. Four patients complained of atypical migranous-like headaches that first began 1.5-3 years following treatment. One patient complained of recurrent vertical diplopia and one patient had a cerebral vascular accident 7 years following therapy. A dose-related association with these neurovascular symptoms approached statistical significance. Only 1 out of 11 (9%) patients who received doses less than or equal

Carbohydrate metabolism during long-term growth hormone (GH) treatment and after discontinuation of GH treatment in girls with Turner syndrome participating in a randomized dose-response study. Dutch Advisory Group on Growth Hormone

NARCIS (Netherlands)

T.C.J. Sas (Theo); S.M.P.F. de Muinck Keizer-Schrama (Sabine); Th. Stijnen (Theo); H-J. Aanstoot (Henk-Jan); S.L.S. Drop (Stenvert)

2000-01-01

textabstractTo assess possible side-effects of GH treatment with supraphysiological doses on carbohydrate (CH) metabolism in girls with Turner syndrome (TS) during long term GH treatment and after discontinuation of GH treatment, the results of oral glucose tolerance

Cancer risk in long-term users of valproate: a population-based case-control study

DEFF Research Database (Denmark)

Hallas, Jesper; Friis, Søren; Bjerrum, Lars

2009-01-01

logistic regression. RESULTS: Among the cases and controls, 81 (0.05%) and 260 (0.04%), respectively, were long-term users of valproate. For cancer overall, the crude and adjusted odds ratios were 1.25 [95% confidence interval (95% CI), 0.97-1.60] and 1.21 (95% CI, 0.95-1.56), respectively. Subgroup...... analyses revealed no dose or duration effect for overall cancer incidence, and no specific cancer site was found to be inversely associated with long-term use of valproate. For lung cancer, we found a positive but imprecise association (adjusted odds ratio, 2.32; 95% CI, 1.12-4.79). CONCLUSION: Long...

Long-Term Quality of Life Improvement in Subjects with Healed Erosive Esophagitis: Treatment with Lansoprazole

Science.gov (United States)

Freston, James W.; Haber, Marian M.; Atkinson, Stuart; Hunt, Barbara; Peura, David A.

2009-01-01

Background Gastroesophageal reflux disease (GERD) is a chronic symptomatic condition and may be associated with erosive esophagitis (EE). Considerable data on the long-term maintenance of healing of EE are available, but data on long-term GERD symptom prevention and patient quality of life (QOL) are limited. Aims To investigate QOL in subjects with healed EE who received 12 months of double-blind maintenance treatment with lansoprazole or ranitidine, followed by long-term open-label lansoprazole therapy to prevent recurrence of EE. Methods Subjects with healed EE received 12 months of double-blind maintenance treatment with lansoprazole 15 mg once daily or ranitidine 150 mg twice daily, followed by dose-titrated, open-label lansoprazole therapy for up to 82 months. Results During double-blind treatment (n = 206), lansoprazole-treated patients showed significantly (P ≤ 0.05) greater improvements than ranitidine-treated patients in the frequency, severity, and ‘bothersomeness’ of heartburn, the symptom index, problems of activity limitation, eating and drinking problems, symptom problems, health distress, and social functioning. During dose-titrated, open-label treatment (n = 195), all disease-specific QOL scales except sleep improved significantly (P lansoprazole for 12 months in healed EE subjects produced significantly greater improvements in QOL indicators than ranitidine. These improvements were sustained during dose-titrated, open-label lansoprazole treatment. PMID:19582579

SOIL AGROCHEMICAL PROPERTIES IMPROVEMENT IN LONG TERM FIELD EXPERIMENT WITH FERTILIZERS

Directory of Open Access Journals (Sweden)

Mihaela Lungu

2005-10-01

Full Text Available Soil fertility is studied in long-term field experiments. Researches are carried out in several agricultural research stations, out of which the following have been chosen for the present paper: Albic Luvisol* at Albota; Haplic Phaeozem at Fundulea; Chromic Luvisol at Şimnic; Calcic Chernozem at Secuieni; and Haplic Chernozem at Podu Iloaiei. Long term fertilization with nitrogen and phosphorus generally improved the soil agrochemical properties. The evolution of organic matter, nitrogen, mobile phosphorus and potassium, and mobile microelements contents were studied, using the standardized method used in the ICPA laboratories. The organic matter and total nitrogen contents didn’t change significantly under the nitrogen and phosphorus long-term fertilization influence. The mobile phosphorus contents have the tendency to grow very significantly with the growth of phosphorus fertilizers. At the same time, slight depletions of these contents are registered as the high nitrogen doses from fertilizers stimulate plant growth and, obviously, nutritive elements absorption. Mobile potassium contents changes very little, with insignificant differences. Significant depletions are registered only with high fertilizers doses, due to the stimulation of the nutritive elements absorption in plants. Microelements contents don’t change almost at all. They are within the normal content limits and no excess or deficiency was registered, in any of the studied stations. For the agricultural practice, economical studies are recommended, about how high fertilizing expenses are covered by the yield growth. Not the least, production quality study in different variants of mineral fertilization could prove interesting.

Cognitive enhancement and antipsychotic-like activity following repeated dosing with the selective M4 PAM VU0467154.

Science.gov (United States)

Gould, Robert W; Grannan, Michael D; Gunter, Barak W; Ball, Jacob; Bubser, Michael; Bridges, Thomas M; Wess, Jurgen; Wood, Michael W; Brandon, Nicholas J; Duggan, Mark E; Niswender, Colleen M; Lindsley, Craig W; Conn, P Jeffrey; Jones, Carrie K

2018-01-01

Although selective activation of the M 1 muscarinic acetylcholine receptor (mAChR) subtype has been shown to improve cognitive function in animal models of neuropsychiatric disorders, recent evidence suggests that enhancing M 4 mAChR function can also improve memory performance. Positive allosteric modulators (PAMs) targeting the M 4 mAChR subtype have shown therapeutic potential for the treatment of multiple symptoms observed in schizophrenia, including positive and cognitive symptoms when assessed in acute preclinical dosing paradigms. Since the cholinergic system has been implicated in multiple stages of learning and memory, we evaluated the effects of repeated dosing with the highly selective M 4 PAM VU0467154 on either acquisition and/or consolidation of learning and memory when dosed alone or after pharmacologic challenge with the N-methyl-d-aspartate subtype of glutamate receptors (NMDAR) antagonist MK-801. MK-801 challenge represents a well-documented preclinical model of NMDAR hypofunction that is thought to underlie some of the positive and cognitive symptoms observed in schizophrenia. In wildtype mice, 10-day, once-daily dosing of VU0467154 either prior to, or immediately after daily testing enhanced the rate of learning in a touchscreen visual pairwise discrimination task; these effects were absent in M 4 mAChR knockout mice. Following a similar 10-day, once-daily dosing regimen of VU0467154, we also observed 1) improved acquisition of memory in a cue-mediated conditioned freezing paradigm, 2) attenuation of MK-801-induced disruptions in the acquisition of memory in a context-mediated conditioned freezing paradigm and 3) reversal of MK-801-induced hyperlocomotion. Comparable efficacy and plasma and brain concentrations of VU0467154 were observed after repeated dosing as those previously reported with an acute, single dose administration of this M 4 PAM. Together, these studies are the first to demonstrate that cognitive enhancing and antipsychotic

Long-term associative learning predicts verbal short-term memory performance.

Science.gov (United States)

Jones, Gary; Macken, Bill

2018-02-01

Studies using tests such as digit span and nonword repetition have implicated short-term memory across a range of developmental domains. Such tests ostensibly assess specialized processes for the short-term manipulation and maintenance of information that are often argued to enable long-term learning. However, there is considerable evidence for an influence of long-term linguistic learning on performance in short-term memory tasks that brings into question the role of a specialized short-term memory system separate from long-term knowledge. Using natural language corpora, we show experimentally and computationally that performance on three widely used measures of short-term memory (digit span, nonword repetition, and sentence recall) can be predicted from simple associative learning operating on the linguistic environment to which a typical child may have been exposed. The findings support the broad view that short-term verbal memory performance reflects the application of long-term language knowledge to the experimental setting.

Cognitive outcome in adolescents and young adults after repeat courses of antenatal corticosteroids.

Science.gov (United States)

Stålnacke, Johanna; Diaz Heijtz, Rochellys; Norberg, Hanna; Norman, Mikael; Smedler, Ann-Charlotte; Forssberg, Hans

2013-08-01

To investigate whether repeat courses of antenatal corticosteroids have long-term effects on cognitive and psychological functioning. In a prospective cohort study, 58 adolescents and young adults (36 males) who had been exposed to 2-9 weekly courses of betamethasone in utero were assessed with neuropsychological tests and behavior self-reports. Unexposed subjects (n = 44, 25 males) matched for age, sex, and gestational age at birth served as a comparison group. In addition, individuals exposed in utero to a single course (n = 25, 14 males) were included for dose-response analysis. Group differences were investigated using multilevel linear modeling. Mean scores obtained in 2 measures of attention and speed were significantly lower in subjects exposed to 2 or more antenatal corticosteroids courses (Symbol Search, P = .009; Digit Span Forward, P = .02), but these were not dose-dependent. Exposure to repeat courses of antenatal corticosteroids was not associated with general deficits in higher cognitive functions, self-reported attention, adaptability, or overall psychological function. Although this study indicates that repeat exposure to antenatal corticosteroids may have an impact on aspects of executive functioning, it does not provide support for the prevailing concern that such fetal exposure will have a major adverse impact on cognitive functions and psychological health later in life. Copyright © 2013 Mosby, Inc. All rights reserved.

Long-term effects of x-ray irradiation on reproductive function in male rats

International Nuclear Information System (INIS)

Varga, S.V.; Demchenko, V.N.; Chajkovskaya, L.V.; Reznikov, A.G.

1994-01-01

Reproductive function in male rats was studied in 1, 3 and 6 months after x-ray irradiation at doses of 2 and 3 Gy. It was been established that long-term effects of irradiation at a dose of 3 Gy are manifested through decrease in spermatozoa content in the epididymis and reduction of nucleie acid and protein content in the testes. Fertility of male rats under study significantly lowered shortly after irradiation and full recovery of fecundating ability was observed 6 months later. The effect of irradiation with a dose of 2 Gy was less pronounced

Intraindividual Variability and Long-Term Changes of Thermal Quantitative Sensory Testing

DEFF Research Database (Denmark)

Krøigård, Thomas; Sothynathan, Isaivani; Sindrup, Søren H

2015-01-01

Thermal threshold examinations are widely used in the clinical setting and in studies to assess the function of the peripheral sensory nervous system. Little is known about the variation from one side of the body to the other and the long-term temporal changes and variability. In this study, 134...... and foot. Bilateral stimulations resulted in relative intertrial variations ranging from 19% to 40%. There was no significant temporal change for repeated measures. Analysis of the individual measurements of each subject at baseline and at 26 weeks, however, resulted in relatively large intertrial...

Changes in heart rate variability are associated with expression of short-term and long-term contextual and cued fear memories.

Directory of Open Access Journals (Sweden)

Jun Liu

Full Text Available Heart physiology is a highly useful indicator for measuring not only physical states, but also emotional changes in animals. Yet changes of heart rate variability during fear conditioning have not been systematically studied in mice. Here, we investigated changes in heart rate and heart rate variability in both short-term and long-term contextual and cued fear conditioning. We found that while fear conditioning could increase heart rate, the most significant change was the reduction in heart rate variability which could be further divided into two distinct stages: a highly rhythmic phase (stage-I and a more variable phase (stage-II. We showed that the time duration of the stage-I rhythmic phase were sensitive enough to reflect the transition from short-term to long-term fear memories. Moreover, it could also detect fear extinction effect during the repeated tone recall. These results suggest that heart rate variability is a valuable physiological indicator for sensitively measuring the consolidation and expression of fear memories in mice.

Long-term safety of the maintenance and decommissioning waste of the encapsulation plant

International Nuclear Information System (INIS)

Nummi, O.; Kylloenen, J.; Eurajoki, T.

2012-12-01

This report, Long-term safety of the maintenance and decommissioning waste of the encapsulation plant, presents the disposal concept for the low and intermediate level waste (L/ILW) that is generated during the operation and decommissioning of the encapsulation plant, and assesses the long-term safety of the disposal of the waste. Radioactive waste originates from the spent nuclear fuel transferred and dried in the encapsulation plant. Radioactive waste accumulates also in the maintenance of the components and systems of the encapsulation plant. The waste is collected, exempted from control if possible and treated for final disposal if necessary. The waste is disposed of in the L/ILW hall which is currently planned to be located at a depth of -180 meters along the access tunnel to the repository for spent fuel. The main engineered barrier in the L/ILW hall is a concrete basin that encases the dried liquid waste. The safety concept of L/ILW disposal is based on the slow release of radioactivity from the L/ILW hall and its limited transport through the bedrock into biosphere. The release and transport of the radioactivity is described by the assessment scenarios, which include expected evolution and unlikely events affecting the long-term safety. The scenarios act as guidelines according to which the conceptual and mathematical models are formed. The long-term safety of the L/ILW hall is assessed using deterministic and probabilistic modeling. Special issues such as human intrusion and radiation effects on other biota are also assessed. The most significant contributor to the dose rates is the short-lived radionuclide 90 Sr followed by long-lived nuclides 129 I and 108 mAg. The annual doses to the public, and release rates of radioactive substances stay below the regulatory constraints in all analyzed scenarios. (orig.)

Long-term outcome of lobar ablation in differentiated thyroid cancer (DTC): a comparative study with patients of completion thyroidectomy

International Nuclear Information System (INIS)

Santra, Amburanjan; Maharjan, S.; Bal, C.

2010-01-01

Full text: Completion thyroidectomy (CT) is usually recommended after partial surgery in patients with differentiated thyroid cancer. Radioiodine lobar ablation (RAILA) is an easy alternative and avoids complications that might be associated with re-surgery. But its effectiveness in terms of long-term outcome and recurrence free survival is yet to be established. This study was aimed to compare long term outcome of RAILA with that of completion thyroidectomy. Materials and Methods: A retrospective analysis was done from the case records of patients treated in our thyroid clinic for last 25 years. Records of all patients of RAILA (364) and CT (372) were analyzed. Complete ablation rate, cumulative dose needed for complete ablation, Recurrence rate and recurrence free survival was estimated in each group. Comparison was made between two groups by statistical method. Results: There was 73% ablation rate at 1st dose of RAILA itself. Second dose in LA and first dose of remnant ablation after CT is comparable (92% and 93% respectively). Cumulative dose to achieve 100% ablation rate is more for RAILA group. Seven patients developed recurrence in RAILA group, compared to 14 in CT group. No statistically significant difference was noted between recurrence rate and recurrence free survival between two groups. Conclusion: Radioiodine Lobar ablation is a safe, effective and less costly alternative to completion thyroidectomy in patients with differentiated thyroid cancer with comparable long term outcome like recurrence rate and recurrence free survival

Long-term, regular remote ischemic preconditioning improves endothelial function in patients with coronary heart disease

Energy Technology Data Exchange (ETDEWEB)

Liang, Y.; Li, Y.P.; He, F.; Liu, X.Q.; Zhang, J.Y. [Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China)

2015-04-28

Remote ischemic preconditioning (RIPre) can prevent myocardial injury. The purpose of this study was to assess the beneficial effects of long-term regular RIPre on human arteries. Forty patients scheduled for coronary artery bypass graft (CABG) surgery were assigned randomly to a RIPre group (n=20) or coronary heart disease (CHD) group (n=20). Twenty patients scheduled for mastectomy were enrolled as a control group. RIPre was achieved by occluding arterial blood flow 5 min with a mercury sphygmomanometer followed by a 5-min reperfusion period, and this was repeated 4 times. The RIPre procedure was repeated 3 times a day for 20 days. In all patients, arterial fragments discarded during surgery were collected to evaluate endothelial function by flow-mediated dilation (FMD), CD34{sup +} monocyte count, and endothelial nitric oxide synthase (eNOS expression). Phosphorylation levels of STAT-3 and Akt were also assayed to explore the underlying mechanisms. Compared with the CHD group, long-term regular RIPre significantly improved FMD after 20 days (8.5±2.4 vs 4.9±4.2%, P<0.05) and significantly reduced troponin after CABG surgery (0.72±0.31 and 1.64±0.19, P<0.05). RIPre activated STAT-3 and increased CD34{sup +} endothelial progenitor cell counts found in arteries. Long-term, regular RIPre improved endothelial function in patients with CHD, possibly due to STAT-3 activation, and this may have led to an increase in endothelial progenitor cells.

The Effect of Zinc Supplementation of Lactating Rats on Short-Term and Long-Term Memory of Their Male Offspring

Directory of Open Access Journals (Sweden)

Mohammad Karami

2013-12-01

Full Text Available Background: In this study the effect of zinc chloride (ZnCl2 administration on the short-term and long-term memory of rats were assessed. Methods: We enrolled six groups of adult female and control group of eight Wistar rats in each group. One group was control group with free access to food and water, and five groups drunk zinc chloride in different doses (20, 30, 50, 70 and 100 mg/kg/day in drinking water for two weeks during lactation .One month after birth, a shuttle box used to short- term and long-term memory and the latency in entering the dark chamber as well. Results: This experiment showed that maternal 70 mg/kg dietary zinc during lactation influenced the working memory of rats’ offspring in all groups. Rats received 100 mg/kg/day zinc during lactation so they had significant impairment in working memory (short-term of their offspring (P<0.05. There was no significant difference in reference (long-term memory of all groups. Conclusion: Drug consumption below70 mg/kg/day zinc chloride during lactation had no effect. While enhanced 100 mg/ kg/ day zinc in lactating rats could cause short-term memory impairment.

Intravenous paracetamol with a lower dose is also effective for the treatment of patent ductus arteriosus in pre-term infants.

Science.gov (United States)

Tekgündüz, Kadir Şerafettin; Ceviz, Naci; Caner, İbrahim; Olgun, Haşim; Demirelli, Yaşar; Yolcu, Canan; Şahin, İrfan Oğuz; Kara, Mustafa

2015-08-01

Haemodynamically significant patent ductus arteriosus is a significant cause of morbidity and mortality in pre-term infants. This retrospective study was conducted to investigate the usefulness of lower-dose paracetamol for the treatment of patent ductus arteriosus in pre-term infants. A total of 13 pre-term infants who received intravenous paracetamol because of contrindications or side effects to oral ibuprofen were retrospectively enrolled. In the first patient, the dose regimen was 15 mg/kg/dose, every 6 hours. As the patient developed significant elevation in transaminase levels, the dose was decreased to 10 mg/kg/dose, every 8 hours in the following 12 patients. Echocardiographic examination was conducted daily. In case of closure, it was repeated after 2 days and when needed thereafter in terms of reopening. A total of 13 patients received intravenous paracetamol. Median gestational age was 29 weeks ranging from 24 to 31 weeks and birth weight was 950 g ranging from 470 to 1390 g. The median postnatal age at the first intravenous paracetamol dose was 3 days ranging from 2 to 9 days. In 10 of the 13 patients (76.9%), patent ductus arteriosus was closed at the median 2nd day of intravenous paracetamol ranging from 1 to 4 days. When the patient who developed hepatotoxicity was eliminated, the closure rate was found to be 83.3% (10/12). Intravenous paracetamol may be a useful treatment option for the treatment of patent ductus arteriosus in pre-term infants with contrindication to ibuprofen. In our experience, lower-dose paracetamol is effective in closing the patent ductus arteriosus in 83.3% of the cases.

Long-term management of chronic spontaneous urticaria with omalizumab.

Science.gov (United States)

Pinto Gouveia, M; Gameiro, A; Pinho, A; Gonçalo, M

2017-10-01

Clinical trials have shown the efficacy of omalizumabs efficacy in refractory chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU), but real-life management strategies are lacking. To assess the long-term efficacy and safety of omalizumab, and to identify predictive factors and optimum dosage regimens. This was a prospective study of 13 patients (11 women, 2 men) with severe CSU [weekly urticaria activity score (UAS7) > 28] resistant to anti-H1 antihistamines. Patients were started on omalizumab 150 mg subcutaneously every 4 weeks. Dose and interval between administrations were adjusted according to clinical response (189 administrations; treatment duration range 2-38 months). Mean UAS7 was 36.3 ± 5.4. Of the 13 patients, all had experienced angio-oedema, while in addition, 7 had delayed pressure urticaria (DPU) and 1 had solar urticaria (SU). After omalizumab treatment, 4 (30.8%) of the 13 patients had complete response (CR), and the remaining 8 (61.5%) had partial response. CR was achieved with a dose of 150 mg every 4 (n = 2 patients) or 5 (n = 2) weeks. One of these patients remained disease-free after stopping treatment. Partial responses were achieved with 150 mg every 4 weeks (n = 4) and with 300 mg (n = 4) at intervals of 5 weeks (n = 1), 4 weeks (n = 2) or 3 weeks (n = 1). Only one patient (7.7%) did not show significant improvement, despite a dose of 300 mg every 4 weeks. There were no significant differences in epidemiological, clinical and laboratory data between the different response groups. Only two adverse events were observed: one was mild headache and the other was severe angio-oedema and aggravation of urticaria within 6 h of omalizumab administration. Omalizumab dose and interval between administrations could be individualized for long-term management of CSU. © 2017 British Association of Dermatologists.

Neurotoxicity of low-dose repeatedly intranasal instillation of nano- and submicron-sized ferric oxide particles in mice

Energy Technology Data Exchange (ETDEWEB)

Wang Bing; Feng Weiyue, E-mail: fengwy@mail.ihep.ac.cn; Zhu Motao; Wang Yun; Wang Meng [Chinese Academy of Sciences, Laboratory for Bio-Environmental Effects of Nanomaterials and Nanosafety and Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics (China); Gu Yiqun [Maternity Hospital of Haidian District (China); Ouyang Hong; Wang Huajian; Li Ming; Zhao Yuliang, E-mail: zhaoyuliang@mail.ihep.ac.cn; Chai Zhifang [Chinese Academy of Sciences, Laboratory for Bio-Environmental Effects of Nanomaterials and Nanosafety and Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics (China); Wang Haifang [Peking University, College of Chemistry and Molecular Engineering (China)

2009-01-15

larger particle did. This is the first study to compare the neurotoxicity of nano- and submicron-sized Fe{sub 2}O{sub 3} particles in the central nervous system after long-term and low-dose intranasal exposure.

Long-Term Single-Dose Efficacy of a Vesicular Stomatitis Virus-Based Andes Virus Vaccine in Syrian Hamsters

Directory of Open Access Journals (Sweden)

Joseph Prescott

2014-01-01

Full Text Available Andes virus (ANDV is highly pathogenic in humans and is the primary etiologic agent of hantavirus cardiopulmonary syndrome (HCPS in South America. Case-fatality rates are as high as 50% and there are no approved vaccines or specific therapies for infection. Our laboratory has recently developed a replication-competent recombinant vesicular stomatitis virus (VSV-based vaccine that expressed the glycoproteins of Andes virus in place of the native VSV glycoprotein (G. This vaccine is highly efficacious in the Syrian hamster model of HCPS when given 28 days before challenge with ANDV, or when given around the time of challenge (peri-exposure, and even protects when administered post-exposure. Herein, we sought to test the durability of the immune response to a single dose of this vaccine in Syrian hamsters. This vaccine was efficacious in hamsters challenged intranasally with ANDV 6 months after vaccination (p = 0.025, but animals were not significantly protected following 1 year of vaccination (p = 0.090. The decrease in protection correlated with a reduction of measurable neutralizing antibody responses, and suggests that a more robust vaccination schedule might be required to provide long-term immunity.

Safety after extended repeated use of ulipristal acetate for uterine fibroids

DEFF Research Database (Denmark)

Fauser, Bart C J M; Donnez, Jacques; Bouchard, Philippe

2017-01-01

OBJECTIVE: To assess long term safety of extended repeated 3-month courses of ulipristal acetate (UPA) 10 mg/day, for up to 8 courses, with focus on endometrial and laboratory safety parameters. METHODS: This long-term, multi-center, open-label cohort, follow up study consisted of up to 8 consecu...

Mild Concussion, but Not Moderate Traumatic Brain Injury, Is Associated with Long-Term Depression-Like Phenotype in Mice.

Directory of Open Access Journals (Sweden)

Nikita M Bajwa

Full Text Available Mild traumatic brain injuries can lead to long-lasting cognitive and motor deficits, increasing the risk of future behavioral, neurological, and affective disorders. Our study focused on long-term behavioral deficits after repeated injury in which mice received either a single mild CHI (mCHI, a repeated mild CHI (rmCHI consisting of one impact to each hemisphere separated by 3 days, or a moderate controlled cortical impact injury (CCI. Shams received only anesthesia. Behavioral tests were administered at 1, 3, 5, 7, and 90 days post-injury (dpi. CCI animals showed significant motor and sensory deficits in the early (1-7 dpi and long-term (90 dpi stages of testing. Interestingly, sensory and subtle motor deficits in rmCHI animals were found at 90 dpi. Most importantly, depression-like behaviors and social passiveness were observed in rmCHI animals at 90 dpi. These data suggest that mild concussive injuries lead to motor and sensory deficits and affective disorders that are not observed after moderate TBI.

Long-term efficacy of a mini-course in radiation-reducing techniques in invasive cardiology

International Nuclear Information System (INIS)

Kuon, E.; Empen, K.; Hummel, A.; Doerr, M.; Reffelmann, T.; Felix, S.B.; Weitmann, K.; Hoffmann, W.; Staudt, A.

2013-01-01

Purpose: To validate the long-term efficacy of a 90-min. educational mini-course in less-irradiating cardiac interventional techniques. Materials and Methods: Before, two months after, and two years after the mini-course (periods I, II, and III), we analyzed the following radiation dose parameters for ten coronary angiographies (CA), performed by each of 7 cardiologists: total dose-area product (DAP), radiographic and fluoroscopic DAP fractions, number of radiographic frames and runs, and fluoroscopy time. Results: The median patient DAP for periods I, II and III was 31.4, 15.8 and 8.5 Gy x cm 2 , respectively. The long-term effect was related to shorter median fluoroscopy times (180, 172, and 120 s), shorter (57, 52, and 45) and fewer (12, 12, and 10) radiographic runs, consistent collimation and restriction to an adequate image quality. Both radiographic DAP/frame (28.7, 17.0, and 18.4 mGy x cm 2 ) and fluoroscopic DAP/second (45.7, 24.2, and 10.0 mGy x cm 2 ) decreased significantly. The multivariate linear regression analysis confirmed the increasing efficacy of the mini-course itself (-44.6 and -60.7 %), and revealed a decreasing influence of the interventionalist's experience (-8.6 % and -4.9 % per 1,000 CAs, lifelong performed until the mini-course). The number of CAs performed after the mini-course did not influence the long-term DAP results. Conclusion: The presented educational mini-course allows a significant, long-lasting, and apparently ongoing reduction of patient radiation exposure due to CA. A self-surveillant documentation of relevant radiation parameters is well suited to monitor and improve each operator's individual long-term radiation-reducing efforts. (orig.)

Radiotherapy for pituitary adenomas: long-term outcome and complications

Energy Technology Data Exchange (ETDEWEB)

Rim, Chai Hong; Yang, Dae Sik; Park, Young Je; Yoon, Won Sup; Lee, Jung AE; Kim, Chul Yong [Korea University Medical Center, Seoul (Korea, Republic of)

2011-09-15

To evaluate long-term local control rate and toxicity in patients treated with external beam radiotherapy (EBRT) for pituitary adenomas. We retrospectively reviewed the medical records of 60 patients treated with EBRT for pituitary adenoma at Korea University Medical Center from 1996 and 2006. Thirty-fi ve patients had hormone secreting tumors, 25 patients had non-secreting tumors. Fifty-seven patients had received postoperative radiotherapy (RT), and 3 had received RT alone. Median total dose was 54 Gy (range, 36 to 61.2 Gy). The definition of tumor progression were as follows: evidence of tumor progression on computed tomography or magnetic resonance imaging, worsening of clinical sign requiring additional operation or others, rising serum hormone level against a previously stable or falling value, and failure of controlling serum hormone level so that the hormone level had been far from optimal range until last follow-up. Age, sex, hormone secretion, tumor extension, tumor size, and radiation dose were analyzed for prognostic significance in tumor control. Median follow-up was 5.7 years (range, 2 to 14.4 years). The 10-year actuarial local control rates for non-secreting and secreting adenomas were 96% and 66%, respectively. In univariate analysis, hormone secretion was significant prognostic factor (p = 0.042) and cavernous sinus extension was marginally significant factor (p = 0.054) for adverse local control. All other factors were not significant. In multivariate analysis, hormone secretion and gender were significant. Fifty-three patients had mass-effect symptoms (headache, dizziness, visual disturbance, hypopituitarism, loss of consciousness, and cranial nerve palsy). A total of 17 of 23 patients with headache and 27 of 34 patients with visual impairment were improved. Twenty-seven patients experienced symptoms of endocrine hypersecretion (galactorrhea, amenorrhea, irregular menstruation, decreased libido, gynecomastia, acromegaly, and Cushing

Radiotherapy for pituitary adenomas: long-term outcome and complications

International Nuclear Information System (INIS)

Rim, Chai Hong; Yang, Dae Sik; Park, Young Je; Yoon, Won Sup; Lee, Jung AE; Kim, Chul Yong

2011-01-01

To evaluate long-term local control rate and toxicity in patients treated with external beam radiotherapy (EBRT) for pituitary adenomas. We retrospectively reviewed the medical records of 60 patients treated with EBRT for pituitary adenoma at Korea University Medical Center from 1996 and 2006. Thirty-fi ve patients had hormone secreting tumors, 25 patients had non-secreting tumors. Fifty-seven patients had received postoperative radiotherapy (RT), and 3 had received RT alone. Median total dose was 54 Gy (range, 36 to 61.2 Gy). The definition of tumor progression were as follows: evidence of tumor progression on computed tomography or magnetic resonance imaging, worsening of clinical sign requiring additional operation or others, rising serum hormone level against a previously stable or falling value, and failure of controlling serum hormone level so that the hormone level had been far from optimal range until last follow-up. Age, sex, hormone secretion, tumor extension, tumor size, and radiation dose were analyzed for prognostic significance in tumor control. Median follow-up was 5.7 years (range, 2 to 14.4 years). The 10-year actuarial local control rates for non-secreting and secreting adenomas were 96% and 66%, respectively. In univariate analysis, hormone secretion was significant prognostic factor (p = 0.042) and cavernous sinus extension was marginally significant factor (p = 0.054) for adverse local control. All other factors were not significant. In multivariate analysis, hormone secretion and gender were significant. Fifty-three patients had mass-effect symptoms (headache, dizziness, visual disturbance, hypopituitarism, loss of consciousness, and cranial nerve palsy). A total of 17 of 23 patients with headache and 27 of 34 patients with visual impairment were improved. Twenty-seven patients experienced symptoms of endocrine hypersecretion (galactorrhea, amenorrhea, irregular menstruation, decreased libido, gynecomastia, acromegaly, and Cushing's disease

Long-term benefit of sunitinib in patients with metastatic renal cell carcinoma in Latin America: retrospective analysis of patient clinical characteristics

Directory of Open Access Journals (Sweden)

Smaletz O

2016-11-01

Full Text Available Oren Smaletz,1 Matias Chacón,2 Ludmila de Oliveira Koch,1 Daniela R de Carvalho Rocha,1 Fernanda C Cardoso1 1Department of Oncology, Hospital Israelita Albert Einstein, São Paulo, Brazil; 2Medical Oncology Department, Alexander Fleming Institute, Buenos Aires, Argentina Objective: To describe the clinical characteristics of Latin American patients with metastatic renal cell carcinoma (mRCC who experienced a progression-free survival (PFS for at least 15 months following treatment with sunitinib. Patients and methods: In this retrospective analysis, mRCC patients in two institutions in Latin America received sunitinib at a starting dose of either 50 mg/day for 4 weeks followed by 2 weeks off treatment (Schedule 4/2 in repeated 6-week cycles or sunitinib 37.5 mg on a continuous daily dosing schedule. Clinical characteristics, tolerability, and PFS data were collected. Results: Twenty-nine patients with long-term clinical benefit from sunitinib were identified between September 2005 and August 2009. Median PFS was 23 months (range: 15–54 months. Two of the 29 patients with prolonged PFS achieved a complete response and additional eleven had a partial response. Most patients were aged <60 years, had good performance status, favorable or intermediate Memorial Sloan Kettering Cancer Center prognostic risk, and disease limited to one or two sites. Dose reduction was necessary in all patients who started sunitinib at 50 mg/day administered on Schedule 4/2. Adverse events leading to dose reduction included grade 3 hand–foot syndrome, mucositis, fatigue, and hypertension. At the time of data cutoff, four patients were still receiving sunitinib treatment. Conclusion: Extended PFS can be achieved in Latin American patients with mRCC treated with sunitinib. Although the small sample size and retrospective nature of this evaluation preclude the identification of pretreatment predictive factors contributing to this benefit, the current analysis warrants

Long-term low-dose α-particle enhanced the potential of malignant transformation in human bronchial epithelial cells through MAPK/Akt pathway

Energy Technology Data Exchange (ETDEWEB)

Liu, Weili; Xiao, Linlin; Dong, Chen; He, Mingyuan; Pan, Yan; Xie, Yuexia; Tu, Wenzhi; Fu, Jiamei; Shao, Chunlin, E-mail: clshao@shmu.edu.cn

2014-05-09

Highlights: • Multi-exposures of 25 mGy α-ray enhanced cell proliferation, adhesion, and invasion. • MAPK/Akt but not JNK/P66 was positively correlated with cell invasive phenotypes. • LDR of α-irradiation triggers cell malignant transformation through MAPK/Akt. - Abstract: Since the wide usage of ionizing radiation, the cancer risk of low dose radiation (LDR) (<0.1 Gy) has become attractive for a long time. However, most results are derived from epidemiologic studies on atomic-bomb survivors and nuclear accidents surrounding population, and the molecular mechanism of this risk is elusive. To explore the potential of a long-term LDR-induced malignant transformation, human bronchial epithelial cells Beas-2B were fractionally irradiated with 0.025 Gy α-particles for 8 times in total and then further cultured for 1–2 months. It was found that the cell proliferation, the abilities of adhesion and invasion, and the protein expressions of p-ERK, p-Akt, especially p-P38 were not only increased in the multiply-irradiated cells but also in their offspring 1–2 months after the final exposure, indicating high potentiality of cell malignant transformation. On opposite, the expressions of p-JNK and p-P66 were diminished in the subcultures of irradiated cells and thus may play a role of negative regulation in canceration. When the cells were transferred with p38 siRNA, the LDR-induced enhancements of cell adhesion and invasion were significantly reduced. These findings suggest that long-term LDR of α-particles could enhance the potential of malignant transformation incidence in human bronchial epithelial cells through MAPK/Akt pathway.

Long-term low-dose α-particle enhanced the potential of malignant transformation in human bronchial epithelial cells through MAPK/Akt pathway

International Nuclear Information System (INIS)

Liu, Weili; Xiao, Linlin; Dong, Chen; He, Mingyuan; Pan, Yan; Xie, Yuexia; Tu, Wenzhi; Fu, Jiamei; Shao, Chunlin

2014-01-01

Highlights: • Multi-exposures of 25 mGy α-ray enhanced cell proliferation, adhesion, and invasion. • MAPK/Akt but not JNK/P66 was positively correlated with cell invasive phenotypes. • LDR of α-irradiation triggers cell malignant transformation through MAPK/Akt. - Abstract: Since the wide usage of ionizing radiation, the cancer risk of low dose radiation (LDR) (<0.1 Gy) has become attractive for a long time. However, most results are derived from epidemiologic studies on atomic-bomb survivors and nuclear accidents surrounding population, and the molecular mechanism of this risk is elusive. To explore the potential of a long-term LDR-induced malignant transformation, human bronchial epithelial cells Beas-2B were fractionally irradiated with 0.025 Gy α-particles for 8 times in total and then further cultured for 1–2 months. It was found that the cell proliferation, the abilities of adhesion and invasion, and the protein expressions of p-ERK, p-Akt, especially p-P38 were not only increased in the multiply-irradiated cells but also in their offspring 1–2 months after the final exposure, indicating high potentiality of cell malignant transformation. On opposite, the expressions of p-JNK and p-P66 were diminished in the subcultures of irradiated cells and thus may play a role of negative regulation in canceration. When the cells were transferred with p38 siRNA, the LDR-induced enhancements of cell adhesion and invasion were significantly reduced. These findings suggest that long-term LDR of α-particles could enhance the potential of malignant transformation incidence in human bronchial epithelial cells through MAPK/Akt pathway

Repeated exposure of adult rats to transient oxidative stress induces various long-lasting alterations in cognitive and behavioral functions.

Directory of Open Access Journals (Sweden)

Yoshio Iguchi

Full Text Available Exposure of neonates to oxidative stress may increase the risk of psychiatric disorders such as schizophrenia in adulthood. However, the effects of moderate oxidative stress on the adult brain are not completely understood. To address this issue, we systemically administrated 2-cyclohexen-1-one (CHX to adult rats to transiently reduce glutathione levels. Repeated administration of CHX did not affect the acquisition or motivation of an appetitive instrumental behavior (lever pressing rewarded by a food outcome under a progressive ratio schedule. In addition, response discrimination and reversal learning were not affected. However, acute CHX administration blunted the sensitivity of the instrumental performance to outcome devaluation, and this effect was prolonged in rats with a history of repeated CHX exposure, representing pro-depression-like phenotypes. On the other hand, repeated CHX administration reduced immobility in forced swimming tests and blunted acute cocaine-induced behaviors, implicating antidepressant-like effects. Multivariate analyses segregated a characteristic group of behavioral variables influenced by repeated CHX administration. Taken together, these findings suggest that repeated administration of CHX to adult rats did not cause a specific mental disorder, but it induced long-term alterations in behavioral and cognitive functions, possibly related to specific neural correlates.

Repeat photography as a tool for detecting and monitoring historical ...

African Journals Online (AJOL)

Repeat photography was used to illustrate long-term changes occurring in coastal habitats in the Western Cape, South Africa. Hi storic images were sourced from books and theses, the public and subject specialists, and repeat photographs were then taken from the same perspectives. Visible changes could be categorised ...

Long-term variations of the UV-B radiation over Central Europe as derived from the reconstructed UV time series

Directory of Open Access Journals (Sweden)

J. W. Krzyscin

2004-04-01

Full Text Available The daily doses of the erythemally weighted UV radiation are reconstructed for three sites in Central Europe: Belsk-Poland (1966–2001, Hradec Kralove-Czech Republic (1964–2001, and Tõravere-Estonia (1967–2001 to discuss the UV climatology and the long-term changes of the UV-B radiation since the mid 1960s. Various reconstruction models are examined: a purely statistical model based on the Multivariate Adaptive Regression Splines (MARS methodology, and a hybrid model combining radiative transfer model calculations with empirical estimates of the cloud effects on the UV radiation. Modeled long-term variations of the surface UV doses appear to be in a reasonable agreement with the observed ones. A simple quality control procedure is proposed to check the homogeneity of the biometer and pyranometer data. The models are verified using the results of UV observations carried out at Belsk since 1976. MARS provides the best estimates of the UV doses, giving a mean difference between the modeled and observed monthly means equal to 0.6±2.5%. The basic findings are: similar climatological forcing by clouds for all considered stations (~30% reduction in the surface UV, long-term variations in UV monthly doses having the same temporal pattern for all stations with extreme low monthly values (~5% below overall mean level at the end of the 1970s and extreme high monthly values (~5% above overall mean level in the mid 1990s, regional peculiarities in the cloud long-term forcing sometimes leading to extended periods with elevated UV doses, recent stabilization of the ozone induced UV long-term changes being a response to a trendless tendency of total ozone since the mid 1990s. In the case of the slowdown of the total ozone trend over Northern Hemisphere mid-latitudes it seems that clouds will appear as the most important modulator of the UV radiation both in long- and short-time scales over next decades. Key words. Atmospheric composition and structure

Long-term variations of the UV-B radiation over Central Europe as derived from the reconstructed UV time series

Directory of Open Access Journals (Sweden)

J. W. Krzyscin

2004-04-01

Full Text Available The daily doses of the erythemally weighted UV radiation are reconstructed for three sites in Central Europe: Belsk-Poland (1966–2001, Hradec Kralove-Czech Republic (1964–2001, and Tõravere-Estonia (1967–2001 to discuss the UV climatology and the long-term changes of the UV-B radiation since the mid 1960s. Various reconstruction models are examined: a purely statistical model based on the Multivariate Adaptive Regression Splines (MARS methodology, and a hybrid model combining radiative transfer model calculations with empirical estimates of the cloud effects on the UV radiation. Modeled long-term variations of the surface UV doses appear to be in a reasonable agreement with the observed ones. A simple quality control procedure is proposed to check the homogeneity of the biometer and pyranometer data. The models are verified using the results of UV observations carried out at Belsk since 1976. MARS provides the best estimates of the UV doses, giving a mean difference between the modeled and observed monthly means equal to 0.6±2.5%. The basic findings are: similar climatological forcing by clouds for all considered stations (~30% reduction in the surface UV, long-term variations in UV monthly doses having the same temporal pattern for all stations with extreme low monthly values (~5% below overall mean level at the end of the 1970s and extreme high monthly values (~5% above overall mean level in the mid 1990s, regional peculiarities in the cloud long-term forcing sometimes leading to extended periods with elevated UV doses, recent stabilization of the ozone induced UV long-term changes being a response to a trendless tendency of total ozone since the mid 1990s. In the case of the slowdown of the total ozone trend over Northern Hemisphere mid-latitudes it seems that clouds will appear as the most important modulator of the UV radiation both in long- and short-time scales over next decades.

Key words. Atmospheric composition and

Detection of Variation in Long-Term Micropropagated Mature Pistachio via DNA-Based Molecular Markers.

Science.gov (United States)

Akdemir, Hülya; Suzerer, Veysel; Tilkat, Engin; Onay, Ahmet; Çiftçi, Yelda Ozden

2016-12-01

Determination of genetic stability of in vitro-grown plantlets is needed for safe and large-scale production of mature trees. In this study, genetic variation of long-term micropropagated mature pistachio developed through direct shoot bud regeneration using apical buds (protocol A) and in vitro-derived leaves (protocol B) was assessed via DNA-based molecular markers. Randomly amplified polymorphic DNA (RAPD), inter-simple sequence repeat (ISSR), and amplified fragment length polymorphism (AFLP) were employed, and the obtained PIC values from RAPD (0.226), ISSR (0.220), and AFLP (0.241) showed that micropropagation of pistachio for different periods of time resulted in "reasonable polymorphism" among donor plant and its 18 clones. Mantel's test showed a consistence polymorphism level between marker systems based on similarity matrices. In conclusion, this is the first study on occurrence of genetic variability in long-term micropropagated mature pistachio plantlets. The obtained results clearly indicated that different marker approaches used in this study are reliable for assessing tissue culture-induced variations in long-term cultured pistachio plantlets.

Groundwater modeling for the long-term safety assessment of uranium tailings ponds

International Nuclear Information System (INIS)

Nair, R.N.

2010-01-01

Uranium tailings ponds contain naturally occurring long lived radionuclides such as 238 U, 234 U, 230 Th and 226 Ra as sources which are the parents of a very long radionuclide decay chain. Uranium tailings ponds by the virtue of the longevity of its contents may pose as a long-term radiological hazard if not designed and monitored properly. The principal radiation risks from uranium tailings are gamma radiation: windblown radioactive dust dispersion; and radon gas and its progenies. Uranium tailings ponds are also a major source of surface and groundwater contamination due to leaching of radioactive and other toxic elements. In many countries, the tailings ponds are designed to control the radiological hazards for up to 1000 years, to the extent achievable, and in any case for at least 200 years. Stringent regulations stipulations exist worldwide for the safe design, operation and closure of uranium tailings ponds. The long- term radiological impact assessment of uranium tailings ponds, hence, is an extremely important exercise in uranium mining industry. The simulations conducted for uranium over a period of 1000 years indicate that contaminant fronts from the source with a paste permeability of 1x10 -4 m/day would migrate a probable distance of less than 50 m. The maximum computed distance for this case is less than 300 m. Indian studies show that the total annual effective dose to members of the public at 1.0 km from the centre of the tailings pond is trivial up to a period of 4000 y. The estimated dose is 0.01 mSv/y after 10,000 years and it is 10 times lower than 0.1 mSv/y, which is considered as a safe dose limit for drinking water pathway. (author)

Long-term hematopoietic stem cell damage after external irradiation with X rays

International Nuclear Information System (INIS)

Grande, M.T.; Varas, F.; Bueren, J.A.

1997-01-01

We have investigated the functionality of the lympho-hematopoietic stem cells long-term (9 months) after the irradiation (X rays) of mice at different stages of development, by means of a competitive bone marrow repopulation assay. Our data revealed that a dose of 1 Gy was only capable of inducing significant long-term failures in the functionality of the primitive repopulating cells in mice irradiated at the young-adult stage (12 week-old), but not in mice irradiated at the late stages of foetus development (17 day-old fetuses) nor at the early development of the embryo (4 day-old embryos). The differential generation of long-term stem cell defects as a function of the age was confirmed in mice irradiated with 3 Gy. While no significant effects in the long-term repopulating cells were observed in 4 day-old embryos, significant repopulation deficiencies were observed in this population when mice were irradiated at the 17 day of foetus development, and more markedly at the adult stage of growth. These data offer new evidence about the influence of the developmental stage of the animal on the generation of residual hematopoietic dysfunctions by external irradiation, with particular relevance to the very primitive lympho-hematopoietic stem cells. (author)

Responses and damages during long-term continuous irradiation in plants

International Nuclear Information System (INIS)

Watanabe, Yoshito

2011-01-01

Effects of long-term continuous irradiation are relevant to studies in radiation ecotoxicology. To investigate plants biological responses to continuous irradiation, we performed metabolome and transcriptome analysis in a model plant, arabidopsis. Comprehensive analysis of primary metabolites using capillary electrophoresis mass spectrometry revealed extensive metabolic changes at early onset of growth inhibition in plants exposed to gamma rays at the dose rate of 20 Gy/day. The changes included elevated levels of B vitamins and second metabolites, commonly responsive to many abiotic and biotic stresses. Responses at early onset of growth inhibition were also observed in the transcriptome analysis using microarray, which showed up-regulation of 55 genes in plants exposed to gamma rays at 20 Gy/day. Although about a half of the up-regulated genes were also responsive just after acute irradiation, the other half was responsive only during long-term continuous irradiation. Database analyses showed that the specifically up-regulated genes to long-term continuous irradiation included genes relating to general stress responses and protein metabolism. The results of these analyses appear to reflect plants responses to progressive radiation damages, from radiation-specific responses, which repair primary DNA damage, to more general stress responses, which maintain homoeostasis against secondary damages. (author)

Long-term biological consequences of nuclear war

International Nuclear Information System (INIS)

Ehrlich, P.R.; Harte, J.; Harwell, M.A.

1983-01-01

Subfreezing temperatures, low light levels, and high doses of ionizing and ultraviolet radiation extending for many months after a large-scale nuclear war could destroy the biological support systems of civilization, at least in the Northern Hemisphere. Productivity in natural and agricultural ecosystems could be severely restricted for a year or more. Postwar survivors would face starvation as well as freezing conditions in the dark and be exposed to near-lethal doses of radiation. If, as now seems possible, the Southern Hemisphere were affected also, global disruption of the biosphere could ensue, In any event, there would be severe consequences, even in the areas not affected directly, because of the interdependence of the world economy. In either case the extinction of a large fraction of the Earth's animals, plants, and microorganisms seems possible. The population size of Homo sapiens conceivably could be reduced to prehistoric levels or below and extinction of the human species itself cannot be excluded. These conclusions are the concensus from the meeting on Long-Term Worldwide Biological Consequences of Nuclear War

Association of High-Dose Ibuprofen Use, Lung Function Decline, and Long-Term Survival in Children with Cystic Fibrosis.

Science.gov (United States)

Konstan, Michael W; VanDevanter, Donald R; Sawicki, Gregory S; Pasta, David J; Foreman, Aimee J; Neiman, Evgueni A; Morgan, Wayne J

2018-04-01

.04) during the corresponding 2-year period, a 37.5% slower decline among users compared with nonusers (95% confidence interval; 0.4%, 71.3%; P = 0.046). The users had better subsequent survival (P cystic fibrosis, we observed an association between high-dose ibuprofen use and both slower lung function decline and improved long-term survival. These results are consistent with the hypothesis that treatment-associated reduction of lung function decline in children with cystic fibrosis leads to improved survival.

Biochemical effects on long-term frozen human costal cartilage

Energy Technology Data Exchange (ETDEWEB)

Santin, Stefany P.; Martinho Junior, Antonio C.; Yoshito, Daniele; Soares, Fernando A.N.; Mathor, Monica B., E-mail: mathor@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2011-07-01

Currently, the progresses on treatment of musculoskeletal diseases with the evolving of artificial implants and the success of tissue transplantation between genetically different individuals have conducted to an increase in radiosterilization. Regarding to tissue transplantation, it is essential to have sterile tissue and many tissue banks use radiosterilization as an effective method to sterilize these tissues. However, high doses of ionizing radiation and the preservation method may induce structural modifications in the tissues, as degradation of structural scaffold, decreasing its mechanical properties. Particularly, cartilage have been preserved in high concentrations of glycerol or deep-frozen at -70 degree C for storage after radiosterilization. Therefore, it is important to study the modifications induced in cartilage by preservation methods and by radiosterilization to determine the appropriated parameters for high quality of human allografts. Costal cartilages were obtained from cadaveric donors and were frozen at -20 degree C for 2 years long in order to compare with previous studies for fresh, deep-frozen and glycerolised cartilages. The mechanical tests were carried out in a universal testing machine until sample failure. According our results, there is no significant statistical difference between stress at break of fresh, long-term - 20 degree C frozen cartilages and deep-frozen cartilage. This early result suggests, regarding to tensile property, that long-term - 20 degree C frozen cartilages corresponds to glycerolised costal cartilages irradiated with 25 kGy or deep-frozen cartilages irradiated with 25 and 50 kGy. Thus, this long-term frozen cartilages may be used for tissue banks, but more studies about effects of ionizing radiation are necessary. (author)

Biochemical effects on long-term frozen human costal cartilage

International Nuclear Information System (INIS)

Santin, Stefany P.; Martinho Junior, Antonio C.; Yoshito, Daniele; Soares, Fernando A.N.; Mathor, Monica B.

2011-01-01

Currently, the progresses on treatment of musculoskeletal diseases with the evolving of artificial implants and the success of tissue transplantation between genetically different individuals have conducted to an increase in radiosterilization. Regarding to tissue transplantation, it is essential to have sterile tissue and many tissue banks use radiosterilization as an effective method to sterilize these tissues. However, high doses of ionizing radiation and the preservation method may induce structural modifications in the tissues, as degradation of structural scaffold, decreasing its mechanical properties. Particularly, cartilage have been preserved in high concentrations of glycerol or deep-frozen at -70 degree C for storage after radiosterilization. Therefore, it is important to study the modifications induced in cartilage by preservation methods and by radiosterilization to determine the appropriated parameters for high quality of human allografts. Costal cartilages were obtained from cadaveric donors and were frozen at -20 degree C for 2 years long in order to compare with previous studies for fresh, deep-frozen and glycerolised cartilages. The mechanical tests were carried out in a universal testing machine until sample failure. According our results, there is no significant statistical difference between stress at break of fresh, long-term - 20 degree C frozen cartilages and deep-frozen cartilage. This early result suggests, regarding to tensile property, that long-term - 20 degree C frozen cartilages corresponds to glycerolised costal cartilages irradiated with 25 kGy or deep-frozen cartilages irradiated with 25 and 50 kGy. Thus, this long-term frozen cartilages may be used for tissue banks, but more studies about effects of ionizing radiation are necessary. (author)

The Barrier code for predicting long-term concrete performance

International Nuclear Information System (INIS)

Shuman, R.; Rogers, V.C.; Shaw, R.A.

1989-01-01

There are numerous features incorporated into a LLW disposal facility that deal directly with critical safety objectives required by the NRC in 10 CFR 61. Engineered barriers or structures incorporating concrete are commonly being considered for waste disposal facilities. The Barrier computer code calculates the long-term degradation of concrete structures in LLW disposal facilities. It couples this degradation with water infiltration into the facility, nuclide leaching from the waste, contaminated water release from the facility, and associated doses to members of the critical population group. The concrete degradation methodology of Barrier is described

Trace Element Status (Zinc, Copper, Selenium, Iron, Manganese) in Patients with Long-Term Home Parenteral Nutrition.

Science.gov (United States)

Dastych, Milan; Šenkyřík, Michal; Dastych, Milan; Novák, František; Wohl, Petr; Maňák, Jan; Kohout, Pavel

2016-01-01

The objective of the present study was to determine concentrations of zinc (Zn), copper (Cu), iron (Fe), selenium (Se) in blood plasma and manganese (Mn) in the whole blood in patients with long-term home parenteral nutrition (HPN) in comparison to the control group. We examined 68 patients (16 men and 52 women) aged from 28 to 68 years on a long-term HPN lasting from 4 to 96 months. The short bowel syndrome was an indication for HPN. The daily doses of Zn, Cu, Fe, Se and Mn in the last 3 months were determined. No significant differences in blood plasma were found for Zn, Cu and Fe in patients with HPN and in the control group (p > 0.05). The concentration of Mn in whole blood was significantly increased in HPN patients (p < 0.0001), while Se concentration in these patients was significantly decreased (p < 0.005). The concentration of Mn in the whole blood of 16 patients with cholestasis was significantly increased compared to the patients without cholestasis (p < 0.001). The Cu concentration was increased with no statistical significance. In long-term HPN, the status of trace elements in the patients has to be continually monitored and the daily substitution doses of these elements have to be flexibly adjusted. Dosing schedule needs to be adjusted especially in cases of cholestatic hepatopathy. A discussion about the optimal daily dose of Mn in patients on HPN is appropriate. For clinical practice, the availability of a substitution mixture of trace elements lacking Mn would be advantageous. © 2016 S. Karger AG, Basel.

Assessment of long-term knowledge retention following single-day simulation training for uncommon but critical obstetrical events

Science.gov (United States)

Vadnais, Mary A.; Dodge, Laura E.; Awtrey, Christopher S.; Ricciotti, Hope A.; Golen, Toni H.; Hacker, Michele R.

2013-01-01

Objective The objectives were to determine (i) whether simulation training results in short-term and long-term improvement in the management of uncommon but critical obstetrical events and (ii) to determine whether there was additional benefit from annual exposure to the workshop. Methods Physicians completed a pretest to measure knowledge and confidence in the management of eclampsia, shoulder dystocia, postpartum hemorrhage and vacuum-assisted vaginal delivery. They then attended a simulation workshop and immediately completed a posttest. Residents completed the same posttests 4 and 12 months later, and attending physicians completed the posttest at 12 months. Physicians participated in the same simulation workshop 1 year later and then completed a final posttest. Scores were compared using paired t-tests. Results Physicians demonstrated improved knowledge and comfort immediately after simulation. Residents maintained this improvement at 1 year. Attending physicians remained more comfortable managing these scenarios up to 1 year later; however, knowledge retention diminished with time. Repeating the simulation after 1 year brought additional improvement to physicians. Conclusion Simulation training can result in short-term and contribute to long-term improvement in objective measures of knowledge and comfort level in managing uncommon but critical obstetrical events. Repeat exposure to simulation training after 1 year can yield additional benefits. PMID:22191668

Partial diel migration: A facultative migration underpinned by long-term inter-individual variation.

Science.gov (United States)

Harrison, Philip M; Gutowsky, Lee F G; Martins, Eduardo G; Patterson, David A; Cooke, Steven J; Power, Michael

2017-09-01

The variations in migration that comprise partial diel migrations, putatively occur entirely as a consequence of behavioural flexibility. However, seasonal partial migrations are increasingly recognised to be mediated by a combination of reversible plasticity in response to environmental variation and individual variation due to genetic and environmental effects. Here, we test the hypothesis that while partial diel migration heterogeneity occurs primarily due to short-term within-individual flexibility in behaviour, long-term individual differences in migratory behaviour also underpin this migration variation. Specifically, we use a hierarchical behavioural reaction norm approach to partition within- and among-individual variation in depth use and diel plasticity in depth use, across short- and long-term time-scales, in a group of 47 burbot (Lota lota) tagged with depth-sensing acoustic telemetry transmitters. We found that within-individual variation at the among-dates-within-seasons and among-seasons scale, explained the dominant proportion of phenotypic variation. However, individuals also repeatedly differed in their expression of migration behaviour over the 2 year study duration. These results reveal that diel migration variation occurs primarily due to short-term within-individual flexibility in depth use and diel migration behaviour. However, repeatable individual differences also played a key role in mediating partial diel migration. These findings represent a significant advancement of our understanding of the mechanisms generating the important, yet poorly understood phenomena of partial diel migration. Moreover, given the pervasive occurrence of diel migrations across aquatic taxa, these findings indicate that individual differences have an important, yet previously unacknowledged role in structuring the temporal and vertical dynamics of aquatic ecosystems. © 2017 The Authors. Journal of Animal Ecology © 2017 British Ecological Society.

Reforming Long-Term Care Funding in Alberta.

Science.gov (United States)

Crump, R Trafford; Repin, Nadya; Sutherland, Jason M

2015-01-01

Like many provinces across Canada, Alberta is facing growing demand for long-term care. Issues with the mixed funding model used to pay long-term care providers had Alberta Health Services concerned that it was not efficiently meeting the demand for long-term care. Consequently, in 2010, Alberta Health Services introduced the patient/care-based funding (PCBF) model. PCBF is similar to activity-based funding in that it directly ties the complexity and care needs of long-term care residents to the payment received by long-term care providers. This review describes PCBF and discusses some of its strengths and weaknesses. In doing so, this review is intended to inform other provinces faced with similar long-term care challenges and contemplating their own funding reforms.

Role of "Aplysia" Cell Adhesion Molecules during 5-HT-Induced Long-Term Functional and Structural Changes

Science.gov (United States)

Han, Jin-Hee; Lim, Chae-Seok; Lee, Yong-Seok; Kandel, Eric R.; Kaang, Bong-Kiun

2004-01-01

We previously reported that five repeated pulses of 5-HT lead to down-regulation of the TM-apCAM isoform at the surface of "Aplysia" sensory neurons (SNs). We here examined whether apCAM down-regulation is required for 5-HT-induced long-term facilitation. We also analyzed the role of the cytoplasmic and extracellular domains by overexpressing…

Quantum key distribution with two-segment quantum repeaters

Energy Technology Data Exchange (ETDEWEB)

Kampermann, Hermann; Abruzzo, Silvestre; Bruss, Dagmar [Theoretische Physik III, Heinrich-Heine-Universitaet Duesseldorf (Germany)

2014-07-01

Quantum repeaters represent one possible way to achieve long-distance quantum key distribution. One way of improving the repeater rate and decreasing the memory coherence time is the usage of multiplexing. Motivated by the experimental fact that long-range connections are practically demanding, we extend the analysis of the quantum repeater multiplexing protocol to the case of short-range connections. We derive formulas for the repeater rate and we show that short-range connections lead to most of the benefits of a full-range multiplexing protocol. A less demanding QKD-protocol without quantum memories was recently introduced by Lo et al. We generalize this measurement-device-independent quantum key Distribution protocol to the scenario where the repeater Station contains also heralded quantum memories. We assume either single-photon sources or weak coherent pulse sources plus decay states. We show that it is possible to significantly outperform the original proposal, even in presence of decoherence of the quantum memory. We give formulas in terms of device imperfections i.e., the quantum bit error rate and the repeater rate.

Safety analysis SFR 1. Long-term safety

Energy Technology Data Exchange (ETDEWEB)

2008-12-15

An updated assessment of the long-term safety of SKB's final repository for radioactive operational waste, SFR 1, is presented in this report. The report is included in the safety analysis report for SFR 1. The most recent account of long-term safety was submitted to the regulatory authorities in 2001. The present report has been compiled on SKB's initiative to address the regulatory authorities' viewpoints regarding the preceding account of long-term safety. Besides the new mode of working with safety functions there is another important difference between the 2001 safety assessment and the current assessment: The time horizon in the current assessment has been extended to 100,000 years in order to include the effect of future climate changes. The purpose of this renewed assessment of the long-term safety of SFR 1 is to show with improved data that the repository is capable of protecting human health and the environment against ionizing radiation in a long-term perspective. This is done by showing that calculated risks lie below the risk criteria stipulated by the regulatory authorities. SFR 1 is built to receive, and after closure serve as a passive repository for, low. and intermediate-level radioactive waste. The disposal chambers are situated in rock beneath the sea floor, covered by about 60 metres of rock. The underground part of the facility is reached via two tunnels whose entrances are near the harbour. The repository has been designed so that it can be abandoned after closure without further measures needing to be taken to maintain its function. The waste in SFR 1 is short-lived low- and intermediate-level waste. After 100 years the activity is less than half, and after 1,000 years only about 2% of the original activity remains. The report on long-term safety comprises eleven chapters. Chapter 1 Introduction. The chapter describes the purpose, background, format and contents of SAR-08, applicable regulations and injunctions, and the regulatory

Safety analysis SFR 1. Long-term safety

International Nuclear Information System (INIS)

2008-12-01

An updated assessment of the long-term safety of SKB's final repository for radioactive operational waste, SFR 1, is presented in this report. The report is included in the safety analysis report for SFR 1. The most recent account of long-term safety was submitted to the regulatory authorities in 2001. The present report has been compiled on SKB's initiative to address the regulatory authorities' viewpoints regarding the preceding account of long-term safety. Besides the new mode of working with safety functions there is another important difference between the 2001 safety assessment and the current assessment: The time horizon in the current assessment has been extended to 100,000 years in order to include the effect of future climate changes. The purpose of this renewed assessment of the long-term safety of SFR 1 is to show with improved data that the repository is capable of protecting human health and the environment against ionizing radiation in a long-term perspective. This is done by showing that calculated risks lie below the risk criteria stipulated by the regulatory authorities. SFR 1 is built to receive, and after closure serve as a passive repository for, low. and intermediate-level radioactive waste. The disposal chambers are situated in rock beneath the sea floor, covered by about 60 metres of rock. The underground part of the facility is reached via two tunnels whose entrances are near the harbour. The repository has been designed so that it can be abandoned after closure without further measures needing to be taken to maintain its function. The waste in SFR 1 is short-lived low- and intermediate-level waste. After 100 years the activity is less than half, and after 1,000 years only about 2% of the original activity remains. The report on long-term safety comprises eleven chapters. Chapter 1 Introduction. The chapter describes the purpose, background, format and contents of SAR-08, applicable regulations and injunctions, and the regulatory

Safety analysis SFR 1. Long-term safety

Energy Technology Data Exchange (ETDEWEB)

2008-12-15

An updated assessment of the long-term safety of SKB's final repository for radioactive operational waste, SFR 1, is presented in this report. The report is included in the safety analysis report for SFR 1. The most recent account of long-term safety was submitted to the regulatory authorities in 2001. The present report has been compiled on SKB's initiative to address the regulatory authorities' viewpoints regarding the preceding account of long-term safety. Besides the new mode of working with safety functions there is another important difference between the 2001 safety assessment and the current assessment: The time horizon in the current assessment has been extended to 100,000 years in order to include the effect of future climate changes. The purpose of this renewed assessment of the long-term safety of SFR 1 is to show with improved data that the repository is capable of protecting human health and the environment against ionizing radiation in a long-term perspective. This is done by showing that calculated risks lie below the risk criteria stipulated by the regulatory authorities. SFR 1 is built to receive, and after closure serve as a passive repository for, low. and intermediate-level radioactive waste. The disposal chambers are situated in rock beneath the sea floor, covered by about 60 metres of rock. The underground part of the facility is reached via two tunnels whose entrances are near the harbour. The repository has been designed so that it can be abandoned after closure without further measures needing to be taken to maintain its function. The waste in SFR 1 is short-lived low- and intermediate-level waste. After 100 years the activity is less than half, and after 1,000 years only about 2% of the original activity remains. The report on long-term safety comprises eleven chapters. Chapter 1 Introduction. The chapter describes the purpose, background, format and contents of SAR-08, applicable regulations and injunctions, and the

Assessing the Long-term Impact of Microcredit on Rural Poverty: Does the Timing and Length of Participation Matter?

NARCIS (Netherlands)

Berhane, G.; Gardebroek, C.

2012-01-01

In recent years, microfinance institutions are seen as beacons of hope to help eradicate poverty through, among others, providing credit to poor rural households. Availability of small but repeated loans is, in the long-term, expected to impact on poverty. However, decades after the introduction of

Liquid nitrogen spray cryotherapy in Barrett's esophagus with high-grade dysplasia: long-term results.

Science.gov (United States)

Gosain, Sonia; Mercer, Kim; Twaddell, William S; Uradomo, Lance; Greenwald, Bruce D

2013-08-01

Liquid nitrogen endoscopic spray cryotherapy can safely and effectively eradicate high-grade dysplasia in Barrett's esophagus (BE-HGD). Long-term data on treatment success and safety are lacking. To assess the long-term safety and efficacy of spray cryotherapy in patients with BE-HGD. Single-center, retrospective study. Tertiary-care referral center. A total of 32 patients with BE-HGD of any length. Patients were treated with liquid nitrogen spray cryotherapy every 8 weeks until complete eradication of HGD (CE-HGD) and intestinal metaplasia (CE-IM) was found by endoscopic biopsy. Surveillance endoscopy with biopsies was performed for at least 2 years. CE-HGD, CE-IM, durability of response, disease progression, and adverse events. CE-HGD was 100% (32/32), and CE-IM was 84% (27/32) at 2-year follow-up. At last follow-up (range 24-57 months), CE-HGD was 31/32 (97%), and CE-IM was 26/32 (81%). Recurrent HGD was found in 6 (18%), with CE-HGD in 5 after repeat treatment. One patient progressed to adenocarcinoma, downgraded to HGD after repeat cryotherapy. BE segment length ≥3 cm was associated with a higher recurrence of IM (P = .004; odds ratio 22.6) but not HGD. No serious adverse events occurred. Stricture was seen in 3 patients (9%), all successfully dilated. Retrospective study design, small sample size. In patients with BE-HGD, liquid nitrogen spray cryotherapy has an acceptable safety profile and success rate for eliminating HGD and IM and is associated with a low rate of recurrence or progression to cancer with long-term follow-up. Copyright © 2013 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Safety and performance indicators for the assessment of long-term safety of deep geological disposal of radioactive waste

International Nuclear Information System (INIS)

Hugi, M.; Schneider, J.W.; Dorp, F. van; Zuidema, P.

2005-01-01

The evaluation of the ability to isolate radioactive waste and the assessment of the long-term safety of a deep geological repository is usually done in terms of the calculated dose and/or risk for an average individual of the population which is potentially most affected by the potential impacts of the repository. At present, various countries and international organisations are developing so-called complementary indicators to supplement such calculations. These indicators are called ''safety indicators'' if they refer to the safety of the whole repository system; if they address the isolation capability of individual system components or the whole system from a more technical perspective, they are called ''performance indicators''. The need for complementary indicators follows from the long time frames which characterise the safety assessment of a geological repository, and the corresponding uncertainty of the calculated radiation dose. The main reason for these uncertainties is associated with the uncertain long-term prognosis of the surface environment and the related human behaviour. (orig.)

A study to assess the long-term stability of the ionization chamber reference system in the LNMRI

Science.gov (United States)

Trindade Filho, O. L.; Conceição, D. A.; da Silva, C. J.; Delgado, J. U.; de Oliveira, A. E.; Iwahara, A.; Tauhata, L.

2018-03-01

Ionization chambers are used as secondary standard in order to maintain the calibration factors of radionuclides in the activity measurements in metrology laboratories. Used as radionuclide calibrator in nuclear medicine clinics to control dose in patients, its long-term performance is not evaluated systematically. A methodology for long-term evaluation for its stability is monitored and checked. Historical data produced monthly of 2012 until 2017, by an ionization chamber, electrometer and 226Ra, were analyzed via control chart, aiming to follow the long-term performance. Monitoring systematic errors were consistent within the limits of control, demonstrating the quality of measurements in compliance with ISO17025.

A study to assess the long-term stability of the ionization chamber reference system in the LNMRI

Energy Technology Data Exchange (ETDEWEB)

Filho, Octavio L.T.; Conceição, Dayana A. da; Silva, Carlos J. da; Delgado, José U.; Oliveira, Antônio E. de; Iwahara, Akira; Tauhata, Luiz, E-mail: octavio@ird.gov.br [Instituto de Radioproteção e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

2017-07-01

Ionization chambers are used as secondary standard in order to maintain the calibration factors of radionuclides in the activity measurements in metrology laboratories. Used as radionuclide calibrator in nuclear medicine clinics to control dose in patients, its long-term performance is not evaluated systematically. A methodology for long-term evaluation for its stability is monitored and checked. Historical data were analyzed via control chart, produced between 2012-2017 by an ionization chamber, electrometer and {sup 226}Ra, aiming to follow the long-term performance. The results for monitoring systematic errors were consistent within the limits of control, demonstrating the quality of measurements in compliance with ISO17025. (author)

Study of feasibility of detecting effects of low-dose radiation in shipyard workers. Final report, May 15-August 15, 1978

International Nuclear Information System (INIS)

Matanoski, G.M.

1982-12-01

There is very little information available on the chronic health effects from repeated low-level doses of radiation. This study examines the adequacy of determining radiation exposure doses in shipyard workers, the procedures used in the radiation control programs, and the feasibility of establishing an appropriate population of nuclear and non-nuclear shipyard workers for long-term studies of low-level radiation. The availability of records and the methods of population identification and of measurement of radiation dose were determined during initial visits to the yards. Personnel, industrial hygiene, radiation and medical records were examined for suitability, completeness and accuracy. It was necessary to assure that no possible errors or omissions in personnel and radiation records existed in order that the final data will have validity. Preliminary investigations on the methods of follow-up in the Portsmouth population and the time required for each procedure were also undertaken in order to have a better estimate of the total cost for a long term study

Industrial Foundations as Long-Term Owners

DEFF Research Database (Denmark)

Thomsen, Steen; Poulsen, Thomas; Børsting, Christa Winther

Short-termism has become a serious concern for corporate governance, and this has inspired a search for institutional arrangements to promote long-term decision-making. In this paper, we call attention to long-term ownership by industrial foundations, which is common in Northern Europe but little...... known in the rest of the world. We use a unique Danish data set to document that industrial foundations are long-term owners that practice long-term governance. We show that foundation ownership is highly stable compared to other ownership structures. Foundation-owned companies replace managers less...... frequently. They have conservative capital structures with low financial leverage. They score higher on an index of long-termism in finance, investment, and employment. They survive longer. Overall, our paper supports the hypothesis that corporate time horizons are influenced by ownership structures...

Long-term associative learning predicts verbal short-term memory performance

OpenAIRE

Jones, Gary; Macken, Bill

2017-01-01

Studies using tests such as digit span and nonword repetition have implicated short-term memory across a range of developmental domains. Such tests ostensibly assess specialized processes for the short-term manipulation and maintenance of information that are often argued to enable long-term learning. However, there is considerable evidence for an influence of long-term linguistic learning on performance in short-term memory tasks that brings into question the role of a specialized short-term...

Long-term efficacy of a mini-course in radiation-reducing techniques in invasive cardiology

Energy Technology Data Exchange (ETDEWEB)

Kuon, E. [Klinik Fraenkische Schweiz, Ebermannstadt (Germany). Abt. fuer Kardiologie; Empen, K.; Hummel, A.; Doerr, M.; Reffelmann, T.; Felix, S.B. [Ernst-Moritz-Arndt-Universitaet, Greifswald (Germany). Abt. fuer Innere Medizin B; Weitmann, K.; Hoffmann, W. [Ernst-Moritz-Arndt-Universitaet, Greifswald (Germany). Inst. fuer Versorgungsmedizin; Staudt, A. [Helios Kliniken, Schwerin (Germany). Abt. fuer Kardiologie und Angiologie

2013-08-15

Purpose: To validate the long-term efficacy of a 90-min. educational mini-course in less-irradiating cardiac interventional techniques. Materials and Methods: Before, two months after, and two years after the mini-course (periods I, II, and III), we analyzed the following radiation dose parameters for ten coronary angiographies (CA), performed by each of 7 cardiologists: total dose-area product (DAP), radiographic and fluoroscopic DAP fractions, number of radiographic frames and runs, and fluoroscopy time. Results: The median patient DAP for periods I, II and III was 31.4, 15.8 and 8.5 Gy x cm{sup 2}, respectively. The long-term effect was related to shorter median fluoroscopy times (180, 172, and 120 s), shorter (57, 52, and 45) and fewer (12, 12, and 10) radiographic runs, consistent collimation and restriction to an adequate image quality. Both radiographic DAP/frame (28.7, 17.0, and 18.4 mGy x cm{sup 2}) and fluoroscopic DAP/second (45.7, 24.2, and 10.0 mGy x cm{sup 2}) decreased significantly. The multivariate linear regression analysis confirmed the increasing efficacy of the mini-course itself (-44.6 and -60.7 %), and revealed a decreasing influence of the interventionalist's experience (-8.6 % and -4.9 % per 1,000 CAs, lifelong performed until the mini-course). The number of CAs performed after the mini-course did not influence the long-term DAP results. Conclusion: The presented educational mini-course allows a significant, long-lasting, and apparently ongoing reduction of patient radiation exposure due to CA. A self-surveillant documentation of relevant radiation parameters is well suited to monitor and improve each operator's individual long-term radiation-reducing efforts. (orig.)

Short- and long-term efficacy of intra-articular injections with betamethasone as part of a treat-to-target strategy in early rheumatoid arthritis

DEFF Research Database (Denmark)

Hetland, Merete Lund; Østergaard, Mikkel; Ejbjerg, Bo

2012-01-01

To investigate the short-term and long-term efficacy of intra-articular betamethasone injections, and the impact of joint area, repeated injections, MRI pathology, anticyclic citrullinated peptide (CCP) and immunoglobulin M rheumatoid factor (IgM-RF) status in patients with early rheumatoid arthr...

Robotic UV-Vis apparatus for long-term characterization of drug release from nanochannels

International Nuclear Information System (INIS)

Geninatti, T; Grattoni, A; Small, E

2014-01-01

Reliable monitoring of the kinetics of molecular release from drug delivery devices is crucial for their therapeutic success. Commercially available UV-Vis spectrophotometers provide reliable quantification of analyte concentrations directly correlated to the absorbance of fluids. However, they are not suitable for long-term measurements requiring high frequency of sampling from a large number of replicates and continuous fluid mixing, all of which are necessary for evaluation of drug delivery devices. To address this need, we developed a novel robotic apparatus serially connected to a commercial UV-Vis spectrophotometer. The robotic apparatus enables us to automatically and reliably acquire long-term data for up to 48 samples with high frequency of measurements and independent magnetic stirring. We equipped the robotic apparatus with independent connectors that allowed us to apply an electric potential to each sample for electrokinetic studies. The apparatus repeatability and accuracy was demonstrated in comparison to a commercial UV-Vis spectrophotometer. The system was successfully employed to characterize the diffusion kinetics of acetone and doxorubicin through nanochannel membranes (nDS) designed for long-term drug delivery. Dendritic fullerene 1 was used to show that the robotic apparatus routes the electric potential to nanochannel membranes enabling us to investigate the actively controlled release of molecules. Our results demonstrate that the robotic apparatus could widely broaden the range of applications of UV-Vis spectrophotometry, especially in the case of large sample processing and for long-term diffusive and electrokinetic studies in drug delivery. (technical design note)

The effect of zinc supplementation of lactating rats on short-term and long-term memory of their male offspring.

Science.gov (United States)

Karami, Mohammad; Ehsanivostacolaee, Simin; Moazedi, Ali Ahmad; Nosrati, Anahita

2013-01-01

In this study the effect of zinc chloride (ZnCl2) administration on the short-term and long-term memory of rats were assessed. We enrolled six groups of adult female and control group of eight Wistar rats in each group. One group was control group with free access to food and water, and five groups drunk zinc chloride in different doses (20, 30, 50, 70 and 100 mg/kg/day) in drinking water for two weeks during lactation .One month after birth, a shuttle box used to short- term and long-term memory and the latency in entering the dark chamber as well. This experiment showed that maternal 70 mg/kg dietary zinc during lactation influenced the working memory of rats' offspring in all groups. Rats received 100 mg/kg/day zinc during lactation so they had significant impairment in working memory (short-term) of their offspring (Plong-term) memory of all groups. Drug consumption below70 mg/kg/day zinc chloride during lactation had no effect. While enhanced 100 mg/ kg/ day zinc in lactating rats could cause short-term memory impairment.

Long term exposure to low dose neurotoxic pesticides affects hatching, viability and cholinesterase activity of Artemia sp.

Science.gov (United States)

Gambardella, Chiara; Nichino, Daniela; Iacometti, Camillo; Ferrando, Sara; Falugi, Carla; Faimali, Marco

2018-03-01

The brine shrimp Artemia was used as a model organism to test toxicity of several neuroactive pesticides (chlorpyrifos (CLP), chlorpyrifos oxon (CLP ox), diazinon (DZN), carbaryl (CBR)) following exposure to far below than lethal doses. Cysts were exposed to the pesticides in order to test a scenario similar to actual coastal environment contamination, by analyzing different responses. Cysts were rehydrated in water containing the pesticides at concentrations ranging from 10 -11 to 10 -5  M, for 72, 96 and 192 h, respectively. For these exposure times, morpho-functional and biochemical parameters, such as hatching speed and viability were investigated in the larvae together with cholinesterase (ChE) activity quantification and histochemical localization. Finally, ChE inhibition was also compared with conventional selective ChE inhibitors. Results showed that CLP ox and CBR caused a significant dose-dependent decrease in hatching speed, followed by high percentages of larval death, while CLP and DZN were responsible for irregular hatching patterns. In addition, the pesticides mostly caused larval death some days post-hatching, whereas this effect was negligible for the specific ChE inhibitors, suggesting that part of pesticide toxicity may be due to molecules other than the primary target. ChE activity was observed in the protocerebrum lobes, linked to the development of pair eyes. Such activity was inhibited in larvae exposed to all pesticides. When compared to conventional selective inhibitors of ChE activities, this inhibition demonstrated that the selected pesticides mainly affect acetylcholinesterase and, to a lesser extent, pseudocholinesterases. In conclusion, the brine shrimp is a good model to test the environmental toxicity of long term exposure to cholinergic pesticides, since changes in hatching speed, viability and ChE activity were observed. Copyright © 2018 Elsevier B.V. All rights reserved.

Long term results after fractionated stereotactic radiotherapy (FSRT) in patients with craniopharyngioma: maximal tumor control with minimal side effects

International Nuclear Information System (INIS)

Harrabi, Semi B; Adeberg, Sebastian; Welzel, Thomas; Rieken, Stefan; Habermehl, Daniel; Debus, Jürgen; Combs, Stephanie E

2014-01-01

There are already numerous reports about high local control rates in patients with craniopharyngioma but there are only few studies with follow up times of more than 10 years. This study is an analysis of long term control, tumor response and side effects after fractionated stereotactic radiotherapy (FSRT) for patients with craniopharyngioma. 55 patients who were treated with FSRT for craniopharyngioma were analyzed. Median age was 37 years (range 6–70 years), among them eight children < 18 years. Radiotherapy (RT) was indicated for progressive disease after neurosurgical resection or postoperatively after repeated resection or partial resection. A median dose of 52.2 Gy (50 – 57.6 Gy) was applied with typical dose per fraction of 1.8 Gy five times per week. The regular follow up examinations comprised in addition to contrast enhanced MRI scans thorough physical examinations and clinical evaluation. During median follow up of 128 months (2 – 276 months) local control rate was 95.3% after 5 years, 92.1% after 10 years and 88.1% after 20 years. Overall survival after 10 years was 83.3% and after 20 years 67.8% whereby none of the deaths were directly attributed to craniopharyngioma. Overall treatment was tolerated well with almost no severe acute or chronic side effects. One patient developed complete anosmia, another one’s initially impaired vision deteriorated further. In 83.6% of the cases with radiological follow up a regression of irradiated tumor residues was monitored, in 7 cases complete response was achieved. 44 patients presented themselves initially with endocrinologic dysfunction none of them showed signs of further deterioration during follow up. No secondary malignancies were observed. Long term results for patients with craniopharyngioma after stereotactic radiotherapy are with respect to low treatment related side effects as well as to local control and overall survival excellent

Long-term impairment of social memory in the rat after social defeat is not restored by desglycinamide-vasopressin

NARCIS (Netherlands)

Reijmers, L.G.J.E.; Hoekstra, K.; Burbach, J.P.H.; Ree, van J.M.; Spruijt, B.M.

2001-01-01

Repeated social defeat followed by individual housing caused a long-term impairment of social memory in male rats. Social memory, as assessed in the social discrimination test using an intertrial interval of 3 min, was impaired for at least 8 weeks after the social defeat experience. Since social

Characterization of the rapid transcriptional response to long-term sensitization training in Aplysia californica.

Science.gov (United States)

Herdegen, Samantha; Holmes, Geraldine; Cyriac, Ashly; Calin-Jageman, Irina E; Calin-Jageman, Robert J

2014-12-01

We used a custom-designed microarray and quantitative PCR to characterize the rapid transcriptional response to long-term sensitization training in the marine mollusk Aplysia californica. Aplysia were exposed to repeated noxious shocks to one side of the body, a procedure known to induce a long-lasting, transcription-dependent increase in reflex responsiveness that is restricted to the side of training. One hour after training, pleural ganglia from the trained and untrained sides of the body were harvested; these ganglia contain the sensory nociceptors which help mediate the expression of long-term sensitization memory. Microarray analysis from 8 biological replicates suggests that long-term sensitization training rapidly regulates at least 81 transcripts. We used qPCR to test a subset of these transcripts and found that 83% were confirmed in the same samples, and 86% of these were again confirmed in an independent sample. Thus, our new microarray design shows strong convergent and predictive validity for analyzing the transcriptional correlates of memory in Aplysia. Fully validated transcripts include some previously identified as regulated in this paradigm (ApC/EBP and ApEgr) but also include novel findings. Specifically, we show that long-term sensitization training rapidly up-regulates the expression of transcripts which may encode Aplysia homologs of a C/EBPγ transcription factor, a glycine transporter (GlyT2), and a vacuolar-protein-sorting-associated protein (VPS36). Copyright © 2014 Elsevier Inc. All rights reserved.

Repeated rat-forced swim test: reducing the number of animals to evaluate gradual effects of antidepressants.

Science.gov (United States)

Mezadri, T J; Batista, G M; Portes, A C; Marino-Neto, J; Lino-de-Oliveira, C

2011-02-15

The forced swim test (FST) is a pre-clinical test to short and long term treatment with antidepressant drugs (ADT), which requires between-subject designs. Herein a modified protocol of the FST using within-subject design (repeated rat-FST) was evaluated. Male Wistar rats were submitted to 15 min of swimming (Day 1: pretest) followed by three subsequent 5 min-swimming tests one week apart (Day 2: test, Day 7: retest 1, Day 14: retest 2). To determine the temporal and factorial characteristics of the variables scored in the repeated rat-FST, the protocol was carried out in untreated animals (E1). To validate the method, daily injections of Fluoxetine (FLX, 2.5mg/kg, i.p.) or saline were given over a 2-week period (E2). Tests and retests have been videotaped for further register of the latency, frequency and duration of behaviors. Over retesting the latency to immobility decreased whereas duration of immobility tended to increase. Factorial analysis revealed that the test, the retest 1 as well as the retest 2 have variables suitable to detection of antidepressant-like effects of ADT. Compared to saline, FLX chronically administrated reduced duration of immobility whereas increased duration of swimming in retest 2. The data suggest that repeated rat-FST detected the gradual increase in the efficacy of low doses of FLX over time. Therefore, repeated rat-FST seemed suitable to detect short and long term effects of selective serotonin reuptake inhibitors, or other ADT, thus reducing the number of animals used in the screenings of this type of compounds. © 2010 Elsevier B.V. All rights reserved.

Long-term collections

CERN Multimedia

Collectes à long terme

2007-01-01

The Committee of the Long Term Collections (CLT) asks for your attention for the following message from a young Peruvian scientist, following the earthquake which devastated part of her country a month ago.

Acute toxicity and the 28-day repeated dose study of a Siddha medicine Nuna Kadugu in rats

Directory of Open Access Journals (Sweden)

Ramaswamy Ramaswamy

2012-10-01

Full Text Available Abstract Background Nuna Kadugu (NK, a Siddha medicine prepared from leaves and fruits of Morinda Pubescens, used for the treatment of various skin diseases. Though NK has been widely used for several decades, no scientific report was available on its safety. Present study was undertaken to demonstrate the oral toxicity of NK in Sprague Dawley rats. Methods Acute and 28-day repeated oral toxicity studies were performed following OECD test guidelines 423 and 407, respectively, with minor modifications. In acute oral toxicity study, NK was administered at 2000mg/kg b.wt., p.o and animals were observed for toxic signs at 0, 0.5, 1, 4, 24 h and for next 14 days. Gross pathology was performed at the end of the study. In repeated dose, the 28- day oral toxicity study, NK was administered at 300, 600 and 900 mg/kg b.wt./p.o/day. Two satellite groups (control and high dose were also maintained to determine the delayed onset toxicity of NK. Animals were observed for mortality, morbidity, body weight changes, feed and water intake. Haematology, clinical biochemistry, electrolytes, gross pathology, relative organ weight and histopathological examination were performed. Results In acute toxicity study, no treatment related death or toxic signs were observed with NK administration. In the repeated dose study, no significant differences in body weight changes, food / water intake, haematology, clinical biochemistry and electrolytes content were observed between control and NK groups. No gross pathological findings and difference in relative organ weights were observed between control and NK treated rats. Histopathological examination revealed no abnormalities with NK treatment. Conclusion Acute study reveals that the LD50 of NK is greater than 2000mg/kg, b.wt. in fasted female rats and can be classified as Category 5. 28-day repeated oral toxicity demonstrates that the No Observed Adverse Effect Level of NK is greater than 900 mg/kg b.wt./day, p.o in rats

Effect of Long-Term Freezing and Freeze–Thaw Cycles on Indigenous and Inoculated Microorganisms in Dewatered Blackwater

DEFF Research Database (Denmark)

Gunnarsdottir, Ragnhildur; Müller, Karoline; Jensen, Pernille Erland

2012-01-01

Wastewater treatment in many Arctic regions is inadequate, even nonexisting. Natural freezing of wastewater in those areas may be beneficial for reduction of microorganisms. The aim of this study was to investigate the effect of long-term freezing, and repeated freezing and thawing, on indigenous...... coliforms, fecal streptococci, and antibiotic-resistant (AR) bacteria, and inoculated Salmonella Enteriditis and E. coli bacteriophage ΦX174 in dewatered blackwater. At the end of the long-term freezing experiment (10 months), an MPN recovery study was done, including the microbial groups that had shown...... the largest reduction, using tryptone soy broth at incubation temperatures of 10 and 20 °C overnight for the coliforms and AR bacteria, and buffered peptone water at incubation temperature of 37 °C for 18–20 h for Salmonella. Fecal streptococci were more resistant to long-term freezing than the coliform group...

Repeated-dose toxicological studies of Tithonia diversifolia (Hemsl.) A. gray and identification of the toxic compounds.

Science.gov (United States)

Passoni, Flávia Donaire; Oliveira, Rejane Barbosa; Chagas-Paula, Daniela Aparecida; Gobbo-Neto, Leonardo; Da Costa, Fernando Batista

2013-05-20

Tithonia diversifolia (Hemsl.) A. Gray has been commonly used in folk medicine to treat abscesses, microbiological infections, snake bites, malaria and diabetes. Both anti-inflammatory and anti-malarial properties have been identified using appropriate assays, but the effective doses have demonstrated toxic effects for the experimental animals. Most of the pharmacological activities have been attributed to sesquiterpene lactones (STLs) and some chlorogenic acid derivatives (CAs) in the leaves of this species. This work aimed to evaluate the repeated-dose toxicity of an aqueous extract (AE) from Tithonia diversifolia leaves and to compare the results with an extract rich in STLs (LRE) and a polar extract (PE) without STLs but rich in CAs. The purpose of this work was to provide insights into the identity of the compounds responsible for the toxic effects of Tithonia diversifolia. The major classes of compounds were confirmed in each extract by IR spectra and HPLC-UV-DAD profiling using previously isolated or standard compounds. The toxicity of each extract was evaluated in a repeated-dose toxicity study in Wistar rats for 90 days. The AE is composed of both STLs and CAs, the LRE is rich in STLs, and the PE is rich in CAs. The AE caused alterations in haematological parameters but few alterations in biochemical parameters and was relatively safe at doses lower than 100mg/kg. However, the PE and LRE demonstrated several adverse effects by damaging the liver and kidneys, respectively. STLs and CAs can be toxic in prolonged use at higher doses in extracts prepared from Tithonia diversifolia by affecting the kidneys and liver. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The Long-Term Multicenter Observational Study of Dabigatran Treatment in Patients With Atrial Fibrillation (RELY-ABLE) Study

DEFF Research Database (Denmark)

Connolly, S. J.; Wallentin, L.; Ezekowitz, M. D.

2013-01-01

. There is a need for longer-term follow-up of patients on dabigatran and for further data comparing the 2 dabigatran doses. Methods and Results Patients randomly assigned to dabigatran in RE-LY were eligible for the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY...

Free recall in Williams syndrome: is there a dissociation between short- and long-term memory?

Science.gov (United States)

Brock, Jon; Brown, Gordon D A; Boucher, Jill

2006-04-01

Two experiments used the free recall paradigm to investigate verbal memory abilities in Williams syndrome (WS)--a rare genetic disorder. In an earlier free recall study, Vicari et al. (1996a) reported that, unlike TD controls, children with WS showed a recency effect but failed to show a primacy effect. These authors interpreted their findings as evidence for a dissociation between relatively strong verbal short-term memory and relatively impaired verbal long-term memory. In Experiment 1 of the current study, children with WS and TD controls showed comparable improvements in performance with repeated testing of the same material, indicating similar long-term learning of the test items. Neither group showed evidence of primacy effects. However, the extent of primacy effects in free recall is known to depend on the rehearsal strategy that participants adopt. In Experiment 2, therefore, participants were encouraged to engage in overt cumulative rehearsal. This manipulation resulted in significant and comparable primacy effects in both groups, although neither group demonstrated a significant change in overall performance. There was therefore no evidence from either experiment for a dissociation between short- and long-term verbal memory in WS.

Long-term retention of 133Ba in the rat trachea following local administration as barium sulfate particles

International Nuclear Information System (INIS)

Takahashi, S.; Patrick, G.

1987-01-01

Long-term retention of 133 Ba in the trachea from intratracheally administered BaSO 4 particles was determined by both serial sacrifice and external scanning methods up to 6 months after injection. The amount of 133 Ba retained 1 week after injection in the caudal region of the trachea, where the tip of the cannula had been at injection, was 0.41% of the initial dose. Thereafter the 133 Ba was cleared exponentially with a mean half-time of 88 days, as determined from the autopsy samples. The cranial region of the trachea, including the site of the tracheostomy, contained 133 Ba at 10 times the level in the caudal region 1 week after injection and was cleared with a half-time of 66 days. These clearance rates were confirmed by repeated external scanning over the trachea. The 133Ba was drained to the lymph nodes not only in the thoracic cavity but also in the cervical region, suggesting the possibility of lymphatic drainage from the trachea to the cervical lymph nodes

Assessment of the long-term safety of repositories. Scientific basis

International Nuclear Information System (INIS)

Noseck, Ulrich; Becker, Dirk; Fahrenholz, Christine

2008-12-01

The project contributed to increase the scientific knowledge on the long-term safety assessment and the safety cases of a radioactive waste repository. International guidelines and more recent safety cases from other countries were evaluated. The feasibility study of the three safety indicators ''individual dose rate'', ''radiotoxicity concentration in the biosphere water'' and ''radiotoxicity flux from the geosphere'' showed that due to the independently derived corresponding reference values these indicators describe three different safety statements. The combination of the three values can give a stronger argument for the safety of the repository system. Another important methodological aspect of the safety cases is the definition and selection of scenarios, one of these the human intrusion scenario. Various human intrusion scenarios are considered in the different nations, which differ significantly with respect to type and time scale, the exposition type and exposition pathway. Further progress has been achieved in how to treat human intrusion scenarios in a German post-closure safety case. Another port of the project dealt with the impact of specific geochemical processes on the long-term safety of the repository. The impact of climate changes on the long-term safety of a radioactive waste repository in rock salt was investigated with respect to processes in the overburden and the biosphere where highest impact is expected. Sofa simplified models and only discrete climate estates have been considered

Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice.

Science.gov (United States)

Tsokas, Panayiotis; Hsieh, Changchi; Yao, Yudong; Lesburguères, Edith; Wallace, Emma Jane Claire; Tcherepanov, Andrew; Jothianandan, Desingarao; Hartley, Benjamin Rush; Pan, Ling; Rivard, Bruno; Farese, Robert V; Sajan, Mini P; Bergold, Peter John; Hernández, Alejandro Iván; Cottrell, James E; Shouval, Harel Z; Fenton, André Antonio; Sacktor, Todd Charlton

2016-05-17

PKMζ is a persistently active PKC isoform proposed to maintain late-LTP and long-term memory. But late-LTP and memory are maintained without PKMζ in PKMζ-null mice. Two hypotheses can account for these findings. First, PKMζ is unimportant for LTP or memory. Second, PKMζ is essential for late-LTP and long-term memory in wild-type mice, and PKMζ-null mice recruit compensatory mechanisms. We find that whereas PKMζ persistently increases in LTP maintenance in wild-type mice, PKCι/λ, a gene-product closely related to PKMζ, persistently increases in LTP maintenance in PKMζ-null mice. Using a pharmacogenetic approach, we find PKMζ-antisense in hippocampus blocks late-LTP and spatial long-term memory in wild-type mice, but not in PKMζ-null mice without the target mRNA. Conversely, a PKCι/λ-antagonist disrupts late-LTP and spatial memory in PKMζ-null mice but not in wild-type mice. Thus, whereas PKMζ is essential for wild-type LTP and long-term memory, persistent PKCι/λ activation compensates for PKMζ loss in PKMζ-null mice.

Clopidogrel plus long-term aspirin after femoro-popliteal stenting. The CLAFS project: 1- and 2-year results

Energy Technology Data Exchange (ETDEWEB)

Strecker, Ernst-Peter K.; Boos, Irene B.L.; Goettmann, Dieter; Vetter, Sylvia [Department of Imaging, Interventional Radiology, and Nuclear Medicine, Diakonissen Hospital, Diakonissenstrasse 28, 76199, Karlsruhe (Germany)

2004-02-01

The aim of this study was to determine the patency rate after femoro-popliteal stenting followed by oral clopidogrel plus long-term aspirin. In a prospective trial, 31 patients with a total of 33 femoro-popliteal artery lesions (21 stenoses, 12 occlusions; 24 femoral, 9 popliteal) were treated with flexible tantalum stents after unsuccessful percutaneous transluminal angioplasty (PTA) preceded by local fibrinolysis in 5 of 12 patients with total occlusion. Post-interventionally, oral aspirin 100 mg was started simultaneously for the long term and was combined with an oral loading dose of 300 mg clopidogrel, followed by 75 mg clopidogrel daily for 28 days. Patients were followed for at least 12 months (maximum 34 months) by clinical examination, Doppler pressure measurement, color and duplex sonography, and angiography in case of suspicion of restenosis. In a retrospective analysis, the results were compared with those of historical groups of patients having received aspirin only (41 patients) or a long-term high-dose low molecular weight heparin (LMWH)+aspirin treatment (42 patients). Three small puncture aneurysms were treated successfully by conservative means and were categorized as minor bleeding complication. Cumulative primary patency rate (PPR) was 76{+-}7.5% (1 year), and 70{+-}9.6% (2 years) in the clopidogrel+aspirin group, thus being tendentiously better than in the aspirin-only group showing 75{+-}4.6% (1 year), and 50{+-}8.1% (2 years). Long-term high-dose LMWH+aspirin treatment showed 87{+-}5.8% (1 year), and 72{+-}9.1% (2 years), thus being superior to the other treatment regimes, with a statistically significant difference (p<0.05) between the LMWH+aspirin and the aspirin group. Clopidogrel plus aspirin is a safe medication regimen and may be effective in the prevention of early stent thrombosis. Mid- and long-term patency rate seems to be intermediate as compared with other therapeutic regimens. The LMWH+aspirin seems to be superior compared with

Clopidogrel plus long-term aspirin after femoro-popliteal stenting. The CLAFS project: 1- and 2-year results

International Nuclear Information System (INIS)

Strecker, Ernst-Peter K.; Boos, Irene B.L.; Goettmann, Dieter; Vetter, Sylvia

2004-01-01

The aim of this study was to determine the patency rate after femoro-popliteal stenting followed by oral clopidogrel plus long-term aspirin. In a prospective trial, 31 patients with a total of 33 femoro-popliteal artery lesions (21 stenoses, 12 occlusions; 24 femoral, 9 popliteal) were treated with flexible tantalum stents after unsuccessful percutaneous transluminal angioplasty (PTA) preceded by local fibrinolysis in 5 of 12 patients with total occlusion. Post-interventionally, oral aspirin 100 mg was started simultaneously for the long term and was combined with an oral loading dose of 300 mg clopidogrel, followed by 75 mg clopidogrel daily for 28 days. Patients were followed for at least 12 months (maximum 34 months) by clinical examination, Doppler pressure measurement, color and duplex sonography, and angiography in case of suspicion of restenosis. In a retrospective analysis, the results were compared with those of historical groups of patients having received aspirin only (41 patients) or a long-term high-dose low molecular weight heparin (LMWH)+aspirin treatment (42 patients). Three small puncture aneurysms were treated successfully by conservative means and were categorized as minor bleeding complication. Cumulative primary patency rate (PPR) was 76±7.5% (1 year), and 70±9.6% (2 years) in the clopidogrel+aspirin group, thus being tendentiously better than in the aspirin-only group showing 75±4.6% (1 year), and 50±8.1% (2 years). Long-term high-dose LMWH+aspirin treatment showed 87±5.8% (1 year), and 72±9.1% (2 years), thus being superior to the other treatment regimes, with a statistically significant difference (p<0.05) between the LMWH+aspirin and the aspirin group. Clopidogrel plus aspirin is a safe medication regimen and may be effective in the prevention of early stent thrombosis. Mid- and long-term patency rate seems to be intermediate as compared with other therapeutic regimens. The LMWH+aspirin seems to be superior compared with CLAFS

Is it sufficient to repeat LINEAR accelerator stereotactic radiosurgery in choroidal melanoma?

Science.gov (United States)

Furdova, A; Horkovicova, K; Justusova, P; Sramka, M

One day session LINAC based stereotactic radiosurgery (SRS) at LINAC accelerator is a method of "conservative" attitude to treat the intraocular malignant uveal melanoma. We used model Clinac 600 C/D Varian (system Aria, planning system Corvus version 6.2 verification IMRT OmniPro) with 6 MeV X by rigid immobilization of the eye to the Leibinger frame. The stereotactic treatment planning after fusion of CT and MRI was optimized according to the critical structures (lens, optic nerve, also lens and optic nerve at the contralateral side, chiasm). The first plan was compared and the best plan was applied for therapy at C LINAC accelerator. The planned therapeutic dose was 35.0 Gy by 99 % of DVH (dose volume histogram). In our clinical study in the group of 125 patients with posterior uveal melanoma treated with SRS, in 2 patients (1.6 %) was repeated SRS indicated. Patient age of the whole group ranged from 25 to 81 years with a median of 54 TD was 35.0 Gy. In 2 patients after 5 year interval after stereotactic radiosurgery for uveal melanoma stage T1, the tumor volume increased to 50 % of the primary tumor volume and repeated SRS was necessary. To find out the changes in melanoma characteristics after SRS in long term interval after irradiation is necessary to follow up the patient by an ophthalmologist regularly. One step LINAC based stereotactic radiosurgery with a single dose 35.0 Gy is one of treatment options to treat T1 to T3 stage posterior uveal melanoma and to preserve the eye globe. In some cases it is possible to repeat the SRS after more than 5 year interval (Fig. 8, Ref. 23).

Single thrombopoietin dose alleviates hematopoietic stem cells intrinsic short- and long-term ionizing radiation damage. In vivo identification of anatomical cell expansion sites.

Science.gov (United States)

Tronik-Le Roux, Diana; Nicola, Marie-Anne; Vaigot, Pierre; Nurden, Paquita

2015-01-01

Hematopoietic stem cells (HSC) are essential for maintaining the integrity of complex and long-lived organisms. HSC, which are self-renewing, reconstitute the hematopoietic system through out life and facilitate long-term repopulation of myeloablated recipients. We have previously demonstrated that when mice are exposed to sublethal doses of ionizing radiation, subsets of the stem/progenitor compartment are affected. In this study we examine the role of thrombopoietin (TPO) on the regenerative capacities of HSC after irradiation and report the first demonstration of efficacy of a single injection of TPO shortly after in vivo exposure to ionizing radiation for reducing HSC injury and improving their functional outcome. Our results demonstrate that TPO treatment not only reduced the number of apoptotic cells but also induced a significant modification of their intrinsic characteristics. These findings were supported by transplantation assays with long-term HSC that were irradiated or unirradiated, TPO treated or untreated, in CD45.1/CD45.2 systems and by using luciferase-labeled HSC for direct bioluminescence imaging in living animals. Of particular importance, our data demonstrate the skull to be a highly favorable site for the TPO-induced emergence of hematopoietic cells after irradiation, suggesting a TPO-mediated relationship of primitive hematopoietic cells to an anatomical component. Together, the data presented here: provide novel findings about aspects of TPO action on stem cells, open new areas of investigation for therapeutic options in patients who are treated with radiation therapy, and show that early administration of a clinically suitable TPO-agonist counteracts the previously observed adverse effects.

Successful Treatment of Sudden Hepatitis Induced by Long-Term Nivolumab Administration

Directory of Open Access Journals (Sweden)

Keisuke Imafuku

2017-04-01

Full Text Available Immune checkpoint inhibitors have drastically changed in the treatment of many kinds of malignancies, especially malignant melanoma. The focus of the recent experiments has not only been on their efficacy but also immune-related adverse events (irAEs. We report a case of fulminant hepatitis due to nivolumab. In this case, the patient had undergone long-term nivolumab therapy. He did not complain of any symptoms but his liver enzyme levels were extremely elevated (grade 4. We promptly decided to start oral corticosteroids in the patient. His liver function rapidly improved. The dose of corticosteroids was gradually reduced. Our case demonstrates that sudden onset fulminant hepatitis can occur despite the safe use of long-term nivolumab therapy. The irAE can improve rapidly with proper corticosteroid treatment. This report will be useful for the physicians who always use immune checkpoint inhibitors.

Mechanism underlying the effect of long-term exposure to low dose of pesticides on DNA integrity.

Science.gov (United States)

Alleva, Renata; Manzella, Nicola; Gaetani, Simona; Bacchetti, Tiziana; Bracci, Massimo; Ciarapica, Veronica; Monaco, Federica; Borghi, Battista; Amati, Monica; Ferretti, Gianna; Tomasetti, Marco

2018-04-01

Pesticides, including herbicides, insecticides and fungicides, are widely used in intensive agriculture. Recently, the long-term effects of pesticide exposure were found to be associated with many diseases. In this study, we evaluated the long-term effect of low-level exposure to a mixture of pesticides on DNA damage response (DDR) in relation to individual detoxifying variability. A residential population chronically exposed to pesticides was enrolled, biological/environmental pesticide levels; paroxonase 1 (PON-1) activity and 192 Q/R polymorphism and DDR were evaluated at three different periods of pesticide exposure. OGG1-dependent DNA repair activity was decreased in relation to pesticide exposure. The increase of DNA lesions and pesticide levels in the intensive pesticide-spraying period was independent on PON-1 activity. Next, human bronchial epithelial and neuronal cells were used as a model for in vitro evaluation of the mechanistic effect of pesticides. Pesticides induced mitochondrial dysfunction leading to ROS formation. ROS from mitochondria induced DNA damage, which in turn induced OGG1-dependent DNA repair activity through 8-oxoguanine DNA glycosylase 1 (OGG1) expression and activation. Even though OGG1 was overexpressed, an inhibition of its activity, associated with DNA lesion accumulation, was found at prolonged pesticide-exposure. A post-translational regulation of OGG1 by pesticide may be postulated. Taken together, long-term exposure to low-levels of pesticides affects DDR resulting in accumulation of DNA lesions that eventually may lead to cancer or neurological disorders. © 2018 Wiley Periodicals, Inc.

Sexuality and Physical Intimacy in Long Term Care: Sexuality, long term care, capacity assessment

OpenAIRE

Lichtenberg, Peter A.

2014-01-01

Sexuality and sexual needs in older adults remains a neglected area of clinical intervention, particularly so in long term care settings. Because older adults in medical rehabilitation and long term care beds present with significant frailties, and often significant neurocognitive disorders it makes it difficult for occupational therapists and other staff to evaluate the capacity of an older adult resident to participate in sexual relationships. The current paper reviews the current literatur...

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 22). Effects of 2- and 4-week administration of theobromine on the testis.

Science.gov (United States)

Funabashi, H; Fujioka, M; Kohchi, M; Tateishi, Y; Matsuoka, N

2000-10-01

The effects of theobromine, a xanthine derivative, on the testis were compared between rats dosed for 2 and 4 weeks to determine whether a 2-week dosing period is long enough to detect toxicity. Theobromine was administered orally to male Sprague-Dawley rats at dose levels of 250 and 500 mg/kg for 2 weeks starting at the age of 6 or 8 weeks, and for 4 weeks from the age of 6 weeks. Histopathological examination of reproductive organs revealed toxic findings in the testis at 500 mg/kg after 2 weeks of dosing at both ages, and at 250 and 500 mg/kg after 4 weeks of dosing. The primary findings were degeneration/necrosis and desquamation of spermatids and spermatocytes, vacuolization of seminiferous tubules, and multinucleated giant cell formation. These findings were present mainly in stages I-VI and XII-XIV. From these results, it is concluded that the toxic effects of theobromine on the testis can be detected by repeated dosing for 2 weeks as well as for 4 weeks.

Differences in health status between long-term and short-term benzodiazepine users.

NARCIS (Netherlands)

Zandstra, S.M.; Furer, J.W.; Lisdonk, E.H. van de; Bor, J.H.J.; Zitman, F.G.; Weel, C. van

2002-01-01

BACKGROUND: Despite generally accepted advice to keep treatment short, benzodiazepines are often prescibed for more than six months. Prevention of long-term benzodiazepine use could be facilitated by the utilisation of risk indicators for long-term use. However, the characteristics of long-term

Validity of food frequency questionnaire-based estimates of long-term long-chain n-3 polyunsaturated fatty acid intake.

Science.gov (United States)

Wallin, Alice; Di Giuseppe, Daniela; Burgaz, Ann; Håkansson, Niclas; Cederholm, Tommy; Michaëlsson, Karl; Wolk, Alicja

2014-01-01

To evaluate how long-term dietary intake of long-chain n-3 polyunsaturated fatty acids (LCn-3 PUFAs), estimated by repeated food frequency questionnaires (FFQs) over 15 years, is correlated with LCn-3 PUFAs in adipose tissue (AT). Subcutaneous adipose tissue was obtained in 2003-2004 (AT-03) from 239 randomly selected women, aged 55-75 years, after completion of a 96-item FFQ (FFQ-03). All participants had previously returned an identical FFQ in 1997 (FFQ-97) and a 67-item version in 1987-1990 (FFQ-87). Pearson product-moment correlations were used to evaluate associations between intake of total and individual LCn-3 PUFAs as estimated by the three FFQ assessments and AT-03 content (% of total fatty acids). FFQ-estimated mean relative intake of LCn-3 PUFAs (% of total fat intake) increased between all three assessments (FFQ-87, 0.55 ± 0.34; FFQ-97, 0.74 ± 0.64; FFQ-03, 0.88 ± 0.56). Validity, in terms of Pearson correlations between FFQ-03 estimates and AT-03 content, was 0.41 (95% CI 0.30-0.51) for total LCn-3 PUFA and ranged from 0.29 to 0.48 for individual fatty acids; lower correlation was observed among participants with higher percentage body fat. With regard to long-term intake estimates, past dietary intake was also correlated with AT-03 content, with correlation coefficients in the range of 0.21-0.33 and 0.21-0.34 for FFQ-97 and FFQ-87, respectively. The correlations were improved by using average estimates from two or more FFQ assessments. Exclusion of fish oil supplement users (14%) did not alter the correlations. These data indicate reasonable validity of FFQ-based estimates of long-term (up to 15 years) LCn-3 PUFA intake, justifying their use in studies of diet-disease associations.

Short- and long-term effects of real-time medication monitoring with short message service (SMS) reminders for missed doses on the refill adherence of people with Type 2 diabetes: evidence from a randomised controlled trial.

NARCIS (Netherlands)

Vervloet, M.; Dijk, L. van; Bakker, D.H. de; Souverein, P.C.; Santen-Reestman, J.; Vlijmen, B. van; Aarle, M.C.W. van; Hoek, L.S. van der; Bouvy, M.L.

2014-01-01

Aims: To investigate short- and long-term effects of real-time monitoring medication use combined with short message service (SMS) reminders for missed doses on refill adherence to oral anti-diabetic medication. Methods: A randomized controlled trial with two intervention groups and one control

Long-term effects of an intracavitary treatment with californium-252 on normal tissue

International Nuclear Information System (INIS)

Sullivan, M.F.; Beamer, J.L.; Mahony, T.D.; Cross, F.T.; Lund, J.E.; Endres, G.W.R.

1976-01-01

About one hundred fifty swine were exposed to either radium-226 or californium-252 sources in the uterine cervix to determine an RBE for both acute and long-term effects. That value for early changes in the tissues at risk in the treatment of cervical cancer was between 6.2 and 6.8. The incidence of complications increased with time after exposure, especially among animals treated with 252 Cf. Analysis of rectal injury showed that ulceration occurred frequently within a year postexposure at doses between 1600 and 2400 rad calculated at 2 cm lateral to the source midline. Fat necrosis and smooth muscle atrophy, resulting in a local rectal stricture, were delayed changes observed in some animals. The lower ureter was the site for a greater frequency of complications than the GI tract. Ureteral stricture often occurred at doses of 1200 rad from 252 Cf and 7000 rad from 226 Ra. Observation of delayed effects in the uterine-cervix in animals held up to 4 years postexposure indicate that the RBE for 252 Cf may be increased to a value as high as 18, while repair may have even decreased it to about 5.6 in the rectum. Fifty swine are still being observed for long-term effects after doses above 800 rad from 252 Cf and 5000 rad from 226 Ra

Prestroke physical activity is associated with severity and long-term outcome from first-ever stroke

DEFF Research Database (Denmark)

Krarup, L.H.; Truelsen, T.; Gluud, C.

2008-01-01

were randomized in the ExStroke Pilot Trial to an intervention of repeated instructions and encouragement to increase the level of physical activity or to a control group. Prestroke level of physical activity was assessed retrospectively by interview using the Physical Activity Scale for the Elderly......OBJECTIVE: To determine whether prestroke level of physical activity influenced stroke severity and long-term outcome. METHODS: Patients included into the present analyses represent a subset of patients with first-ever stroke enrolled into the ExStroke Pilot Trial. Patients with ischemic stroke...... (PASE) questionnaire. The PASE questionnaire quantifies the amount of physical activity done during a 7-day period. In this prospectively collected patient population initial stroke severity was measured using the Scandinavian Stroke Scale and long-term outcome was assessed after 2 years using...

Scientific Understanding from Long Term Observations: Insights from the Long Term Ecological Research (LTER) Program

Science.gov (United States)

Gosz, J.

2001-12-01

The network dedicated to Long Term Ecological Research (LTER) in the United States has grown to 24 sites since it was formed in 1980. Long-term research and monitoring are performed on parameters thatare basic to all ecosystems and are required to understand patterns, processes, and relationship to change. Collectively, the sites in the LTER Network provide opportunities to contrast marine, coastal, and continental regions, the full range of climatic gradients existing in North America, and aquatic and terrestrial habitats in a range of ecosystem types. The combination of common core areas and long-term research and monitoring in many habitats have allowed unprecedented abilities to understand and compare complex temporal and spatial dynamics associated with issues like climate change, effects of pollution, biodiversity and landuse. For example, McMurdo Dry Valley in the Antarctic has demonstrated an increase in glacier mass since 1993 which coincides with a period of cooler than normal summers and more than average snowfall. In contrast, the Bonanza Creek and Toolik Lake sites in Alaska have recorded a warming period unprecedented in the past 200 years. Nitrogen deposition effects have been identified through long-term watershed studies on biogeochemical cycles, especially at Coweeta Hydrological Lab, Harvard Forest, and the Hubbard Brook Experimental Forest. In aquatic systems, such as the Northern Temperate Lakes site, long-term data revealed time lags in effects of invaders and disturbance on lake communities. Biological recovery from an effect such as lake acidification was shown to lag behind chemical recovery. The long-term changes documented over 2 decades have been instrumental in influencing management practices in many of the LTER areas. In Puerto Rico, the Luquillo LTER demonstrated that dams obstruct migrations of fish and freshwater shrimp and water abstraction at low flows can completely obliterate downstream migration of juveniles and damage

Heat treatment effect on structure and long-term rupture strength of γ/γ'-MeC nickel eutectic. Length memory effect

International Nuclear Information System (INIS)

Kishkin, S.T.; Svetlov, I.L.; Sorokina, L.P.; Morozova, S.G.; Golubovskij, E.R.; Yushakova, F.V.

1983-01-01

Heat treatment effect on structure, phase composition and long-term rupture strength of the directional eutectics on the nickel base with γ/γ'-MeC structure is studied at 900-1100 deg C. It is shown that quenching from the temperature of complete dissolving of γ'-phase and ageing (900 deg - 30 hr) provide an optimum size and morphology of the γ-phase and an increase of the long-term rupture strength at 900 and 1000 deg C. Repeated thermal treatment of cimens tested during definite time restores their structure, mechanical properties and dimensions

Enhanced long-term and impaired short-term spatial memory in GluA1 AMPA receptor subunit knockout mice: evidence for a dual-process memory model.

Science.gov (United States)

Sanderson, David J; Good, Mark A; Skelton, Kathryn; Sprengel, Rolf; Seeburg, Peter H; Rawlins, J Nicholas P; Bannerman, David M

2009-06-01

The GluA1 AMPA receptor subunit is a key mediator of hippocampal synaptic plasticity and is especially important for a rapidly-induced, short-lasting form of potentiation. GluA1 gene deletion impairs hippocampus-dependent, spatial working memory, but spares hippocampus-dependent spatial reference memory. These findings may reflect the necessity of GluA1-dependent synaptic plasticity for short-term memory of recently visited places, but not for the ability to form long-term associations between a particular spatial location and an outcome. This hypothesis is in concordance with the theory that short-term and long-term memory depend on dissociable psychological processes. In this study we tested GluA1-/- mice on both short-term and long-term spatial memory using a simple novelty preference task. Mice were given a series of repeated exposures to a particular spatial location (the arm of a Y-maze) before their preference for a novel spatial location (the unvisited arm of the maze) over the familiar spatial location was assessed. GluA1-/- mice were impaired if the interval between the trials was short (1 min), but showed enhanced spatial memory if the interval between the trials was long (24 h). This enhancement was caused by the interval between the exposure trials rather than the interval prior to the test, thus demonstrating enhanced learning and not simply enhanced performance or expression of memory. This seemingly paradoxical enhancement of hippocampus-dependent spatial learning may be caused by GluA1 gene deletion reducing the detrimental effects of short-term memory on subsequent long-term learning. Thus, these results support a dual-process model of memory in which short-term and long-term memory are separate and sometimes competitive processes.

Effects of long-term grassland management on the carbon and nitrogen pools of different soil aggregate fractions.

Science.gov (United States)

Egan, Gary; Crawley, Michael J; Fornara, Dario A

2018-02-01

Common grassland management practices include animal grazing and the repeated addition of lime and nutrient fertilizers to soils. These practices can greatly influence the size and distribution of different soil aggregate fractions, thus altering the cycling and storage of carbon (C) and nitrogen (N) in grassland soils. So far, very few studies have simultaneously addressed the potential long-term effect that multiple management practices might have on soil physical aggregation. Here we specifically ask whether and how grazing, liming and nutrient fertilization might influence C and N content (%) as well as C and N pools of different soil aggregate fractions in a long-term grassland experiment established in 1991 at Silwood Park, Berkshire, UK. We found that repeated liming applications over 23years significantly decreased the C pool (i.e. gCKg -1 soil) of Large Macro Aggregate (LMA>2mm) fractions and increased C pools within three smaller soil aggregate fractions: Small Macro Aggregate (SMA, 250μm-2mm), Micro Aggregate (MiA, 53-250μm), and Silt Clay Aggregate (SCAfractions was mainly caused by positive liming effects on aggregate fraction mass rather than on changes in soil C (and N) content (%). Liming effects could be explained by increases in soil pH, as this factor was significantly positively related to greater soil C and N pools of smaller aggregate fractions. Long-term grazing and inorganic nutrient fertilization had much weaker effects on both soil aggregate-fraction mass and on soil C and N concentrations, however, our evidence is that these practices could also contribute to greater C and N pools of smaller soil fractions. Overall our study demonstrates how agricultural liming can contribute to increase C pools of small (more stable) soil fractions with potential significant benefits for the long-term C balance of human-managed grassland soils. Copyright © 2017 Elsevier B.V. All rights reserved.

The short-term and decade-long effects of divorce on women's midlife health.

Science.gov (United States)

Lorenz, Frederick O; Wickrama, K A S; Conger, Rand D; Elder, Glen H

2006-06-01

We hypothesize that divorce immediately increases psychological distress and has long-term negative consequences for the physical health of divorced people. In addition, we hypothesize that divorce indirectly causes long-term increases in distress through stressful midlife events. The hypotheses are tested using data from 416 rural Iowa women who were interviewed repeatedly in the early 1990s when they were mothers of adolescent children; the women were interviewed again in 2001. The data support the hypotheses. In the years immediately after their divorce (1991-1994), divorced women reported significantly higher levels ofpsychological distress than married women but no differences in physical illness. A decade later (in 2001), the divorced women reported significantly higher levels of illness, even after controlling for age, remarriage, education, income, and prior health. Compared to their married counterparts, divorced women reported higher levels of stressful life events between 1994 and 2000, which led to higher levels of depressive symptoms in 2001.

Long-term use of mizoribine in rheumatoid arthritis patients on hemodialysis.

Science.gov (United States)

Saisho, K; Kurosawa, O; Fukanoki, T; Hanafusa, A; Tajima, N

2001-06-01

Abstract Small doses of mizoribine (MZR) were administered to five rheumatoid arthritis (RA) patients on hemodialysis (HD). A maintenance dose of 25 mg or less was administered either once per day or once following HD. The Lansbury activity index improved in all patients. The blood concentrations of MZR before and after HD were 0.33-1.79 μg/ml and 0-0.93 μg/ml, respectively. Hence, the rate of elimination by HD ranged from 50.3% to 83.4%. As far as side effects were concerned, alopecia was seen in two patients, and one patient developed shingles. However, the severity of these symptoms was mild and, after discontinuing or reducing the dose of MZR for a certain period of time, we were able to continue its administration. These findings suggest that the long-term administration of MZR is a useful treatment for RA patients on HD.

Long term results of 125I for treatment of hyperthyroidism

International Nuclear Information System (INIS)

Bremner, W.F.; McDougall, I.R.; Greig, W.R.; Ratcliffe, J.G.

1976-01-01

125 I emits very low energy conversion and Auger electrons. This radionuclide has been used in place of 131 I with the hope of reducing the incidence of post treatment hypothyroidism. 303 of 360 patients treated have been reviewed. Originally very large doses of 125 I were prescribed (751-1,600 μCi/g) but 9 out of 15 patients (60%) became hypothyroid, therefore 4 smaller therapeutic regimes were employed. (1) 55 patients received doses of 200 μCi or less/g thyroid, 69% are euthyroid and 24% hypothyroid after an average of 33 months from treatment. (2) 87 patients received doses of 201-350 μCi/g thyroid, 67% are euthyroid and 21% hypothyroid after an average follow up of 30 months. (3) 70 patients received doses of 351-500 μCi/g thyroid, 77% are euthyroid and 18% hypothyroid 36 months after treatment and (4) 76 patients received doses of 501-750 μCi/g, 41% are euthyroid and 56% hypothyroid 49 months after therapy. No long term complications such as thyroid cancer or leukaemia have occurred but because 125 I does not eliminate or reduce the incidence of post treatment hypothyroidism it probably should not be used in preference to 131 I for the routine treatment of hyperthyroidism

Very long-term sequelae of craniopharyngioma.

Science.gov (United States)

Wijnen, Mark; van den Heuvel-Eibrink, Marry M; Janssen, Joseph A M J L; Catsman-Berrevoets, Coriene E; Michiels, Erna M C; van Veelen-Vincent, Marie-Lise C; Dallenga, Alof H G; van den Berge, J Herbert; van Rij, Carolien M; van der Lely, Aart-Jan; Neggers, Sebastian J C M M

2017-06-01

Studies investigating long-term health conditions in patients with craniopharyngioma are limited by short follow-up durations and generally do not compare long-term health effects according to initial craniopharyngioma treatment approach. In addition, studies comparing long-term health conditions between patients with childhood- and adult-onset craniopharyngioma report conflicting results. The objective of this study was to analyse a full spectrum of long-term health effects in patients with craniopharyngioma according to initial treatment approach and age group at craniopharyngioma presentation. Cross-sectional study based on retrospective data. We studied a single-centre cohort of 128 patients with craniopharyngioma treated from 1980 onwards (63 patients with childhood-onset disease). Median follow-up since craniopharyngioma presentation was 13 years (interquartile range: 5-23 years). Initial craniopharyngioma treatment approaches included gross total resection ( n  = 25), subtotal resection without radiotherapy ( n  = 44), subtotal resection with radiotherapy ( n  = 25), cyst aspiration without radiotherapy ( n  = 8), and 90 Yttrium brachytherapy ( n  = 21). Pituitary hormone deficiencies (98%), visual disturbances (75%) and obesity (56%) were the most common long-term health conditions observed. Different initial craniopharyngioma treatment approaches resulted in similar long-term health effects. Patients with childhood-onset craniopharyngioma experienced significantly more growth hormone deficiency, diabetes insipidus, panhypopituitarism, morbid obesity, epilepsy and psychiatric conditions compared with patients with adult-onset disease. Recurrence-/progression-free survival was significantly lower after initial craniopharyngioma treatment with cyst aspiration compared with other therapeutic approaches. Survival was similar between patients with childhood- and adult-onset craniopharyngioma. Long-term health conditions were comparable after

[Long-term follow-up of patients with suprasellar germinomas].

Science.gov (United States)

Bauditz, Juergen; Lochs, Herbert; Ventz, Manfred

2007-10-15

Suprasellar germinomas are rare intracranial neoplasms, which mainly occur in children and adolescents and manifest with endocrine symptoms and/or compression syndromes. The clinical, hormonal and morphological findings as well as treatment and complications were investigated in seven patients (six male, one female) with germinomas. Mean age at diagnosis was 19.7 years (range 15-32 years). First disease-related symptoms were diabetes insipidus (three patients), loss of libido (two patients), pseudopubertas praecox (one patient), and dwarfism (one patient). However, decisive symptoms leading to final diagnosis were visual disturbances (five patients), pubertas tarda (one patient), and hypogonadism (one patient). All patients were treated by transcranial radiation with a dose of 40-54 Gy. One patient received additional chemotherapy with cisplatin, etoposide, and ifosfamide (PEI). Patients were followed up for 14.6 years (range 7-27 years). Intracranial and pulmonary relapses were observed in two patients. Panhypopituitarism and diabetes insipidus were seen in all patients after treatment. Two patients suffered from loss of vision, two further patients from unilateral amaurosis. One patient developed epilepsy and persistent cognitive impairment. Long-term follow-up shows that two patients died from recurrent disease and decompensated liver cirrhosis, respectively. The other patients are long-term survivors. Full social integration with employment was possible in one case. Suprasellar germinomas cause endocrine symptoms during early tumor stages, however, diagnosis is generally established when ocular symptoms related to tumor compression are already present. Long-term survival is characterized by panhypopituitarism, diabetes insipidus and, partly, ocular or cerebral defects.

Long-term prisoner in prison isolation

Directory of Open Access Journals (Sweden)

Karolina Grudzińska

2013-06-01

Full Text Available Long-term prisoner belongs to a particular category of people who are imprisoned in prisons. On the one hand in this group are often heavily demoralized people who committed the most serious crimes, on the other hand it is a group of prisoners, who should be well thought out and programmed the impact of rehabilitation. The situation of man trapped for years poses in a complicated situation not only the prisoners, but also the entire prison staff. They have to take care of the fact that the prison isolation did not cause the state in which convicts form itself in learned helplessness and lack of skills for self-planning and decision-making. In addition, planning the rehabilitation impact of long-term prisoners should not be forgotten that these prisoners in the short or the long term will return to the libertarian environment therefore, should prevent any negative effects of long-term imprisonment. This article presents the main issues related to the execution of imprisonment against long-term prisoners. It is an attempt to systematize the knowledge of this category of people living in prison isolation.

Selenium homeostasis and induction of thioredoxin reductase during long term selenite supplementation in the rat

DEFF Research Database (Denmark)

Erkhembayar, Suvd; Mollbrink, Annelie; Eriksson, Malin

2011-01-01

-dependent increase in blood and liver selenium levels, with plateaus at 6 and 8weeks, respectively. These plateaus were reached at the same level of selenium regardless of dose, and no further accumulation was observed. A selenium-dependent increase in the activity of TrxR1 in parallel with the increase in liver...... selenium levels was also seen, and the induction of TrxR1 mRNA was seen only during the first three days of treatment, when the levels of selenium in the liver were increasing. Sodium selenite at 1 and 5μg/mL did not affect body weight or relative liver mass. We concluded that long-term treatment...... with selenite did not cause accumulation of selenium and that the activity of TrxR1 in the liver rose with the selenium levels. We therefore suggest that sodium selenite at doses up to 5μg/mL could be used for long-term tumour prevention....

The basic approaches to evaluation of effects of the long-therm radiation exposure in a range of 'low' doses

International Nuclear Information System (INIS)

Takhauov, R.M.; Karpov, A.B.; Litvyakov, N.V.

2010-01-01

The previously performed research allowed forming the main concepts about deterministic effects of radiation impact and defining the main postulates of radiation medicine with respect to average and high levels of exposure. At the same time the research performed to evaluate stochastic effects caused by 'low' doses of ionizing radiation influence failed to find a single-valued answer relating both to dose impact inducing the effect development and to the spectrum of recorded pathologic processes or diseases. In this connection on our opinion the most prospective decision of present problem are studies in follow directions: 1. The evaluation of radiation productions personal and residents of nearby territories mortality and morbidity structure and dynamics. 2. The estimation of risk main diseases development with long-term radiation exposure and analysis of radiation factor role in its pathogenesis. 3. The study of genetic disturbances of persons and their descendants exposed long-term ionizing radiation in 'low' doses. 4. The study of individual radio sensitivity genetic markers. 5. The evaluation of structural and functional homeostasis disturbances inducing the radiation exposure in 'low' doses. The object of study is the Close administrative territorial formation Seversk population and mainly Siberian Group Chemical Enterprises (SGCE) personal - the largest complex productions of atomic industry in the world. The Regional Medico-Dosimetric Register (RMDR), creating since 2001 is the basis for epidemiological studies. The register database contain the information concerning to about 66 000 SGCE workers (it is a whole number of workers in all years of SGCE existence from 1950 to now day). The 35 000 from 66 000 workers are the workers of so-called main productions. About 96% workers exposed external radiation has cumulative dose less 500 mSv. On the base of laboratory of genomic medicine it was created and constantly enriched the bank DNA and biological material

Long-term respiratory health effects in textile workers.

Science.gov (United States)

Lai, Peggy S; Christiani, David C

2013-03-01

Over 60 million people worldwide work in the textile or clothing industry. Recent studies have recognized the contribution of workplace exposures to chronic lung diseases, in particular chronic obstructive pulmonary disease (COPD). Early studies in textile workers have focused on the relationship between hemp or cotton dust exposure and the development of a syndrome termed byssinosis. The purpose of this review is to evaluate the effect of long-term exposure to organic dust in textile workers on chronic respiratory disease in the broader context of disease classifications, such as reversible or irreversible obstructive lung disease (i.e. asthma or COPD), and restrictive lung disease. Cessation of exposure to cotton dust leads to improvement in lung function. Recent animal models have suggested a shift in the lung macrophage:dendritic cell population ratio as a potential mechanistic explanation for persistent inflammation in the lung due to repeated cotton dust-related endotoxin exposure. Other types of textile dust, such as silk, may contribute to COPD in textile workers. Textile dust-related obstructive lung disease has characteristics of both asthma and COPD. Significant progress has been made in the understanding of chronic lung disease due to organic dust exposure in textile workers.

Enhancement of long-term spatial memory in adult rats by the noncompetitive NMDA receptor antagonists, memantine and neramexane.

Science.gov (United States)

Zoladz, Phillip R; Campbell, Adam M; Park, Collin R; Schaefer, Daniela; Danysz, Wojciech; Diamond, David M

2006-10-01

Memantine and neramexane are noncompetitive NMDA receptor antagonists which have been investigated for their promising effects in aiding memory in people with dementia. Memantine is approved for the treatment of Alzheimer's disease, and neramexane is currently under development for this indication. Therefore, the present study provided a comparative assessment of the effects of equimolar doses of memantine and neramexane on spatial (hippocampus-dependent) memory. Adult male rats were given only 3 training trials to learn the location of a hidden platform in a water maze. In control (vehicle-injected) rats, this minimal amount of training produced intact short-term (15 min), but poor long-term (24 h), memory. Pre-training administration of memantine or neramexane produced a dose-dependent enhancement of long-term memory. Pharmacokinetic experiments with equimolar doses of both agents indicated that lower plasma levels of neramexane were more effective than memantine at enhancing memory. The effective doses of both agents in the current study produced plasma levels (and extrapolated brain CSF levels) within a range of activity at NMDA receptors and plasma levels seen in patients with Alzheimer's disease. These findings provide support for the use of neramexane as a pharmacological intervention in the treatment of dementia.

[A case of brain metastasis discovered after surgery for lung cancer based on changes in CEA, in which long-term survival was obtained by repeated gammaknife irradiation].

Science.gov (United States)

Kakeya, Hiroshi; Inoue, Yuichi; Sawai, Toyomitsu; Ikuta, Yasushi; Ohno, Hideaki; Yanagihara, Katsunori; Higashiyama, Yasuhito; Miyazaki, Yoshitsugu; Soda, Hiroshi; Tashiro, Takayoshi; Kohno, Shigeru

2005-12-01

A 58-year-old man underwent right lower lobectomy for lung adenocarcinoma in June 1998. Since a high level of tumor marker CEA persisted after surgery, chemotherapy was additionally performed, and the CEA level subsequently normalized. However, the CEA level increased in April 1999, and brain metastasis was found in the left occipital lobe, and the first gammaknife irradiation was performed. Multiple brain metastases were found when CEA increased again in August 1999, and the second gammaknife irradiation was performed. Moreover, brain metastases were found in the left frontal and occipital lobes in February 2000, and the third gammaknife irradiation was performed. CEA normalized thereafter, but increased in February 2001. Brain metastasis was found in the right occipital lobe, and the fourth gammaknife irradiation was performed. CEA has remained within the normal range for about 4 years thereafter. Long-term survival was possible by repeated gammaknife irradiation for brain metastases. Monitoring of CEA played an important role in finding recurrent brain metastasis in this patient.

Competitive short-term and long-term memory processes in spatial habituation.

Science.gov (United States)

Sanderson, David J; Bannerman, David M

2011-04-01

Exposure to a spatial location leads to habituation of exploration such that, in a novelty preference test, rodents subsequently prefer exploring a novel location to the familiar location. According to Wagner's (1981) theory of memory, short-term and long-term habituation are caused by separate and sometimes opponent processes. In the present study, this dual-process account of memory was tested. Mice received a series of exposure training trials to a location before receiving a novelty preference test. The novelty preference was greater when tested after a short, rather than a long, interval. In contrast, the novelty preference was weaker when exposure training trials were separated by a short, rather than a long interval. Furthermore, it was found that long-term habituation was determined by the independent effects of the amount of exposure training and the number of exposure training trials when factors such as the intertrial interval and the cumulative intertrial interval were controlled. A final experiment demonstrated that a long-term reduction of exploration could be caused by a negative priming effect due to associations formed during exploration. These results provide evidence against a single-process account of habituation and suggest that spatial habituation is determined by both short-term, recency-based memory and long-term, incrementally strengthened memory.

Short- and long-term effectiveness of intracavitary urokinase in loculated thoracic empyema

International Nuclear Information System (INIS)

Jeong, Tae Gon; Han, Young Min; Chang, Suk Kyeong; Chung, Gyung Ho; Sohn, Myung Hee; Kim, Chong Soo; Choi, Ki Chul

1995-01-01

The purpose of this study was to evaluate the short-and long-term effectiveness of intracavitary urokinase with percutaneous catheter drainage in loculated thoracic empyemas. 15 patients were identified as second stage of loculated thoracic empyema by estimating nature of pleural fluid, chest PA, lateral decubitus view and CT scan. Under the guidance of fluoroscopy or ultrasound, catheter was inserted percutaneously. Instillation of urokinase was started when amount of drained fluid became less than 30 ml per day with 100,000U of urokinase mixed with 100 ml of normal saline. Trial of urokinase was repeated until complete drainage of empyema was demonstrated on plain chest film obtained after 48 hours. Successful complete drainage was achieved in 14 of 15 patients. In long-term study, complete resorption was demonstrated in 11 of 12 patients. Average dosage of used urokinase was 330,000U and mean duration of catheter insertion was 35 days. Intracavitary urokinase with percutaneous catheter drainage is a safe and effective method to facilitate drainage of loculated empyema and to prevent recurrence

Long term liquidity analysis of the firm

Directory of Open Access Journals (Sweden)

Jaroslav Gonos

2009-09-01

Full Text Available Liquidity control is a very difficult and important function. If the business is not liquid in the long term, it is under threatof bankruptcy, and on the other hand surplus of the cash in hand threaten its future efficiency, because the cash in hand is a sourceof only limited profitability. Long term liquidity is related to the ability of the short term and long term liabilities payment. Articleis trying to point out to the monitoring and analyzing of the long term liquidity in the concrete business, in this case the printing industrycompany. Hereby at the end of the article mentioned monitored and analyzed liquidity is evaluated in the five years time period.

Effects of estrogen on low density lipoprotein metabolism in males. Short-term and long-term studies during hormonal treatment of prostatic carcinoma

International Nuclear Information System (INIS)

Eriksson, M.; Berglund, L.; Rudling, M.; Henriksson, P.; Angelin, B.

1989-01-01

To characterize the effects of estrogen treatment on the metabolism of LDL we studied six males with metastatic prostatic carcinoma before and during the initiation of therapy; a repeated study was performed in five participants after 3-6 mo of treatment. The fractional catabolic rate (FCR) of autologous 125 I-LDL was calculated both from elimination curves of plasma radioactivity and from urine/plasma (U/P) radioactivity ratios. Within 1-2 d of onset of estrogen therapy a more rapid decay of plasma radioactivity occurred, and FCR measured from U/P ratios increased by 20%. Concomitantly, LDL cholesterol levels decreased by 16%. After 3-6 mo of treatment FCR determined by both techniques was almost doubled, and LDL cholesterol was reduced by 34%. This occurred despite a 29% increase in the calculated synthesis rate of LDL. Tissue culture studies demonstrated that the receptor affinity of LDL isolated from patients on long-term estrogen therapy was reduced. We conclude that a profound increase in LDL catabolism is induced through administration of pharmacological doses of estrogen in males, and hypothesize that this is the consequence of an increased expression of hepatic LDL receptors. This enhanced catabolism of LDL leaves LDL particles in plasma with lower affinity for the LDL receptor

Impaired intracortical transmission in G2019S leucine rich-repeat kinase Parkinson patients.

Science.gov (United States)

Ponzo, Viviana; Di Lorenzo, Francesco; Brusa, Livia; Schirinzi, Tommaso; Battistini, Stefania; Ricci, Claudia; Sambucci, Manolo; Caltagirone, Carlo; Koch, Giacomo

2017-05-01

A mutation in leucine-rich repeat kinase 2 is the most common cause of hereditary Parkinson's disease (PD), yet the neural mechanisms and the circuitry potentially involved are poorly understood. We used different transcranial magnetic stimulation protocols to explore in the primary motor cortex the activity of intracortical circuits and cortical plasticity (long-term potentiation) in patients with the G2019S leucine-rich repeat kinase 2 gene mutation when compared with idiopathic PD patients and age-matched healthy subjects. Paired pulse transcranial magnetic stimulation was used to investigate short intracortical inhibition and facilitation and short afferent inhibition. Intermittent theta burst stimulation, a form of repetitive transcranial magnetic stimulation, was used to test long-term potentiation-like cortical plasticity. Leucine-rich repeat kinase 2 and idiopathic PD were tested both in ON and in OFF l-dopa therapy. When compared with idiopathic PD and healthy subjects, leucine-rich repeat kinase 2 PD patients showed a remarkable reduction of short intracortical inhibition in both ON and in OFF l-dopa therapy. This reduction was paralleled by an increase of intracortical facilitation in OFF l-dopa therapy. Leucine-rich repeat kinase 2 PD showed abnormal long-term potentiation-like cortical plasticity in ON l-dopa therapy. The motor cortex in leucine-rich repeat kinase 2 mutated PD patients is strongly disinhibited and hyperexcitable. These abnormalities could be a result of an impairment of inhibitory (gamma-Aminobutyric acid) transmission eventually related to altered neurotransmitter release. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Long term effect of radioactive iodine treatment in nontoxic multinodular goitre

International Nuclear Information System (INIS)

Nygaard, B.; Hegedues, L.; Gervil, M.; Hjalgrim Jensen, H.; Soee-Jensen, P.; Moelholm hansen, J.E.

1994-01-01

The aim of this study was to investigate the long term effect of 131 I treatment on thyroid function and size in patients with non-toxic multinodular goitre. The subjects were 69 consecutive patients with multinodular non-toxic goitre selected for 131 I treatment and followed for a minimum of 12 months. Outcome measures were standard thyroid function variable and ultrasonically determined thyroid volume before and after treatment. Fifty-nine patients were treated with a single dose of 131 I, 12 with tow doses, and one with four doses. In 45 patients treated with one dose who remained euthyroid the median thyroid volume was reduced from 73 (interquartile range 50-106) ml to 29 (interquartile range 23-48) ml at 24 months. The median reuction was 40 (22-48) ml, half of which occurred within three months. Patients treated with two doses as well as those developing hypo- or hyper-thyroidism also had a significant reduction in thyroid volume. Eleven patients develeoped hypothyroidism (cumulative five year risk 22%). Side effects were few. In conclusion we find that 131 I treatment of multinodular non-toxic goitre is an attractive alternative to surgery. (au) (19 refs.)

A New Look at the Old Problem of a Reasonable Expectation: The Reasonableness of Repeated Renewals of Fixed Term Contracts as Opposed to Indefinite Employment

Directory of Open Access Journals (Sweden)

E Gericke

2011-04-01

Full Text Available In South Africa, the Labour Relations Act 66 of 1995 (LRA regulates and protects the position of the employee who reasonably expects that a fixed-term contract will be renewed on the same or similar terms while the employer only offered to renew the contract on less favourable terms or in some instances was not prepared torenew the fixed-term contract at all. The LRA regards the latter conduct as a dismissal, as long as the employee can prove that the employer was responsible for creating the reasonable expectation of contractual renewal. In contrast to this position, the LRA does not regulate or protect the position of the employee whose fixed-term contract was repeatedly renewed on the same, similar or even improved terms, while the employer was in a position to offer the employee indefinite employment. The employer may even have created a reasonable expectation that repeated renewals would result in permanent employment. The exploitation and abuse of the fixed-term contract to the extent that an employee is deprived of employment security and the benefits linked to an employment relationship of indefinite duration have prompted a comparative investigation into this particular field of law.

LINAC-radiosurgery for nonsecreting pituitary adenomas. Long-term results

Energy Technology Data Exchange (ETDEWEB)

Runge, M.J.R.; Maarouf, M.; Hunsche, S.; Ruge, M.I.; El Majdoub, F.; Treuer, H.; Sturm, V. [Koeln Univ. (Germany). Dept. of Stereotaxy and Functional Neurosurgery; Kocher, M.; Mueller, R.P. [Koeln Univ. (Germany). Dept. of Radiation Oncology; Voges, J. [Magdeburg Univ. (Germany). Dept. of Stereotactic Neurosurgery

2012-04-15

Stereotactic linear accelerator-based radiosurgery (LINAC-RS) is increasingly used for microsurgically inaccessible or recurrent pituitary adenomas. This single-center study evaluates the long-term follow-up after LINAC-RS of nonsecreting pituitary adenomas (NSA). Patients and methods: Between 1992 and August 2008, 65 patients with NSA were treated. Patient treatment and follow-up were conducted according to a prospective protocol. Indications for LINAC-RS were (1) tumor recurrence or (2) residual tumor. Three patients were treated primarily. For analysis of prognostic factors, patients were grouped according to epidemiological or treatment-associated characteristics. Results: A total of 61 patients with a follow-up {>=} 12 months (median 83 months, range 15-186 months, longest follow-up of published radiosurgery series) were evaluated with regard to their clinical, radiological, and endocrinological course. The median tumor volume was 3.5 ml ({+-} 4.3 ml, range 0.3-17.3 ml) treated with a median surface and maximum dose of 13.0 Gy and 29.7 Gy, respectively. Local tumor control was achieved in 98%. One patient died of unrelated cause after 36 months and 1 patient developed a radiation-induced seizure disorder. Visual complications did not occur. In 37 of 41 patients (90.2%), pituitary function remained stable. Maximum dose to the pituitary {<=} 16 Gy and female gender were positive prognostic factors for the preservation of pituitary function. Conclusion: LINAC-RS is a minimally invasive, safe, and effective treatment for recurrent NSA or microsurgically inaccessible residual tumor. LINAC-RS yielded a high rate of local long-term tumor control with a small number of radiation-induced side effects. (orig.)

LINAC-radiosurgery for nonsecreting pituitary adenomas. Long-term results

International Nuclear Information System (INIS)

Runge, M.J.R.; Maarouf, M.; Hunsche, S.; Ruge, M.I.; El Majdoub, F.; Treuer, H.; Sturm, V.; Kocher, M.; Mueller, R.P.; Voges, J.

2012-01-01

Stereotactic linear accelerator-based radiosurgery (LINAC-RS) is increasingly used for microsurgically inaccessible or recurrent pituitary adenomas. This single-center study evaluates the long-term follow-up after LINAC-RS of nonsecreting pituitary adenomas (NSA). Patients and methods: Between 1992 and August 2008, 65 patients with NSA were treated. Patient treatment and follow-up were conducted according to a prospective protocol. Indications for LINAC-RS were (1) tumor recurrence or (2) residual tumor. Three patients were treated primarily. For analysis of prognostic factors, patients were grouped according to epidemiological or treatment-associated characteristics. Results: A total of 61 patients with a follow-up ≥ 12 months (median 83 months, range 15-186 months, longest follow-up of published radiosurgery series) were evaluated with regard to their clinical, radiological, and endocrinological course. The median tumor volume was 3.5 ml (± 4.3 ml, range 0.3-17.3 ml) treated with a median surface and maximum dose of 13.0 Gy and 29.7 Gy, respectively. Local tumor control was achieved in 98%. One patient died of unrelated cause after 36 months and 1 patient developed a radiation-induced seizure disorder. Visual complications did not occur. In 37 of 41 patients (90.2%), pituitary function remained stable. Maximum dose to the pituitary ≤ 16 Gy and female gender were positive prognostic factors for the preservation of pituitary function. Conclusion: LINAC-RS is a minimally invasive, safe, and effective treatment for recurrent NSA or microsurgically inaccessible residual tumor. LINAC-RS yielded a high rate of local long-term tumor control with a small number of radiation-induced side effects. (orig.)

Perturbations in different forms of cost/benefit decision making induced by repeated amphetamine exposure.

Science.gov (United States)

Floresco, Stan B; Whelan, Jennifer M

2009-08-01

Psychostimulant abuse has been linked to impairments in cost-benefit decision making. We assessed the effects of repeated amphetamine (AMPH) treatment in rodents on two distinct forms of decision making. Separate groups of rats were trained for 26 days on either a probabilistic (risk) or effort-discounting task, each consisting of four discrete blocks of ten choice trials. One lever always delivered a smaller reward (one or two pellets), whereas another lever delivered a four-pellet reward. For risk-discounting, the probability of receiving the larger reward decreased across trial blocks (100-12.5%), whereas on the effort task, four pellets could be obtained after a ratio of presses that increased across blocks (2-20). After training, rats received 15 saline or AMPH injections (escalating from 1 to 5 mg/kg) and were then retested during acute and long-term withdrawal. Repeated AMPH administration increased risky choice 2-3 weeks after drug exposure, whereas these treatments did not alter effort-based decision making in a separate group of animals. However, prior AMPH exposure sensitized the effects of acute AMPH on both forms of decision making, whereby lower doses were effective at inducing "risky" and "lazy" patterns of choice. Repeated AMPH exposure leads to relatively long-lasting increases in risky choice, as well as sensitization to the effects of acute AMPH on different forms of cost/benefit decision making. These findings suggest that maladaptive decision-making processes exhibited by psychostimulant abusers may be caused in part by repeated drug exposure.

Long-term high-physiological-dose growth hormone reduces intra-abdominal fat in HIV-infected patients with a neutral effect on glucose metabolism

DEFF Research Database (Denmark)

Hansen, B R; Haugaard, S B; Jensen, Frank Krieger

2010-01-01

, glucose tolerance, and total plasma cholesterol and triglycerides did not significantly change during intervention. CONCLUSIONS: Daily 0.7 mg rhGH treatment for 40 weeks reduced abdominal visceral fat and trunk fat mass in HIV-infected patients. This treatment appeared to be safe with respect to glucose......OBJECTIVES: The aim of the study was to investigate the effect of long-term high-physiological-dose recombinant human growth hormone (rhGH) therapy on fat distribution and glucose metabolism in HIV-infected patients. METHODS: Forty-six HIV-infected Caucasian men on highly active antiretroviral...... between 1 and 3 pm for 40 weeks. Endpoints included changes in visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), limb fat mass, percentage of limb fat, plasma lipids, insulin resistance and glucose tolerance. RESULTS: VAT and trunk fat mass decreased significantly in the GH group compared...

Soil-plant-relationships and ecological forecast of human internal doses from long-lived radionuclides. Dose 'cost' of the transformation of radionuclides bioavailability

International Nuclear Information System (INIS)

Kravets, A.P.; Grodzinsky, D.M.

1999-01-01

Soil pathway of radionuclides pollution of agricultural production becomes the main one at the recovery stage of postaccidental period. For this stage dynamics of the human foodstuffs cleaning and rate of internal dose due to consumption are results , of the interaction of three main factors, namely, the rate of the decrease of soil contamination, structure of soil use and transformations of bioavailability of radionuclides. Representation of these ideas in quantitative form, documentation and analysis of the main ecological causes that determine the intensity of the radionuclides mobility in the biological cycle is essential increase the accuracy of the long-term forecast of human dose formation and promote the development of adequate strategies for countermeasures. General formal model and practical method of the ecological forecast of human internal doses has been proposed and used for estimation. Refs. 5 (author)

Mechanisms of long-term concrete degradation in LLW disposal facilities

International Nuclear Information System (INIS)

Rogers, V.C.

1987-01-01

Most low-level waste (LLW) disposal alternatives, except shallow land burial and improved shallow land burial, involve the use of concrete as an extra barrier for containment. Because concrete is a porous-type material, its moisture retention and transport properties can be characterized with parameters that are also used to characterize the geohydrologic properties of soils. Several processes can occur with the concrete to degrade it and to increase both the movement of water and contaminants through the disposal facility. The effect of these processes must be quantified in designing and estimating the long-term performance of disposal facilities. Modeling the long-term performance of LLW disposal technologies involves, first, estimating the degradation rate of the concrete in a particular facility configuration and environmental setting; second, calculating the water flow through the facility as a function of time; third, calculating the contaminant leaching usually by diffusion or dissolution mechanisms, and then coupling the facility water and contaminant outflow to a hydrogeological and environmental uptake model for environmental releases or doses

The effects of prenatal irradiation with a low doses of gamma-rays on spatial memory in adult rats

International Nuclear Information System (INIS)

Tomasova, L.; Smajda, B.

2008-01-01

Pregnant females of Wistar-strain rats were irradiated (sham-irradiated) with a dose of 1 Gy of gamma-rays on the 16 th day of pregnancy. The progeny of both irradiated and control animals was tested in Morris' water maze for spatial memory at age of 4 months. The time needed to find the hidden platform and the swimming-track were recorded using a computer aided video-tracking method. The test was repeated after 24 hours (short-time memory) and after one week (long-time memory). In short-time memory test the irradiated females needed in comparison with controls a statistically significantly longer time and a longer swimming track to find the platform. No significant differences were found in male. In long-term memory test no significant differences in both parameters followed were found in either of sexes. The results suggest, that irradiation with a low dose of gamma-rays during the period of the embryonic development of the brain can negatively influence the short-term spatial memory, but has no effect on long-time memory in rats. (authors)

Long-term follow-up reveals low toxicity of radiosurgery for vestibular schwannoma

International Nuclear Information System (INIS)

Rutten, Isabelle; Baumert, Brigitta G.; Seidel, Laurence; Kotolenko, Snezana; Collignon, Jacques; Kaschten, Bruno; Albert, Adelin; Martin, Didier; Deneufbourg, Jean-Marie; Demanez, Jean-Pierre; Stevenaert, Achille

2007-01-01

Aim: The long-term effects of radiosurgery of vestibular schwannomas were investigated in a group of consecutively treated patients. Methods and materials: Between 1995 and 2001, 26 patients (median age: 67, range: 30-82) with a vestibular schwannoma were treated by Linac-based stereotactic radiosurgery (SRS). The median follow-up was 49 months (16-85 months). Only progressive tumours were treated. The median size of tumours was 18 mm (range 9-30 mm). Before SRS, 11 patients had a useful hearing (Gardner-Robertson classes 1 and 2). Single doses of 10-14 Gy were prescribed at the 80% isodose at the tumour margin. The follow-up consisted of regular imaging with MRI the first 3-6 months after the intervention, followed by additional yearly MRIs, a hearing test and a neurological examination. Result: The 5-year-probability of tumour control (defined as stabilization or decrease in size) was 95%. Five-year-probability of preservation of hearing and facial nerve function was 96% and 100%, respectively. Hearing was preserved in 10 out of 11 patients who had a normal or useful hearing at the time of treatment. Mild and transient trigeminal toxicity occurred in 2 (8%) patients. It appeared to be significantly correlated to the dose used (p = 0.044). However, only a tendency to significance could be demonstrated in the relationship between the two factors when using the Cox analysis (hazard ratio = 1.7; 95% CI: 0.7-3.9; p = 0.23). Conclusions: With the doses used, our study demonstrates that SRS provides an equivalent tumour control rate when compared to surgery, as well as on a long-term basis, an excellent preservation of the facial and the acoustic nerves. Although no permanent trigeminal toxicity was observed, our data confirm that doses below 14 Gy can avoid transient dysesthesias

Long-term contracts vs. short-term trade of natural gas - a European perspective

International Nuclear Information System (INIS)

Neuhoff, Karsten; Hirschhausen, Christian von

2005-01-01

This paper analyses the economics of long-term gas contracts under changing institutional conditions, mainly gas sector liberalisation. The paper is motivated by the increasingly tense debate in continental Europe, UK and the US on the security of long-term gas supply. We discuss the main issues regarding long-term contracts, i.e. the changing role of the flexibility clause, the effect of abandoning the destination clause, and the strategic behaviour of producers between long-term sales and spot-sales. The literature suggests consumers and producers benefit from risk hedging through long-term contracts. Furthermore long-term contracts may reduce exercise of market power. Our analysis adds an additional benefit if the long-run demand elasticity is significantly lower than the short-run elasticity, both strategic producers and consumers benefit from lower prices and larger market volume. Some policy implications of the findings are also discussed. (Author)

The uranium industry: long-term planning for short-term competition

International Nuclear Information System (INIS)

Vottero, X.; Georges Capus, G.

2001-01-01

Long term planning for short term competition Today, uranium producers face new challenges in terms of both production (new regulatory, environmental and social constraints) and market conditions (new sources of uranium supply, very low prices and tough competition). In such a context, long-term planning is not just a prerequisite to survive in the nuclear fuel cycle industry. In fact, it also contributes to sustaining nuclear electricity generation facing fierce competition from other energy sources in increasingly deregulated markets. Firstly, the risk of investing in new mining projects in western countries is growing because, on the one hand, of very erratic market conditions and, on the other hand, of increasingly lengthy, complex and unpredictable regulatory conditions. Secondly, the supply of other sources of uranium (uranium derived from nuclear weapons, uranium produced in CIS countries, ...) involve other risks, mainly related to politics and commercial restrictions. Consequently, competitive uranium supply requires not only technical competence but also financial strength and good marketing capabilities in order to anticipate long-term market trends, in terms of both demand and supply. It also requires taking into account new parameters such as politics, environment, regulations, etc. Today, a supplier dedicated to the sustainable production of nuclear electricity must manage a broad range of long-term risks inherent to the procurement of uranium. Taking into account all these parameters in a context of short-term, fast-changing market is a great challenge for the future generation. World Uranium Civilian Supply and Demand. (authors)

Repeated dose intramuscular injection of the CIMAvax-EGF vaccine in Sprague Dawley rats induces local and systemic toxicity.

Science.gov (United States)

Mancebo, A; Casacó, A; González, B; Ledón, N; Sorlozabal, J; León, A; Gómez, D; González, Y; Bada, A M; González, C; Arteaga, M E; Ramírez, H; Fuentes, D

2012-05-09

CIMAvax-EGF consists of a human recombinant epidermal growth factor (EGF), coupled to P64k, a recombinant carrier protein from N. meningitis, and Montanide ISA 51 as adjuvant. The vaccine immunization induces a specific antibody production, inhibiting the EGF/EGF-R interaction through EGF deprivation. The objective of this study was to assess the CIMAvax-EGF toxicity in Sprague Dawley rats after intramuscular administration of repeated doses (6 months) and at the same time to determine if rat is a relevant species for studying CIMAvax-EGF vaccine. Rats were randomly distributed into four groups: control, Montanide ISA 51, treated with 1× and 15× of human total dose of the antigen. Animals were immunized weekly during 9 weeks, plus 9 immunizations every 14 days. Rats were inspected daily for clinical signs. Body weight, food consumption, and rectal temperature were measured during the administration of doses. Blood samples were collected for hematological, serum biochemical determinations and EGF titles at the beginning, three months and at the end of experimentation. Gross necropsy and histological examination of tissues were performed on animals at the end of the assay. Vaccine provoked the apparition of antibodies against EGF in the rats, demonstrating rat species relevance in these studies. Body weight gain, food and water consumption were not affected. CIMAvax-EGF and Montanide ISA 51 produced local damage at the administration site, showing multiple cysts and granulomas. Both vaccine-treated groups showed neutrophil elevation, besides an AST increase probably related to the damage at the administration site. Rectal temperature was found to be significantly higher in 15× treated group after immunizations, probably induced by the inflammatory process at the injection site. In summary, the clinical pathology findings together with the body temperature results, appear to be caused by the inflammatory reaction at the administration site of the vaccine, mainly

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.

Long term radioactive waste management

International Nuclear Information System (INIS)

Lavie, J.M.

1984-01-01

In France, waste management, a sensitive issue in term of public opinion, is developing quickly, and due to twenty years of experience, is now reaching maturity. With the launching of the French nuclear programme, the use of radioactive sources in radiotherapy and industry, waste management has become an industrial activity. Waste management is an integrated system dealing with the wastes from their production to the long term disposal, including their identification, sortage, treatment, packaging, collection and transport. This system aims at guaranteing the protection of present and future populations with an available technology. In regard to their long term management, and the design of disposals, radioactive wastes are divided in three categories. This classification takes into account the different radioisotopes contained, their half life and their total activity. Presently short-lived wastes are stored in the shallowland disposal of the ''Centre de la Manche''. Set up within the French Atomic Energy Commission (CEA), the National Agency for waste management (ANDRA) is responsible within the framework of legislative and regulatory provisions for long term waste management in France [fr

[Inhibitor influence on conditional food aversion long-term memory retention and reconsolidation in snail].

Science.gov (United States)

Nikitin, V P; Solntseva, S V; Kozyrev, S A

2014-08-01

In snails trained for conditional food aversion, the effect of ZIP-protein kinase Mzeta (PKMzeta) inhibitor on mechanisms of memory retention and reconsolidation was studied. It was shown that two days after ZIP injections the dose of 1.25 mg/kg, which were not combined with a reminding procedure, there was no effects, but in dose of 2.5 mg/kg a transient memory impairment after 1 day after the injection with its spontaneous recovery on day 10 was disclosed. ZIP injection in a dose of 5 mg/kg without reminding procedure caused memory impairment and the development of persistent amnesia. During animal repeating training after 11 days after amnesia induction caused by ZIP in dose 5 mg/kg, the number of combined food and reinforcing stimulus needed for memory formation was similar to that seen in the initial training. ZIP in doses of 5 or 10 mg/kg combined with a reminding procedure caused the development of amnesia, however, repeating training after 11 days resulted in a dose-dependent and more rapid formation of memory than in the initial training. It was proposed that in snails trained to conditional food aversion without reminding procedure, inhibition of PKMzeta-like enzyme might cause "erase the memory trace" and in repeating training a new memory was formed. PKMzeta apparently not directly involved in the processes of memory reconsolidation, however, a reminding decreased amnesic effect of ZIP.

Modeling long-term dynamics of electricity markets

International Nuclear Information System (INIS)

Olsina, Fernando; Garces, Francisco; Haubrich, H.-J.

2006-01-01

In the last decade, many countries have restructured their electricity industries by introducing competition in their power generation sectors. Although some restructuring has been regarded as successful, the short experience accumulated with liberalized power markets does not allow making any founded assertion about their long-term behavior. Long-term prices and long-term supply reliability are now center of interest. This concerns firms considering investments in generation capacity and regulatory authorities interested in assuring the long-term supply adequacy and the stability of power markets. In order to gain significant insight into the long-term behavior of liberalized power markets, in this paper, a simulation model based on system dynamics is proposed and the underlying mathematical formulations extensively discussed. Unlike classical market models based on the assumption that market outcomes replicate the results of a centrally made optimization, the approach presented here focuses on replicating the system structure of power markets and the logic of relationships among system components in order to derive its dynamical response. The simulations suggest that there might be serious problems to adjust early enough the generation capacity necessary to maintain stable reserve margins, and consequently, stable long-term price levels. Because of feedback loops embedded in the structure of power markets and the existence of some time lags, the long-term market development might exhibit a quite volatile behavior. By varying some exogenous inputs, a sensitivity analysis is carried out to assess the influence of these factors on the long-run market dynamics

Short-term memory and long-term memory are still different.

Science.gov (United States)

Norris, Dennis

2017-09-01

A commonly expressed view is that short-term memory (STM) is nothing more than activated long-term memory. If true, this would overturn a central tenet of cognitive psychology-the idea that there are functionally and neurobiologically distinct short- and long-term stores. Here I present an updated case for a separation between short- and long-term stores, focusing on the computational demands placed on any STM system. STM must support memory for previously unencountered information, the storage of multiple tokens of the same type, and variable binding. None of these can be achieved simply by activating long-term memory. For example, even a simple sequence of digits such as "1, 3, 1" where there are 2 tokens of the digit "1" cannot be stored in the correct order simply by activating the representations of the digits "1" and "3" in LTM. I also review recent neuroimaging data that has been presented as evidence that STM is activated LTM and show that these data are exactly what one would expect to see based on a conventional 2-store view. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Annual coral bleaching and the long-term recovery capacity of coral

Science.gov (United States)

Schoepf, Verena; Grottoli, Andréa G.; Levas, Stephen J.; Aschaffenburg, Matthew D.; Baumann, Justin H.; Matsui, Yohei; Warner, Mark E.

2015-01-01

Mass bleaching events are predicted to occur annually later this century. Nevertheless, it remains unknown whether corals will be able to recover between annual bleaching events. Using a combined tank and field experiment, we simulated annual bleaching by exposing three Caribbean coral species (Porites divaricata, Porites astreoides and Orbicella faveolata) to elevated temperatures for 2.5 weeks in 2 consecutive years. The impact of annual bleaching stress on chlorophyll a, energy reserves, calcification, and tissue C and N isotopes was assessed immediately after the second bleaching and after both short- and long-term recovery on the reef (1.5 and 11 months, respectively). While P. divaricata and O. faveolata were able to recover from repeat bleaching within 1 year, P. astreoides experienced cumulative damage that prevented full recovery within this time frame, suggesting that repeat bleaching had diminished its recovery capacity. Specifically, P. astreoides was not able to recover protein and carbohydrate concentrations. As energy reserves promote bleaching resistance, failure to recover from annual bleaching within 1 year will likely result in the future demise of heat-sensitive coral species. PMID:26582020

Long-Term Collections

CERN Multimedia

Comité des collectes à long terme

2011-01-01

It is the time of the year when our fireman colleagues go around the laboratory for their traditional calendars sale. A part of the money of the sales will be donated in favour of the long-term collections. We hope that you will welcome them warmly.

Short-Term Dosage Regimen for Stimulation-Induced Long-Lasting Desynchronization

Directory of Open Access Journals (Sweden)

Thanos Manos

2018-04-01

Full Text Available In this paper, we computationally generate hypotheses for dose-finding studies in the context of desynchronizing neuromodulation techniques. Abnormally strong neuronal synchronization is a hallmark of several brain disorders. Coordinated Reset (CR stimulation is a spatio-temporally patterned stimulation technique that specifically aims at disrupting abnormal neuronal synchrony. In networks with spike-timing-dependent plasticity CR stimulation may ultimately cause an anti-kindling, i.e., an unlearning of abnormal synaptic connectivity and neuronal synchrony. This long-lasting desynchronization was theoretically predicted and verified in several pre-clinical and clinical studies. We have shown that CR stimulation with rapidly varying sequences (RVS robustly induces an anti-kindling at low intensities e.g., if the CR stimulation frequency (i.e., stimulus pattern repetition rate is in the range of the frequency of the neuronal oscillation. In contrast, CR stimulation with slowly varying sequences (SVS turned out to induce an anti-kindling more strongly, but less robustly with respect to variations of the CR stimulation frequency. Motivated by clinical constraints and inspired by the spacing principle of learning theory, in this computational study we propose a short-term dosage regimen that enables a robust anti-kindling effect of both RVS and SVS CR stimulation, also for those parameter values where RVS and SVS CR stimulation previously turned out to be ineffective. Intriguingly, for the vast majority of parameter values tested, spaced multishot CR stimulation with demand-controlled variation of stimulation frequency and intensity caused a robust and pronounced anti-kindling. In contrast, spaced CR stimulation with fixed stimulation parameters as well as singleshot CR stimulation of equal integral duration failed to improve the stimulation outcome. In the model network under consideration, our short-term dosage regimen enables to robustly induce

Short-Term Dosage Regimen for Stimulation-Induced Long-Lasting Desynchronization.

Science.gov (United States)

Manos, Thanos; Zeitler, Magteld; Tass, Peter A

2018-01-01

In this paper, we computationally generate hypotheses for dose-finding studies in the context of desynchronizing neuromodulation techniques. Abnormally strong neuronal synchronization is a hallmark of several brain disorders. Coordinated Reset (CR) stimulation is a spatio-temporally patterned stimulation technique that specifically aims at disrupting abnormal neuronal synchrony. In networks with spike-timing-dependent plasticity CR stimulation may ultimately cause an anti-kindling, i.e., an unlearning of abnormal synaptic connectivity and neuronal synchrony. This long-lasting desynchronization was theoretically predicted and verified in several pre-clinical and clinical studies. We have shown that CR stimulation with rapidly varying sequences (RVS) robustly induces an anti-kindling at low intensities e.g., if the CR stimulation frequency (i.e., stimulus pattern repetition rate) is in the range of the frequency of the neuronal oscillation. In contrast, CR stimulation with slowly varying sequences (SVS) turned out to induce an anti-kindling more strongly, but less robustly with respect to variations of the CR stimulation frequency. Motivated by clinical constraints and inspired by the spacing principle of learning theory, in this computational study we propose a short-term dosage regimen that enables a robust anti-kindling effect of both RVS and SVS CR stimulation, also for those parameter values where RVS and SVS CR stimulation previously turned out to be ineffective. Intriguingly, for the vast majority of parameter values tested, spaced multishot CR stimulation with demand-controlled variation of stimulation frequency and intensity caused a robust and pronounced anti-kindling. In contrast, spaced CR stimulation with fixed stimulation parameters as well as singleshot CR stimulation of equal integral duration failed to improve the stimulation outcome. In the model network under consideration, our short-term dosage regimen enables to robustly induce long-term

Tumor vaccine composed of C-class CpG oligodeoxynucleotides and irradiated tumor cells induces long-term antitumor immunity

Directory of Open Access Journals (Sweden)

Cerkovnik Petra

2010-09-01

Full Text Available Abstract Background An ideal tumor vaccine should activate both effector and memory immune response against tumor-specific antigens. Beside the CD8+ T cells that play a central role in the generation of a protective immune response and of long-term memory, dendritic cells (DCs are important for the induction, coordination and regulation of the adaptive immune response. The DCs can conduct all of the elements of the immune orchestra and are therefore a fundamental target and tool for vaccination. The present study was aimed at assessing the ability of tumor vaccine composed of C-class CpG ODNs and irradiated melanoma tumor cells B16F1 followed by two additional injections of CpG ODNs to induce the generation of a functional long-term memory response in experimental tumor model in mice (i.p. B16F1. Results It has been shown that the functional memory response in vaccinated mice persists for at least 60 days after the last vaccination. Repeated vaccination also improves the survival of experimental animals compared to single vaccination, whereas the proportion of animals totally protected from the development of aggressive i.p. B16F1 tumors after vaccination repeated three times varies between 88.9%-100.0%. Additionally, the long-term immune memory and tumor protection is maintained over a prolonged period of time of at least 8 months. Finally, it has been demonstrated that following the vaccination the tumor-specific memory cells predominantly reside in bone marrow and peritoneal tissue and are in a more active state than their splenic counterparts. Conclusions In this study we demonstrated that tumor vaccine composed of C-class CpG ODNs and irradiated tumor cells followed by two additional injections of CpG ODNs induces a long-term immunity against aggressive B16F1 tumors.

A flow-cytometric NK-cytotoxicity assay adapted for use in rat repeated dose toxicity studies

International Nuclear Information System (INIS)

Marcusson-Staahl, Maritha; Cederbrant, Karin

2003-01-01

A recent regulatory document for immunotoxicity testing of new pharmaceutical drugs includes cytotoxic natural killer (NK)-cell function as a required parameter in repeated dose toxicity studies. The classical 51 Cr-release assay is the conventional test for cytotoxicity testing but several drawbacks with this assay has increased the demand for new reliable test systems. Here, we describe the optimisation of a flow-cytometric cytotoxicity assay especially adapted for regulatory rat studies in drug development. The test principle is based on target cell labelling with 5-(6)-carboxy-fluorescein succinimidyl ester (CFSE) and subsequent DNA-labelling with propidium iodide (PI) for identification of target cells with compromised cell membranes. The results are expressed as percentage of dead targets on a cell-to-cell basis. The final format of the assay includes 0.5 ml peripheral blood, 1.25x10 5 effector cells per sample, and collection of 500 target events by flow-cytometry. When NKR-P1+ cells were removed from the effector cell population by magnetic depletion the relative proportion decreased from 6 to 0.08%. The corresponding cytotoxic activity decreased from 68 to 8%. Also, the cytotoxic activity showed a significant and positive correlation with the proportion of NK-cells present in the effector cell suspension. Thus, the cytotoxicity measured is almost exclusively exerted by NK-cells. The current flow-cytometric test benefits from using peripheral blood as a source for effector cells since it will not conflict with the use of spleen for histopathological investigations in repeated dose toxicity studies. Additionally, since only a minimal number of effector cells are required per sample repeated testing of the same animal is enabled

Phosphodiesterase 10A inhibition attenuates sleep deprivation-induced deficits in long-term fear memory.

Science.gov (United States)

Guo, Lengqiu; Guo, Zhuangli; Luo, Xiaoqing; Liang, Rui; Yang, Shui; Ren, Haigang; Wang, Guanghui; Zhen, Xuechu

2016-12-02

Sleep, particularly rapid eye movement (REM) sleep, is implicated in the consolidation of emotional memories. In the present study, we investigated the protective effects of a phosphodiesterase 10A (PDE10A) inhibitor MP-10 on deficits in long-term fear memory induced by REM sleep deprivation (REM-SD). REM-SD caused deficits in long-term fear memory, however, MP-10 administration ameliorated the deleterious effects of REM-SD on long term fear memory. Brain-derived neurotropic factor (BDNF) and phosphorylated cAMP response element-binding protein (pCREB) were altered in specific brain regions associated with learning and memory in REM-SD rats. Accordingly, REM-SD caused a significant decrease of pCREB in hippocampus and striatum and a significant decrease of BDNF in the hippocampus, striatum and amygdala, however, MP-10 reversed the effects of REM-SD in a dose-dependent manner. Our findings suggest that REM-SD disrupts the consolidation of long-term fear memory and that administration of MP-10 protects the REM-SD-induced deficits in fear memory, which may be due to the MP-10-induced expression of BDNF in the hippocampus, striatum and amygdala, and phosphorylation of CREB in the hippocampus and striatum. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Long-Term Memory Performance in Adult ADHD.

Science.gov (United States)

Skodzik, Timo; Holling, Heinz; Pedersen, Anya

2017-02-01

Memory problems are a frequently reported symptom in adult ADHD, and it is well-documented that adults with ADHD perform poorly on long-term memory tests. However, the cause of this effect is still controversial. The present meta-analysis examined underlying mechanisms that may lead to long-term memory impairments in adult ADHD. We performed separate meta-analyses of measures of memory acquisition and long-term memory using both verbal and visual memory tests. In addition, the influence of potential moderator variables was examined. Adults with ADHD performed significantly worse than controls on verbal but not on visual long-term memory and memory acquisition subtests. The long-term memory deficit was strongly statistically related to the memory acquisition deficit. In contrast, no retrieval problems were observable. Our results suggest that memory deficits in adult ADHD reflect a learning deficit induced at the stage of encoding. Implications for clinical and research settings are presented.

Candidate Dosimetric Predictors of Long-Term Swallowing Dysfunction After Oropharyngeal Intensity-Modulated Radiotherapy

International Nuclear Information System (INIS)

Schwartz, David L.; Hutcheson, Katherine; Barringer, Denise; Tucker, Susan L.; Kies, Merrill; Holsinger, F. Christopher; Ang, K. Kian; Morrison, William H.; Rosenthal, David I.; Garden, Adam S.; Dong Lei; Lewin, Jan S.

2010-01-01

Purpose: To investigate long-term swallowing function in oropharyngeal cancer patients treated with intensity-modulated radiotherapy (IMRT), and to identify novel dose-limiting criteria predictive for dysphagia. Methods and Materials: Thirty-one patients with Stage IV oropharyngeal squamous carcinoma enrolled on a Phase II trial were prospectively evaluated by modified barium swallow studies at baseline, and 6, 12, and 24 months post-IMRT treatment. Candidate dysphagia-associated organs at risk were retrospectively contoured into original treatment plans. Twenty-one (68%) cases were base of tongue and 10 (32%) were tonsil. Stage distribution was T1 (12 patients), T2 (10), T3 (4), T4 (2), and TX (3), and N2 (24), N3 (5), and NX (2). Median age was 52.8 years (range, 42-78 years). Thirteen patients (42%) received concurrent chemotherapy during IMRT. Thirteen (42%) were former smokers. Mean dose to glottic larynx for the cohort was limited to 18 Gy (range, 6-39 Gy) by matching IMRT to conventional low-neck fields. Results: Dose-volume constraints (V30 < 65% and V35 < 35% for anterior oral cavity and V55 < 80% and V65 < 30% for high superior pharyngeal constrictors) predictive for objective swallowing dysfunction were identified by univariate and multivariate analyses. Aspiration and feeding tube dependence were observed in only 1 patient at 24 months. Conclusions: In the context of glottic laryngeal shielding, we describe candidate oral cavity and superior pharyngeal constrictor organs at risk and dose-volume constraints associated with preserved long-term swallowing function; these constraints are currently undergoing prospective validation. Strict protection of the glottic larynx via beam-split IMRT techniques promises to make chronic aspiration an uncommon outcome.

Long term effects of low doses of ionising radiation: facts and fallacies

International Nuclear Information System (INIS)

Iyer, G.K.

1993-01-01

Health effects of low doses of ionising radiation have been a public concern. The public perception of these low effects is that it causes cancer and genetic effects. Enormous amount of work regarding this cancer has been done all over the world, on occupational workers exposed to low doses of ionising radiation. These studies do not show any adverse effect on them. Epidemiological studies done on members of public staying near nuclear facilities also have shown that there is no health risk involved in staying near these facilities. Genetic effects have also shown negative results. These two aspects of health effects of low dose of radiation are discussed in detail. (author). 5 refs., 1 tab

Gastroesophageal Acid Reflux Control 5 Years After Antireflux Surgery, Compared With Long-term Esomeprazole Therapy.

Science.gov (United States)

Hatlebakk, Jan G; Zerbib, Frank; Bruley des Varannes, Stanislas; Attwood, Stephen E; Ell, Christian; Fiocca, Roberto; Galmiche, Jean-Paul; Eklund, Stefan; Långström, Göran; Lind, Tore; Lundell, Lars R

2016-05-01

We compared the ability of laparoscopic antireflux surgery (LARS) and esomeprazole to control esophageal acid exposure, over a 5-year period, in patients with chronic gastroesophageal reflux disease (GERD). We also studied whether intraesophageal and intragastric pH parameters off and on therapy were associated with long-term outcomes. We analyzed data from a prospective, randomized, open-label trial comparing the efficacy and safety of LARS vs esomeprazole (20 or 40 mg/d) over 5 years in patients with chronic GERD. Ambulatory intraesophageal and intragastric 24-hour pH monitoring data were compared between groups before LARS or the start of esomeprazole treatment, and 6 months and 5 years afterward. A secondary aim was to evaluate the association between baseline and 6-month pH parameters and esomeprazole dose escalation, reappearance of GERD symptoms, and treatment failure over 5 years in patients receiving LARS or esomeprazole. In the LARS group (n = 116), the median 24-hour esophageal acid exposure was 8.6% at baseline and 0.7% after 6 months and 5 years (P acid exposure was 8.8% at baseline, 2.1% after 6 months, and 1.9% after 5 years (P acidity was stable in both groups. Patients who required a dose increase to 40 mg/d had more severe supine reflux at baseline, and decreased esophageal acid exposure (P acidity after dose escalation. Esophageal and intragastric pH parameters, off and on therapy, did not predict long-term symptom breakthrough. In a prospective study of patients with chronic GERD, esophageal acid reflux was reduced greatly by LARS or esomeprazole therapy. However, patients receiving LARS had significantly greater reductions in 24-hour esophageal acid exposure after 6 months and 5 years. Esophageal and gastric pH, off and on therapy, did not predict long-term outcomes of patients. Abnormal supine acid exposure predicted esomeprazole dose escalation. ClinicalTrials.Gov identifier: NCT00251927 (available: http://clinicaltrials.gov/ct2/show

A Long-term Plan for Kalk

DEFF Research Database (Denmark)

2017-01-01

In this case, the author demonstrates together with the owner-manager of KALK A/S, Mr Rasmus Jorgensen, how to use the Family Business Map to frame a constructive discussion about long-term planning. The Family Business Map is a tool for long-term planning in family firms developed by Professor...

Virtual Models of Long-Term Care

Science.gov (United States)

Phenice, Lillian A.; Griffore, Robert J.

2012-01-01

Nursing homes, assisted living facilities and home-care organizations, use web sites to describe their services to potential consumers. This virtual ethnographic study developed models representing how potential consumers may understand this information using data from web sites of 69 long-term-care providers. The content of long-term-care web…

Sleep facilitates long-term face adaptation

OpenAIRE

Ditye, Thomas; Javadi, Amir Homayoun; Carbon, Claus-Christian; Walsh, Vincent

2013-01-01

Adaptation is an automatic neural mechanism supporting the optimization of visual processing on the basis of previous experiences. While the short-term effects of adaptation on behaviour and physiology have been studied extensively, perceptual long-term changes associated with adaptation are still poorly understood. Here, we show that the integration of adaptation-dependent long-term shifts in neural function is facilitated by sleep. Perceptual shifts induced by adaptation to a distorted imag...

Prevalence of Long-Term Opioid Use in Long-Stay Nursing Home Residents.

Science.gov (United States)

Hunnicutt, Jacob N; Chrysanthopoulou, Stavroula A; Ulbricht, Christine M; Hume, Anne L; Tjia, Jennifer; Lapane, Kate L

2018-01-01

Overall and long-term opioid use among older adults have increased since 1999. Less is known about opioid use in older adults in nursing homes (NHs). Cross-sectional. U.S. NHs (N = 13,522). Long-stay NH resident Medicare beneficiaries with a Minimum Data Set 3.0 (MDS) assessment between April 1, 2012, and June 30, 2012, and 120 days of follow-up (N = 315,949). We used Medicare Part D claims to measure length of opioid use in the 120 days from the index assessment (short-term: ≤30 days, medium-term: >30-89 days, long-term: ≥90 days), adjuvants (e.g., anticonvulsants), and other pain medications (e.g., corticosteroids). MDS assessments in the follow-up period were used to measure nonpharmacological pain management use. Modified Poisson models were used to estimate adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) for age, gender, race and ethnicity, cognitive and physical impairment, and long-term opioid use. Of all long-stay residents, 32.4% were prescribed any opioid, and 15.5% were prescribed opioids long-term. Opioid users (versus nonusers) were more commonly prescribed pain adjuvants (32.9% vs 14.9%), other pain medications (25.5% vs 11.0%), and nonpharmacological pain management (24.5% vs 9.3%). Long-term opioid use was higher in women (aPR = 1.21, 95% CI = 1.18-1.23) and lower in racial and ethnic minorities (non-Hispanic blacks vs whites: APR = 0.93, 95% CI = 0.90-0.94) and those with severe cognitive impairment (vs no or mild impairment, aPR = 0.82, 95% CI = 0.79-0.83). One in seven NH residents was prescribed opioids long-term. Recent guidelines on opioid prescribing for pain recommend reducing long-term opioid use, but this is challenging in NHs because residents may not benefit from nonpharmacological and nonopioid interventions. Studies to address concerns about opioid safety and effectiveness (e.g., on pain and functional status) in NHs are needed. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics

Repeat Gamma Knife Radiosurgery for Trigeminal Neuralgia

International Nuclear Information System (INIS)

Aubuchon, Adam C.; Chan, Michael D.; Lovato, James F.; Balamucki, Christopher J.; Ellis, Thomas L.; Tatter, Stephen B.; McMullen, Kevin P.; Munley, Michael T.; Deguzman, Allan F.; Ekstrand, Kenneth E.; Bourland, J. Daniel; Shaw, Edward G.

2011-01-01

Purpose: Repeat gamma knife stereotactic radiosurgery (GKRS) for recurrent or persistent trigeminal neuralgia induces an additional response but at the expense of an increased incidence of facial numbness. The present series summarized the results of a repeat treatment series at Wake Forest University Baptist Medical Center, including a multivariate analysis of the data to identify the prognostic factors for treatment success and toxicity. Methods and Materials: Between January 1999 and December 2007, 37 patients underwent a second GKRS application because of treatment failure after a first GKRS treatment. The mean initial dose in the series was 87.3 Gy (range, 80–90). The mean retreatment dose was 84.4 Gy (range, 60–90). The dosimetric variables recorded included the dorsal root entry zone dose, pons surface dose, and dose to the distal nerve. Results: Of the 37 patients, 81% achieved a >50% pain relief response to repeat GKRS, and 57% experienced some form of trigeminal dysfunction after repeat GKRS. Two patients (5%) experienced clinically significant toxicity: one with bothersome numbness and one with corneal dryness requiring tarsorraphy. A dorsal root entry zone dose at repeat treatment of >26.6 Gy predicted for treatment success (61% vs. 32%, p = .0716). A cumulative dorsal root entry zone dose of >84.3 Gy (72% vs. 44%, p = .091) and a cumulative pons surface dose of >108.5 Gy (78% vs. 44%, p = .018) predicted for post-GKRS numbness. The presence of any post-GKRS numbness predicted for a >50% decrease in pain intensity (100% vs. 60%, p = .0015). Conclusion: Repeat GKRS is a viable treatment option for recurrent trigeminal neuralgia, although the patient assumes a greater risk of nerve dysfunction to achieve maximal pain relief.

Repeat Gamma Knife Radiosurgery for Trigeminal Neuralgia

Energy Technology Data Exchange (ETDEWEB)

Aubuchon, Adam C., E-mail: acaubuchon@gmail.com [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Chan, Michael D. [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Lovato, James F. [Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Balamucki, Christopher J. [Department of Radiation Oncology, University of Florida, Gainesville, FL (United States); Ellis, Thomas L.; Tatter, Stephen B. [Department of Neurosurgery, Wake Forest University School of Medicine, Winston-Salem, NC (United States); McMullen, Kevin P.; Munley, Michael T.; Deguzman, Allan F.; Ekstrand, Kenneth E.; Bourland, J. Daniel; Shaw, Edward G. [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States)

2011-11-15

Purpose: Repeat gamma knife stereotactic radiosurgery (GKRS) for recurrent or persistent trigeminal neuralgia induces an additional response but at the expense of an increased incidence of facial numbness. The present series summarized the results of a repeat treatment series at Wake Forest University Baptist Medical Center, including a multivariate analysis of the data to identify the prognostic factors for treatment success and toxicity. Methods and Materials: Between January 1999 and December 2007, 37 patients underwent a second GKRS application because of treatment failure after a first GKRS treatment. The mean initial dose in the series was 87.3 Gy (range, 80-90). The mean retreatment dose was 84.4 Gy (range, 60-90). The dosimetric variables recorded included the dorsal root entry zone dose, pons surface dose, and dose to the distal nerve. Results: Of the 37 patients, 81% achieved a >50% pain relief response to repeat GKRS, and 57% experienced some form of trigeminal dysfunction after repeat GKRS. Two patients (5%) experienced clinically significant toxicity: one with bothersome numbness and one with corneal dryness requiring tarsorraphy. A dorsal root entry zone dose at repeat treatment of >26.6 Gy predicted for treatment success (61% vs. 32%, p = .0716). A cumulative dorsal root entry zone dose of >84.3 Gy (72% vs. 44%, p = .091) and a cumulative pons surface dose of >108.5 Gy (78% vs. 44%, p = .018) predicted for post-GKRS numbness. The presence of any post-GKRS numbness predicted for a >50% decrease in pain intensity (100% vs. 60%, p = .0015). Conclusion: Repeat GKRS is a viable treatment option for recurrent trigeminal neuralgia, although the patient assumes a greater risk of nerve dysfunction to achieve maximal pain relief.