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Monoamine reuptake site occupancy of sibutramine: Relationship to antidepressant-like and thermogenic effects in rats.

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Li, Yu-Wen; Langdon, Shaun; Pieschl, Rick; Strong, Todd; Wright, Robert N; Rohrbach, Kenneth; Lelas, Snjezana; Lodge, Nicholas J

2014-08-15

Sibutramine was formerly marketed as an anti-obesity agent. The current study investigated the relationships between monoamine reuptake site occupancy for sibutramine and both its antidepressant-like efficacy and thermogenic effects. Sibutramine's effects on locomotor activity (LMA) and food intake were also evaluated. Sibutramine occupied monoamine reuptake binding sites with the rank order of potency of NET>SERT>DAT; at 10mg/kg, po, occupancy was 95% NET, 81% SERT and 73% DAT. Sibutramine produced antidepressant-like behavior in the forced swim test; at the lowest effective dose (3mg/kg, po) occupancy was 61%, 90% and 23% at SERT, NET and DAT sites, respectively. Sibutramine also increased body core temperature in a dose- and time-dependent manner; at the lowest effective dose (30mg/kg) SERT, NET and DAT occupancies were respectively 78%, 86% and 59%. A significant decrease in food consumption was observed at 3 and 10mg/kg, po. LMA was increased at ≥10mg/kg, sc. The relationship between efficacy in the FST and occupancy was also determined for citalopram, fluoxetine and reboxetine. Similarly, the relationship between thermogenesis and target occupancy for several single or double/triple reuptake inhibitors was measured and showed that >40-50% DAT binding was required for thermogenesis. Thermogenesis was blocked by the D1 antagonist SCH39166 (3mg/kg, sc). Our findings indicate that the antidepressant-like effect of sibutramine may result from additive or synergistic actions on the three reuptake binding targets. At higher doses, sibutramine produces thermogenesis; DAT inhibition and activation of dopamine D1 receptors are required for this effect. Published by Elsevier B.V.
Demonstration of clomipramine and venlafaxine occupation at serotonin reuptake sites in man in vivo.

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Malizia, A L; Melichar, J M; Brown, D J; Gunn, R N; Reynolds, A; Jones, T; Nutt, D J

1997-01-01

We describe the use of 11CRTI-55 and the Multiple Objects Coincidences Counter (MOCC) to detect in-vivo binding to peripheral serotonin reuptake sites (left chest comprising platelet and lung serotonin reuptake sites) in man. Displacement and preloading experiments with clomipramine and venlafaxine in two healthy volunteers demonstrated that 11CRTI-55 binding is decreased in a dose-dependent fashion by both these drugs which bind to the serotonin transporter. In addition parallel data from the total head curve (representing 11CRTI-55 binding to central serotonin and dopamine (DA) reuptake sites) suggest that prior blockade of the serotonin transporter may be a useful strategy to maximize radioactive counts in the head when measuring the DA transporter. The MOCC is likely to be useful to determine sequential indices of relative serotonin reuptake blockade in patients on treatment.
Fractal analysis of striatal dopamine re-uptake sites

International Nuclear Information System (INIS)

Kuikka, J.T.; Bergstroem, K.A.; Tiihonen, J.; Raesaenen, P.; Karhu, J.

1997-01-01

Spatial variation in regional blood flow, metabolism and receptor density within the brain and in other organs is measurable even with a low spatial resolution technique such as emission tomography. It has been previously shown that the observed variance increases with increasing number of subregions in the organ/tissue studied. This resolution-dependent variance can be described by fractal analysis. We studied striatal dopamine re-uptake sites in 39 healthy volunteers with high-resolution single-photon emission tomography using iodine-123 labelled 2β-carbomethoxy-3β-(4-iodophenyl)tropane ([ 123 I]β-CIT). The mean fractal dimension was 1.15±0.07. The results indicate that regional striatal dopamine re-uptake sites involve considerable spatial heterogeneity which is higher than the uniform density (dimension=1.00) but much lower than complete randomness (dimension=1.50). There was a gender difference, with females having a higher heterogeneity in both the left and the right striatum. In addition, we found striatal asymmetry (left-to-right heterogeneity ratio of 1.19±0.15; P<0.001), suggesting functional hemispheric lateralization consistent with the control of motor behaviour and integrative functions. (orig.). With 5 figs., 1 tab
Fractal analysis of striatal dopamine re-uptake sites

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Kuikka, J.T.; Bergstroem, K.A. [Department of Clinical Physiology, Kuopio University Hospital, Kuopio (Finland); Tiihonen, J.; Raesaenen, P. [Department of Forensic Psychiatry, University of Kuopio and Niuvanniemi Hospital, Kuopio (Finland); Karhu, J. [Department of Clinical Neurophysiology, Kuopio University Hospital, Kuopio (Finland)

1997-09-01

Spatial variation in regional blood flow, metabolism and receptor density within the brain and in other organs is measurable even with a low spatial resolution technique such as emission tomography. It has been previously shown that the observed variance increases with increasing number of subregions in the organ/tissue studied. This resolution-dependent variance can be described by fractal analysis. We studied striatal dopamine re-uptake sites in 39 healthy volunteers with high-resolution single-photon emission tomography using iodine-123 labelled 2{beta}-carbomethoxy-3{beta}-(4-iodophenyl)tropane ([{sup 123}I]{beta}-CIT). The mean fractal dimension was 1.15{+-}0.07. The results indicate that regional striatal dopamine re-uptake sites involve considerable spatial heterogeneity which is higher than the uniform density (dimension=1.00) but much lower than complete randomness (dimension=1.50). There was a gender difference, with females having a higher heterogeneity in both the left and the right striatum. In addition, we found striatal asymmetry (left-to-right heterogeneity ratio of 1.19{+-}0.15; P<0.001), suggesting functional hemispheric lateralization consistent with the control of motor behaviour and integrative functions. (orig.). With 5 figs., 1 tab.
In vivo evaluation of striatal dopamine reuptake sites using 11C-nomifensine and positron emission tomography

International Nuclear Information System (INIS)

Aquilonius, S.-M.; Bergstroem, K.; Eckernaes, S.-Aa.; Leenders, K.L.; Hartvig, P.; Lundquist, H.; Antoni, G.; Gee, A.; Rimland, A.; Uhlin, J.; Langstroem, B.

1987-01-01

In vitro nomifensine demonstrates high affinity and specificity for dopamine reuptake sites in the brain. In the present study 11 C-nomifensine was administered i.v. in trace amounts (10-50 μg) to ketamine anaesthetized Rhesus monkeys (6-10 kg b.w.) and the timecourse of radioactivity within different brain regions was measured by positron emission tomography (PET). Six base-line experiments lasting for 60-80 min were performed. The procedure was repeated after pretreatment with nomifensine (2-6 mg/kg i.v.), another reuptake inhibitor, mazindol (0.3 mg/kg i.v.), desipramine (0.5 mg/kg i.v.) or spiperone (0.3 mg/kg i.v.) before the administration of a second 11 C-nomifensine dose. The highest radioactivity uptake was found in the dopamine innervated striatum and the lowest in a region containing the cerebellum, known to be almost devoid of dopaminergic neurons. The difference between striatal and cerebellar uptake of 11 C-nomifensine derived radioactivity was markedly reduced after nomifensine and mazindol but not after desipramine and spiperone. These results indicate that in vivo the striatal uptake of 11 C-nomifensine, as measured with PET, involves specific binding with the dopamine reuptake sites. In the first human applications of 11 C-nomifensine and PET in a healthy volunteer, the regional uptake of radioactivity was similar to that in base-line experiments with Rhesus monkeys. In the healthy subject the striatal/cerebellar ratio was 1.6, 50 min after the injection of 11 C-nomifensine. In a hemi-parkinsonian patient this ratio was 1.1 contralaterally and 1.3 ipsilaterally to the affected side. 11 C-nomifensine and PET seems to be an auspicious method to measure the striatal dopaminergic nerve terminals of man in vivo. (author)
Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)

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Serotonin and norepinephrine reuptake inhibitors (SNRIs) Antidepressant SNRIs help relieve depression symptoms, such as irritability and sadness, ... effects they may cause. By Mayo Clinic Staff Serotonin and norepinephrine reuptake inhibitors (SNRIs) are a class ...
Monoamine depletion by reuptake inhibitors

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Hinz M

2011-10-01

Full Text Available Marty Hinz1, Alvin Stein2, Thomas Uncini31Clinical Research, NeuroResearch Clinics Inc, Cape Coral, FL; 2Stein Orthopedic Associates, Plantation, FL; 3DBS Labs Inc, Duluth, MN, USABackground: Disagreement exists regarding the etiology of cessation of the observed clinical results with administration of reuptake inhibitors. Traditionally, when drug effects wane, it is known as tachyphylaxis. With reuptake inhibitors, the placebo effect is significantly greater than the drug effect in the treatment of depression and attention deficit hyperactivity disorder, leading some to assert that waning of drug effects is placebo relapse, not tachyphylaxis.Methods: Two groups were retrospectively evaluated. Group 1 was composed of subjects with depression and Group 2 was composed of bariatric subjects treated with reuptake inhibitors for appetite suppression.Results: In Group 1, 200 subjects with depression were treated with citalopram 20 mg per day. A total of 46.5% (n = 93 achieved relief of symptoms (Hamilton-D rating score ≤ 7, of whom 37 (39.8% of whom experienced recurrence of depression symptoms, at which point an amino acid precursor formula was started. Within 1–5 days, 97.3% (n = 36 experienced relief of depression symptoms. In Group 2, 220 subjects were treated with phentermine 30 mg in the morning and citalopram 20 mg at 4 pm. In this group, 90.0% (n = 198 achieved adequate appetite suppression. The appetite suppression ceased in all 198 subjects within 4–48 days. Administration of an amino acid precursor formula restored appetite suppression in 98.5% (n = 195 of subjects within 1–5 days.Conclusion: Reuptake inhibitors do not increase the total number of monoamine molecules in the central nervous system. Their mechanism of action facilitates redistribution of monoamines from one place to another. In the process, conditions are induced that facilitate depletion of monoamines. The "reuptake inhibitor monoamine depletion theory" of this paper
Selective serotonin reuptake inhibitors and risk for gastrointestinal bleeding

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Batić-Mujanović Olivera

2014-01-01

Full Text Available The most of the known effects of selective serotonin reuptake inhibitors, beneficial or harmful, are associated with the inhibitory action of the serotonin reuptake transporter. This mechanism is present not only in neurons, but also in other cells such as platelets. Serotoninergic mechanism seems to have an important role in hemostasis, which has long been underestimated. Abnormal activation may lead to a prothrombotic state in patients treated with selective serotonin reuptake inhibitors. On one hand there may be an increased risk of bleeding, and on the other hand reduction in thrombotic risk may be possible. Serotonin is critical to maintain a platelet haemostatic function, such as platelet aggregation. Evidences from the studies support the hypothesis that antidepressants with a relevant blockade of action of serotonin reuptake mechanism may increase the risk of bleeding, which can occur anywhere in the body. Epidemiological evidences are, however, the most robust for upper gastrointestinal bleeding. It is estimated that this bleeding can occur in 1 in 100 to 1 in 1.000 patient-years of exposure to the high-affinity selective serotonin reuptake inhibitors, with very old patients at the highest risk. The increased risk may be of particular relevance when selective serotonin reuptake inhibitors are taken simultaneously with nonsteroidal anti-inflammatory drugs, low dose of aspirin or warfarin.
Serotonin and noradrenaline reuptake inhibitors improve micturition control in mice.

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Marco Redaelli

Full Text Available Poor micturition control may cause profound distress, because proper voiding is mandatory for an active social life. Micturition results from the subtle interplay of central and peripheral components. It involves the coordination of autonomic and neuromuscular activity at the brainstem level, under the executive control of the prefrontal cortex. We tested the hypothesis that administration of molecules acting as reuptake inhibitors of serotonin, noradrenaline or both may exert a strong effect on the control of urine release, in a mouse model of overactive bladder. Mice were injected with cyclophosphamide (40 mg/kg, to increase micturition acts. Mice were then given one of four molecules: the serotonin reuptake inhibitor imipramine, its metabolite desipramine that acts on noradrenaline reuptake, the serotonin and noradrenaline reuptake inhibitor duloxetine or its active metabolite 4-hydroxy-duloxetine. Cyclophosphamide increased urine release without inducing overt toxicity or inflammation, except for increase in urothelium thickness. All the antidepressants were able to decrease the cyclophosphamide effects, as apparent from longer latency to the first micturition act, decreased number of urine spots and volume of released urine. These results suggest that serotonin and noradrenaline reuptake inhibitors exert a strong and effective modulatory effect on the control of urine release and prompt to additional studies on their central effects on brain areas involved in the social and behavioral control of micturition.
Analytical Strategies for the Determination of Norepinephrine Reuptake Inhibitors in Pharmaceutical Formulations and Biological Fluids.

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Saka, Cafer

2016-01-01

Norepinephrine reuptake inhibitors (NRIs) are a class of antidepressant drugs that act as reuptake inhibitors for the neurotransmitters norepinephrine and epinephrine. The present review provides an account of analytical methods published in recent years for the determination of NRI drugs. NRIs are atomoxetine, reboxetine, viloxazine and maprotiline. NRIs with less activity at other sites are mazindol, bupropion, tapentadol, and teniloxazine. This review focuses on the analytical methods including chromatographic, spectrophotometric, electroanalytical, and electrophoresis techniques for NRI analysis from pharmaceutical formulations and biological samples. Among all of the published methods, liquid chromatography with UV-vis or MS-MS detection is the most popular technique. The most the common sample preparation techniques in the analytical methods for NRIs include liquid-liquid extraction and solid-phase extraction. Besides the analytical methods for single components, some of the simultaneous determinations are also included in this review.
Relative contributions of norepinephrine and serotonin transporters to antinociceptive synergy between monoamine reuptake inhibitors and morphine in the rat formalin model.

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Fei Shen

Full Text Available Multimodal analgesia is designed to optimize pain relief by coadministering drugs with distinct mechanisms of action or by combining multiple pharmacologies within a single molecule. In clinical settings, combinations of monoamine reuptake inhibitors and opioid receptor agonists have been explored and one currently available analgesic, tapentadol, functions as both a µ-opioid receptor agonist and a norepinephrine transporter inhibitor. However, it is unclear whether the combination of selective norepinephrine reuptake inhibition and µ-receptor agonism achieves an optimal antinociceptive synergy. In this study, we assessed the pharmacodynamic interactions between morphine and monoamine reuptake inhibitors that possess different affinities and selectivities for norepinephrine and serotonin transporters. Using the rat formalin model, in conjunction with measurements of ex vivo transporter occupancy, we show that neither the norepinephrine-selective inhibitor, esreboxetine, nor the serotonin-selective reuptake inhibitor, fluoxetine, produce antinociceptive synergy with morphine. Atomoxetine, a monoamine reuptake inhibitor that achieves higher levels of norepinephrine than serotonin transporter occupancy, exhibited robust antinociceptive synergy with morphine. Similarly, a fixed-dose combination of esreboxetine and fluoxetine which achieves comparable levels of transporter occupancy potentiated the antinociceptive response to morphine. By contrast, duloxetine, a monoamine reuptake inhibitor that achieves higher serotonin than norepinephrine transporter occupancy, failed to potentiate the antinociceptive response to morphine. However, when duloxetine was coadministered with the 5-HT3 receptor antagonist, ondansetron, potentiation of the antinociceptive response to morphine was revealed. These results support the notion that inhibition of both serotonin and norepinephrine transporters is required for monoamine reuptake inhibitor and opioid
An improved automated synthesis and in vivo evaluation of PET radioligand for serotonin re-uptake sites. [11C]McN5652X

International Nuclear Information System (INIS)

Sasaki, Masahiro; Suhara, Tetsuya; Suzuki, Kazutoshi; Kubodera, Akiko.

1996-01-01

Carbon-11 labeled serotonin (5-HT) re-uptake inhibitor, [ 11 C]McN5 652X ((6S,10bR)-trans-( + )-1,2,3,5,6,10b-hexahydro-6-[4-(methylthio)phenyl]pyrrolo-[2,1-a]-isoquinoline), has recently been reported to be favorable for studying human 5-HT re-uptake site by positron emission tomography (PET) because of its rapid and high specific binding characteristics as radioligands. [ 11 C]McN5652X has been synthesized by S-methylation of the corresponding des-methyl precursor A with [ 11 C]iodomethane. One serious disadvantage of this procedure, however, is the lack of stability of A. The improved method for the synthesis of A has been desired. We have found that the decomposition of A is significantly reduced by adding a protecting agent for SH groups, dithiothreitol (DTT), into the reaction medium immediately after the demethylation of McN5652X. By using this stabilized precursor A, we have developed an automated procedure giving [ 11 C]McN5652X with 98.6±0.4% radiochemical purity in high specific activity (181.3±7.4GBq/μmol). Preclinical evaluation of the produ ct was carried out by injecting the solution of [ 11 C]McN5652X obtained by this procedure into mice. [ 11 C]McN5652X showed the high accumulation into mouse thalamus, striatum and cerebral cortex, organs known to have high level of 5-HT receptor density, after intravenous injection. Human PET studies also showed the high uptakes of this radioligand into the thalamus, striatum and midbrain
Use of selective-serotonin reuptake inhibitors and platelet aggregation inhibitors among individuals with co-occurring atherosclerotic cardiovascular disease and depression or anxiety

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J Douglas Thornton

2016-12-01

Full Text Available Objective: Medications commonly used to treat heart disease, anxiety, and depression can interact resulting in an increased risk of bleeding, warranting a cautious approach in medical decision making. This retrospective, descriptive study examined the prevalence and the factors associated with the use of both selective-serotonin reuptake inhibitor and platelet aggregation inhibitor among individuals with co-occurring atherosclerotic cardiovascular disease and anxiety or depression. Methods: Respondents aged 22 years and older, alive throughout the study period, and diagnosed with co-occurring atherosclerotic cardiovascular disease and anxiety or depression (n = 1507 in years 2007 through 2013 of the Medical Expenditures Panel Survey were included. The use of treatment was grouped as follows: selective-serotonin reuptake inhibitor and platelet aggregation inhibitor, selective-serotonin reuptake inhibitor or platelet aggregation inhibitor, and neither selective-serotonin reuptake inhibitor nor platelet aggregation inhibitor. Results: Overall, 16.5% used both selective-serotonin reuptake inhibitor and platelet aggregation inhibitor, 61.2% used selective-serotonin reuptake inhibitor or platelet aggregation inhibitor, and 22.3% used neither selective-serotonin reuptake inhibitor nor platelet aggregation inhibitor. Respondents aged over 65 years (adjusted odds ratio = 1.93 (95% confidence interval = 1.08–3.45 and having a diagnosis of diabetes (adjusted odds ratio = 1.63 (95% confidence interval = 1.15–2.31 and hypertension (adjusted odds ratio = 1.84 (95% confidence interval = 1.04–3.27 were more likely to be prescribed the combination. Conclusion: The drug interaction was prevalent in patients who are already at higher risk of health disparities and worse outcomes thus requiring vigilant evaluation.
Mixture and single-substance toxicity of selective serotonin reuptake inhibitors toward algae and crustaceans

DEFF Research Database (Denmark)

Christensen, Anne Munch; Faaborg-Andersen, S.; Ingerslev, Flemming

2007-01-01

Selective serotonin reuptake inhibitors (SSRIs) are used as antidepressant medications. primarily in the treatment of clinical depression. They are among the pharmaceuticals most often Prescribed in the industrialized countries. Selective serotonin reuptake inhibitors are compounds with an identi......Selective serotonin reuptake inhibitors (SSRIs) are used as antidepressant medications. primarily in the treatment of clinical depression. They are among the pharmaceuticals most often Prescribed in the industrialized countries. Selective serotonin reuptake inhibitors are compounds...... with an identical mechanism of action in mammals (inhibit reuptake of serotonin), and they have been found in different aqeous as well as biological samples collected in the environment. In the present study, we tested the toxicities of five SSRIs (citalopram, fluoxetine, fluoxamine, paroxetine, and sertraline.......027 to 1.6 mg/L, and in daphnids, test EC50s ranged from 0.92 to 20 mg/L, with sertraline being one of the most toxic compounds. The test design and statistical analysis of results from mixture tests were based on isobole analysis. It was demonstrated that the mixture toxicity of the SSRIs in the two...
Monoamine re-uptake sites in the human brain evaluated in vivo by means of /sup 11/C-nomifensine and positron emission tomography: the effects of age and Parkinson's disease

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Tedroff, J; Aquilonius, S -M; Hartvig, P; Lundqvist, H; Gee, A G; Uhlin, J; Laangstroem, B

1988-01-01

Six patients with Parkinson's disease, selected to cover a range of clinical features, and 7 healthy volunteers aged 24-81 years, were examined by positron emission tomography after i.v. injection of racemic /sup 11/C-nomifensine, a catecholamine re-uptake blocking drug. After injection the radiotracer, radioactivity was rapidly distributed to the brain. The highest accumulation of radioactivity was found in areas rich in dopamineric and noradrenergic innervation, such as the striatum and the thalamus. In regions with negible dopaminergic and noradrenergic innervation, such as the cerebellum, radioactivity was lower and evenly distributed. In all investigated brain regions a marked age-related decline in /sup 11/C-nomifensinederived radioactivity relative to the cerebellum was observed in the group of healthy volunteers. Parkinsonian patients did not show such a decline with age. In the group of parkinsonian patients with mainly unilateral involvement, the contralateral putamen exhibited the most pronounced decrease. Only the 3 parkinsonian patients aged 63 and younger showed markedly lower /sup 11/C-nomifensine binding in striatal areas than age-matched healthy volunteers. /sup 11/C-nomifensine seems to be a valuable tool for investigating noradrenergic and dopaminergic re-uptake sites in vivo. Further achievements will most likely be made when the active enantioimer becomes available.
Selective serotonin reuptake inhibitor (SSRI antidepressants, prolactin and breast cancer

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Janet eAshbury

2012-12-01

Full Text Available Selective serotonin reuptake inhibitors (SSRIs are a widely prescribed class of anti-depressants. Laboratory and epidemiologic evidence suggests that a prolactin-mediated mechanism secondary to increased serotonin levels at neuronal synapses could lead to a potentially carcinogenic effect of SSRIs. In this population-based case-control study, we evaluated the association between SSRI use and breast cancer risk as a function of their relative degree of inhibition of serotonin reuptake as a proxy for their impact on prolactin levels. Cases were 2,129 women with primary invasive breast cancer diagnosed from 2003-2007, and controls were 21,297 women randomly selected from the population registry. Detailed information for each SSRI prescription dispensed was compiled using the Saskatchewan prescription database. Logistic regression was used to evaluate the impact of use of high and lower inhibitors of serotonin reuptake and duration of use, as well as to assess the effect of individual high inhibitors on the risk of breast cancer. Exclusive users of high or lower inhibitors of serotonin reuptake were not at increased risk for breast cancer compared with nonusers of SSRIs (OR = 1.01, CI = 0.88-1.17 and OR = 0.91, CI = 0.67-1.25 respectively, regardless of their duration of use or menopausal status. While we cannot rule out the possibility of a clinically important risk increase (OR = 1.83, CI = 0.99-3.40 for long-term users of sertraline (≥24 prescriptions, given the small number of exposed cases (n=12, the borderline statistical significance and the wide confidence interval, these results need to be interpreted cautiously. In this large population-based case-control study, we found no conclusive evidence of breast cancer risk associated with the use of SSRIs even after assessing the degree of serotonin reuptake inhibition and duration of use. Our results do not support the serotonin-mediated pathway for the prolactin-breast cancer hypothesis.
National Ignition Facility site requirements

International Nuclear Information System (INIS)

1996-07-01

The Site Requirements (SR) provide bases for identification of candidate host sites for the National Ignition Facility (NIF) and for the generation of data regarding potential actual locations for the facilities. The SR supplements the NIF Functional Requirements (FR) with information needed for preparation of responses to queries for input to HQ DOE site evaluation. The queries are to include both documents and explicit requirements for the potential host site responses. The Sr includes information extracted from the NIF FR (for convenience), data based on design approaches, and needs for physical and organization infrastructure for a fully operational NIF. The FR and SR describe requirements that may require new construction or may be met by use or modification of existing facilities. The SR do not establish requirements for NIF design or construction project planning. The SR document does not constitute an element of the NIF technical baseline
Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population based case-control study

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de Abajo, Francisco José; Rodríguez, Luis Alberto García; Montero, Dolores

1999-01-01

Objective To examine the association between selective serotonin reuptake inhibitors and risk of upper gastrointestinal bleeding. Design Population based case-control study. Setting General practices included in the UK general practice research database. Subjects 1651 incident cases of upper gastrointestinal bleeding and 248 cases of ulcer perforation among patients aged 40 to 79 years between April 1993 and September 1997, and 10 000 controls matched for age, sex, and year that the case was identified. Interventions Review of computer profiles for all potential cases, and an internal validation study to confirm the accuracy of the diagnosis on the basis of the computerised information. Main outcome measures Current use of selective serotonin reuptake inhibitors or other antidepressants within 30 days before the index date. Results Current exposure to selective serotonin reuptake inhibitors was identified in 3.1% (52 of 1651) of patients with upper gastrointestinal bleeding but only 1.0% (95 of 10 000) of controls, giving an adjusted rate ratio of 3.0 (95% confidence interval 2.1 to 4.4). This effect measure was not modified by sex, age, dose, or treatment duration. A crude incidence of 1 case per 8000 prescriptions was estimated. A small association was found with non-selective serotonin reuptake inhibitors (relative risk 1.4, 1.1 to 1.9) but not with antidepressants lacking this inhibitory effect. None of the groups of antidepressants was associated with ulcer perforation. The concurrent use of selective serotonin reuptake inhibitors with non-steroidal anti-inflammatory drugs increased the risk of upper gastrointestinal bleeding beyond the sum of their independent effects (15.6, 6.6 to 36.6). A smaller interaction was also found between selective serotonin reuptake inhibitors and low dose aspirin (7.2, 3.1 to 17.1). Conclusions Selective serotonin reuptake inhibitors increase the risk of upper gastrointestinal bleeding. The absolute effect is, however
Prenatal exposure to selective serotonin reuptake inhibitors and childhood overweight at 7 years of age

DEFF Research Database (Denmark)

Grzeskowiak, Luke E; Gilbert, Andrew L; Sørensen, Thorkild

2013-01-01

To investigate a possible association between prenatal selective serotonin reuptake inhibitor (SSRI) exposure and childhood overweight at 7 years of age.......To investigate a possible association between prenatal selective serotonin reuptake inhibitor (SSRI) exposure and childhood overweight at 7 years of age....
Comparison of the effects of sibutramine and other monoamine reuptake inhibitors on food intake in the rat

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Jackson, Helen C; Needham, Andrew M; Hutchins, Lisa J; Mazurkiewicz, Sarah E; Heal, David J

1997-01-01

The effects of the potent 5-hydroxytryptamine (5-HT) and noradrenaline reuptake inhibitor (serotonin-noradrenaline reuptake inhibitor, SNRI), sibutramine, on the cumulative food intake of freely-feeding male Sprague-Dawley rats during an 8 h dark period were investigated and compared to those of the selective 5-HT reuptake inhibitor (selective serotonin reuptake inhibitor, SSRI), fluoxetine; the selective noradrenaline reuptake inhibitor, nisoxetine; the 5-HT and noradrenaline reuptake inhibitors, venlafaxine and duloxetine; and the 5-HT releaser and 5-HT reuptake inhibitor, (+)-fenfluramine. Sibutramine (3 and 10 mg kg−1, p.o.) and (+)-fenfluramine (1 and 3 mg kg−1, p.o.) produced a significant, dose-dependent decrease in food intake over the 8 h dark period. These responses became apparent within the first 2 h following drug administration. Fluoxetine (3, 10 and 30 mg kg−1, p.o.), and nisoxetine (3, 10 and 30 mg kg−1, p.o.) had no significant effect on food intake during the 8 h dark period. However, a combination of fluoxetine and nisoxetine (30 mg kg−1, p.o., of each) significantly decreased food intake 2 and 8 h after drug administration. Venlafaxine (100 and 300 mg kg−1, p.o.) and duloxetine (30 mg kg−1, p.o.) also significantly decreased food intake in the 2 and 8 h following drug administration. The results of this study demonstrate that inhibition of 5-HT and noradrenaline reuptake by sibutramine, venlafaxine, duloxetine, or by a combination of fluoxetine and nisoxetine, markedly reduces food intake in freely-feeding rats and suggest that this may be a novel approach for the treatment of obesity. PMID:9283714

Antidepressant drugs specifically inhibiting noradrenaline reuptake enhance recognition memory in rats.

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Feltmann, Kristin; Konradsson-Geuken, Åsa; De Bundel, Dimitri; Lindskog, Maria; Schilström, Björn

2015-12-01

Patients suffering from major depression often experience memory deficits even after the remission of mood symptoms, and many antidepressant drugs do not affect, or impair, memory in animals and humans. However, some antidepressant drugs, after a single dose, enhance cognition in humans (Harmer et al., 2009). To compare different classes of antidepressant drugs for their potential as memory enhancers, we used a version of the novel object recognition task in which rats spontaneously forget objects 24 hr after their presentation. Antidepressant drugs were injected systemically 30 min before or directly after the training phase (Session 1 [S1]). Post-S1 injections were used to test for specific memory-consolidation effects. The noradrenaline reuptake inhibitors reboxetine and atomoxetine, as well as the serotonin noradrenaline reuptake inhibitor duloxetine, injected prior to S1 significantly enhanced recognition memory. In contrast, the serotonin reuptake inhibitors citalopram and paroxetine and the cyclic antidepressant drugs desipramine and mianserin did not enhance recognition memory. Post-S1 injection of either reboxetine or citalopram significantly enhanced recognition memory, indicating an effect on memory consolidation. The fact that citalopram had an effect only when injected after S1 suggests that it may counteract its own consolidation-enhancing effect by interfering with memory acquisition. However, pretreatment with citalopram did not attenuate reboxetine's memory-enhancing effect. The D1/5-receptor antagonist SCH23390 blunted reboxetine's memory-enhancing effect, indicating a role of dopaminergic transmission in reboxetine-induced recognition memory enhancement. Our results suggest that antidepressant drugs specifically inhibiting noradrenaline reuptake enhance cognition and may be beneficial in the treatment of cognitive symptoms of depression. (c) 2015 APA, all rights reserved).
Site evaluation for nuclear installations. Safety requirements

International Nuclear Information System (INIS)

2003-01-01

This Safety Requirements publication supersedes the Code on the Safety of Nuclear Power Plants: Siting, which was issued in 1988 as Safety Series No. 50-C-S (Rev. 1). It takes account of developments relating to site evaluations for nuclear installations since the Code on Siting was last revised. These developments include the issuing of the Safety Fundamentals publication on The Safety of Nuclear Installations, and the revision of various safety standards and other publications relating to safety. Requirements for site evaluation are intended to ensure adequate protection of site personnel, the public and the environment from the effects of ionizing radiation arising from nuclear installations. It is recognized that there are steady advances in technology and scientific knowledge, in nuclear safety and in what is considered adequate protection. Safety requirements change with these advances and this publication reflects the present consensus among States. This Safety Requirements publication was prepared under the IAEA programme on safety standards for nuclear installations. It establishes requirements and provides criteria for ensuring safety in site evaluation for nuclear installations. The Safety Guides on site evaluation listed in the references provide recommendations on how to meet the requirements established in this Safety Requirements publication. The objective of this publication is to establish the requirements for the elements of a site evaluation for a nuclear installation so as to characterize fully the site specific conditions pertinent to the safety of a nuclear installation. The purpose is to establish requirements for criteria, to be applied as appropriate to site and site-installation interaction in operational states and accident conditions, including those that could lead to emergency measures for: (a) Defining the extent of information on a proposed site to be presented by the applicant; (b) Evaluating a proposed site to ensure that the site
The market dynamics of selective serotonin re-uptake inhibitors: a ...

African Journals Online (AJOL)

The market dynamics of selective serotonin re-uptake inhibitors: a private sector study in South Africa. Frasia Oosthuizen, Pariksha Jolene Kondiah, Hawa Bibi Moosa, Siddiqa Naroth, Nabeel Ismail Patel, Divashnee Reddy, Amanda Soobramoney ...
Dependence and withdrawal reactions to benzodiazepines and sellective serotonin reuptake inhibitors: How did the health authorities react?

DEFF Research Database (Denmark)

Nielsen, Margrethe

2013-01-01

AIM: Our objective was to explore communications from drug agencies about benzodiazepine dependence and selective serotonin reuptake inhibitors (SSRIs) withdrawal reactions over time. METHODS: Documentary study. We searched the web-sites of the European Medicines Agency and the drug agencies in USA...... it is difficult for many patients to stop treatment. In the perspective of a precautionary principle, drug agencies have failed to acknowledge that SSRIs can cause dependence and have minimised the problem with regard to its frequency and severity. In the perspective of a risk management principle, the drug...
Requirements of on-site facilities

International Nuclear Information System (INIS)

Burchardt, H.

1977-01-01

1) Requirements of on-site facilities: a) brief description of supplying the site with electricity and water; communication facilities, b) necessary facilities for containment and pipeline installation, c) necessary facilities for storage, safety, accommodation of personnel, housing; workshops; 2) Site management: a) Organisation schedules for 'turn-key-jobs' and 'single commission', b) Duties of the supervisory staff. (orig.) [de
Triple Reuptake Inhibitors: A Premise and Promise

OpenAIRE

Marks, David M.; Pae, Chi-Un; Patkar, Ashwin A.

2008-01-01

On the horizon there is a new class of psychoactive medications which work by inhibiting the neuronal reuptake of serotonin, norepinephrine, and dopamine. There are multiple potential indications for these drugs. Research suggests that they may have a role in treating depressive disorders, and it is plausible they may have potential efficacy in obesity, addiction, and pain syndromes. The current review describes some of the molecules in development presently and explores the research relevant...
Dependence and withdrawal reactions to benzodiazepines and selective serotonin reuptake inhibitors. How did the health authorities react?

DEFF Research Database (Denmark)

Nielsen, Margrethe; Hansen, Ebba Holme; Gøtzsche, Peter C

2013-01-01

Our objective was to explore communications from drug agencies about benzodiazepine dependence and selective serotonin reuptake inhibitors (SSRIs) withdrawal reactions over time.......Our objective was to explore communications from drug agencies about benzodiazepine dependence and selective serotonin reuptake inhibitors (SSRIs) withdrawal reactions over time....
Development of norepinephrine transporter reuptake inhibition assays using SK-N-BE(2C cells

Directory of Open Access Journals (Sweden)

Ann M. Decker

2018-05-01

Full Text Available This report describes efforts to develop and validate novel norepinephrine transporter reuptake inhibition assays using human neuroblastoma SK-N-BE(2C cells in 24-well format. Before conducting the assays, the SK-N-BE(2C cells were first evaluated for their ability to uptake [3H]norepinephrine and were shown to have a saturable uptake with a KM value of 416 nM. Using this determined KM value, reuptake inhibition assays were then conducted with a variety of ligands including antidepressants, as well as piperazine and phenyltropane derivatives. The results obtained with the SK-N-BE(2C cells indicate that this model system can detect a range of ligand potencies, which compare well with other established transporter assays. Our data suggest that SK-N-BE(2C cells have potential utility to serve as another model system to detect norepinephrine reuptake inhibition activity.
The market dynamics of selective serotonin re-uptake inhibitors: a ...

African Journals Online (AJOL)

re-uptake inhibitors: a private sector study in South Africa. Afri Health ... the public and private sectors to reduce medicine costs, and increase ... Fig 1: Comparison between the market volume of generics vs. originators for the period June 2009 ...
Triple Reuptake Inhibitors: The Next Generation of Antidepressants

OpenAIRE

Marks, David M; Pae, Chi-Un; Patkar, Ashwin A

2008-01-01

Depression has been associated with impaired neurotransmission of serotonergic, norepinephrinergic, and dopaminergic pathways, although most pharmacologic treatment strategies for depression enhance only serotonin and norepinephrine neurotransmission. Current drug development efforts are aimed at a new class of antidepressants which inhibit the reuptake of all three neurotransmitters in the hope of creating medications with broader efficacy and/or quicker onset of action. The current review e...
Inhibitors of serotonin reuptake and specific imipramine binding in human blood plasma

International Nuclear Information System (INIS)

Brusov, O.S.; Fomenko, A.M.; Katasonov, A.B.; Lidemann, R.R.

1985-01-01

This paper describes a method of extraction of endogenous inhibitors of specific IMI binding and of 5-HT reuptake, from human blood plasma and the heterogeneity of these compounds is demonstrated. Specific binding was determined as the difference between binding of 3 H-IMI in the absence and in the presence of 50 microM IMI. Under these conditions, specific binding amounted to 70-80% of total binding of 3 H-IMI. It is shown that extract obtained from human blood contains a material which inhibits dose-dependently both 5-HT reuptake and specific binding of 3 H-IMI. Gel-chromatography of extracts of human blood plasma on Biogel P-2 is also shown
Mechanism-based PK/PD modeling of selective serotonin reuptake inhibitors

NARCIS (Netherlands)

Geldof, Marian

2007-01-01

The main objective of the investigations was to explore the PK/PD correlations of fluvoxamine, as a prototype for the Selective Serotonin Reuptake Inhibitors (SSRIs). In the various investigations, a spectrum of different biomarkers was used, each reflecting a specific process on the causal path
Commentary: Considerations on the Pharmacological Treatment of Compulsions and Stereotypies with Serotonin Reuptake Inhibitors in Pervasive Developmental Disorders.

Science.gov (United States)

Gordon, C. T.

2000-01-01

This commentary discusses study results that indicate the nonselective serotonin reuptake inhibitor (SRI) clomipramine is more efficacious than the relatively selective norepinephrine reuptake inhibitor desipramine and placebo in treating repetitive or ritualized behaviors in children with autism. The need for concurrent genetic and biochemical…
Triple Reuptake Inhibitors: A Premise and Promise

Science.gov (United States)

Marks, David M.; Patkar, Ashwin A.

2008-01-01

On the horizon there is a new class of psychoactive medications which work by inhibiting the neuronal reuptake of serotonin, norepinephrine, and dopamine. There are multiple potential indications for these drugs. Research suggests that they may have a role in treating depressive disorders, and it is plausible they may have potential efficacy in obesity, addiction, and pain syndromes. The current review describes some of the molecules in development presently and explores the research relevant to possible clinical uses for this class of medications. PMID:20046357
Use of selective serotonin reuptake inhibitors reduces fertility in men

DEFF Research Database (Denmark)

Nørr, L; Bennedsen, Birgit; Fedder, Jens

2016-01-01

Clinical review of the present data on the effects of selective serotonin reuptake inhibitors (SSRIs) on male fertility was the objective of the study. PubMed and Scopus were searched for publications in English or Danish and reviewed. Human trials, animal studies and in vitro studies were included...
Serotonin reuptake inhibitors and bone health: A review of clinical studies and plausible mechanisms

Directory of Open Access Journals (Sweden)

Ravisha Wadhwa

2017-06-01

Full Text Available Selective serotonin reuptake inhibitors (SSRIs are currently the treatment of choice in depression and constitute major portion of prescription in depressive patients. The role of serotonin receptors in bone is emerging, raising certain questions regarding the effect of blockade of serotonin reuptake in the bone metabolism. Clinical studies have reported an association of SSRI antidepressants which with increase in fracture and decrease in bone mineral density. This review focus on recent evidence that evaluate the association of SSRIs with the risk of fracture and bone mineral density and also the probable mechanisms that might be involved in such effects.
[ I - 123 ] IPT SPECT Dopamine Reuptake Site Imaging : Differences in Normal Controls and Parkinson's Patients by Semiquantitat

International Nuclear Information System (INIS)

Kim, Hee Joung; Yang, Seoung Oh; Ryu, Jin Sook; Choi, Yun Young; Lee, Hee Kyung; Im, Joo Hyuck; Lee, Myung Chong

1996-01-01

Dopamine transporter concentrations have been known to decrease in Parkinson's disease (PD) or increase in Tourette's disorder. The purpose of this study was to evaluate the effectiveness of [I-123]N-(3-iodopropene-2-yl)-2β-carbomethoxy-3β-(4-chlorophenyl) tropane (IPT) as an imaging agent for measuring changes in transporter concentrations with PD. IPT labelled with 6.69+/-0.64 mCi (247.53+/-23.68 MBq) of I-123 was intravenously injected into ten patients(age: 55+/-11) with PD, and six normal controls(NC)(age: 46+/-14) as a bolus. Dynamic SPECT scans of the brain were then performed for 5 minutes each over 120 minutes on a triple headed camera. Time activity curves were generated for the left basal ganglia(LBG), right basal ganglia(RBG), and occipital cortex(OCC). The statistical parameters included the time to peak activity, the contrast ratio of LEG and RBG to OCC at several time points, and the accumulated specific binding counts/mCi/pixel (ASBC) from 0 to 115 minutes. The uptake of IPT in the brains of PD and NC peaked within 10 minutes of injection in all subjects. The maximum target to background ratio in the basal ganglia of PD and NC occurred at 85+/-20 min and 110-+/-6 min of injection, respectively. The BG/OCC ratios at 115 minutes for PD and NC were 2.15+/-0.54 and 4.26+/-0.73, respectively. The ASBC at 115 minutes for PD and NC were 152.91+/-50.09 and 289.51+/-49.00, respectively. The ratio of BG/OCC for the NC was significantly higher than the ratio for PD. SPECT data matched with clinical diagnosis for PDs. The ratio between BG and OCC and the ASBC for PD were clearly separated from NC and may be useful outcome measures for clinical diagnosis. The findings suggest that IPT may be a very useful tracer for early diagnosis of PD and study of dopamine reuptake site.
Site safety requirements for high level waste disposal

International Nuclear Information System (INIS)

Chen Weiming; Wang Ju

2006-01-01

This paper outlines the content, status and trend of site safety requirements of International Atomic Energy Agency, America, France, Sweden, Finland and Japan. Site safety requirements are usually represented as advantageous vis-a-vis disadvantagous conditions, and potential advantage vis-a-vis disadvantage conditions, respectively in aspects of geohydrology, geochemistry, lithology, climate and human intrusion etc. Study framework and steps of site safety requirements for China are discussed under the view of systems science. (authors)
Chloride binding site of neurotransmitter sodium symporters

DEFF Research Database (Denmark)

Kantcheva, Adriana Krassimirova; Quick, Matthias; Shi, Lei

2013-01-01

Neurotransmitter:sodium symporters (NSSs) play a critical role in signaling by reuptake of neurotransmitters. Eukaryotic NSSs are chloride-dependent, whereas prokaryotic NSS homologs like LeuT are chloride-independent but contain an acidic residue (Glu290 in LeuT) at a site where eukaryotic NSSs...
CYP450 genotype and aggressive behavior on selective serotonin reuptake inhibitors

NARCIS (Netherlands)

Ekhart, Corine; Matic, Maja; Kant, Agnes; Schaik, Ron van; van Puijenbroek, Eugène

2017-01-01

AIM: Genetic variants for selective serotonin reuptake inhibitor (SSRI) metabolizing enzymes have been hypothesized to be a risk factor for aggression as adverse drug effect of SSRIs. Our aim was to assess the possible involvement of these polymorphisms on aggression when using SSRIs. MATERIALS &

Selective Serotonin Reuptake Inhibitor-Induced Sexual Dysfunction in Adolescents: A Review.

Science.gov (United States)

Scharko, Alexander M.

2004-01-01

Objective: To review the existing literature on selective serotonin reuptake inhibitor (SSRI)-induced sexual dysfunction in adolescents. Method: A literature review of SSRI-induced adverse effects in adolescents focusing on sexual dysfunction was done. Nonsexual SSRI-induced adverse effects were compared in adult and pediatric populations.…
Understanding the pharmacogenetics of selective serotonin reuptake inhibitors.

Science.gov (United States)

Fabbri, Chiara; Minarini, Alessandro; Niitsu, Tomihisa; Serretti, Alessandro

2014-08-01

The genetic background of antidepressant response represents a unique opportunity to identify biological markers of treatment outcome. Encouraging results alternating with inconsistent findings made antidepressant pharmacogenetics a stimulating but often discouraging field that requires careful discussion about cumulative evidence and methodological issues. The present review discusses both known and less replicated genes that have been implicated in selective serotonin reuptake inhibitors (SSRIs) efficacy and side effects. Candidate genes studies and genome-wide association studies (GWAS) were collected through MEDLINE database search (articles published till January 2014). Further, GWAS signals localized in promising genetic regions according to candidate gene studies are reported in order to assess the general comparability of results obtained through these two types of pharmacogenetic studies. Finally, a pathway enrichment approach is applied to the top genes (those harboring SNPs with p pharmacogenetics, the present review discusses the proposal of moving from the analysis of individual polymorphisms to genes and molecular pathways, and from the separation across different methodological approaches to their combination. Efforts in this direction are justified by the recent evidence of a favorable cost-utility of gene-guided antidepressant treatment.
77 FR 55108 - Explosive Siting Requirements

Science.gov (United States)

2012-09-07

... energy, or a chemical explosion requiring a chemical reaction. Furthermore, an accident may happen... for energetic liquids. \\4\\ Crowl, D.A., Understanding Explosions, AIAA Center for Chemical Process... chemical hazards of energetic liquids used at commercial launch sites. Finally, a site map must now be at a...
Serotonin synthesis, release and reuptake in terminals: a mathematical model

Directory of Open Access Journals (Sweden)

Best Janet

2010-08-01

Full Text Available Abstract Background Serotonin is a neurotransmitter that has been linked to a wide variety of behaviors including feeding and body-weight regulation, social hierarchies, aggression and suicidality, obsessive compulsive disorder, alcoholism, anxiety, and affective disorders. Full understanding of serotonergic systems in the central nervous system involves genomics, neurochemistry, electrophysiology, and behavior. Though associations have been found between functions at these different levels, in most cases the causal mechanisms are unknown. The scientific issues are daunting but important for human health because of the use of selective serotonin reuptake inhibitors and other pharmacological agents to treat disorders in the serotonergic signaling system. Methods We construct a mathematical model of serotonin synthesis, release, and reuptake in a single serotonergic neuron terminal. The model includes the effects of autoreceptors, the transport of tryptophan into the terminal, and the metabolism of serotonin, as well as the dependence of release on the firing rate. The model is based on real physiology determined experimentally and is compared to experimental data. Results We compare the variations in serotonin and dopamine synthesis due to meals and find that dopamine synthesis is insensitive to the availability of tyrosine but serotonin synthesis is sensitive to the availability of tryptophan. We conduct in silico experiments on the clearance of extracellular serotonin, normally and in the presence of fluoxetine, and compare to experimental data. We study the effects of various polymorphisms in the genes for the serotonin transporter and for tryptophan hydroxylase on synthesis, release, and reuptake. We find that, because of the homeostatic feedback mechanisms of the autoreceptors, the polymorphisms have smaller effects than one expects. We compute the expected steady concentrations of serotonin transporter knockout mice and compare to
Are Selective Serotonin Reuptake Inhibitors Safe for Drivers? What is the Evidence?

NARCIS (Netherlands)

Ravera, Silvia; Ramaekers, Johannes G.; de Jong-van den Berg, Lolkje T. W.; de Gier, Johan J.; de Jong-van den Berg, [No Value

Background: Selective serotonin reuptake inhibitors (SSRIs) are widely used medications to treat several psychiatric diseases and, above all, depression. They seem to be as effective as older antidepressants but have a different adverse effect profile. Despite their favorable safety profile, little
Paediatric outcomes following intrauterine exposure to serotonin reuptake inhibitors: a systematic review

DEFF Research Database (Denmark)

Fenger-Grøn, Jesper; Thomsen, Morten; Andersen, Kristian Skytte

2011-01-01

The use of serotonine reuptake inhibitors (SRIs) is increasing among Danish pregnant women. This systematic review addresses the potential adverse effects on the foetus and child of maternal SRI medication. The literature indicates a slightly increased risk of cardiovascular malformations...
Effects of tryptophan depletion on selective serotonin reuptake inhibitor-remitted patients with obsessive compulsive disorder.

Science.gov (United States)

Hood, Sean D; Broyd, Annabel; Robinson, Hayley; Lee, Jessica; Hudaib, Abdul-Rahman; Hince, Dana A

2017-12-01

Serotonergic antidepressants are first-line medication therapies for obsessive-compulsive disorder, however it is not known if synaptic serotonin availability is important for selective serotonin reuptake inhibitor efficacy. The present study tested the hypothesis that temporary reduction in central serotonin transmission, through acute tryptophan depletion, would result in an increase in anxiety in selective serotonin reuptake inhibitor-remitted obsessive-compulsive disorder patients. Eight patients (four males) with obsessive-compulsive disorder who showed sustained clinical improvement with selective serotonin reuptake inhibitor treatment underwent acute tryptophan depletion in a randomized, double-blind, placebo-controlled, within-subjects design, over two days one week apart. Five hours after consumption of the depleting/sham drink the participants performed a personalized obsessive-compulsive disorder symptom exposure task. Psychological responses were measured using the Spielberger State Anxiety Inventory, Yale-Brown Obsessive Compulsive Scale and Visual Analogue Scales. Free plasma tryptophan to large neutral amino acid ratio decreased by 93% on the depletion day and decreased by 1% on the sham day, as anticipated. Psychological rating scores as measured by Visual Analogue Scale showed a significant decrease in perceived control and increase in interfering thoughts at the time of provocation on the depletion day but not on the sham day. A measure of convergent validity, namely Visual Analogue Scale Similar to past, was significantly higher at the time of provocation on both the depletion and sham days. Both the depletion and time of provocation scores for Visual Analogue Scale Anxiety, Spielberger State Anxiety Inventory, Yale-Brown Obsessive Compulsive Scale and blood pressure were not significant. Acute tryptophan depletion caused a significant decrease in perceived control and increase in interfering thoughts at the time of provocation. Acute tryptophan
A concise total synthesis of (R)-fluoxetine, a potent and selective serotonin reuptake inhibitor

International Nuclear Information System (INIS)

Fatima, Angelo de; Lapis, Alexandre Augusto M.; Pilli, Ronaldo A.

2005-01-01

(R)-Fluoxetine, potent and selective serotonin reuptake inhibitor, has been synthesized in six steps, 50% overall yield and 99% ee from benzaldehyde via catalytic asymmetric allylation with Maruoka's catalyst. (author)
A concise total synthesis of (R)-fluoxetine, a potent and selective serotonin reuptake inhibitor

Energy Technology Data Exchange (ETDEWEB)

Fatima, Angelo de; Lapis, Alexandre Augusto M.; Pilli, Ronaldo A. [Universidade Estadual de Campinas, SP (Brazil). Inst. de Quimica]. E-mail: pilli@iqm.unicamp.br

2005-05-15

(R)-Fluoxetine, potent and selective serotonin reuptake inhibitor, has been synthesized in six steps, 50% overall yield and 99% ee from benzaldehyde via catalytic asymmetric allylation with Maruoka's catalyst. (author)
Treatment of selective mutism: focus on selective serotonin reuptake inhibitors.

Science.gov (United States)

Kaakeh, Yaman; Stumpf, Janice L

2008-02-01

Abstract Selective mutism is a pediatric psychiatric disorder that occurs when a child consistently fails to speak in specific situations in which speaking is expected, such as at school and social gatherings, but speaks appropriately in other settings. Selective mutism often is diagnosed when a child starts school and does not talk to teachers or peers, but talks to family members at home; the condition is frequently accompanied by anxiety and shyness. Although the underlying etiology of the condition remains unclear, psychotherapy is the preferred initial treatment, with the support of parents and teachers. If the child does not respond to psychotherapy, addition of pharmacologic treatment should be considered, depending on the severity of symptoms and presence of other illnesses. Although data are limited to case reports and trials with small patient populations and short follow-up periods, some patients with selective mutism respond to therapy with selective serotonin reuptake inhibitors (SSRIs). Fluoxetine is the most studied SSRI as treatment for the condition, although further investigation is required to determine the optimal dosage and duration of therapy.
Effects of acute administration of selective serotonin reuptake inhibitors on sympathetic nerve activity

International Nuclear Information System (INIS)

Tiradentes, R.V.; Pires, J.G.P.; Silva, N.F.; Ramage, A.G.; Santuzzi, C.H.; Futuro, H.A. Neto

2014-01-01

Serotonergic mechanisms have an important function in the central control of circulation. Here, the acute effects of three selective serotonin (5-HT) reuptake inhibitors (SSRIs) on autonomic and cardiorespiratory variables were measured in rats. Although SSRIs require 2-3 weeks to achieve their full antidepressant effects, it has been shown that they cause an immediate inhibition of 5-HT reuptake. Seventy male Wistar rats were anesthetized with urethane and instrumented to record blood pressure, heart rate, renal sympathetic nerve activity (RSNA), and respiratory frequency. At lower doses, the acute cardiovascular effects of fluoxetine, paroxetine and sertraline administered intravenously were insignificant and variable. At middle and higher doses, a general pattern was observed, with significant reductions in sympathetic nerve activity. At 10 min, fluoxetine (3 and 10 mg/kg) reduced RSNA by -33±4.7 and -31±5.4%, respectively, without changes in blood pressure; 3 and 10 mg/kg paroxetine reduced RSNA by -35±5.4 and -31±5.5%, respectively, with an increase in blood pressure +26.3±2.5; 3 mg/kg sertraline reduced RSNA by -59.4±8.6%, without changes in blood pressure. Sympathoinhibition began 5 min after injection and lasted approximately 30 min. For fluoxetine and sertraline, but not paroxetine, there was a reduction in heart rate that was nearly parallel to the sympathoinhibition. The effect of these drugs on the other variables was insignificant. In conclusion, acute peripheral administration of SSRIs caused early autonomic cardiovascular effects, particularly sympathoinhibition, as measured by RSNA. Although a peripheral action cannot be ruled out, such effects are presumably mostly central
Effects of acute administration of selective serotonin reuptake inhibitors on sympathetic nerve activity

Energy Technology Data Exchange (ETDEWEB)

Tiradentes, R.V. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Centro Universitário do Espírito Santo, Colatina, ES (Brazil); Pires, J.G.P. [Centro Universitário do Espírito Santo, Colatina, ES (Brazil); Escola de Medicina da Empresa Brasileira de Ensino, Vitória, ES (Brazil); Silva, N.F. [Departamento de Morfologia, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Ramage, A.G. [Department of Neuroscience, Physiology and Pharmacology, University College London, London (United Kingdom); Santuzzi, C.H. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Centro Universitário do Espírito Santo, Colatina, ES (Brazil); Futuro, H.A. Neto [Escola de Medicina da Empresa Brasileira de Ensino, Vitória, ES (Brazil); Departamento de Morfologia, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Escola Superior de Ciências da Saúde, Santa Casa de Misericórdia de Vitória, Vitória, ES (Brazil)

2014-05-30

Serotonergic mechanisms have an important function in the central control of circulation. Here, the acute effects of three selective serotonin (5-HT) reuptake inhibitors (SSRIs) on autonomic and cardiorespiratory variables were measured in rats. Although SSRIs require 2-3 weeks to achieve their full antidepressant effects, it has been shown that they cause an immediate inhibition of 5-HT reuptake. Seventy male Wistar rats were anesthetized with urethane and instrumented to record blood pressure, heart rate, renal sympathetic nerve activity (RSNA), and respiratory frequency. At lower doses, the acute cardiovascular effects of fluoxetine, paroxetine and sertraline administered intravenously were insignificant and variable. At middle and higher doses, a general pattern was observed, with significant reductions in sympathetic nerve activity. At 10 min, fluoxetine (3 and 10 mg/kg) reduced RSNA by -33±4.7 and -31±5.4%, respectively, without changes in blood pressure; 3 and 10 mg/kg paroxetine reduced RSNA by -35±5.4 and -31±5.5%, respectively, with an increase in blood pressure +26.3±2.5; 3 mg/kg sertraline reduced RSNA by -59.4±8.6%, without changes in blood pressure. Sympathoinhibition began 5 min after injection and lasted approximately 30 min. For fluoxetine and sertraline, but not paroxetine, there was a reduction in heart rate that was nearly parallel to the sympathoinhibition. The effect of these drugs on the other variables was insignificant. In conclusion, acute peripheral administration of SSRIs caused early autonomic cardiovascular effects, particularly sympathoinhibition, as measured by RSNA. Although a peripheral action cannot be ruled out, such effects are presumably mostly central.
Comparative efficacy and safety of selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors in older adults: a network meta-analysis.

Science.gov (United States)

Thorlund, Kristian; Druyts, Eric; Wu, Ping; Balijepalli, Chakrapani; Keohane, Denis; Mills, Edward

2015-05-01

To establish the comparative efficacy and safety of selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors in older adults using the network meta-analysis approach. Systematic review and network meta-analysis. Individuals aged 60 and older. Data on partial response (defined as at least 50% reduction in depression score from baseline) and safety (dizziness, vertigo, syncope, falls, loss of consciousness) were extracted. A Bayesian network meta-analysis was performed on the efficacy and safety outcomes, and relative risks (RRs) with 95% credible intervals (CrIs) were produced. Fifteen randomized controlled trials were eligible for inclusion in the analysis. Citalopram, escitalopram, paroxetine, duloxetine, venlafaxine, fluoxetine, and sertraline were represented. Reporting on partial response and dizziness was sufficient to conduct a network meta-analysis. Reporting on other outcomes was sparse. For partial response, sertraline (RR=1.28), paroxetine (RR=1.48), and duloxetine (RR=1.62) were significantly better than placebo. The remaining interventions yielded RRs lower than 1.20. For dizziness, duloxetine (RR=3.18) and venlafaxine (RR=2.94) were statistically significantly worse than placebo. Compared with placebo, sertraline had the lowest RR for dizziness (1.14) and fluoxetine the second lowest (1.31). Citalopram, escitalopram, and paroxetine all had RRs between 1.4 and 1.7. There was clear evidence of the effectiveness of sertraline, paroxetine, and duloxetine. There also appears to be a hierarchy of safety associated with the different antidepressants, although there appears to be a dearth of reporting of safety outcomes. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.
The effect of selective serotonin reuptake inhibitors in healthy subjects. A systematic review

DEFF Research Database (Denmark)

Knorr, Ulla; Kessing, Lars Vedel; Knorr, Ulla

2010-01-01

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) show antidepressant properties in many patients with a diagnosis of depression. An understanding of the underlying mechanisms of the effect of SSRIs in healthy patients may lead to an understanding of the yet unclear pathophysiology of d...
Increased Bleeding Risk With Concurrent Use of Selective Serotonin Reuptake inhibitors and Coumarins

NARCIS (Netherlands)

Schalekamp, Tom; Klungel, Olaf H; Souverein, Patrick C; de Boer, Anthonius

2008-01-01

BACKGROUND: Treatment with vitamin K antagonists (coumarins) is associated with an increased risk of bleeding. Because use of selective serotonin reuptake inhibitors (SSRIs) is also associated with an increased risk of bleeding, we assessed the odds ratio (OR) of abnormal bleeding associated with
[ I - 123 ] IPT SPECT Dopamine Reuptake Site Imaging : Differences in Normal Controls and Parkinson's Patients by Semiquantitat

Energy Technology Data Exchange (ETDEWEB)

Kim, Hee Joung; Yang, Seoung Oh; Ryu, Jin Sook; Choi, Yun Young; Lee, Hee Kyung [Asan Medical Center, University of Ulsan, Seoul (Korea, Republic of); Im, Joo Hyuck; Lee, Myung Chong [Asan Medical Center, University of Ulsan, Seoul (Korea, Republic of)

1996-03-15

Dopamine transporter concentrations have been known to decrease in Parkinson's disease (PD) or increase in Tourette's disorder. The purpose of this study was to evaluate the effectiveness of [I-123]N-(3-iodopropene-2-yl)-2{beta}-carbomethoxy-3{beta}-(4-chlorophenyl) tropane (IPT) as an imaging agent for measuring changes in transporter concentrations with PD. IPT labelled with 6.69+/-0.64 mCi (247.53+/-23.68 MBq) of I-123 was intravenously injected into ten patients(age: 55+/-11) with PD, and six normal controls(NC)(age: 46+/-14) as a bolus. Dynamic SPECT scans of the brain were then performed for 5 minutes each over 120 minutes on a triple headed camera. Time activity curves were generated for the left basal ganglia(LBG), right basal ganglia(RBG), and occipital cortex(OCC). The statistical parameters included the time to peak activity, the contrast ratio of LEG and RBG to OCC at several time points, and the accumulated specific binding counts/mCi/pixel (ASBC) from 0 to 115 minutes. The uptake of IPT in the brains of PD and NC peaked within 10 minutes of injection in all subjects. The maximum target to background ratio in the basal ganglia of PD and NC occurred at 85+/-20 min and 110-+/-6 min of injection, respectively. The BG/OCC ratios at 115 minutes for PD and NC were 2.15+/-0.54 and 4.26+/-0.73, respectively. The ASBC at 115 minutes for PD and NC were 152.91+/-50.09 and 289.51+/-49.00, respectively. The ratio of BG/OCC for the NC was significantly higher than the ratio for PD. SPECT data matched with clinical diagnosis for PDs. The ratio between BG and OCC and the ASBC for PD were clearly separated from NC and may be useful outcome measures for clinical diagnosis. The findings suggest that IPT may be a very useful tracer for early diagnosis of PD and study of dopamine reuptake site.
Improved preclinical cardiovascular therapeutic indices with long-term inhibition of norepinephrine reuptake using reboxetine

NARCIS (Netherlands)

Fossa, Anthony A.; Wisialowski, Todd A.; Cremers, Thomas; van der Hart, Marieke; Tseng, Elaine; Deng, Shibing; Rollema, Hans; Wang, Ellen Q.

2012-01-01

Norepinephrine reuptake inhibitors (NRIs) acutely increase norepinephrine (NE) levels, but therapeutic antidepressant activity is only observed after weeks of treatment because central NE levels progressively increase during continued drug exposure. Similarly, while NRIs acutely increase blood
The treatment of kleptomania with serotonin reuptake inhibitors.

Science.gov (United States)

Lepkifker, E; Dannon, P N; Ziv, R; Iancu, I; Horesh, N; Kotler, M

1999-01-01

Kleptomania is characterized by an irresistible impulse to steal objects not needed for personal use or for their monetary value. Several recent case reports have shown that Serotonin Specific Reuptake Inhibitors (SSRIs) could be effective in the treatment of kleptomania just as it is in other obsessive-compulsive spectrum disorders. We report five cases of kleptomania patients who were successfully treated with fluoxetine or paroxetine in combination with a psychotherapeutic intervention. In one case, the discontinuation of the medication repeatedly led to the resurgence of the kleptomanic behavior. Our case series illustrates the effectiveness of SSRIs in kleptomania. It thus supports the assumption that this syndrome involves a dysfunctional serotoninergic mechanism.
In utero exposure to selective serotonin reuptake inhibitors and risk for autism spectrum disorder

DEFF Research Database (Denmark)

Gidaya, Nicole B; Lee, Brian K; Burstyn, Igor

2014-01-01

We investigated whether there is an association between increased risk for autism spectrum disorders (ASD) and selective serotonin reuptake inhibitors (SSRIs) used during pregnancy. This study used Denmark's health and population registers to obtain information regarding prescription drugs, ASD...
Anhedonia Predicts Poorer Recovery among Youth with Selective Serotonin Reuptake Inhibitor Treatment-Resistant Depression

Science.gov (United States)

McMakin, Dana L.; Olino, Thomas M.; Porta, Giovanna; Dietz, Laura J.; Emslie, Graham; Clarke, Gregory; Wagner, Karen Dineen; Asarnow, Joan R.; Ryan, Neal D.; Birmaher, Boris; Shamseddeen, Wael; Mayes, Taryn; Kennard, Betsy; Spirito, Anthony; Keller, Martin; Lynch, Frances L.; Dickerson, John F.; Brent, David A.

2012-01-01

Objective: To identify symptom dimensions of depression that predict recovery among selective serotonin reuptake inhibitor (SSRI) treatment-resistant adolescents undergoing second-step treatment. Method: The Treatment of Resistant Depression in Adolescents (TORDIA) trial included 334 SSRI treatment-resistant youth randomized to a medication…

In Utero Exposure to Selective Serotonin Reuptake Inhibitors and Risk for Autism Spectrum Disorder

Science.gov (United States)

Gidaya, Nicole B.; Lee, Brian K.; Burstyn, Igor; Yudell, Michael; Mortensen, Erik L.; Newschaffer, Craig J.

2014-01-01

We investigated whether there is an association between increased risk for autism spectrum disorders (ASD) and selective serotonin reuptake inhibitors (SSRIs) used during pregnancy. This study used Denmark's health and population registers to obtain information regarding prescription drugs, ASD diagnosis, and health and socioeconomic status. There…
An Open-Label Pilot Study of Combined Augmentation With Creatine Monohydrate and 5-Hydroxytryptophan for Selective Serotonin Reuptake Inhibitor- or Serotonin-Norepinephrine Reuptake Inhibitor-Resistant Depression in Adult Women.

Science.gov (United States)

Kious, Brent M; Sabic, Hana; Sung, Young-Hoon; Kondo, Douglas G; Renshaw, Perry

2017-10-01

Many women with major depressive disorder (MDD) respond inadequately to standard treatments. Augmentation of conventional antidepressants with creatine monohydrate and 5-hydroxytryptophan (5-HTP) could correct deficits in serotonin production and brain bioenergetics associated with depression in women, yielding synergistic benefit. We describe an open-label study of 5-HTP and creatine augmentation in women with MDD who had failed selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) monotherapy. Fifteen women who were adequately adherent to an SSRI or SNRI and currently experiencing MDD, with a 17-item Hamilton Depression Rating Scale (HAM-D) score of 16 or higher, were treated with 5 g of creatine monohydrate daily and 100 mg of 5-HTP twice daily for 8 weeks, with 4 weeks of posttreatment follow-up. The primary outcome was change in mean HAM-D scores. Mean HAM-D scores declined from 18.9 (SD, 2.5) at pretreatment visits to 7.5 (SD, 4.4) (P creatine and 5-HTP may represent an effective augmentation strategy for women with SSRI- or SNRI-resistant depression. Given the limitations of this small, open-label trial, future study in randomized, placebo-controlled trials is warranted.
The age-dependent effects of selective serotonin reuptake inhibitors in humans and rodents: A review.

NARCIS (Netherlands)

Olivier, J.D.A.; Blom, T.; Arentsen, T.; Homberg, J.R.

2011-01-01

The selective serotonin reuptake inhibitor (SSRI) Prozac(R) (fluoxetine) is widely prescribed for the treatment of depression and anxiety-related disorders. While extensive research has established that fluoxetine is safe for adults, safety is not guaranteed for (unborn) children and adolescents.
Are Selective Serotonin Reuptake Inhibitors Safe for Drivers? What is the Evidence?

OpenAIRE

Ravera, Silvia; Ramaekers, Johannes G.; de Jong-van den Berg, Lolkje T. W.; de Gier, Johan J.; de Jong-van den Berg, [No Value

2012-01-01

Background: Selective serotonin reuptake inhibitors (SSRIs) are widely used medications to treat several psychiatric diseases and, above all, depression. They seem to be as effective as older antidepressants but have a different adverse effect profile. Despite their favorable safety profile, little is known about their influence on traffic safety. Objective: To conduct a literature review to summarize the current evidence on the role of SSRIs in traffic safety, particularly concerning undesir...
Helicobacter pylori and risk of upper gastrointestinal bleeding among users of selective serotonin reuptake inhibitors

DEFF Research Database (Denmark)

Dall, Michael; Schaffalitzky de Muckadell, Ove B; Møller Hansen, Jane

2011-01-01

A number of studies have reported a possible association between use of selective serotonin reuptake inhibitors (SSRIs) and serious upper gastrointestinal bleeding (UGB). We conducted this case-control study to assess if Helicobacter pylori (H. pylori) potentiates the risk of serious UGB in SSRI ...
High-mesembrine Sceletium extract (Trimesemine™) is a monoamine releasing agent, rather than only a selective serotonin reuptake inhibitor.

Science.gov (United States)

Coetzee, Dirk D; López, Víctor; Smith, Carine

2016-01-11

Extracts from and alkaloids contained in plants in the genus Sceletium have been reported to inhibit ligand binding to serotonin transporter. From this, the conclusion was made that Sceletium products act as selective serotonin-reuptake inhibitors. However, other mechanisms which may similarly result in the anxiolytic or anti-depressant effect ascribed to Sceletium, such as monoamine release, have not been investigated. The current study investigated simultaneously and at two consecutive time points, the effect of high-mesembrine Sceletium extract on both monoamine release and serotonin reuptake into both human astrocytes and mouse hippocampal neurons, as well as potential inhibitory effects on relevant enzyme activities. Human astrocytes and mouse hippocampal cells were treated with citalopram or Sceletium extract for 15 and 30min, after which protein expression levels of serotonin transporter (SERT) and vesicular monoamine transporter-2 (VAMT-2) was assessed using fluorescent immunocytochemistry and digital image analysis. Efficacy of inhibition of acetylcholinesterase (AChE) and monoamine oxidate-A (MAO-A) activity were assessed using the Ellman and Olsen methods (and appropriate controls) respectively. We report the first investigation of mechanism of action of Sceletium extract in the context of serotonin transport, release and reuptake in a cellular model. Cell viability was not affected by Sceletium treatment. High-mesembrine Sceletium extract down-regulated SERT expression similarly to citalopram. In addition, VMAT-2 was upregulated significantly in response to Sceletium treatment. The extract showed only relatively mild inhibition of AChE and MAO-A. We conclude that the serotonin reuptake inhibition activity ascribed to the Sceletium plant, is a secondary function to the monoamine-releasing activity of high-mesembrine Sceletium extract (Trimesemine(TM)). Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Discovery of a potent, dual serotonin and norepinephrine reuptake inhibitor.

Science.gov (United States)

Dreyfus, Nicolas; Myers, Jason K; Badescu, Valentina O; de Frutos, Oscar; de la Puente, Maria Luz; Ding, Chunjin; Filla, Sandra A; Fynboe, Karsten; Gernert, Douglas L; Heinz, Beverly A; Hemrick-Luecke, Susan K; Johnson, Kirk W; Johnson, Michael P; López, Pilar; Love, Patrick L; Martin, Laura J; Masquelin, Thierry; McCoy, Michael J; Mendiola, Javier; Morrow, Denise; Muhlhauser, Mark; Pascual, Gustavo; Perun, Thomas J; Pfeifer, Lance A; Phebus, Lee A; Richards, Simon J; Rincón, Juan Antonio; Seest, Eric P; Shah, Jikesh; Shaojuan, Jia; Simmons, Rosa Maria A; Stephenson, Gregory A; Tromiczak, Eric G; Thompson, Linda K; Walter, Magnus W; Weber, Wayne W; Zarrinmayeh, Hamideh; Thomas, Craig E; Joshi, Elizabeth; Iyengar, Smriti; Johansson, Anette M

2013-06-13

The objective of the described research effort was to identify a novel serotonin and norepinephrine reuptake inhibitor (SNRI) with improved norepinephrine transporter activity and acceptable metabolic stability and exhibiting minimal drug-drug interaction. We describe herein the discovery of a series of 3-substituted pyrrolidines, exemplified by compound 1. Compound 1 is a selective SNRI in vitro and in vivo, has favorable ADME properties, and retains inhibitory activity in the formalin model of pain behavior. Compound 1 thus represents a potential new probe to explore utility of SNRIs in central nervous system disorders, including chronic pain conditions.
Synthesis and evaluation of racemic [11C]NS2456 and its enantiomers as selective serotonin reuptake radiotracers for PET

International Nuclear Information System (INIS)

Smith, D.F.; Bender, D.; Marthi, K.; Cumming, P.; Hansen, S.B.; Peters, D.; Oestergaard Nielsen, E.; Scheel-Krueger, J.; Gjedde, A.

2001-01-01

Positron emission tomography (PET) radiotracers are needed for quantifying serotonin uptake sites in the living brain. Therefore, we evaluated a new selective serotonin reuptake inhibitor, NS2456, to determine whether it is suited for use in PET. Racemic NS2456 [(1RS,5SR)-8-methyl-3-[4-trifluoromethoxyphenyl]-8-azabicyclo [3.2.1]oct-2-ene] and its N-demethylated analog, racemic NS2463, selectively inhibited serotonin uptake in rat brain synaptosomes; their IC 50 values were 3000-fold lower for [ 3 H]serotonin than for either [ 3 H]dopamine or [ 3 H]noradrenaline. The enantiomers of NS2463 were also potent inhibitors of serotonin uptake in vitro, but they failed to show stereoselectivity. Racemic NS2463 as well as its enantiomers were radiolabelled by N-methylation with C-11, yielding [ 11 C]NS2456 for use in PET of the living porcine brain. The compounds crossed the blood-brain barrier rapidly and accumulated preferentially in regions rich in serotonin uptake sites (e.g., brainstem, subthalamus and thalamus). However, their binding potentials were relatively low and no stereoselectivity was found. Thus, neither racemic [ 11 C]NS2456 nor its [ 11 C]-labelled enantiomers are ideal for PET neuroimaging of neuronal serotonin uptake sites
Combined Norepinephrine / Serotonergic Reuptake Inhibition: Effects on Maternal Behavior, Aggression and Oxytocin in the Rat

Directory of Open Access Journals (Sweden)

Elizabeth Thomas Cox

2011-06-01

Full Text Available BACKGROUND: Few systematic studies exist on the effects of chronic reuptake of monoamine neurotransmitter systems during pregnancy on the regulation of maternal behavior, although many drugs act primarily through one or more of these systems. Previous studies examining fluoxetine and amfonelic acid treatment during gestation on subsequent maternal behavior in rodents indicated significant alterations in postpartum maternal care, aggression and oxytocin levels. In this study, we extended our studies to include chronic gestational treatment with desipramine or amitriptyline to examine differential effects of reuptake inhibition of norepinephrine and combined noradrenergic and serotonergic systems on maternal behavior, aggression, and oxytocin system changes. METHODS: Pregnant Sprague-Dawley rats were treated throughout gestation with saline or one of three doses of either desipramine, which has a high affinity for the norepinephrine monoamine transporter, or amitriptyline, an agent with high affinity for both the norepinephrine and serotonin monoamine transporters. Maternal behavior and postpartum aggression were assessed on postpartum days one and six respectively. Oxytocin levels were measured in relevant brain regions on postpartum day seven. Predictions were that amitriptyline would decrease maternal behavior and increase aggression relative to desipramine, particularly at higher doses. Amygdaloidal oxytocin was expected to decrease with increased aggression. RESULTS: Amitriptyline and desiprimine differentially reduced maternal behavior, and at higher doses reduced aggressive behavior. Hippocampal oxytocin levels were lower after treatment with either drug but were not correlated with specific behavioral effects. These results, in combination with previous findings following gestational treatment with other selective neurotransmitter reuptake inhibitors, highlight the diverse effects of multiple monoamine systems thought to be involved in
Environmental assessments required to support nomination of sites

International Nuclear Information System (INIS)

Mussler, R.M.

1984-01-01

The Nuclear Waste Policy Act of 1982 establishes a schedule for siting the nation's first repository for nuclear waste and spent fuel. The Act assigns the primary responsibility for conducting this siting program to the Department ofEnergy. The provisions of the Act are reviewed, including six legal requirements that must be considered for each environmental assessment, each of which is discussed in detail
Selective serotonin reuptake inhibitor antidepressant use in first trimester pregnancy and risk of specific congenital anomalies

DEFF Research Database (Denmark)

Wemakor, Anthony; Casson, Karen; Garne, Ester

2015-01-01

Evidence of an association between early pregnancy exposure to selective serotonin reuptake inhibitors (SSRI) and congenital heart defects (CHD) has contributed to recommendations to weigh benefits and risks carefully. The objective of this study was to determine the specificity of association be...
Switching antidepressants after a first selective serotonin reuptake inhibitor in major depressive disorder: a systematic review

NARCIS (Netherlands)

Ruhé, Henricus G.; Huyser, Jochanan; Swinkels, Jan A.; Schene, Aart H.

2006-01-01

OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) are frequently used as a first antidepressant for major depressive disorder but have response rates of 50% to 60% in daily practice. For patients with insufficient response to SSRIs, switching is often applied. This article aims to
The selective serotonin reuptake inhibitor, escitalopram, enhances inhibition of prepotent responding and spatial reversal learning

Science.gov (United States)

Brown, Holden D.; Amodeo, Dionisio A.; Sweeney, John A.; Ragozzino, Michael E.

2011-01-01

Previous findings indicate treatment with a selective serotonin reuptake inhibitor (SSRI) facilitates behavioral flexibility when conditions require inhibition of a learned response pattern. The present experiment investigated whether acute treatment with the SSRI, escitalopram, affects behavioral flexibility when conditions require inhibition of a naturally-biased response pattern (elevated conflict test) and/or reversal of a learned response pattern (spatial reversal learning). An additional experiment was carried out to determine whether escitalopram, at doses that affected behavioral flexibility, also reduced anxiety as tested in the elevated plus-maze. In each experiment, Long-Evans rats received an intraperitoneal injection of either saline or escitalopram (0.03, 0.3 or 1.0 mg/kg) 30 minutes prior to behavioral testing. Escitalopram, at all doses tested, enhanced acquisition in the elevated conflict test, but did not affect performance in the elevated plus-maze. Escitalopram (0.3 and 1.0 mg/kg) did not alter acquisition of the spatial discrimination, but facilitated reversal learning. In the elevated conflict and spatial reversal learning test, escitalopram enhanced the ability to maintain the relevant strategy after being initially selected. The present findings suggest that enhancing serotonin transmission with a SSRI facilitates inhibitory processes when conditions require a shift away from either a naturally-biased response pattern or a learned choice pattern. PMID:22219222
Use of selective serotonin reuptake inhibitors and risk of re-operation due to post-surgical bleeding in breast cancer patients: a Danish population-based cohort study

DEFF Research Database (Denmark)

Gärtner, Rune; Cronin-Fenton, Deirdre; Hundborg, Heidi Holmager

2010-01-01

Selective serotonin reuptake inhibitors (SSRI) decrease platelet-function, which suggests that SSRI use may increase the risk of post-surgical bleeding. Few studies have investigated this potential association.......Selective serotonin reuptake inhibitors (SSRI) decrease platelet-function, which suggests that SSRI use may increase the risk of post-surgical bleeding. Few studies have investigated this potential association....
Maternal use of selective serotonin reuptake inhibitors during pregnancy is associated with Hirschsprung's disease in newborns - a nationwide cohort study

DEFF Research Database (Denmark)

Nielsen, Sebastian Werngreen; Møller Ljungdalh, Pernille; Nielsen, Jan

2017-01-01

of the association between maternal use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy and development of Hirschsprung's Disease in the newborn child. The study examined a nationwide, unselected cohort of children born in Denmark from 1 January 1996 until 12 March 2016 (n = 1,256,317). We...... of Hirschsprung's disease was 16/19.807 (0.08%) compared to 584/1.236.510 (0.05%) in the unexposed cohort. In women who redeemed a minimum of one prescription of selective serotonin reuptake inhibitors, the adjusted odds ratio for development of Hirschsprung's disease was 1.76 (95%CI: 1.07-2.92). In women who...
Dependence and withdrawal reactions to benzodiazepines and selective serotonin reuptake inhibitors. How did the health authorities react?

Science.gov (United States)

Nielsen, Margrethe; Hansen, Ebba Holme; Gøtzsche, Peter C

2013-01-01

Our objective was to explore communications from drug agencies about benzodiazepine dependence and selective serotonin reuptake inhibitors (SSRIs) withdrawal reactions over time. Documentary study. We searched the web-sites of the European Medicines Agency and the drug agencies in USA, UK, and Denmark for documents mentioning benzodiazepines or SSRIs. We supplemented with other relevant literature that could contribute to our study. The searches were performed in 2009 in PubMed, Google, BMJ and JAMA. It took many years before the drug regulators acknowledged benzodiazepine dependence and SSRI withdrawal reactions and before the prescribers and the public were informed. Drug regulators relied mainly on the definitions of dependence and withdrawal reactions from the diagnostic psychiatric manuals, which contributed to the idea that SSRIs do not cause dependence, although it is difficult for many patients to stop treatment. In the perspective of a precautionary principle, drug agencies have failed to acknowledge that SSRIs can cause dependence and have minimised the problem with regard to its frequency and severity. In the perspective of a risk management principle, the drug agencies have reacted in concordance with the slowly growing knowledge of adverse drug reactions and have sharpened the information to the prescribers and the public over time. However, solely relying on spontaneous reporting of adverse effects leads to underestimation and delayed information about the problems. Given the experience with the benzodiazepines, we believe the regulatory bodies should have required studies from the manufacturers that could have elucidated the dependence potential of the SSRIs before marketing authorization was granted.
Treatment of Selective Serotonin Reuptake Inhibitor-Resistant Depression in Adolescents: Predictors and Moderators of Treatment Response

Science.gov (United States)

Asarnow, Joan Rosenbaum; Emslie, Graham; Clarke, Greg; Wagner, Karen Dineen; Spirito, Anthony; Vitiello, Benedetto; Iyengar, Satish; Shamseddeen, Wael; Ritz, Louise; Birmaher, Boris; Ryan, Neal; Kennard, Betsy; Mayes, Taryn; DeBar, Lynn; McCracken, James; Strober, Michael; Suddath, Robert; Leonard, Henrietta; Porta, Giovanna; Keller, Martin; Brent, David

2009-01-01

Adolescents who did not improve with Selective Serotonin Reuptake Inhibitor (SSRI) were provided an alternative SSRI plus cognitive-behavioral therapy (CBT). The superiority of the CBT/combined treatment as compared to medication alone is more evident in youths who had more comorbid disorders, no abuse history, and lower hopelessness.
Serotonin noradrenaline reuptake inhibitors: New hope for the treatment of chronic pain.

Science.gov (United States)

Delgado, Pedro L

2006-01-01

Depression and painful symptoms occur frequently together. Over 75% of depressed patients report painful symptoms such as headache, stomach pain, neck and back pain as well as non-specific generalized pain. In addition, World Health Organization data have shown that primary care patients with chronic pain have a four fold greater risk of becoming depressed than pain-free patients. Increasingly, pain is considered as an integral symptom of depression and there evidence to suggest that pain and depression may arise from a common neurobiological dysfunction. Serotonergic cell bodies, in the raphe nucleus, and noradrenergic cell bodies in the locus coeruleus send projections to various parts of the brain, where they are involved in the control of mood, movement, cognitive functioning and emotions. In addition both serotonergic and noradrenergic neurons project to the spinal cord. These descending pathways serve to inhibit input from the intestines, skeletal muscles and other sensory inputs. Usually, these inhibitory effects are modest, but in times of stress, in the interest of the survival of the individual, they can completely inhibit the input from painful stimuli. A dysfunction of the serotonergic and noradrenergic neurons can thus affect both the ascending and descending pathways resulting in the psychological symptoms of depression and somatic pain symptoms such as chronic pain, fibromyalgia, non-cardiac chest pain, or irritable bowel syndrome. In view of this, it is not surprising that tricyclic antidepressants have been a standard treatment of chronic pain for many years. In contrast and in spite of their improved tolerance, selective serotonin reuptake inhibitors do not appear to be particularly effective in the treatment of pain. Recently, a number of open and controlled trials with selective serotonin and noradrenaline reuptake inhibitors such as venlafaxine, milnacipran and duloxetine, suggest that these compounds may be more effective in relieving pain
Effects of selective serotonin reuptake inhibition on neural activity related to risky decisions and monetary rewards in healthy males

DEFF Research Database (Denmark)

Macoveanu, Julian; Fisher, Patrick M; Haahr, Mette E

2014-01-01

the involvement of the normally functioning 5HT-system in decision-making under risk and processing of monetary rewards. The data suggest that prolonged SSRI treatment might reduce emotional engagement by reducing the impact of risk during decision-making or the impact of reward during outcome evaluation.......Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are commonly prescribed antidepressant drugs targeting the dysfunctional serotonin (5-HT) system, yet little is known about the functional effects of prolonged serotonin reuptake inhibition in healthy individuals. Here we used...... functional MRI (fMRI) to investigate how a three-week fluoxetine intervention influences neural activity related to risk taking and reward processing. Employing a double-blinded parallel-group design, 29 healthy young males were randomly assigned to receive 3 weeks of a daily dose of 40 mg fluoxetine...
Maternal use of selective serotonin reuptake inhibitors and risk of miscarriage

DEFF Research Database (Denmark)

Johansen, Rie Laurine Rosenthal; Mortensen, Laust Hvas; Andersen, Anne-Marie Nybo

2015-01-01

-exposed pregnancies were characterised by an unhealthier maternal lifestyle and mental health profile than unexposed pregnancies, whereas no convincing differences were observed between pregnancies exposed to SSRIs during versus before pregnancy. Substantial disagreement was found between prescriptions and self......BACKGROUND: The use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy has been associated with miscarriage, but the association may be biased by maternal mental illness, lifestyle and exposure misclassification. METHODS: A register study on all pregnancies in Denmark between 1996......-reported use of SSRIs, but it did not affect the estimated hazard ratios. CONCLUSION: Confounding by indication and lifestyle in pregnancy may explain the association between SSRI use and miscarriage....

Selective serotonin reuptake inhibitorprescribing before, during and after pregnancy

DEFF Research Database (Denmark)

Charlton, Ra; Jordan, S; Pierini, A

2015-01-01

OBJECTIVE: To explore the prescribing patterns of selective serotonin reuptake inhibitors (SSRIs) before, during and after pregnancy in six European population-based databases. DESIGN: Descriptive drug utilisation study. SETTING: Six electronic healthcare databases in Denmark, the Netherlands......, Italy (Emilia Romagna/Tuscany), Wales and the rest of the UK. POPULATION: All women with a pregnancy ending in a live or stillbirth starting and ending between 2004 and 2010. METHODS: A common protocol was implemented across databases to identify SSRI prescriptions issued (UK) or dispensed (non......-UK) in the year before, during or in the year following pregnancy. MAIN OUTCOME MEASURES: The percentage of deliveries in which the woman received an SSRI prescription in the year before, during or in the year following pregnancy. We also compared the choice of SSRIs and changes in prescribing over the study...
National Ignition Facility subsystem design requirements NIF site improvements SSDR 1.2.1

International Nuclear Information System (INIS)

Kempel, P.; Hands, J.

1996-01-01

This Subsystem Design Requirements (SSDR) document establishes the performance, design, and verification requirements associated with the NIF Project Site at Lawrence Livermore National Laboratory (LLNL) at Livermore, California. It identifies generic design conditions for all NIF Project facilities, including siting requirements associated with natural phenomena, and contains specific requirements for furnishing site-related infrastructure utilities and services to the NIF Project conventional facilities and experimental hardware systems. Three candidate sites were identified as potential locations for the NIF Project. However, LLNL has been identified by DOE as the preferred site because of closely related laser experimentation underway at LLNL, the ability to use existing interrelated infrastructure, and other reasons. Selection of a site other than LLNL will entail the acquisition of site improvements and infrastructure additional to those described in this document. This SSDR addresses only the improvements associated with the NIF Project site located at LLNL, including new work and relocation or demolition of existing facilities that interfere with the construction of new facilities. If the Record of Decision for the PEIS on Stockpile Stewardship and Management were to select another site, this SSDR would be revised to reflect the characteristics of the selected site. Other facilities and infrastructure needed to support operation of the NIF, such as those listed below, are existing and available at the LLNL site, and are not included in this SSDR. Office Building. Target Receiving and Inspection. General Assembly Building. Electro- Mechanical Shop. Warehousing and General Storage. Shipping and Receiving. General Stores. Medical Facilities. Cafeteria services. Service Station and Garage. Fire Station. Security and Badging Services
Disposal facilities for radioactive waste - legislative requirements for siting

International Nuclear Information System (INIS)

Markova-Mihaylova, Radosveta

2015-01-01

The specifics of radioactive waste, namely the content of radionuclides require the implementation of measures to protect human health and the environment against the hazards arising from ionizing radiation, including disposal of waste in appropriate facilities. The legislative requirements for siting of such facilities, and classification of radioactive waste, as well as the disposal methods, are presented in this publication
Effects of sustained serotonin reuptake inhibition on the firing of dopamine neurons in the rat ventral tegmental area

NARCIS (Netherlands)

Dremencov, Eliyahu; El Mansari, Mostafa; Blier, Pierre

Background: Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are efficacious in depression because of their ability to increase 5-HT neurotransmission. However, owing to a purported inhibitory effect of 5- HT on dopamine (DA) neuronal activity in the ventral tegmental area (VTA), this increase
The effect of antenatal depression and selective serotonin reuptake inhibitor treatment on nerve growth factor signaling in human placenta

NARCIS (Netherlands)

Kaihola, Helena; Olivier, Jocelien; Poromaa, Inger Sundström; Åkerud, Helena

2015-01-01

Depressive symptoms during pregnancy are common and may have impact on the developing child. Selective serotonin reuptake inhibitors (SSRIs) are the most prescribed antidepressant treatment, but unfortunately, these treatments can also negatively affect the behavioral development and health of a
The monoamine reuptake inhibitor BTS 74 398 fails to evoke established dyskinesia but does not synergise with levodopa in MPTP-treated primates.

Science.gov (United States)

Hansard, Matthew J; Smith, Lance A; Jackson, Michael J; Cheetham, Sharon C; Jenner, Peter

2004-01-01

Long-term treatment of Parkinson's disease (PD) with levodopa (L-dopa) induces dyskinesia that, once established, is provoked by each dose of L-dopa or a dopamine (DA) agonist. In contrast, monoamine reuptake inhibitors may reverse motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated primates without provoking established involuntary movements. We now examine whether the potent monoamine reuptake blocker BTS 74 398 induces established dyskinesia in MPTP-treated common marmosets primed previously with L-dopa and whether co-administration of BTS 74 398 with L-dopa potentiates motor behaviour and dyskinesia induced by acute L-dopa treatment. Administration of BTS 74 398 (2.5, 5.0, or 10.0 mg/kg, p.o.) in MPTP-treated common marmosets increased locomotor activity and reduced motor disability in a dose-related manner but did not provoke involuntary movements. BTS 74 398 (2.5, 5.0, or 10.0 mg/kg p.o.) co-administered with a threshold dose of L-dopa (2.5 mg/kg p.o.) did not evoke a motor response or induce dyskinesia. Similarly, concomitant administration of BTS 74 398 (5.0 mg/kg p.o.) with a submaximal L-dopa dose (12.5 mg/kg p.o.) did not potentiate the motor response produced by L-dopa alone and there was no alteration in the dyskinesia provoked by L-dopa challenge. BTS 74 398 reverses motor abnormalities in MPTP-treated marmosets without evoking established dyskinesia but no additive improvement occurs when administered in combination with L-dopa. The lack of synergy with L-dopa may suggest different sites of drug action. Copyright 2003 Movement Disorder Society
Differences in the dynamics of serotonin reuptake transporter occupancy may explain superior clinical efficacy of escitalopram versus citalopram.

Science.gov (United States)

Kasper, Siegfried; Sacher, Julia; Klein, Nikolas; Mossaheb, Nilufar; Attarbaschi-Steiner, Trawat; Lanzenberger, Rupert; Spindelegger, Christoph; Asenbaum, Susanne; Holik, Alexander; Dudczak, Robert

2009-05-01

Escitalopram the S-enantiomer of the racemate citalopram, is clinically more effective than citalopram in the treatment of major depressive disorder. However, the precise mechanism by which escitalopram achieves superiority over citalopram is yet to be determined. It has been hypothesized that the therapeutically inactive R-enantiomer competes with the serotonin-enhancing S-enantiomer at a low-affinity allosteric site on serotonin reuptake transporters (SERTs), and reduces the effectiveness of the S-enantiomer at the primary, high-affinity serotonin-binding site. This study summarizes the results of two recent single-photon emission computerized tomography studies measuring SERT occupancy in citalopram-treated and escitalopram-treated healthy volunteers, after a single dose and multiple doses (i.e. under steady-state conditions). The single-dose study showed no attenuating effect of R-citalopram. After multiple dosing, however, SERT occupancy was significantly reduced in the presence of R-citalopram. Under steady-state conditions, R-enantiomer concentrations were greater than for the S-enantiomer because of slower clearance of R-citalopram. A pooled analysis suggests that build-up of the R-enantiomer after repeated citalopram dosing may lead to increased inhibition of S-enantiomer occupancy of SERT. This review adds to the growing body of evidence regarding differences in the dynamics of SERT occupancy, that is, molecular mechanisms underlying the often-observed superior clinical efficacy of escitalopram compared with citalopram in major depressive disorder.
There is an association between selective serotonin reuptake inhibitor use and uncomplicated peptic ulcers: a population-based case-control study

DEFF Research Database (Denmark)

Dall, M; Schaffalitzky de Muckadell, O B; Lassen, Annmarie Touborg

2010-01-01

Persons who use serotonin reuptake inhibitors (SSRIs) seem to be at increased risk of having serious upper gastrointestinal bleeding. In vitro studies have shown that SSRIs inhibit platelet aggregation. It remains unknown if SSRIs have a direct ulcerogenic effect....
A Concise Total Synthesis of (R)-Fluoxetine, a Potent and Selective Serotonin Reuptake Inhibitor

OpenAIRE

de Fátima, Ângelo; Lapis, Alexandre Augusto M.; Pilli, Ronaldo A.

2005-01-01

(R)-Fluoxetine, potent and selective serotonin reuptake inhibitor, has been synthesized in six steps, 50% overall yield and 99% ee from benzaldehyde via catalytic asymmetric allylation with Maruoka's catalyst. (R)-Fluoxetina, um inibidor potente e seletivo da recaptação da serotonina, foi sintetizada em seis etapas, 50% de rendimento total e 99% de excesso enantiomérico a partir do benzaldeído via alilação catalítica assimétrica empregando-se o sistema catalítico desenvolvido por Maruoka e...
Early Neurological Outcome of Young Infants Exposed to Selective Serotonin Reuptake Inhibitors during Pregnancy : Results from the Observational SMOK Study

NARCIS (Netherlands)

de Vries, N.K.S.; van der Veere, C.N.; Reijneveld, S.A.; Bos, A.F.

2013-01-01

Background: Use of selective serotonin reuptake inhibitors (SSRI) during pregnancy is common while the effect on the infant's neurological outcome is unknown. Our objective was to determine the effects of prenatal SSRI-exposure on the infants' neurological functioning, adjusted for maternal mental
Geochemical Parameters Required from the SKB Site Characterisation Programme

International Nuclear Information System (INIS)

Bath, Adrian

2002-01-01

SKB has described its approach to site characterisation in a number of Technical Reports. One of the scientific topics in which specific information requirements and priorities are set out is geochemistry. This report for SKI examines critically whether the geochemical parameters identified in the SKB programme documents will be adequate for safety and regulatory requirements. It also examines some of the details of parameter requirements and interpretation tools that will be necessary to convert site investigation data into knowledge about chemical conditions and groundwater movements. The SKB strategy for geochemical data focuses on a small number of 'suitability indicators', primarily dissolved oxygen, pH and salinity. Their parameter requirements aim to assess those primary characteristics, as well as to acquire a wider range of data that will support those assessments and provide a broader understanding of candidate areas. An initial observation in this review that, though it is a primary suitability indicator, dissolved oxygen apparently will not be measured and instead will be inferred from other redox indicators. This raises a number of issues about sampling and monitoring measures, analytical data reliability and sensitivity, and the degree of confidence in geochemical understanding. A geochemical programme involves reconnaissance by desk study and acquisition of new data at levels of details that are appropriate to the stage of site investigations. As early as possible, a conceptual model of a candidate area should help to define the objectives of geochemical measurements on both rock and groundwater samples. It is recommended that parameters requirements should be defined and considered not only in terms of isolated measurements but more in terms of addressing broader objectives that relate to safety and also to geoscientific understanding. The safety priorities remain (e.g. dissolved oxygen) but will then be supported by an understanding of processes
Geochemical Parameters Required from the SKB Site Characterisation Programme

Energy Technology Data Exchange (ETDEWEB)

Bath, Adrian [Intellisci Ltd., Loughborough (United Kingdom)

2002-01-01

SKB has described its approach to site characterisation in a number of Technical Reports. One of the scientific topics in which specific information requirements and priorities are set out is geochemistry. This report for SKI examines critically whether the geochemical parameters identified in the SKB programme documents will be adequate for safety and regulatory requirements. It also examines some of the details of parameter requirements and interpretation tools that will be necessary to convert site investigation data into knowledge about chemical conditions and groundwater movements. The SKB strategy for geochemical data focuses on a small number of 'suitability indicators', primarily dissolved oxygen, pH and salinity. Their parameter requirements aim to assess those primary characteristics, as well as to acquire a wider range of data that will support those assessments and provide a broader understanding of candidate areas. An initial observation in this review that, though it is a primary suitability indicator, dissolved oxygen apparently will not be measured and instead will be inferred from other redox indicators. This raises a number of issues about sampling and monitoring measures, analytical data reliability and sensitivity, and the degree of confidence in geochemical understanding. A geochemical programme involves reconnaissance by desk study and acquisition of new data at levels of details that are appropriate to the stage of site investigations. As early as possible, a conceptual model of a candidate area should help to define the objectives of geochemical measurements on both rock and groundwater samples. It is recommended that parameters requirements should be defined and considered not only in terms of isolated measurements but more in terms of addressing broader objectives that relate to safety and also to geoscientific understanding. The safety priorities remain (e.g. dissolved oxygen) but will then be supported by an understanding of
Environmental Restoration Program quality system requirements for the Hanford Site

International Nuclear Information System (INIS)

Cote, R.F.

1993-11-01

This document defines the quality system requirements for the US Department of Energy, Richland Operations Office, Environmental Restoration Program at the Hanford Site. The Quality System Requirements (OSR) for the Hanford Site integrates quality assurance requirements from the US Department of Energy Orders, the Hanford Federal Facility Agreement and Consent Order (Tri-Party Agreement), and applicable industry standards into a single source document for the development of quality systems applicable to the Environmental Restoration Program activities. This document, based on fifteen criteria and divided intro three parts, provides user organizations with the flexibility to incorporate only those criteria and parts applicable to their specific scopes of work. The requirements of this document shall be applied to activities that affect quality based on a graded approach that takes into consideration the risk inherent in, as well as the importance of, specific items, services, and activities in terms of meeting ER Program objectives and customer expectations. The individual quality systems developed in accordance with this document are intended to provide an integrated management control system that assures the conduct of ER Program activities in a manner that protects human health and the environment
Mapping the Binding Site for Escitalopram and Paroxetine in the Human Serotonin Transporter Using Genetically Encoded Photo-Cross-Linkers

DEFF Research Database (Denmark)

Rannversson, Hafsteinn; Andersen, Jacob; Bang-Andersen, Benny

2017-01-01

amber codon suppression in hSERT to encode the photo-cross-linking unnatural amino acid p-azido-l-phenylalanine into the suggested high- and low-affinity binding sites. We then employ UV-induced cross-linking with azF to map the binding site of escitalopram and paroxetine, two prototypical selective...... serotonin reuptake inhibitors (SSRIs). We find that the two antidepressant drugs exclusively cross-link to azF incorporated at the high-affinity binding site of hSERT, while cross-linking is not observed at the low-affinity binding site. Combined with previous homology models and recent structural data on h...
Evidentiary requirements to identify potentially acceptable sites (PAS) in crystalline rock

International Nuclear Information System (INIS)

Comella, P.A.; Smith, B.H.

1985-01-01

This report contains information on the evidentiary requirements to identify potentially acceptable sites in crystalline rock for waste disposal. Topics addressed include: chronology, key regulatory assumptions, statutory framework for identifying potentially acceptable sites, application of 10 disqualifiers, consideration of favorable and potentially adverse conditions, a composite favorability analysis, and a proposed outline for PAS identification decision document
Diminished Neural Processing of Aversive and Rewarding Stimuli During Selective Serotonin Reuptake Inhibitor Treatment

Science.gov (United States)

McCabe, Ciara; Mishor, Zevic; Cowen, Philip J.; Harmer, Catherine J.

2010-01-01

Background Selective serotonin reuptake inhibitors (SSRIs) are popular medications for anxiety and depression, but their effectiveness, particularly in patients with prominent symptoms of loss of motivation and pleasure, has been questioned. There are few studies of the effect of SSRIs on neural reward mechanisms in humans. Methods We studied 45 healthy participants who were randomly allocated to receive the SSRI citalopram, the noradrenaline reuptake inhibitor reboxetine, or placebo for 7 days in a double-blind, parallel group design. We used functional magnetic resonance imaging to measure the neural response to rewarding (sight and/or flavor of chocolate) and aversive stimuli (sight of moldy strawberries and/or an unpleasant strawberry taste) on the final day of drug treatment. Results Citalopram reduced activation to the chocolate stimuli in the ventral striatum and the ventral medial/orbitofrontal cortex. In contrast, reboxetine did not suppress ventral striatal activity and in fact increased neural responses within medial orbitofrontal cortex to reward. Citalopram also decreased neural responses to the aversive stimuli conditions in key “punishment” areas such as the lateral orbitofrontal cortex. Reboxetine produced a similar, although weaker effect. Conclusions Our findings are the first to show that treatment with SSRIs can diminish the neural processing of both rewarding and aversive stimuli. The ability of SSRIs to decrease neural responses to reward might underlie the questioned efficacy of SSRIs in depressive conditions characterized by decreased motivation and anhedonia and could also account for the experience of emotional blunting described by some patients during SSRI treatment. PMID:20034615
Combinatorial support vector machines approach for virtual screening of selective multi-target serotonin reuptake inhibitors from large compound libraries.

Science.gov (United States)

Shi, Z; Ma, X H; Qin, C; Jia, J; Jiang, Y Y; Tan, C Y; Chen, Y Z

2012-02-01

Selective multi-target serotonin reuptake inhibitors enhance antidepressant efficacy. Their discovery can be facilitated by multiple methods, including in silico ones. In this study, we developed and tested an in silico method, combinatorial support vector machines (COMBI-SVMs), for virtual screening (VS) multi-target serotonin reuptake inhibitors of seven target pairs (serotonin transporter paired with noradrenaline transporter, H(3) receptor, 5-HT(1A) receptor, 5-HT(1B) receptor, 5-HT(2C) receptor, melanocortin 4 receptor and neurokinin 1 receptor respectively) from large compound libraries. COMBI-SVMs trained with 917-1951 individual target inhibitors correctly identified 22-83.3% (majority >31.1%) of the 6-216 dual inhibitors collected from literature as independent testing sets. COMBI-SVMs showed moderate to good target selectivity in misclassifying as dual inhibitors 2.2-29.8% (majority virtual hits correlate with the reported effects of their predicted targets. COMBI-SVM is potentially useful for searching selective multi-target agents without explicit knowledge of these agents. Copyright © 2011 Elsevier Inc. All rights reserved.
Great boast, small roast on effects of selective serotonin reuptake inhibitors

DEFF Research Database (Denmark)

Katakam, Kiran Kumar; Sethi, Naqash Javaid; Jakobsen, Janus Christian

2018-01-01

Our systematic review in BMC Psychiatry concluded that selective serotonin reuptake inhibitors (SSRIs) compared with placebo significantly increase the risk of serious adverse events (SAEs) in patients with major depression and the potential beneficial effects of SSRIs seem to be outweighed...... by the harms. Hieronymus et al. accused us of methodological inaccuracies and blatant errors. In their post-hoc analysis of our data, they reported that SSRIs only increase the risk of SAEs in elderly and seems safe for non-elderly patients. They also found our review misleading because our efficacy analyses...... were based on the 17-item Hamilton Depression Rating Scale; we included suboptimal SSRI doses; and we missed some 'pivotal trials'. We do not agree with Hieronymus et al. regarding several of the 'errors' they claim that we have made. However, we acknowledge that they have identified minor errors...
Use of dihydro-isobenzofuran in combination with serotonin reuptake inhibitors for CNS disease e.g. depression, anxiety, bipolar disorder, obsessive compulsory disorder

DEFF Research Database (Denmark)

2013-01-01

NOVELTY - For treatment of a CNS disease in a patient, dihydro-isobenzofuran compound (I) in combination with serotonin reuptake inhibitor, is used. USE - For treatment of CNS disease (claimed) including depression, anxiety, bipolar disorder, obsessive compulsory disorder, post traumatic stress d...
Nevada test site defense waste acceptance criteria, certification, and transfer requirements

International Nuclear Information System (INIS)

1988-10-01

The Nevada Test Site (NTS) Defense Waste Acceptance Criteria, Certification and Transfer Requirements establishes procedures and criteria for safe transfer, disposal, and storage of defense transuranic, low-level, and mixed waste at the NTS. Included are an overview of the NTS defense waste management program; the NTS waste acceptance criteria for transuranic, low-level, and mixed wastes; waste certification requirements and guidance; application to submit waste; and requirements for waste transfer and receipt. 5 figs., 16 tabs

Site specific statutory compliance planning for the salt repository project at the Deaf Smith County Site, Texas: Requirements, strategy, and status: Revision 4

International Nuclear Information System (INIS)

1986-06-01

This document and the requirements and actions it presents are addressed to the Deaf Smith County Site, Texas. The proposed actions upon which the plan is based are those described in Chapters 4 and 5 of the final EA for the site. Similarly, the environmental and health and safety requirements covered in the plan are those identified in the EA as being potentially applicable to the salt repository project at the Deaf Smith site. 12 figs., 8 tabs
Death and dependence: current controversies over the selective serotonin reuptake inhibitors.

Science.gov (United States)

Nutt, David J

2003-12-01

Recent years have seen a considerable media interest in the adverse effects of the selective serotonin reuptake inhibitors (SSRIs). This has led to claims that these antidepressants may lead to suicide and homicide and that they cause dependence or even addiction. Such claims have caused great concerns to many patients and have confused doctors in both primary care and psychiatric practice. In this article I review the basis of these claims and show that many seem to emerge from the misinterpretation of evidence and the use of imprecise definitions. Although the SSRIs are not free of problems they compare very favourably with other antidepressants and other classes of psychotropic drugs. There is no evidence they are addictive in the formal sense of leading to a drug dependence syndrome. Some suggestions on the way these issues can be more precisely defined and studied in future are given.
A controlled study of a serotonin reuptake blocker, zimelidine, in the treatment of chronic pain.

Science.gov (United States)

Gourlay, G K; Cherry, D A; Cousins, M J; Love, B L; Graham, J R; McLachlan, M O

1986-04-01

Zimelidine inhibits the central neuronal reuptake of serotonin and has undergone clinical evaluation as an antidepressant. Twenty patients with chronic pain of non-malignant origin (mean duration 15.8 years) were entered into a double blind cross-over study of the analgesic efficacy of zimelidine and placebo. The duration of each treatment phase was 6 weeks and there was a comprehensive assessment of each patient prior to the commencement and at the completion of the study, during a brief period of hospitalisation. Zimelidine was superior (P less than 0.05) to placebo with respect to pain relief based on a global assessment (by the clinical investigators) performed at the completion of each treatment phase. However, there was no significant difference in analgesic efficacy between the zimelidine and placebo treatment phases based on the following criteria: (a) changes in the minimum effective blood concentration of pethidine necessary to provide pain relief in each patient, measured during a pethidine infusion of 1.67 mg/min for 60 min; (b) changes in pain scores estimated by patients using the visual analogue pain scale (VAPS); (c) changes in patients' estimates of pain intensity associated with various daily activities. Significant pain relief was apparent within 2-3 days in those patients who had a beneficial effect, which contrasts with the documented 3-4 weeks for maximal antidepressant effects. The results of this study suggest that serotonin reuptake blockers do not provide consistent pain relief in patients with chronic pain, but may contribute an analgesic effect in the treatment of some patients.
Global gene expression in larval zebrafish (Danio rerio) exposed to selective serotonin reuptake inhibitors (fluoxetine and sertraline) reveals unique expression profiles and potential biomarkers of exposure

International Nuclear Information System (INIS)

Park, June-Woo; Heah, Tze Ping; Gouffon, Julia S.; Henry, Theodore B.; Sayler, Gary S.

2012-01-01

Larval zebrafish (Danio rerio) were exposed (96 h) to selective serotonin reuptake inhibitors (SSRIs) fluoxetine and sertraline and changes in transcriptomes analyzed by Affymetrix GeneChip ® Zebrafish Array were evaluated to enhance understanding of biochemical pathways and differences between these SSRIs. The number of genes differentially expressed after fluoxetine exposure was 288 at 25 μg/L and 131 at 250 μg/L; and after sertraline exposure was 33 at 25 μg/L and 52 at 250 μg/L. Same five genes were differentially regulated in both SSRIs indicating shared molecular pathways. Among these, the gene coding for FK506 binding protein 5, annotated to stress response regulation, was highly down-regulated in all treatments (results confirmed by qRT-PCR). Gene ontology analysis indicated at the gene expression level that regulation of stress response and cholinesterase activities were influenced by these SSRIs, and suggested that changes in transcription of these genes could be used as biomarkers of SSRI exposure. - Highlights: ► Exposure of zebrafish to selective serotonin reuptake inhibitors (SSRIs). ► Fluoxetine and sertraline generate different global gene expression profiles. ► Genes linked to stress response and acetylcholine esterase affected by both SSRIs. - Global gene expression profiles in zebrafish exposed to selective serotonin reuptake inhibitors.
Regulatory requirements for nuclear power plant site selection in Malaysia-a review.

Science.gov (United States)

Basri, N A; Hashim, S; Ramli, A T; Bradley, D A; Hamzah, K

2016-12-01

Malaysia has initiated a range of pre-project activities in preparation for its planned nuclear power programme. Clearly one of the first steps is the selection of sites that are deemed suitable for the construction and operation of a nuclear power plant. Here we outline the Malaysian regulatory requirements for nuclear power plant site selection, emphasizing details of the selection procedures and site characteristics needed, with a clear focus on radiation safety and radiation protection in respect of the site surroundings. The Malaysia Atomic Energy Licensing Board (AELB) site selection guidelines are in accord with those provided in International Atomic Energy Agency (IAEA) and United Stated Nuclear Regulatory Commission (USNRC) documents. To enhance the suitability criteria during selection, as well as to assist in the final decision making process, possible assessments using the site selection characteristics and information are proposed.
Exposure to selective serotonin reuptake inhibitors and the risk of congenital malformations

DEFF Research Database (Denmark)

Solem, Espen Victor Jimenez; Andersen, Jon Thor Trærup; Petersen, Morten

2012-01-01

Objectives:To analyse the relation between selective serotonin reuptake inhibitor (SSRI) use and major congenital malformations, with focus on malformations of the heart. DESIGN: Register-based retrospective nationwide cohort study, using the Danish Medical Birth Registry. SETTING: Denmark...... exposure during pregnancy. RESULTS: The authors identified 848¿786 pregnancies; 4183 were exposed to an SSRI throughout the first trimester and 806 pregnancies paused exposure during pregnancy. Risks of congenital malformations of the heart were similar for pregnancies exposed to an SSRI throughout...... the first trimester, adjusted OR 2.01 (95% CI 1.60 to 2.53), and for pregnancies with paused SSRI treatment during pregnancy, adjusted OR 1.85 (95% CI 1.07 to 3.20), p value for difference: 0.94. The authors found similar increased risks of specific congenital malformations of the heart for the individual...
Simultaneous initiation (coinitiation) of pharmacotherapy with triiodothyronine and a selective serotonin reuptake inhibitor for major depressive disorder: a quantitative synthesis of double-blind studies

NARCIS (Netherlands)

Papakostas, George I.; Cooper-Kazaz, Rena; Appelhof, Bente C.; Posternak, Michael A.; Johnson, Daniel P.; Klibanski, Anne; Lerer, Bernard; Fava, Maurizio

2009-01-01

To examine the efficacy and overall tolerability of the simultaneous initiation of treatment (coinitiation) with triiodothyronine (T3) and a selective serotonin reuptake inhibitor (SSRI) for major depressive disorder (MDD). Sources of date were Medline/Pubmed, EMBASE, the Cochrane database, and
Interferon and ribavarin associated depression in hcv patients and role of selective serotonin reuptake inhibitors

International Nuclear Information System (INIS)

Bashir, K.; Hussain, C.A.; Amer, K.

2013-01-01

Objective: To determine the frequency and severity of depression associated with antiviral therapy of Hepatitis C Virus (HCV) infection and effect of selective serotonin reuptake Inhibitors (SSRIs) to treat these depressive symptoms. Type of Study: Observational Analytical study. Place of Study and Duration: The study was conducted at Psychiatry, Medicine and Pathology department of Combined Military Hospital Sialkot Pakistan from February 2009 to July 2010. Subjects and Methods: All the patients in this study were suffering from HCV infection and were managed with Interferon (3 m.i.u. s/c thrice weekly) and Cap Ribavirin (400 mg bid) for six months. Patients were assessed by Hospital Anxiety and Depression Scale (HADS) - Urdu Version and Beck's Depressive Inventory (BDI) Scores after twelve weeks of antiviral therapy. Depressed patients were managed with selective serotonin reuptake inhibitors (SSRIs) for six weeks and again evaluated on HADS and BDI Scores. Response to SSRIs was defined as complete response, partial response and no response. Results: A total of 105 patients were studied out of which 75 were male and 30 were female with mean age 29.4 years. Out of these 54 (51.43%) patients developed depression and this tendency to develop depression was not related with the age and sex of the patients. The mean HADS and BDI scores before and after treatments with SSRIs were compared for significance and it was quite significant. There was not a single patient who did not show response to SSRIs. Conclusion: Depression is frequently associated with antiviral therapy of HCV RNA viraemia with interferon and SSRIs have proved an effective and safe remedy in these patients. (author)
Review of data requirements for groundwater flow and solute transport modelling and the ability of site investigation methods to meet these requirements

International Nuclear Information System (INIS)

McEwen, T.J.; Chapman, N.A.; Robinson, P.C.

1990-08-01

This report describes the data requirements for the codes that may be used in the modelling of groundwater flow and radionuclide transport during the assessment of a Nirex site for the deep disposal of low and intermediate level radioactive waste and also the site investigation methods that exist to supply the data for these codes. The data requirements for eight codes are reviewed, with most emphasis on three of the more significant codes, VANDAL, NAMMU and CHEMTARD. The largest part of the report describes and discusses the site investigation techniques and each technique is considered in terms of its ability to provide the data necessary to characterise the geological and hydrogeological environment around a potential repository. (author)
Non-tricyclic and Non-selective Serotonin Reuptake Inhibitor Antidepressants and Recurrent Falls in Frail Older Women.

Science.gov (United States)

Naples, Jennifer G; Kotlarczyk, Mary P; Perera, Subashan; Greenspan, Susan L; Hanlon, Joseph T

2016-12-01

To determine the risk of recurrent falls associated with antidepressants other than tricyclics (TCAs) and selective serotonin reuptake inhibitors (SSRIs) among frail older women. This is a secondary analysis of the Zoledronic acid in frail Elders to STrengthen bone, or ZEST, trial data treated as a longitudinal cohort in 181 frail, osteoporotic women aged ≥65 years in long-term care. The primary exposure was individual non-TCA/non-SSRI antidepressants (i.e., serotonin norepinephrine reuptake inhibitors, mirtazapine, trazodone, and bupropion) at baseline and 6 months. The main outcome was recurrent (at least two) falls within 6 months after antidepressant exposure. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were derived using a generalized estimating equations model. At least 15% of women experienced recurrent falls between 0-6 and 6-12 months. At baseline and 6 months, 18.2% and 6.9% had a non-TCA/non-SSRI antidepressant, respectively. Adjusting for demographics, health status, and other drugs that increase risk of falls, non-TCA/non-SSRI antidepressant exposure significantly increased the risk of recurrent falls (AOR: 2.14; 95% CI: 1.01-4.54). Fall risk further increased after removing bupropion from the non-TCA/non-SSRI antidepressant group in sensitivity analyses (AOR: 2.73; 95% CI: 1.24-6.01). Other antidepressant classes may not be safer than TCAs/SSRIs with respect to recurrent falls in frail older women. Copyright Â© 2016 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.
Main phases of siting for nuclear power plants with review of required investigations

International Nuclear Information System (INIS)

Malbasa, N.

1984-01-01

The purpose of the article is a short description of the main phases in the process of siting for nuclear power plants as interpreted and applied by the Institut za elektroprivredu, Zagreb in the screening, comparison and evaluation of the sites for NPPs in the SR of Croatia. The scope and purpose, as well as review of required data and investigations for each particular phase are given. Common used methods for the comparison of sites are described and example of rejection criteria applicable for early phases of the siting is proposed. It is given a list of the most important activities which detailed analysis id indispensable for ending of the evaluation and getting a site permit from the regulatory body. A legal and regulatory basis for carrying out the siting process is also described. (author)
Possible role of selective serotonin reuptake inhibitor sertraline on oxidative stress responses.

Science.gov (United States)

Battal, D; Yalin, S; Eker, E D; Aktas, A; Sahin, N O; Cebo, M; Berköz, M

2014-01-01

The naphthylamine derivative sertraline is a potent and selective inhibitor of serotonin reuptake into presynaptic terminals and the most widely used that has been shown to have both antidepressant and antianxiety effects. In the present study the possible role of sertraline (acute and chronically doses) was evaluated on lipid peroxidation levels and antioxidant enzyme activities in plasma and brain tissues of (10, 40, 80 mg/kg) sertraline treated Wistar albino rats (n=48). Lipid peroxidation levels (MDA) of plasma and brain tissue increased in all acute and chronic sertraline treated rats (p Catalase (CAT) levels of plasma and brain tissue and paraoxonase (PON) levels of plasma decreased (p < 0.05) as compared with vehicle group. Based on the data, it can be concluded that high dose sertraline administration enhances oxidative stress. Therefore, dose adjustment in depression patients seems significant as it may help prevention of further prognosis of the diseases.
Preliminary site requirements and considerations for a monitored retrievable storage facility

International Nuclear Information System (INIS)

1991-08-01

This report presents preliminary requirements and considerations for siting monitored retrievable storage (MRS) facility. It purpose is to provide guidance for assessing the technical suitability of potential sites for the facility. It has been reviewed by the NRC staff, which stated that this document is suitable for ''guidance in making preliminary determinations concerning MRS site suitability.'' The MRS facility will be licensed by the US Nuclear Regulatory Commission. It will receive spent fuel from commercial nuclear power plants and provide a limited amount of storage for this spent fuel. When a geologic repository starts operations, the MRS facility will also stage spent-fuel shipments to the repository. By law, storage at the MRS facility is to be temporary, with permanent disposal provided in a geologic repository to be developed by the DOE
Investigation of the mechanisms underlying the hypophagic effects of the 5-HT and noradrenaline reuptake inhibitor, sibutramine, in the rat

Science.gov (United States)

Jackson, Helen C; Bearham, M Clair; Hutchins, Lisa J; Mazurkiewicz, Sarah E; Needham, Andrew M; Heal, David J

1997-01-01

Sibutramine is a novel 5-hydroxytryptamine (5-HT) and noradrenaline reuptake inhibitor (serotonin- noradrenaline reuptake inhibitor, SNRI) which is currently being developed as a treatment for obesity. Sibutramine has been shown to decrease food intake in the rat. In this study we have used a variety of monoamine receptor antagonists to examine the pharmacological mechanisms underlying sibutramine-induced hypophagia. Individually-housed male Sprague-Dawley rats were maintained on reversed phase lighting with free access to food and water. Drugs were administered at 09 h 00 min and food intake was monitored over the following 8 h dark period. Sibutramine (10 mg kg−1, p.o.) produced a significant decrease in food intake during the 8 h following drug administration. This hypophagic response was fully antagonized by the α1-adrenoceptor antagonist, prazosin (0.3 and 1 mg kg−1, i.p.), and partially antagonized by the β1-adrenoceptor antagonist, metoprolol (3 and 10 mg kg−1, i.p.) and the 5-HT receptor antagonists, metergoline (non-selective; 0.3 mg kg−1, i.p.); ritanserin (5-HT2A/2C; 0.1 and 0.5 mg kg−1, i.p.) and SB200646 (5-HT2B/2C; 20 and 40 mg kg−1, p.o.). By contrast, the α2-adrenoceptor antagonist, RX821002 (0.3 and 1 mg kg−1, i.p.) and the β2-adrenoceptor antagonist, ICI 118,551 (3 and 10 mg kg−1, i.p.) did not reduce the decrease in food intake induced by sibutramine. These results demonstrate that β1-adrenoceptors, 5-HT2A/2C-receptors and particularly α1-adrenoceptors, are involved in the effects of sibutramine on food intake and are consistent with the hypothesis that sibutramine-induced hypophagia is related to its ability to inhibit the reuptake of both noradrenaline and 5-HT, with the subsequent activation of a variety of noradrenaline and 5-HT receptor systems. PMID:9283694
Selective serotonin reuptake inhibitors and intraoperative blood pressure.

Science.gov (United States)

van Haelst, Ingrid M M; van Klei, Wilton A; Doodeman, Hieronymus J; Kalkman, Cor J; Egberts, Toine C G

2012-02-01

The influence of selective serotonin reuptake inhibitors (SSRIs) on blood pressure is poorly understood. We hypothesized that if SSRIs have an influence on blood pressure, this might become manifest in changes in intraoperative blood pressure. We aimed to study the association between perioperative use of SSRIs and changes in intraoperative blood pressure by measuring the occurrence of intraoperative hyper- and hypotension. We conducted a retrospective observational follow-up study among patients who underwent elective primary total hip arthroplasty. The index group included users of SSRIs. The reference group included a random sample (ratio 1:3) of nonusers of an antidepressant agent. The outcome was the occurrence of intraoperative hypo- and hypertensive episodes (number, mean and total duration, and area under the curve (AUC)). The outcome was adjusted for confounding factors using regression techniques. The index group included 20 users of an SSRI. The reference group included 60 nonusers. Users of SSRIs showed fewer intraoperative hypotensive episodes, a shorter mean and total duration, and a smaller AUC when compared to the reference group. After adjustment for confounders, SSRI use was associated with a significantly shorter total duration of hypotension: mean difference of -29.4 min (95% confidence interval (CI) -50.4 to -8.3). Two users of an SSRI and two patients in the reference group had a hypertensive episode. Continuation of treatment with SSRIs before surgery was associated with a briefer duration of intraoperative hypotension.
Synthesis of [11C]dapoxetine·HCl, a serotonin re-uptake inhibitor: biodistribution in rat and preliminary PET imaging in the monkey

International Nuclear Information System (INIS)

Livni, E.; Satterlee, W.; Robey, R.L.

1994-01-01

[ 11 C]Dapoxetine · HCl, S-(+)-N,N-dimethyl-a-[2-(naphthalenyloxy)ethyl] benzenemethanamine hydrochloride, a potent serotonin re-uptake inhibitor was prepared from its mono-methyl precursor, S-(+)-N-methyl-a-[2-(naphthalenyloxy)ethyl]benzene methanamine hydrochloride. Biodistribution was determined in rats at 5, 30 and 60 min after injection and preliminary PET studies were performed in a Rhesus monkey. 11 CH 3 I was bubbled into a solution of S-(+)-N-methyl-α-[2-(naphthalenyloxy)ethyl]benzene methanamine hydrochloride (3.0 mg in DMSO) and the mixture was heated at 110 o C for 8 min. [ 11 C]Dapoxetine · HCl was purified by HPLC on a C 18 cartridge eluted with MeOH: phosphate buffer, pH 7.2 (75:25) with a 10% yield (end of synthesis). The time required for the synthesis was 40 min, from the end of bombardment. Radiochemical purity of the final product was > 99% and specific activity was routinely > 400 mCi/μmol [EOS]. (author)
Rate of improvement during and across three treatments for panic disorder with or without agoraphobia : Cognitive behavioral therapy, selective serotonin reuptake inhibitor or both combined

NARCIS (Netherlands)

Van Apeldoorn, Franske J.; Van Hout, Wiljo J. P. J.; Timmerman, Marieke E.; Mersch, Peter Paul A.; den Boer, Johan A.

2013-01-01

Background: Existing literature on panic disorder (PD) yields no data regarding the differential rates of improvement during Cognitive Behavioral Therapy (CBT), Selective Serotonin Reuptake Inhibitor (SSRI) or both combined (CBT+SSRI). Method: Patients were randomized to CBT, SSRI or CBT+SSRI which
An AOP analysis of selective serotonin reuptake inhibitors (SSRIs) for fish.

Science.gov (United States)

McDonald, M Danielle

2017-07-01

Pharmaceuticals and personal care products (PPCPs) are found in measureable quantities within the aquatic environment. Selective serotonin reuptake inhibitor (SSRI) antidepressants are one class of pharmaceutical compound that has received a lot of attention. Consistent with most PPCPs, the pharmacokinetics and physiological impacts of SSRI treatment have been well-studied in small mammals and humans and this, combined with the evolutionary conservation of the serotonergic system across vertebrates, allows for the read-across of known SSRI effects in mammals to potential SSRI impacts on aquatic organisms. Using an Adverse Outcome Pathway (AOP) framework, this review examines the similarities and differences between the mammalian and teleost fish SSRI target, the serotonin transporter (SERT; SLC6A4), and the downstream impacts of elevated extracellular serotonin (5-HT; 5-hydroxytryptamine), the consequence of SERT inhibition, on organ systems and physiological processes within teleost fish. This review also intends to reveal potentially understudied endpoints for SSRI toxicity based on what is known to be controlled by 5-HT in fish. Copyright © 2017 Elsevier Inc. All rights reserved.
An Association Between Selective Serotonin Reuptake Inhibitor Use and Serious Upper Gastrointestinal Bleeding

DEFF Research Database (Denmark)

Dall, Michael; Schaffalitzky de Muckadell, Ove B; Lassen, Annmarie Touborg

2009-01-01

BACKGROUND & AIMS: In vitro studies have shown that selective serotonin reuptake inhibitors (SSRIs) inhibit platelet aggregation. It is controversial whether use of SSRIs is a cause of clinically important bleeding; results from observational studies have been equivocal. METHODS: A population......-based case-control study was conducted in the county of Funen, Denmark. The 3652 cases all had a first discharge diagnosis of serious upper gastrointestinal bleeding (UGB) from 1995 to 2006. All cases were manually validated. Controls (n = 36,502), matched for age and sex, were selected by risk-set sampling....... Data on drug exposure and medical history were retrieved from a prescription database and the county's patient register. Confounders were controlled for by conditional logistic regression and the case-crossover design. RESULTS: The adjusted odds ratio (OR) of UGB among current, recent, and past users...
Risk of preeclampsia after gestational exposure to selective serotonin reuptake inhibitors and other antidepressants: A study from The Norwegian Mother and Child Cohort Study.

Science.gov (United States)

Lupattelli, Angela; Wood, Mollie; Lapane, Kate; Spigset, Olav; Nordeng, Hedvig

2017-10-01

To describe the risk of early- and late-onset preeclampsia across pregnancies exposed to antidepressants and to evaluate the impact of timing and length of gestational exposure to antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), on preeclampsia. The Norwegian Mother and Child Cohort, a prospective population-based study, and the Medical Birth Registry of Norway provided information on antidepressant exposure, depression, and anxiety symptoms in pregnancy, preeclampsia diagnoses, and important covariates. Within a pregnancy cohort of depressed women, we compared the risk of late-onset preeclampsia between SSRI-exposed and nonmedicated pregnancies using marginal structural models (weighted) and modified Poisson regression models. Of the 5887 pregnancies included, 11.1% were exposed at any time before week 34 to SSRIs, 1.3% to serotonin-norepinephrine reuptake inhibitors, 0.4% to tricyclic antidepressants, and 0.5% to other antidepressants. The risks of early- and late-onset preeclampsia by exposure status in pregnancy were 0.3% and 3.6% (nonmedicated), 0.4% and 3.7% (SSRIs), 1.5% and 4.1% (serotonin-norepinephrine reuptake inhibitors), and 7.1% and 10.0% (tricyclic antidepressants). Compared with nonmedicated pregnancies, SSRI-exposed in mid and late gestation had adjusted relative risks for late-onset mild preeclampsia of 0.76 (95% confidence interval, 0.38-1.53) and 1.56 (0.71-3.44) (weighted models), respectively. There was no association between SSRI exposure in pregnancy and severe late-onset preeclampsia. We have provided evidence that SSRI use in early and midpregnancy does not substantially increase the risk of late-onset preeclampsia. © 2017 The Authors. Pharmacoepidemiology & Drug Safety published by John Wiley & Sons Ltd.

Characterization of the binding of /sup 3/H-norzimeldine, a 5-HT uptake inhibitor, to rat brain homogenates

Energy Technology Data Exchange (ETDEWEB)

Hall, H. (Department of Biochemical Neuropharmacology, Research and Development Laboratories, Astra Laekemedel, Soedertaelje, Sweden)

1984-01-01

The binding of radiolabelled norzimeldine, a potent selective 5-HT reuptake inhibitor, to rat brain homogenates is described. /sup 3/H-Norzimeldine binds to a site with high affinity (Ksub(D) = 10.5 nM) in a saturable manner (Bsub(max) = 15.4 pmol/g wet weight in the cerebral cortex). The number of binding sites in the various regions of the brain parallels the capacity of the 5-HT reuptake mechanism. Drugs that inhibit the reuptake of 5-HT are also potent inhibitors of the /sup 3/H-norzimeldine binding, as are the tricyclic antidepressants, which are non-specific inhibitors of the noradrenaline and the 5-HT reuptake. Lesioning experiments using DSP4 (a NA neurotoxin) and p-chloroamphetamine (a 5-HT neurotoxin) suggest that the binding site is located on the presynaptic 5-HT nerve terminal, although a small component of the binding may be to noradrenergic uptake sites as well.
Characterization of the binding of 3H-norzimeldine, a 5-HT uptake inhibitor, to rat brain homogenates

International Nuclear Information System (INIS)

Hall, H.

1984-01-01

The binding of radiolabelled norzimeldine, a potent selective 5-HT reuptake inhibitor, to rat brain homogenates is described. 3 H-Norzimeldine binds to a site with high affinity (Ksub(D) = 10.5 nM) in a saturable manner (Bsub(max) = 15.4 pmol/g wet weight in the cerebral cortex). The number of binding sites in the various regions of the brain parallels the capacity of the 5-HT reuptake mechanism. Drugs that inhibit the reuptake of 5-HT are also potent inhibitors of the 3 H-norzimeldine binding, as are the tricyclic antidepressants, which are non-specific inhibitors of the noradrenaline and the 5-HT reuptake. Lesioning experiments using DSP4 (a NA neurotoxin) and p-chloroamphetamine (a 5-HT neurotoxin) suggest that the binding site is located on the presynaptic 5-HT nerve terminal, although a small component of the binding may be to noradrenergic uptake sites as well.(author)
A chiral synthesis of dapoxetine hydrochloride, a serotonin re-uptake inhibitor, and its 14C isotopomer

International Nuclear Information System (INIS)

Wheeler, W.J.; O'Bannon, D.D.

1992-01-01

The 14 C-isotopmer of dapoxetine-[ 14 C] HCl (S (+) -N,N-dimethyl-α[2-(1-naphthalenyloxy)ethyl-2- 14 C]benzenemeth a-n amine hydrochloride, 1a), a potent serotonin re-uptake inhibitor has been prepared by a chiral synthesis, starting with tert. -butyloxyphenylglycine (3). Borane reduction, followed by activation of the resulting alcohol 4 as its mesylate 5b, provided the chiral starting material. The radiolabel was introduced by reaction of 5b with sodium cyanide-[ 14 C]. The desired product (1) was then elaborated from nitrile 6a,b via a five step synthesis in an overall 19.5% radiochemical yield. (Author)
The selective serotonin reuptake inhibitor fluoxetine does not change rectal sensitivity and symptoms in patients with irritable bowel syndrome: a double blind, randomized, placebo-controlled study

NARCIS (Netherlands)

Kuiken, Sjoerd D.; Tytgat, Guido N. J.; Boeckxstaens, Guy E. E.

2003-01-01

BACKGROUND & AIMS: Although widely prescribed, the evidence for the use of antidepressants for the treatment of irritable bowel syndrome (IBS) is limited. In this study, we hypothesized that fluoxetine (Prozac), a selective serotonin reuptake inhibitor, has visceral analgesic properties, leading to
Automated container transportation using self-guided vehicles: Fernald site requirements

International Nuclear Information System (INIS)

Hazen, F.B.

1993-09-01

A new opportunity to improve the safety and efficiency of environmental restoration operations, using robotics has emerged from advances in industry, academia, and government labs. Self-Guided Vehicles (SGV's) have recently been developed in industry and early systems have already demonstrated much, though not all, of the functionality necessary to support driverless transportation of waste within and between processing facilities. Improved materials databases are being developed by at least two DOE remediation sites, the Fernald Environmental Management Project (FEME) in the State of Ohio and the Hanford Complex in the State of Washington. SGV's can be developed that take advantage of the information in these databases and yield improved dispatch, waste tracking, report and shipment documentation. In addition, they will reduce the radiation hazard to workers and the risk of damaging containers through accidental collision. In this document, features of remediation sites that dictate the design of both the individual SGV's and the collective system of SGV's are presented, through the example of the site requirements at Fernald. Some concepts borrowed from the world of manufacturing are explained and then used to develop an integrated, holistic view of the remediation site as a pseudo-factory. Transportation methods at Fernald and anticipated growth in transport demand are analyzed. The new site-wide database under development at Fernald is presented so that advantageous and synergistic links between SGV's and information systems can be analyzed. Details of the SGV development proposed are submitted, and some results of a recently completed state of the art survey for SGV use in this application are also presented
Design and synthesis of 4-heteroaryl 1,2,3,4-tetrahydroisoquinolines as triple reuptake inhibitors.

Science.gov (United States)

Liu, Shuang; Zha, Congxiang; Nacro, Kassoum; Hu, Min; Cui, Wenge; Yang, Yuh-Lin; Bhatt, Ulhas; Sambandam, Aruna; Isherwood, Matthew; Yet, Larry; Herr, Michael T; Ebeltoft, Sarah; Hassler, Carla; Fleming, Linda; Pechulis, Anthony D; Payen-Fornicola, Anne; Holman, Nicholas; Milanowski, Dennis; Cotterill, Ian; Mozhaev, Vadim; Khmelnitsky, Yuri; Guzzo, Peter R; Sargent, Bruce J; Molino, Bruce F; Olson, Richard; King, Dalton; Lelas, Snjezana; Li, Yu-Wen; Johnson, Kim; Molski, Thaddeus; Orie, Anitra; Ng, Alicia; Haskell, Roy; Clarke, Wendy; Bertekap, Robert; O'Connell, Jonathan; Lodge, Nicholas; Sinz, Michael; Adams, Stephen; Zaczek, Robert; Macor, John E

2014-07-10

A series of 4-bicyclic heteroaryl 1,2,3,4-tetrahydroisoquinoline inhibitors of the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT) was discovered. The synthesis and structure-activity relationship (SAR) of these triple reuptake inhibitors (TRIs) will be discussed. Compound 10i (AMR-2), a very potent inhibitor of SERT, NET, and DAT, showed efficacy in the rat forced-swim and mouse tail suspension models with minimum effective doses of 0.3 and 1 mg/kg (po), respectively. At efficacious doses in these assays, 10i exhibited substantial occupancy levels at the three transporters in both rat and mouse brain. The study of the metabolism of 10i revealed the formation of a significant active metabolite, compound 13.
Site infrastructure as required during the construction and erection of nuclear power plants

International Nuclear Information System (INIS)

Haas, K.F.; Wagner, H.

1978-01-01

In general, in an exchange of experience on constructing nuclear power plants priority is given to design and lay-out, financing, quality assurance etc., but in this paper an attempt has been made to describe range and type of site infrastructure required during construction and erection. Site infrastructure will make considerable demands on the planning, supply of material and maintenance that may result from the frequently very isolated location of power plant sites. Examples for specific values and experiences are given for a nuclear power plant with two units on the 1300-MW type at present under construction of the Persian Gulf in Iran. Data concerning the site infrastructure, including examples, are given and explained on the basis of graphs. The site is split up into a technical and a social infrastructure. The main concern of the technical site infrastructure is the timely provision and continuous availability of electric energy, water, communication grids, workshops, warehouses, offices, transport and handling facilities, as well as the provision of heavy load roads, harbour facilities, etc. The social site infrastructure in general comprises accommodation, food supplies and the care and welfare of all site personnel, which includes a hospital, school, self-service shop, and sport and recreation facilities. (author)
Exposure to Selective Serotonin Reuptake Inhibitors in Early Pregnancy and the Risk of Miscarriage

DEFF Research Database (Denmark)

Andersen, Jon Thor Trærup; Andersen, Nadia Lyhne; Horwitz, Henrik

2014-01-01

OBJECTIVE: To investigate whether exposure to selective serotonin reuptake inhibitors (SSRIs) in early pregnancy is associated with miscarriage. METHODS: This was a nationwide cohort study identifying all registered pregnancies in Denmark from 1997 to 2010. All births were identified using...... the Medical Birth Registry, and all records of induced abortion or miscarriage were gathered from the National Hospital Register. Data on SSRI use were gathered from the National Prescription Register. Cox proportional hazard regression models were used to calculate the hazard of miscarriage in women exposed...... to an SSRI in early pregnancy and the hazard of miscarriage in women discontinuing treatment before pregnancy. RESULTS: We identified 1,279,840 pregnancies (911,569 births, 142,093 miscarriages, 226,178 induced abortions). Of the 22,884 exposed to an SSRI during the first 35 days of pregnancy, 12.6% (2...
Serum Prolactin Levels in Patients with Major Depressive Disorder Receiving Selective Serotonin-Reuptake Inhibitor Monotherapy for 3 Months: A Prospective Study

OpenAIRE

Park, Young-Min

2017-01-01

Objective It is unclear whether selective serotonin-reuptake inhibitors (SSRIs) can significantly increase the prolactin level. The purpose of this study was to identify the relationship between the prolactin level and the administration of SSRIs such as escitalopram and sertraline. An additional purpose was to determine whether the elevation of prolactin differs between escitalopram and sertraline treatment. Methods Serum prolactin levels were measured at baseline and after 3 months in 23 pa...
78 FR 12676 - Timing Requirements for the Submission of a Site Assessment Plan (SAP) or General Activities Plan...

Science.gov (United States)

2013-02-25

...: BOEM-2012-0077] RIN 1010-AD77 Timing Requirements for the Submission of a Site Assessment Plan (SAP) or... would amend the timing requirements for submitting a Site Assessment Plan (SAP) or General Activities... and grants will have a preliminary term of 12 months in which a lessee or grantee must submit a SAP or...
Bioimpedance in monitoring of effects of selective serotonin reuptake inhibitor treatment

Directory of Open Access Journals (Sweden)

Kuznecova LV

2011-06-01

Full Text Available Vasiliy Grigorievich Alexeev, Ludmila Vasilievna KuznecovaDepartment of Physiology, SP Botkin Moscow City Clinical Hospital, Moscow, RussiaBackground: Bioimpedance has been shown to be a safe technique when used in a number of biomedical applications. In this study, we used the Electro Interstitial Scan (EIS to perform bioimpedance measurements to follow up the efficacy of selective serotonin reuptake inhibitor (SSRI treatment in subjects diagnosed to have major depressive disorder.Methods: We recruited 59 subjects (38 women, 21 men aged 17–76 (mean 47 years diagnosed with major depressive disorder by psychiatric assessment at the Botkin Hospital according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV. Baseline Clinical Global Impression scores and EIS (electrical conductivity and dispersion α parameter measurements were done before starting SSRI therapy. Treatment follow-up was undertaken using EIS bioimpedance measurements and by treatment response based on the Hamilton Depression Scale and Clinical Global Impression, every 15 days for 60 days. At day 45, we classified the patients into two groups, ie, Group 1, including treatment responders, and Group 2, including nonresponders. At day 60, patients were classified into two further groups, ie, Group 3, comprising treatment responders, and Group 4, comprising nonresponders.Results: Comparing Group 1 and Group 2, electrical conductivity measurement of the pathway between the two forehead electrodes had a specificity of 72% and a sensitivity of 85.3% (P < 0.0001, with a cutoff >4.32. Comparing Group 3 and Group 4, electrical conductivity measurements in the same pathway had a specificity of 47.6% and a sensitivity of 76.3% (P < 0.16, with a cutoff >5.92. Comparing Group 1 and Group 2, the electrical dispersion α parameter of the pathway between the two disposable forehead electrodes had a specificity of 80% and a sensitivity of 85.2% (P < 0.0001 with a
Regulatory requirements of the integrated technology demonstration program, Savannah River Site (U)

International Nuclear Information System (INIS)

Bergren, C.L.

1992-01-01

The integrated demonstration program at the Savannah River Site (SRS) involves demonstration, testing and evaluation of new characterization, monitoring, drilling and remediation technologies for soils and groundwater impacted by organic solvent contamination. The regulatory success of the demonstration program has developed as a result of open communications between the regulators and the technical teams involved. This open dialogue is an attempt to allow timely completion of applied environmental restoration demonstrations while meeting all applicable regulatory requirements. Simultaneous processing of multiple regulatory documents (satisfying RCRA, CERCLA, NEPA and various state regulations) has streamlined the overall permitting process. Public involvement is achieved as various regulatory documents are advertised for public comment consistent with the site's community relations plan. The SRS integrated demonstration has been permitted and endorsed by regulatory agencies, including the Environmental Protection Agency (EPA) and the South Carolina Department of Health and Environmental Control. EPA headquarters and regional offices are involved in DOE's integrated Demonstration Program. This relationship allows for rapid regulatory acceptance while reducing federal funding and time requirements. (author)
Morphological changes of intestinal mucosa in patients with different clinical variants of irritable bowel syndrome using tetracyclic antidepressants and selective serotonin reuptake inhibitor

OpenAIRE

Nagieva S.; Svintsitskyy A.; Kuryk O.; Korendovych I.

2015-01-01

Objective. To assess histological changes of colonic mucosa in patients with clinically different types of irritable bowel syndrome (IBS) before and after the treatment with tetracyclic antidepressant and selective serotonin reuptake inhibitor. Methods. Adult patients (over 18 years) with confirmed diagnosis of IBS were examined. Biopsy specimens were taken from colon during colonoscopy for the next histological examination. One expert gastrointestinal pathologist assessed all tissue samples....
30 CFR 71.500 - Sanitary toilet facilities at surface work sites; installation requirements.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Sanitary toilet facilities at surface work sites; installation requirements. 71.500 Section 71.500 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY HEALTH STANDARDS-SURFACE COAL MINES AND...
Effects of selective serotonin reuptake inhibitors on thought-action fusion, metacognitions, and thought suppression in obsessive-compulsive disorder.

Science.gov (United States)

Besiroglu, Lutfullah; Çetinkaya, Nuralay; Selvi, Yavuz; Atli, Abdullah

2011-01-01

We aimed to assess whether cognitive processes change over time in patients with obsessive-compulsive disorder (OCD) receiving selective serotonin reuptake inhibitors without cognitive behavioral therapy and to investigate the factors associated with probable cognitive changes. During the 16 weeks of the study, 55 patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for OCD received open-label treatment with sertraline (100-200 mg/d) or fluoxetine (40-80 mg/d) and were assessed using the Yale-Brown Obsessive-Compulsive Scale, Beck Depression Inventory (BDI), Thought-Action Fusion Scale (TAFS), Metacognitions Questionnaire (MCQ-30), and White Bear Suppression Inventory (WBSI). The Yale-Brown Obsessive-Compulsive Scale (P < .001), BDI (P < .001), TAFS morality (P < .005), MCQ-30 (P < .01), and WBSI (P < .005) scores at follow-up were significantly lower than baseline scores. When we excluded OCD patients with depressive disorder (n = 12), statistical significance in paired comparisons for MCQ and WBSI disappeared. Similarly, when OCD patients with religious obsessions (n = 16) were excluded, paired comparisons for MCQ and TAF morality were not statistically significant. Changes in BDI, TAFS morality, MCQ-30, and WBSI (P < .005) were significantly correlated with changes in severity of obsessions, but not that of compulsions. After controlling for the change in depression severity, significant correlations between changes in obsessive and cognitive scales did not continue to have statistical significance. The BDI changes (P < .05) significantly explained the changes in symptom severity in a linear regression model. Our findings suggest that selective serotonin reuptake inhibitors can change appraisals of obsessive intrusions via their effects on negative emotions. Copyright © 2011 Elsevier Inc. All rights reserved.
A non-selective (amitriptyline), but not a selective (citalopram), serotonin reuptake inhibitor is effective in the prophylactic treatment of chronic tension-type headache.

OpenAIRE

Bendtsen, L; Jensen, R; Olesen, J

1996-01-01

OBJECTIVES: Although the tricyclic antidepressant amitriptyline is extensively used in the prophylactic treatment of chronic tension-type headache, only few studies have investigated the efficacy of this treatment and the results are contradictory. In addition, the new selective serotonin reuptake inhibiting antidepressants, which are widely used in depression and of potential value in pain management, have never been investigated in a placebo controlled study of tension-type headache. The ai...
Selective serotonin reuptake inhibitor antidepressant use in first trimester pregnancy and risk of congenital anomalies

DEFF Research Database (Denmark)

Wemakor, A.; Casson, K.; Garne, E.

2015-01-01

Objective / Background The Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants are widely prescribed in pregnancy, but there is evidence that they may cause congenital anomalies, particularly congenital heart defects (CHD). Objective: To determine the specificity of association between...... first trimester pregnancy exposure to individual SSRI and specific congenital anomalies (CAs). Methods Population-based case-malformed control study covering 3.3 million births from 12 EUROCAT registries 1995-2009. CAs included non-syndromic live births, fetal deaths and terminations of pregnancy......% confidence intervals (CI) were calculated adjusted for registry. Results SSRI use in first trimester pregnancy was associated with CHD overall (OR 1.38, 95 % CI 1.05-1.82, n=109); and with severe CHDs (OR 1.56, 95 % CI 1.03-2.38, n=29). Specific associations between SSRI and Tetralogy of Fallot (OR 3.36, 95...
QT interval prolongation in users of selective serotonin reuptake inhibitors in an elderly surgical population

DEFF Research Database (Denmark)

van Haelst, Ingrid M M; van Klei, Wilton A; Doodeman, Hieronymus J

2014-01-01

OBJECTIVE: To investigate the association between the use of a selective serotonin reuptake inhibitor (SSRI) and the occurrence of QT interval prolongation in an elderly surgical population. METHOD: A cross-sectional study was conducted among patients (> 60 years) scheduled for outpatient...... preanesthesia evaluation in the period 2007 until 2012. The index group included elderly users of an SSRI. The reference group of nonusers of antidepressants was matched to the index group on sex and year of scheduled surgery (ratio, 1:1). The primary outcome was the occurrence of QT interval prolongation shown...... on electrocardiogram. The QT interval was corrected for heart rate (QTc interval). The secondary outcome was the duration of the QTc interval. The outcomes were adjusted for confounding by using regression techniques. RESULTS: The index and reference groups included 397 users of an SSRI and 397 nonusers, respectively...
47 CFR 22.939 - Site availability requirements for applications competing with cellular renewal applications.

Science.gov (United States)

2010-10-01

... competing with cellular renewal applications. 22.939 Section 22.939 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.939 Site availability requirements for applications competing with cellular renewal applications. In...
Selective Serotonin Reuptake Inhibitors in Human Pregnancy: To Treat or Not to Treat?

Directory of Open Access Journals (Sweden)

Orna Diav-Citrin

2012-01-01

Full Text Available Selective serotonin reuptake inhibitors (SSRIs are increasingly prescribed during pregnancy. The purpose of the present paper is to summarize and evaluate the current evidence for the risk/benefit analysis of SSRI use in human pregnancy. The literature has been inconsistent. Although most studies have not shown an increase in the overall risk of major malformations, several studies have suggested that SSRIs may be associated with a small increased risk for cardiovascular malformations. Others have noted associations between SSRIs and specific types of rare major malformations. In some studies, there appears to be a small increased risk for miscarriages, which may be associated with the underlying maternal condition. Neonatal effects have been described in up to 30% of neonates exposed to SSRIs late in pregnancy. Persistent pulmonary hypertension of the newborn has also been described with an absolute risk of <1%. The risk associated with treatment discontinuation, for example, higher frequency of relapse and increased risk of preterm delivery, should also be considered. The overall benefit of treatment seems to outweigh the potential risks.

Atomoxetine, a norepinephrine reuptake inhibitor, reduces seizure-induced respiratory arrest.

Science.gov (United States)

Zhang, Honghai; Zhao, Haiting; Feng, Hua-Jun

2017-08-01

Sudden unexpected death in epilepsy (SUDEP) is a devastating epilepsy complication, and no effective preventive strategies are currently available for this fatal disorder. Clinical and animal studies of SUDEP demonstrate that seizure-induced respiratory arrest (S-IRA) is the primary event leading to death after generalized seizures in many cases. Enhancing brain levels of serotonin reduces S-IRA in animal models relevant to SUDEP, including the DBA/1 mouse. Given that serotonin in the brain plays an important role in modulating respiration and arousal, these findings suggest that deficits in respiration and/or arousal may contribute to S-IRA. It is well known that norepinephrine is an important neurotransmitter that modulates respiration and arousal in the brain as well. Therefore, we hypothesized that enhancing noradrenergic neurotransmission suppresses S-IRA. To test this hypothesis, we examined the effect of atomoxetine, a norepinephrine reuptake inhibitor (NRI), on S-IRA evoked by either acoustic stimulation or pentylenetetrazole in DBA/1 mice. We report the original observation that atomoxetine specifically suppresses S-IRA without altering the susceptibility to seizures evoked by acoustic stimulation, and atomoxetine also reduces S-IRA evoked by pentylenetetrazole in DBA/1 mice. Our data suggest that the noradrenergic signaling is importantly involved in S-IRA, and that atomoxetine, a medication widely used to treat attention deficit hyperactivity disorder (ADHD), is potentially useful to prevent SUDEP. Copyright © 2017 Elsevier Inc. All rights reserved.
Design methodology for the physical protection upgrade rule requirements for fixed sites. Technical report

International Nuclear Information System (INIS)

Evans, L.J. Jr.; Allen, T.

1980-06-01

This Design Methodology document aids the licensee in understanding how the fixed site requirements of the Physical Protection Upgrade Rule affect the design of physical protection systems for fuel processing plants, fuel manufacturing plants, or other fixed site special nuclear material operations involving possession or use of formula quantities of strategic special nuclear material. The document consists of three major elements: Logic Trees, Safeguards Jobs and Component Matrices, and Effectiveness Test Questionnaires. The work is based upon a previous study conducted by Sandia Laboratories for the Nuclear Regulatory Commission
17β-Estradiol augments antidepressant efficacy of escitalopram in ovariectomized rats: Neuroprotective and serotonin reuptake transporter modulatory effects.

Science.gov (United States)

Ibrahim, Weam W; Safar, Marwa M; Khattab, Mahmoud M; Agha, Azza M

2016-12-01

The prevalence or recurrence of depression is seriously increased in women during the transition to and after menopause. The chronic hypo-estrogenic state of menopause may reduce the response to antidepressants; however the influence of estrogen therapy on their efficacy is still controversial. This study aimed at investigating the effects of combining escitalopram with 17β-estradiol on depression and cognitive impairment induced by ovariectomy, an experimental model of human menopause. Young adult female Wistar rats were subjected to either sham operation or ovariectomy. Ovariectomized animals were treated chronically with escitalopram (10mg/kg/day, i.p) alone or with four doses of 17β-estradiol (40μg/kg, s.c) given prior to the behavioral tests. Co-administration of 17β-estradiol improved escitalopram-induced antidepressant effect in forced swimming test verified as more prominent decrease in the immobility time without opposing its memory enhancing effect in Morris water maze. 17β-estradiol augmented the modulatory effects of escitalopram on the hippocampal levels of brain-derived neurotrophic factor and serotonin reuptake transporter as well as tumor necrosis factor-alpha without altering its effects on the gene expressions of serotonin receptor 1A, estrogen receptors alpha and beta, or acetylcholinestearase content. This combined therapy afforded synergistic protective effects on the brain histopathological architecture, particularly, the hippocampus. The antidepressant effect of 17β-estradiol was abolished by pretreatment with estrogen receptor antagonist, tamoxifen (10mg/kg, p.o). In conclusion, 17β-estradiol-induced antidepressant effect was confined to intracellular estrogen receptors activation. Moreover, 17β-estradiol enhanced escitalopram's efficiency in ameliorating menopausal-like depression, via exerting synergistic neuroprotective and serotonin reuptake transporter modulatory effects, without impeding escitalopram-mediated cognitive
Projecting future solid waste management requirements on the Hanford Site

International Nuclear Information System (INIS)

Shaver, S.R.; Stiles, D.L.; Holter, G.M.; Anderson, B.C.

1990-09-01

The problem of treating and disposing of hazardous transuranic (TRU), low-level radioactive, and mixed waste has become a major concern of the public and the government. At the US Department of Energy's Hanford Site in Washington state, the problem is compounded by the need to characterize, retrieve, and treat the solid waste that was generated and stored for retrieval during the past 20 years. This paper discusses the development and application of a Solid Waste Projection Model that uses forecast volumes and characteristics of existing and future solid waste to address the treatment, storage, and disposal requirements at Hanford. The model uses a data-driven, object-oriented approach to assess the storage and treatment throughout requirements for each operation for each of the distinct waste classes and the accompanying cost of the storage and treatment operations. By defining the elements of each alternative for the total waste management system, the same database can be used for numerous analyses performed at different levels of detail. This approach also helps a variety of users with widely varying information requirements to use the model and helps achieve the high degree of flexibility needed to cope with changing regulations and evolving treatment and disposal technologies. 2 figs
Novel selective and potent 5-HT reuptake inhibitors with 5-HT1D antagonist activity: chemistry and pharmacological evaluation of a series of thienopyran derivatives.

Science.gov (United States)

Torrado, Alicia; Lamas, Carlos; Agejas, Javier; Jiménez, Alma; Diaz, Nuria; Gilmore, Jeremy; Boot, John; Findlay, Jeremy; Hayhurst, Lorna; Wallace, Louise; Broadmore, Richard; Tomlinson, Rosemarie

2004-10-15

A series of compounds combining the naphthylpiperazine and thienopyran scaffolds has been prepared and evaluated for 5-HT reuptake inhibition with 5-HT1D antagonist activity. The design of these compounds has been based on the 'overlapping type' strategy where two pharmacophores are linked in a single molecule. The resultant dual pharmacological profile has the potential to deliver a more efficient treatment for depression.
Effects of selective serotonin reuptake inhibitor treatment on plasma oxytocin and cortisol in major depressive disorder.

Science.gov (United States)

Keating, Charlotte; Dawood, Tye; Barton, David A; Lambert, Gavin W; Tilbrook, Alan J

2013-04-29

Oxytocin is known for its capacity to facilitate social bonding, reduce anxiety and for its actions on the stress hypothalamopituitary adrenal (HPA) axis. Since oxytocin can physiologically suppress activity of the HPA axis, clinical applications of this neuropeptide have been proposed in conditions where the function of the HPA axis is dysregulated. One such condition is major depressive disorder (MDD). Dysregulation of the HPA system is the most prominent endocrine change seen with MDD, and normalizing the HPA axis is one of the major targets of recent treatments. The potential clinical application of oxytocin in MDD requires improved understanding of its relationship to the symptoms and underlying pathophysiology of MDD. Previous research has investigated potential correlations between oxytocin and symptoms of MDD, including a link between oxytocin and treatment related symptom reduction. The outcomes of studies investigating whether antidepressive treatment (pharmacological and non-pharmacological) influences oxytocin concentrations in MDD, have produced conflicting outcomes. These outcomes suggest the need for an investigation of the influence of a single treatment class on oxytocin concentrations, to determine whether there is a relationship between oxytocin, the HPA axis (e.g., oxytocin and cortisol) and MDD. Our objective was to measure oxytocin and cortisol in patients with MDD before and following treatment with selective serotonin reuptake inhibitors, SSRI. We sampled blood from arterial plasma. Patients with MDD were studied at the same time twice; pre- and post- 12 weeks treatment, in an unblinded sequential design (clinicaltrials.govNCT00168493). Results did not reveal differences in oxytocin or cortisol concentrations before relative to following SSRI treatment, and there were no significant relationships between oxytocin and cortisol, or these two physiological variables and psychological symptom scores, before or after treatment. These outcomes
In Vivo Investigation of Escitalopram’s Allosteric Site on the Serotonin Transporter

Science.gov (United States)

Murray, Karen E.; Ressler, Kerry J.; Owens, Michael J.

2015-01-01

Escitalopram is a commonly prescribed antidepressant of the selective serotonin reuptake inhibitor class. Clinical evidence and mapping of the serotonin transporter (SERT) identified that escitalopram, in addition to its binding to a primary uptake-blocking site, is capable of binding to the SERT via an allosteric site that is hypothesized to alter escitalopram’s kinetics at the SERT. The studies reported here examined the in vivo role of the SERT allosteric site in escitalopram action. A knockin mouse model that possesses an allosteric-null SERT was developed. Autoradiographic studies indicated that the knockin protein was expressed at a lower density than endogenous mouse SERT (approximately 10–30% of endogenous mouse SERT), but the knockin mice are a viable tool to study the allosteric site. Microdialysis studies in the ventral hippocampus found no measurable decrease in extracellular serotonin response after local escitalopram challenge in mice without the allosteric site compared to mice with the site (p = 0.297). In marble burying assays there was a modest effect of the absence of the allosteric site, with a larger systemic dose of escitalopram (10-fold) necessary for the same effect as in mice with intact SERT (p = 0.023). However, there was no effect of the allosteric site in the tail suspension test. Together these data suggest that there may be a regional specificity in the role of the allosteric site. The lack of a robust effect overall suggests that the role of the allosteric site for escitalopram on the SERT may not produce meaningful in vivo effects. PMID:26621784
A C-terminal, cysteine-rich site in poliovirus 2C(ATPase) is required for morphogenesis.

Science.gov (United States)

Wang, Chunling; Ma, Hsin-Chieh; Wimmer, Eckard; Jiang, Ping; Paul, Aniko V

2014-06-01

The morphogenesis of viruses belonging to the genus Enterovirus in the family Picornaviridae is still poorly understood despite decades-long investigations. However, we recently provided evidence that 2C(ATPase) gives specificity to poliovirus encapsidation through an interaction with capsid protein VP3. The polypeptide 2C(ATPase) is a highly conserved non-structural protein of enteroviruses with important roles in RNA replication, encapsidation and uncoating. We have identified a site (K279/R280) near the C terminus of the polypeptide that is required for morphogenesis. The aim of the current project was to search for additional functional sites near the C terminus of the 2C(ATPase) polypeptide, with particular interest in those that are required for encapsidation. We selected for analysis a cysteine-rich site of the polypeptide and constructed four mutants in which cysteines or a histidine was changed to an alanine. The RNA transcripts were transfected into HeLa cells yielding two lethal, one temperature-sensitive and one quasi-infectious mutants. All four mutants exhibited normal protein translation in vitro and three of them possessed severe RNA replication defects. The quasi-infectious mutant (C286A) yielded variants with a pseudo-reversion at the original site (A286D), but some also contained one additional mutation: A138V or M293V. The temperature-sensitive mutant (C272A/H273A) exhibited an encapsidation and possibly also an uncoating defect at 37 °C. Variants of this mutant revealed suppressor mutations at three different sites in the 2C(ATPase) polypeptide: A138V, M293V and K295R. We concluded that the cysteine-rich site near the C terminus of 2C(ATPase) is involved in encapsidation, possibly through an interaction with an upstream segment located between boxes A and B of the nucleotide-binding domain. © 2014 The Authors.
Determining the number of samples required for decisions concerning remedial actions at hazardous waste sites

International Nuclear Information System (INIS)

Skiles, J.L.; Redfearn, A.; White, R.K.

1991-01-01

The processing of collecting, analyzing, and assessing the data needed to make to make decisions concerning the cleanup of hazardous waste sites is quite complex and often very expensive. This is due to the many elements that must be considered during remedial investigations. The decision maker must have sufficient data to determine the potential risks to human health and the environment and to verify compliance with regulatory requirements, given the availability of resources allocated for a site, and time constraints specified for the completion of the decision making process. It is desirable to simplify the remedial investigation procedure as much as possible to conserve both time and resources while, simultaneously, minimizing the probability of error associated with each decision to be made. With this in mind, it is necessary to have a practical and statistically valid technique for estimating the number of on-site samples required to ''guarantee'' that the correct decisions are made with a specified precision and confidence level. Here, we will examine existing methodologies and then develop our own approach for determining a statistically defensible sample size based on specific guidelines that have been established for the risk assessment process
Reviewing the serotonin reuptake inhibitors (SSRIs) footprint in the aquatic biota: Uptake, bioaccumulation and ecotoxicology

International Nuclear Information System (INIS)

a Comba, 3000-548 Coimbra (Portugal))" data-affiliation=" (REQUIMTE, Group of Bromatology, Pharmacognosy and Analytical Sciences, Faculty of Pharmacy, University of Coimbra, Polo III, Azinhaga de Sta Comba, 3000-548 Coimbra (Portugal))" >Silva, Liliana J.G.; a Comba, 3000-548 Coimbra (Portugal))" data-affiliation=" (REQUIMTE, Group of Bromatology, Pharmacognosy and Analytical Sciences, Faculty of Pharmacy, University of Coimbra, Polo III, Azinhaga de Sta Comba, 3000-548 Coimbra (Portugal))" >Pereira, André a Comba, 3000-548 Coimbra (Portugal))" data-affiliation=" (REQUIMTE, Group of Bromatology, Pharmacognosy and Analytical Sciences, Faculty of Pharmacy, University of Coimbra, Polo III, Azinhaga de Sta Comba, 3000-548 Coimbra (Portugal))" >M.P.T.; Meisel, Leonor M.; a Comba, 3000-548 Coimbra (Portugal))" data-affiliation=" (REQUIMTE, Group of Bromatology, Pharmacognosy and Analytical Sciences, Faculty of Pharmacy, University of Coimbra, Polo III, Azinhaga de Sta Comba, 3000-548 Coimbra (Portugal))" >Lino, Celeste M.; a Comba, 3000-548 Coimbra (Portugal))" data-affiliation=" (REQUIMTE, Group of Bromatology, Pharmacognosy and Analytical Sciences, Faculty of Pharmacy, University of Coimbra, Polo III, Azinhaga de Sta Comba, 3000-548 Coimbra (Portugal))" >Pena, Angelina

2015-01-01

Selective serotonin re-uptake inhibitors (SSRIs) antidepressants are amongst the most prescribed pharmaceutical active substances throughout the world. Their presence, already described in different environmental compartments such as wastewaters, surface, ground and drinking waters, and sediments, and their remarkable effects on non-target organisms justify the growing concern about these emerging environmental pollutants. A comprehensive review of the literature data with focus on their footprint in the aquatic biota, namely their uptake, bioaccumulation and both acute and chronic ecotoxicology is presented. Long-term multigenerational exposure studies, at environmental relevant concentrations and in mixtures of related compounds, such as oestrogenic endocrine disruptors, continue to be sparse and are imperative to better know their environmental impact. - Highlights: • Current knowledge of uptake and bioaccumulation of SSRIs. • Ecotoxicology and effects of SSRIs in the aquatic biota. • Identification of existing knowledge gaps. - A comprehensive review focussing SSRIs antidepressants footprint in the aquatic biota, namely their uptake, bioaccumulation, and both acute and chronic ecotoxicology is presented
A randomized controlled trial of a novel mixed monoamine reuptake inhibitor in adults with ADHD

Directory of Open Access Journals (Sweden)

Wesnes Keith

2008-06-01

Full Text Available Abstract Background NS2359 is a potent reuptake blocker of noradrenalin, dopamine, and serotonin. The aim of the study was to investigate the efficacy, safety and cognitive function of NS2359 in adults with a DSM IV diagnosis of ADHD. Methods The study was a multi-centre, double-blind, randomized placebo-controlled, parallel group design in outpatient adults (18–55 years testing 0.5 mg NS2359 vs. placebo for 8 weeks. Multiple assessments including computerized neuropsychological evaluation were performed. Results There was no significant difference between NS2359 (n = 63 versus placebo (n = 63 on the primary outcome measure reduction in investigator rated ADHD-RS total score (7.8 versus 6.4; p Conclusion No overall effect of NS2359 was found on overall symptoms of ADHD. There was also a modest signal of improvement in the inattentive adults with ADHD and cognition warranting further exploration using differing doses.
Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) for the prevention of tension-type headache in adults.

Science.gov (United States)

Banzi, Rita; Cusi, Cristina; Randazzo, Concetta; Sterzi, Roberto; Tedesco, Dario; Moja, Lorenzo

2015-05-01

This is an updated version of the Cochrane review published in 2005 on selective serotonin re-uptake inhibitors (SSRIs) for preventing migraine and tension-type headache. The original review has been split in two parts and this review now only regards tension-type headache prevention. Another updated review covers migraine. Tension-type headache is the second most common disorder worldwide and has high social and economic relevance. As serotonin and other neurotransmitters may have a role in pain mechanisms, SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs) have been evaluated for the prevention of tension-type headache. To determine the efficacy and tolerability of SSRIs and SNRIs compared to placebo and other active interventions in the prevention of episodic and chronic tension-type headache in adults. For the original review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2003, Issue 4), MEDLINE (1966 to January 2004), EMBASE (1994 to May 2003), and Headache Quarterly (1990 to 2003). For this update, we revised the original search strategy to reflect the broader type of intervention (SSRIs and SNRIs). We searched CENTRAL (2014, Issue 10) on the Cochrane Library, MEDLINE (1946 to November 2014), EMBASE (1980 to November 2014), and PsycINFO (1987 to November 2014). We also checked the reference lists of retrieved articles and searched trial registries for ongoing trials. We included randomised controlled trials comparing SSRIs or SNRIs with any type of control intervention in participants 18 years and older, of either sex, with tension-type headache. Two authors independently extracted data (headache frequency, index, intensity, and duration; use of symptomatic/analgesic medication; quality of life; and withdrawals) and assessed the risk of bias of trials. The primary outcome is tension-type headache frequency, measured by the number of headache attacks or the number of days with headache per evaluation period. The original
Upper gastrointestinal bleeding in a patient with depression receiving selective serotonin reuptake inhibitor therapy.

Science.gov (United States)

Kumar, Deepak; Saaraswat, Tanuj; Sengupta, S N; Mehrotra, Saurabh

2009-02-01

Serotonin plays an important role in the normal clotting phenomenon and is released by platelets. Platelets are dependent on a serotonin transporter for the uptake of serotonin, as they cannot synthesize it themselves. Selective serotonin reuptake inhibitors (SSRIs) block the uptake of serotonin into platelets and can cause problems with clotting leading to bleeding. This case report highlights the occurrence of upper gastrointestinal bleeding in the index case on initiating SSRI therapy for depression and the prompt resolution of the same on its discontinuation on two separate occasions. SSRIs may cause upper gastrointestinal (GI) bleeding. Physicians should be aware of the same and should try to rule out previous episodes of upper GI bleed or the presence of other risk factors which might predispose to it before prescribing SSRIs; they should also warn the patients about this potential side effect. Also, the presence of thalassemia trait in the index patient deserves special attention and needs to be explored to see if it might in any way contribute in potentiating this side effect of SSRIs.
RCRA and CERCLA requirements affecting cleanup activities at a federal facility superfund site

International Nuclear Information System (INIS)

Walsh, T.J.

1994-01-01

The Fernald Environmental Management Project (FEMP) achieved success on an integrated groundwater monitoring program which addressed both RCRA and CERCLA requirements. The integrated plan resulted in a cost savings of approximately $2.6 million. At present, the FEMP is also working on an integrated closure process to address Hazardous Waste Management Units (HWMUs) at the site. To date, Ohio EPA seems willing to discuss an integrated program with some stipulations. If an integrated program is implemented, a cost savings of several million dollars will be realized since the CERCLA documents can be used in place of a RCRA closure plan. The success of an integrated program at the FEMP is impossible without the support of DOE and the regulators. Since DOE is an owner/operator of the facility and Ohio EPA regulates hazardous waste management activities at the FEMP, both parties must be satisfied with the proposed integration activities. Similarly, US EPA retains CERCLA authority over the site along with a signed consent agreement with DOE, which dictates the schedule of the CERCLA activities. Another federal facility used RCRA closure plans to satisfy CERCLA activities. This federal facility was in a different US EPA Region than the FEMP. While this approach was successful for this site, an integrated approach was required at the FEMP because of the signed Consent Agreement and Consent Decree. For federal facilities which have a large number of HWMUs along with OUs, an integrated approach may result in a timely and cost-effective cleanup
Does selective serotonin reuptake inhibitor (SSRI) fluoxetine affects mussel Mytilus galloprovincialis?

International Nuclear Information System (INIS)

Gonzalez-Rey, Maria; Bebianno, Maria João

2013-01-01

Fluoxetine (FLX) the active pharmaceutical ingredient (API) in Prozac ® is a widely prescribed psychoactive drug which ubiquitous occurrence in the aquatic environment is associated to a poor removal rate in waste-water treatment plant (WWTP) systems. This API acts as a selective serotonin reuptake inhibitor (SSRI) frequently reported to cause disrupting effects in non-target species. The objective of this study includes a multibiomarker response evaluation on mussel Mytilus galloprovincialis during two weeks exposure to 75 ng L −1 FLX assessing antioxidant enzymes activities – superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST); lipid peroxidation (LPO), acetylcholinesterase (AChE) neurotoxic response and endocrine disruption through alkali-labile phosphates (ALP) indirect measurement of vitellogenin-like proteins. Results show transient tissue-specific enzymatic responses and damage affecting mostly mussel gills. However, the clear ALP levels inhibition throughout time in both sex-differentiated gonads gives evidence to FLX reinforced action as an endocrine disruptor rather than an oxidative or neurotoxic inducer. - Highlights: ► Short-time exposure of Mytilus galloprovincialis to antidepressant fluoxetine. ► Tissue-specific transient antioxidant enzymes activities alteration. ► Lipid peroxidation (LPO) induction in exposed-tissues. ► Acetylcholinesterase (AChE) activity upregulation in exposed gills. ► ALP levels downregulation in exposed sex-differentiated mussels. - Exposure to 75 ng L −1 antidepressant fluoxetine (FLX) induces tissue-specific multibiomarker responses alteration in mussel Mytilus galloprovincialis.
Can a Selective Serotonin Reuptake Inhibitor Act as a Glutamatergic Modulator?

Directory of Open Access Journals (Sweden)

Marcos Emilio Frizzo, PhD

2017-01-01

Full Text Available Sertraline (Zoloft and fluoxetine (Prozac are selective serotonin reuptake inhibitors whose antidepressant mechanism of action is classically attributed to an elevation of the extracellular levels of serotonin in the synaptic cleft. However, the biological effects of these drugs seem to be more complex than their traditionally described mechanism of action. Among their actions is the inhibition of different types of Na+ and K+ channels, as well as of glutamate uptake activity. The clearance of extracellular glutamate is essential to maintain the central nervous system within physiological conditions, and this excitatory neurotransmitter is removed from the synaptic cleft by astrocyte transporters. This transport depends upon a hyperpolarized membrane potential in astrocytes that is mainly maintained by Kir4.1 K+ channels. The impairment of the Kir4.1 channel activity reduces driving force for the glutamate transporter, resulting in an accumulation of extracellular glutamate. It has been shown that sertraline and fluoxetine inhibit Kir4.1 K+ channels. Recently, we demonstrated that sertraline reduces glutamate uptake in human platelets, which contain a high-affinity Na+-dependent glutamate uptake system, with kinetic and pharmacological properties similar to astrocytes in the central nervous system. Considering these similarities between human platelets and astrocytes, one might ask if sertraline could potentially reduce glutamate clearance in the synaptic cleft and consequently modulate glutamatergic transmission. This possibility merits investigation, since it may provide additional information regarding the mechanism of action and perhaps the side effects of these antidepressants.
Beyond Section 508: The Spectrum of Legal Requirements for Accessible e-Government Web Sites in the United States

Science.gov (United States)

Jaeger, Paul T.

2004-01-01

In the United States, a number of federal laws establish requirements that electronic government (e-government) information and services be accessible to individuals with disabilities. These laws affect e-government Web sites at the federal, state, and local levels. To this point, research about the accessibility of e-government Web sites has…
Acceptance criteria for the physical protection upgrade rule requirements for fixed sites. Information guide

International Nuclear Information System (INIS)

Dwyer, P.

1980-09-01

This document has been developed as a tool to assist in providing consistent evaluation of upgraded physical security plans submitted in response to the Physical Protection Upgrade Rule, effective March 25, 1980. It presents a means for assuring licensee compliance with every regulatory requirement of particular significance to the protection of the public health and safety. Acceptance criteria are included to determine the extent to which each licensee meets the regulatory requirements. The format parallels Regulatory Guide 5.52, Standard Format and Content of a Licensee Physical Protection Plan for Strategic Special Nuclear Material at Fixed Sites
Selective serotonin reuptake inhibitor suppression of HIV infectivity and replication.

Science.gov (United States)

Benton, Tami; Lynch, Kevin; Dubé, Benoit; Gettes, David R; Tustin, Nancy B; Ping Lai, Jian; Metzger, David S; Blume, Joshua; Douglas, Steven D; Evans, Dwight L

2010-11-01

To test the hypothesis that the selective serotonin reuptake inhibitor (SSRI) citalopram would down-regulate human immunodeficiency virus (HIV) infectivity and that the greatest effects would be seen in people with depression. Depression is a risk factor for morbidity and mortality in HIV/acquired immune deficiency syndrome. Serotonin (5-HT) neurotransmission has been implicated in the pathobiology of depression, and pharmacologic therapies for depression target this system. The 5-HT transporter and 5-HT receptors are widely distributed throughout the central nervous and immune systems. Depression has been associated with suppression of natural killer cells and CD8(+) lymphocytes, key regulators of HIV infection. Ex vivo models for acute and chronic HIV infection were used to study the effects of citalopram on HIV viral infection and replication in 48 depressed and nondepressed women. For both the acute and chronic infection models, HIV reverse transcriptase activity was measured in the citalopram treatment condition and the control condition. The SSRI significantly down-regulated the reverse transcriptase response in both the acute and chronic infection models. Specifically, citalopram significantly decreased the acute HIV infectivity of macrophages. Citalopram also significantly decreased HIV viral replication in the latently infected T-cell line and in the latently infected macrophage cell line. There was no difference in down-regulation by depression status. These studies suggest that an SSRI enhances natural killer/CD8 noncytolytic HIV suppression in HIV/acquired immune deficiency syndrome and decreases HIV viral infectivity of macrophages, ex vivo, suggesting the need for in vivo studies to determine a potential role for agents targeting serotonin in the host defense against HIV.
Decision-tree approach to evaluating inactive uranium-processing sites for liner requirements

International Nuclear Information System (INIS)

Relyea, J.F.

1983-03-01

Recently, concern has been expressed about potential toxic effects of both radon emission and release of toxic elements in leachate from inactive uranium mill tailings piles. Remedial action may be required to meet disposal standards set by the states and the US Environmental Protection Agency (EPA). In some cases, a possible disposal option is the exhumation and reburial (either on site or at a new location) of tailings and reliance on engineered barriers to satisfy the objectives established for remedial actions. Liners under disposal pits are the major engineered barrier for preventing contaminant release to ground and surface water. The purpose of this report is to provide a logical sequence of action, in the form of a decision tree, which could be followed to show whether a selected tailings disposal design meets the objectives for subsurface contaminant release without a liner. This information can be used to determine the need and type of liner for sites exhibiting a potential groundwater problem. The decision tree is based on the capability of hydrologic and mass transport models to predict the movement of water and contaminants with time. The types of modeling capabilities and data needed for those models are described, and the steps required to predict water and contaminant movement are discussed. A demonstration of the decision tree procedure is given to aid the reader in evaluating the need for the adequacy of a liner

In vivo imaging of cerebral serotonin transporter and serotonin(2A) receptor binding in 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") and hallucinogen users

DEFF Research Database (Denmark)

Erritzoe, David; Frøkjær, Vibe; Holst, Klaus K

2011-01-01

Both hallucinogens and 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") have direct agonistic effects on postsynaptic serotonin(2A) receptors, the key site for hallucinogenic actions. In addition, MDMA is a potent releaser and reuptake inhibitor of presynaptic serotonin.......Both hallucinogens and 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") have direct agonistic effects on postsynaptic serotonin(2A) receptors, the key site for hallucinogenic actions. In addition, MDMA is a potent releaser and reuptake inhibitor of presynaptic serotonin....
Different distributions of the 5-HT reuptake complex and the postsynaptic 5-HT(2A) receptors in Brodmann areas and brain hemispheres.

Science.gov (United States)

Rosel, Pilar; Arranz, Belén; Urretavizcaya, Mikel; Oros, Miguel; San, Luis; Vallejo, Julio; Navarro, Miguel Angel

2002-08-30

The aim of the present study was to determine the distribution of the presynaptic 5-HT reuptake complex and the 5-HT(2A) receptors through Brodmann areas from two control subjects, together with the possible existence of laterality between both brain hemispheres. A left laterality was observed in the postsynaptic 5-HT(2A) binding sites, with significantly higher B(max) values in the left frontal and cingulate cortex. In frontal cortex, [3H]imipramine and [3H]paroxetine binding showed the highest B(max) values in areas 25, 10 and 11. In cingulate cortex, the highest [3H]imipramine and [3H]paroxetine B(max) values were noted in Brodmann area 33 followed by area 24, while postsynaptic 5-HT(2A) receptors were mainly distributed through Brodmann areas 23 and 29. In temporal cortex, the highest [3H]imipramine and [3H]paroxetine B(max) was noted in Brodmann areas 28 and 34, followed by areas 35 and 38. All Brodmann areas from parietal cortex (1, 2, 3, 4, 5, 6, 7, 39, 40 and 43) showed similar presynaptic and postsynaptic binding values. In occipital cortex no differences were observed with regard to the brain hemisphere or to the Brodmann area (17, 18 and 19). These results suggest the need to carefully define the brain hemisphere and the Brodmann areas studied, as well to avoid comparisons between studies including different Brodmann areas or brain hemispheres.
Shielding requirements on-site loading and acceptance testing on the Leksell gamma knife

International Nuclear Information System (INIS)

Maitz, A.H.; Lunsford, L.D.; Wu, A.; Lindner, G.; Flickinger, J.C.

1990-01-01

On August 14, 1987, the first stereotactic radiosurgical procedure using the gamma knife was performed in North America. Located in a self-contained radiosurgical suite in the basement of Presbyterian-University Hospital in Pittsburgh, Pennsylvania. This device uses 201 highly focused beams 60Co for the single-treatment closed-skull irradiation of brain lesions localized by stereotactic techniques (radiosurgery). One hundred and fifty-two patients with intracranial arteriovenous malformations or brain tumors were treated in the first year of operation. The Presbyterian University Hospital of Pittsburgh gamma knife is the first such unit in which the 60Co sources were loaded on-site. This effort required us to solve some difficult and unusual problems encountered during site preparation, delivery, and loading of the unit in a busy hospital setting. The solutions developed enabled installation and use of the gamma knife with minimal disruption of hospital activities while maintaining acceptable levels of exposure to radiation. Environmental surveys performed during the loading of the 201 radioactive sources (total, 219 TBq) confirmed that on-site loading is possible and practical. Our experience in the design, construction, and implementation of the first North American gamma knife supports the practicality and safety of on-site loading and may be of value in the planning and development of future gamma knife installations
Increased risk of severe congenital heart defects in offspring exposed to selective serotonin-reuptake inhibitors in early pregnancy

DEFF Research Database (Denmark)

Knudsen, Tanja Majbrit; Hansen, Anne Vinkel; Garne, Ester

2014-01-01

BACKGROUND: Previous studies suggest a possible association between maternal use of selective serotonin-reuptake inhibitors (SSRIs) during early pregnancy and congenital heart defects (CHD). The purpose of this study was to verify this association by using validated data from the Danish EUROCAT...... terminated due to congenital anomalies. The study population consisted of all registered pregnancies (n = 72,280) in Funen, Denmark in the period 1995-2008. SSRI-use was assessed using The Danish National Prescription Registry, information on marital status, maternal educational level, income, and country...... of origin from Statistics Denmark was used as indicators of socioeconomic situation, and the CHD were studied in subgroups defined by EUROCAT. Logistic Regression was used to investigate the association between redeemed prescriptions for SSRIs and CHD. RESULTS: The risk of severe CHD in the offspring...
Rapid screening of selective serotonin re-uptake inhibitors in urine samples using solid-phase microextraction gas chromatography-mass spectrometry.

Science.gov (United States)

Salgado-Petinal, Carmen; Lamas, J Pablo; Garcia-Jares, Carmen; Llompart, Maria; Cela, Rafael

2005-07-01

In this paper a solid-phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS) method is proposed for a rapid analysis of some frequently prescribed selective serotonin re-uptake inhibitors (SSRI)-venlafaxine, fluvoxamine, mirtazapine, fluoxetine, citalopram, and sertraline-in urine samples. The SPME-based method enables simultaneous determination of the target SSRI after simple in-situ derivatization of some of the target compounds. Calibration curves in water and in urine were validated and statistically compared. This revealed the absence of matrix effect and, in consequence, the possibility of quantifying SSRI in urine samples by external water calibration. Intra-day and inter-day precision was satisfactory for all the target compounds (relative standard deviation, RSD, detection limits achieved were detected and tentatively identified.
A role for the serotonin reuptake transporter in the brain and intestinal features of autism spectrum disorders and developmental antidepressant exposure.

Science.gov (United States)

Margolis, Kara Gross

2017-10-01

Many disease conditions considered CNS-predominant harbor significant intestinal comorbidities. Serotonin (5-HT) and the serotonin reuptake transporter (SERT) have increasingly been shown to play important roles in both brain and intestinal development and long-term function. 5-HT and SERT may thus modulate critical functions in the development and perpetuation of brain-gut axis disease. We discuss the potential roles of 5-HT and SERT in the brain and intestinal manifestations of autism spectrum disorders and developmental antidepressant exposure. The potential therapeutic value of 5-HT 4 modulation in the subsequent treatment of these conditions is also addressed. Copyright © 2017 Elsevier B.V. All rights reserved.
In Vivo Imaging of Cerebral Serotonin Transporter and Serotonin(2A) Receptor Binding in 3,4-Methylenedioxymethamphetamine (MDMA or "Ecstasy") and Hallucinogen Users

DEFF Research Database (Denmark)

Erritzoe, David; Frokjaer, Vibe G.; Holst, Klaus K.

2011-01-01

Context: Both hallucinogens and 3,4-methylenedioxy-methamphetamine( MDMA or "ecstasy") have direct agonistic effects on postsynaptic serotonin(2A) receptors, the key site for hallucinogenic actions. In addition, MDMA is a potent releaser and reuptake inhibitor of presynaptic serotonin.Objective: ......Context: Both hallucinogens and 3,4-methylenedioxy-methamphetamine( MDMA or "ecstasy") have direct agonistic effects on postsynaptic serotonin(2A) receptors, the key site for hallucinogenic actions. In addition, MDMA is a potent releaser and reuptake inhibitor of presynaptic serotonin...
Contribution of Helicobacter pylori infection to the risk of peptic ulcer bleeding in patients on nonsteroidal anti-inflammatory drugs, antiplatelet agents, anticoagulants, corticosteroids and selective serotonin reuptake inhibitors.

Science.gov (United States)

Venerito, M; Schneider, C; Costanzo, R; Breja, R; Röhl, F-W; Malfertheiner, P

2018-06-01

Nonsteroidal anti-inflammatory drugs, low-dose aspirin, non-aspirin antiplatelet agents, anticoagulants, selective serotonin reuptake inhibitors and corticosteroids increase the risk of gastroduodenal bleeding. To determine in a retrospective cohort study the contribution of Helicobacter pylori infection to the risk of peptic ulcer bleeding in patients taking these drugs. Among patients with peptic ulcer disease diagnosed by endoscopy from 01/2004 to 12/2014 (N = 1719, 60% males, age 65.8 ± 14.5), 56.9% had peptic ulcer bleeding (cases) and 43.1% uncomplicated peptic ulcer disease (controls). Demographics, intake of nonsteroidal anti-inflammatory drugs, aspirin, non-aspirin antiplatelet agents, anticoagulants, selective serotonin reuptake inhibitors, proton pump inhibitors and corticosteroids were documented. H. pylori status was determined by histology, rapid urease test or serology. Adjusted odds ratios (OR) were estimated by logistic regression analysis. Helicobacter pylori infection increased the risk of peptic ulcer bleeding in nonsteroidal anti-inflammatory drug and aspirin users (OR = 2.91, 95% CI = 1.71-4.98 and OR = 2.23, 95% CI = 1.52-3.28, respectively), but not in patients on anticoagulants, selective serotonin reuptake inhibitor or corticosteroid therapy. H. pylori-positive status substantially increased the risk of peptic ulcer bleeding in patients on non-aspirin antiplatelet agents (OR = 4.37, 95% CI = 1.28-14.99), concomitant aspirin/nonsteroidal anti-inflammatory drug intake (OR = 5.85, 95% CI = 1.68-20.36) and combined antiplatelet therapy (OR = 8.43, 95% CI = 1.09-65.17). After further adjustment for proton pump inhibitor intake, H. pylori infection was still a risk factor for peptic ulcer bleeding in nonsteroidal anti-inflammatory drug and aspirin users. Helicobacter pylori infection increases the risk of peptic ulcer bleeding in peptic ulcer disease patients on nonsteroidal anti-inflammatory drugs, aspirin and non
Selective serotonin reuptake inhibitors and gastrointestinal bleeding: a case-control study.

Directory of Open Access Journals (Sweden)

Alfonso Carvajal

Full Text Available BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs have been associated with upper gastrointestinal (GI bleeding. Given their worldwide use, even small risks account for a large number of cases. This study has been conducted with carefully collected information to further investigate the relationship between SSRIs and upper GI bleeding. METHODS: We conducted a case-control study in hospitals in Spain and in Italy. Cases were patients aged ≥18 years with a primary diagnosis of acute upper GI bleeding diagnosed by endoscopy; three controls were matched by sex, age, date of admission (within 3 months and hospital among patients who were admitted for elective surgery for non-painful disorders. Exposures to SSRIs, other antidepressants and other drugs were defined as any use of these drugs in the 7 days before the day on which upper gastrointestinal bleeding started (index day. RESULTS: 581 cases of upper GI bleeding and 1358 controls were considered eligible for the study; no differences in age or sex distribution were observed between cases and controls after matching. Overall, 4.0% of the cases and 3.3% of controls used an SSRI antidepressant in the week before the index day. No significant risk of upper GI bleeding was encountered for SSRI antidepressants (adjusted odds ratio, 1.06, 95% CI, 0.57-1.96 or for whichever other grouping of antidepressants. CONCLUSIONS: The results of this case-control study showed no significant increase in upper GI bleeding with SSRIs and provide good evidence that the magnitude of any increase in risk is not greater than 2.
Social inequalities in suicide: the role of selective serotonin reuptake inhibitors.

Science.gov (United States)

Clouston, Sean A P; Rubin, Marcie S; Colen, Cynthia G; Link, Bruce G

2014-10-01

We aimed to examine the relationship between socioeconomic status (SES) and suicide associated with the introduction and diffusion of selective serotonin reuptake inhibitors (SSRIs). Negative binomial regression was used to estimate county-level suicide rates among persons aged 25 years or older using death certificate data collated by the National Center for Health Statistics from 1968 to 2009; SES was measured using the decennial US Census. The National Health and Nutrition Examination Survey and the Medical Expenditure Panel Survey were used to measure SSRI use. Once SSRIs became available in 1988, a 1% increase in SSRI usage was associated with a 0.5% lower suicide rate. Prior to the introduction of SSRIs, SES was not related to suicide. However, with each 1% increase in SSRI use, a 1-standard deviation (SD) higher SES was associated with a 0.6% lower suicide rate. In 2009, persons living in counties with SES 1 SD above the national average were 13.6% less likely to commit suicide than those living in counties with SES 1 SD below the national average--a difference of 1.9/100,000 adults aged ≥25 years. Higher SSRI use was associated with lower suicide rates among US residents aged ≥25 years; however, SES inequalities modified the association between SSRI use and suicide. © The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
The second sodium site in the dopamine transporter controls cation permeability and is regulated by chloride

DEFF Research Database (Denmark)

Borre, Lars; Andreassen, Thorvald F; Shi, Lei

2014-01-01

The dopamine transporter (DAT) belongs to the family of neurotransmitter:sodium symporters (NSSs) and controls dopamine (DA) homeostasis by mediating Na(+)- and Cl(-)-dependent reuptake of DA. Here we used two-electrode voltage clamp measurements in Xenopus oocytes together with targeted mutagene......The dopamine transporter (DAT) belongs to the family of neurotransmitter:sodium symporters (NSSs) and controls dopamine (DA) homeostasis by mediating Na(+)- and Cl(-)-dependent reuptake of DA. Here we used two-electrode voltage clamp measurements in Xenopus oocytes together with targeted...
15 CFR 714.1 - Annual declaration requirements for plant sites that produce a Schedule 3 chemical in excess of...

Science.gov (United States)

2010-01-01

... plant sites that produce a Schedule 3 chemical in excess of 30 metric tons. 714.1 Section 714.1 Commerce... SCHEDULE 3 CHEMICALS § 714.1 Annual declaration requirements for plant sites that produce a Schedule 3... in the production of a chemical in any units within the same plant through chemical reaction...
Site specific information in site selection

International Nuclear Information System (INIS)

Aeikaes, T.; Hautojaervi, A.

1998-01-01

The programme for the siting of a deep repository for final disposal of spent nuclear fuel was started already in 1983 and is carried out today by Posiva Oy which continues the work started by Teollisuuden Voima Oy. The programme aims at site selection by the end of the year 2000. The programme has progressed in successive interim stages with defined goals. After an early phase for site identification, five sites were selected in 1987 for preliminary site characterisation. Three of these were selected and judged to be best suited for the more detailed characterisation in 1992. An additional new site was included into the programme based on a separate feasibility study in the beginning of 1997. Since the year 1983 several safety assessments together with technical plans of the facility have been completed. When approaching the site selection the needs for more detailed consideration of the site specific properties in the safety assessment have been increased. The Finnish regulator STUK has published a proposal for general safety requirements for the final disposal of spent nuclear fuel in Finland. This set of requirements has been projected to be used in conjunction of the decision making by the end 2000. Based on the site evaluation all sites can provide a stable environment and there is evidence that the requirements for the longevity of the canister can be fulfilled at each site. In this manner the four candidate sites do not differ too much from each other. The main difference between the sites is in the salinity of the deep groundwater. The significance of differences in the salinity for the long-term safety cannot be defined yet. The differences may contribute to the discussion of the longevity of the bentonite buffer and also to the modelling of the groundwater flow and transport. The use of the geosphere as a transport barrier is basically culminated on the questions about sparse but fast flow routes and 'how bad channeling can be'. To answer these questions
Action of selective serotonin reuptake inhibitor on aggressive behavior in adult rat submitted to the neonatal malnutrition

Directory of Open Access Journals (Sweden)

Medeiros Jairza Maria Barreto

2001-01-01

Full Text Available The effect of the malnutrition during suckling on the aggressiveness was investigated in adult rats treated or not with citalopram, a selective serotonin reuptake inhibitor (SSRI. The animals were divided into two groups according to the diet used: nourished group-- the rats received the control diet with 23% protein during the life; and malnourished group-- the rats had its mothers submitted to diet with 7.8% protein during suckling. At 120 days of age, each group was sub-divided according to the treatment: acute -- consisting a single i.p. injection of saline solution or 20-mg/Kg citalopram; chronic -- consisting the single injections (1 per day during 14 days of saline or 20 mg/Kg citalopram. The acute or chronic treatment with SSRI reduces aggressive response in nourished rats, but not in malnourished ones. Thus, the malnutrition during the critical period of brain development seems to induce durable alterations in the function of the serotoninergic neurotransmission
In vitro anti-Candida activity of selective serotonin reuptake inhibitors against fluconazole-resistant strains and their activity against biofilm-forming isolates.

Science.gov (United States)

Costa Silva, Rose Anny; da Silva, Cecília Rocha; de Andrade Neto, João Batista; da Silva, Anderson Ramos; Campos, Rosana Sousa; Sampaio, Letícia Serpa; do Nascimento, Francisca Bruna Stefany Aires; da Silva Gaspar, Brenda; da Cruz Fonseca, Said Gonçalves; Josino, Maria Aparecida Alexandre; Grangeiro, Thalles Barbosa; Gaspar, Danielle Macedo; de Lucena, David Freitas; de Moraes, Manoel Odorico; Cavalcanti, Bruno Coêlho; Nobre Júnior, Hélio Vitoriano

2017-06-01

Recent research has shown broad antifungal activity of the classic antidepressants selective serotonin reuptake inhibitors (SSRIs). This fact, combined with the increased cross-resistance frequency of the genre Candida regarding the main treatment today, fluconazole, requires the development of novel therapeutic strategies. In that context, this study aimed to assess the antifungal potential of fluoxetine, sertraline, and paroxetine against fluconazole-resistant Candida spp. planktonic cells, as well as to assess the mechanism of action and the viability of biofilms treated with fluoxetine. After 24 h, the fluconazole-resistant Candida spp. strains showed minimum inhibitory concentration (MIC) in the ranges of 20-160 μg/mL for fluoxetine, 10-20 μg/mL for sertraline, and 10-100.8 μg/mL for paroxetine by the broth microdilution method (M27-A3). According to our data by flow cytometry, each of the SSRIs cause fungal death after damaging the plasma and mitochondrial membrane, which activates apoptotic signaling pathways and leads to dose-dependant cell viability loss. Regarding biofilm-forming isolates, the fluoxetine reduce mature biofilm of all the species tested. Therefore, it is concluded that SSRIs are capable of inhibit the growth in vitro of Candida spp., both in planktonic form, as biofilm, inducing cellular death by apoptosis. Copyright © 2017 Elsevier Ltd. All rights reserved.
Impact of prestroke selective serotonin reuptake inhibitor treatment on stroke severity and mortality.

Science.gov (United States)

Mortensen, Janne Kaergaard; Larsson, Heidi; Johnsen, Søren Paaske; Andersen, Grethe

2014-07-01

Selective serotonin reuptake inhibitors (SSRIs) have been associated with an increased risk of bleeding but also a possible neuroprotective effect in stroke. We aimed to examine the implications of prestroke SSRI use in hemorrhagic and ischemic stroke. We conducted a registry-based propensity score-matched follow-up study among first-ever patients with hemorrhage and ischemic stroke in Denmark (2003-2012). Multiple conditional logistic regression was used to compute adjusted odds ratios of severe stroke and death within 30 days. Among 1252 hemorrhagic strokes (626 prestroke SSRI users and 626 propensity score-matched nonusers), prestroke SSRI use was associated with an increased risk of the strokes being severe (adjusted propensity score-matched odds ratios, 1.41; confidence interval, 1.08-1.84) and an increased risk of death within 30 days (adjusted propensity score-matched odds ratios, 1.60; confidence interval, 1.17-2.18). Among 8956 patients with ischemic stroke (4478 prestroke SSRI users and 4478 propensity score-matched nonusers), prestroke SSRI use was not associated with the risk of severe stroke or death within 30 days. Prestroke SSRI use is associated with increased stroke severity and mortality in patients with hemorrhagic stroke. Although prestroke depression in itself may increase stroke severity and mortality, this was not found in SSRI users with ischemic stroke. © 2014 American Heart Association, Inc.
Cellular correlates of enhanced anxiety caused by acute treatment with the selective serotonin reuptake inhibitor fluoxetine in rats

Directory of Open Access Journals (Sweden)

Shilpa eRavinder

2011-12-01

Full Text Available Selective serotonin reuptake inhibitors (SSRIs are used extensively in the treatment of depression and anxiety disorders. The therapeutic benefits of SSRIs typically require several weeks of continuous treatment. Intriguingly, according to clinical reports, symptoms of anxiety may actually increase during the early stages of treatment although more prolonged treatment alleviates affective symptoms. Consistent with earlier studies that have used animal models to capture this paradoxical effect of SSRIs, we find that rats exhibit enhanced anxiety-like behavior on the elevated plus-maze one hour after a single injection of the SSRI fluoxetine. Next we investigated the potential neural substrates underlying the acute anxiogenic effects by analyzing the morphological and physiological impact of acute fluoxetine treatment on principal neurons of the basolateral amygdala (BLA, a brain area that plays a pivotal role in fear and anxiety. Although earlier studies have shown that behavioral or genetic perturbations that are anxiogenic for rodents also increase dendritic spine-density in the BLA, we find that a single injection of fluoxetine does not cause spinogenesis on proximal apical dendritic segments on BLA principal neurons an hour later. However, at the same time point when a single dose of fluoxetine caused enhanced anxiety, it also enhanced action potential firing in BLA neurons in ex vivo slices. Consistent with this finding, in vitro bath application of fluoxetine caused higher spiking frequency and this increase in excitability was correlated with an increase in the input resistance of these neurons. Our results suggest that enhanced excitability of amygdala neurons may contribute to the increase in anxiety-like behavior observed following acute fluoxetine treatment.
Habitat requirements and burrowing depths of rodents in relation to shallow waste burial sites

Energy Technology Data Exchange (ETDEWEB)

Gano, K.A.; States, J.B.

1982-05-01

The purpose of this paper is to provide a review of the literature and summarize information on factors affecting habitat selection and maximum recorded burrowing depths for representative small mammals that we consider most likely to inhibit waste burial sites in arid and semi-arid regions of the West. The information is intended for waste management designers who need to know what to expect from small mammals that may be present at a particular site. Waste repositories oculd be designed to exclude the deep burrowing rodents of a region by creating an unattractive habitat over the waste. Summaries are given for habitat requirements of each group along with generalized modifications that could be employed to deter habitation. Representatives from the major groups considered to be deep burrowers are discussed. Further, detailed information about a particular species can be obtained from the references cited.
Habitat requirements and burrowing depths of rodents in relation to shallow waste burial sites

International Nuclear Information System (INIS)

Gano, K.A.; States, J.B.

1982-05-01

The purpose of this paper is to provide a review of the literature and summarize information on factors affecting habitat selection and maximum recorded burrowing depths for representative small mammals that we consider most likely to inhibit waste burial sites in arid and semi-arid regions of the West. The information is intended for waste management designers who need to know what to expect from small mammals that may be present at a particular site. Waste repositories oculd be designed to exclude the deep burrowing rodents of a region by creating an unattractive habitat over the waste. Summaries are given for habitat requirements of each group along with generalized modifications that could be employed to deter habitation. Representatives from the major groups considered to be deep burrowers are discussed. Further, detailed information about a particular species can be obtained from the references cited
On-site and off-site activities

International Nuclear Information System (INIS)

Martin, H.D.

1986-01-01

Design principles for NPP training programs. Effects of NPP contracts. Effects of domestic industrial activities. The role of international bodies. Requirements for on-site training. Training abroad, technical, financial and social aspects. Training center on-site, an evaluation. (orig.)

What requirements does the KBS-3 repository make on the host rock? Geoscientific suitability indicators and criteria for siting and site evaluation

International Nuclear Information System (INIS)

Andersson, Johan; Stroem, Anders; Svemar, Christer; Almen, Karl-Erik; Ericsson, Lars O.

2000-04-01

This report gives an account of what requirements are made on the rock, what conditions in the rock are advantageous and how the fulfilment of requirements and preferences is to be judged prior to the selection of sites for a site investigation and during a site investigation. The conclusions and results of the report are based on the knowledge and experience acquired by SKB over many years of research and development. The results, and particularly the stipulated criteria, apply to a repository for spent fuel of the KBS-3 type, i.e. a repository where the fuel is contained in copper canisters embedded in bentonite clay at a depth of 400 - 700 m in the Swedish crystalline basement. The report analyzes how the rock's different geological conditions, mechanical, thermal, hydrogeological, chemical and transport properties influence the functions of the deep repository, and whether it is possible to determine requirements and preferences regarding the influence of these properties. Where possible, these requirements or preferences have then been translated into requirements or preferences regarding the individual properties. Criteria are formulated that are based on the quantities that can be measured or estimated at the relevant stage of the investigation. The following requirements are made on the rock: The rock in the repository's deposition zone may not have any ore potential. Regional plastic shear zones shall be avoided if it cannot be demonstrated that the properties of the zone do not deviate from those of the rest of the rock. There may, however, be so-called 'tectonic lenses' near regional plastic shear zones where the bedrock is homogeneous and relatively unaffected. Deposition tunnels and deposition holes for canisters may not pass through or be positioned too close to major regional and major local fracture zones. Deposition holes may not intersect identified local minor fracture zones. The rock's strength, fracture geometry and initial stresses may not be
Off-Site Prefabrication: What Does it Require from the Trade Contractor?

DEFF Research Database (Denmark)

Bekdik, Baris; Hall, Daniel; Aslesen, Sigmund

2016-01-01

The purpose of the paper is to show what is required to industrialize a building process from the standpoint of the trade contractor. Rationalization of building processes has, over the years, caught the attention of numerous IGLC papers. Although significant contributions have been made to further...... understand and improve existing construction processes, relatively few contributions have focused on the opportunities for industrialization from the trade contractor’s perspective. This paper uses an in-depth case study to address the deployment strategy for off-site fabrication techniques and processes...... at only one case study, the conclusions are limited in generalizability to other prefabrication operations. However, it represents an important in-depth case from the trade contractors’ perspective and will contribute to the growing body of research focused on industrialization and prefabrication in lean...
New safety standards of nuclear power station with no requirements of site evaluation. No public dose limit published with possible inappropriateness of reactor site

International Nuclear Information System (INIS)

Takitani, Koichi

2013-01-01

Nuclear Regulation Authority was preparing new safety standards in order to aim at starting safety reviews of existing nuclear power station in July 2013. This article commented on issues of major accident, which was defined as severely damaged core event. Accumulated dose at the site boundary of the Fukushima Daiichi Nuclear Power Station totaled to about 234 mSv on March just after the accident with rare gas of 500 PBq, iodine 131 of 500 PBq, cesium 134 of 10 PBq and cesium 137 of 10 PBq released to the atmosphere, which was beyond 100 mSv. As measures for preventing containment vessel failure after core severely damaged, filtered venting system was required to be installed for low radiological risk to the public. However filter was not effective to rare gas. Accumulated doses at the site boundary of several nuclear power stations after filtered venting with 100% release of rare gas could be estimated to be 2-37 Sv mostly depending on the site condition, which might be surely greater than 100 mSv. Omitting site evaluation for major accident, which was beyond design basis accident, was great concern. (T. Tanaka)
[Selective serotonin reuptake inhibitors in the therapy of various types of endogenous depressions].

Science.gov (United States)

Panteleeva, G P; Abramova, L I; Korenev, A N

2000-01-01

In order to specify differential indications for the use of selective serotonin reuptake inhibitors (SSRI) their therapeutic effect was investigated in apathic-adynamic, melancholic and anxious depressions. Group of 151 patients received monotherapy with one of SSRI-drugs: citalopram--22 patients (mean daily dosage--27.4 mg), paroxetine--47 patients (23 mg), sertraline--19 patients (107 mg), fluvoxamine--28 patients (162 mg), fluoxetine--35 patients (20 mg). The state of the patients was estimated 5 times during 42 days of therapy by clinical estimations and according to Hamilton Depression Scale (HAM-D). Therapeutic effects of the drugs were determined according to the degree of reduction of the total HAM-D scores and they were considered as "significant" (a reduction of the scores by 50% and more), "moderate" (by 21-49%), and "insignificant" (by 1-20%). Positive antidepressive effect, including "significant" was obtained in the case of the use of all the drugs studied. Differential evaluation of the three components of antidepressive activity (thymoleptic, sedative-anxiolytic, and stimulative) according to the degrees and data of expression of drugs' therapeutic effect has allowed to determine indications for the therapy of endogenous depressions by each of SSRI: to recommend cytalopram for the treatment of various types of depressive states mainly, for anxious and apatho-adynamic types; paroxetin--for treatment of melancholic depressions as well as for anxious and apatho-dynamic ones; sertralin++--for depression with anxiety and fobic disorders; fluvoxamine--for melancholic and anxious depression; fluoxetine--for apatho-adynamic depressions.
Anhedonia in depressed patients on treatment with selective serotonin reuptake inhibitor anti-depressant--A two-centered study in Malaysia.

Science.gov (United States)

Yee, Anne; Chin, Soo Cheng; Hashim, Aili Hanim bt; Harbajan Singh, Manveen Kaur A P; Loh, Huai Seng; Sulaiman, Ahmad Hatim; Ng, Chong Guan

2015-01-01

Anhedonia is the reduced ability to experience pleasure. It is a core symptom of depression and is particularly difficult to treat. This study aims to compare the level of anhedonia between depressed patients on anti-depressants and healthy subjects. A total of 111 depressed patients on selective serotonin reuptake inhibitor (SSRI) and 82 healthy subjects were recruited from the outpatient psychiatric services at two major general hospitals in a cross-sectional study. Subjects were assessed using the Mini International Neuropsychiatric Interview 5.0.0 or MINI, Beck's Depression Index (BDI), and Snaith-Hamilton Pleasure Scale (SHAPS). Relevant personal and sociodemographic information were also collected. There was a significant association between educational level and SHAPS-M scores (P depressed subjects treated with anti-depressant compared with the healthy subjects, after adjusting the confounding factors, BDI score, and educational level. Anhedonia often persists in depressed patients despite on SSRI anti-depressant treatment.
Blockade of the high-affinity noradrenaline transporter (NET) by the selective 5-HT reuptake inhibitor escitalopram: an in vivo microdialysis study in mice

Science.gov (United States)

Nguyen, Hai T; Guiard, Bruno P; Bacq, Alexandre; David, Denis J; David, Indira; Quesseveur, Gaël; Gautron, Sophie; Sanchez, Connie; Gardier, Alain M

2013-01-01

BACKGROUND AND PURPOSE Escitalopram, the S(+)-enantiomer of citalopram is the most selective 5-HT reuptake inhibitor approved. Although all 5-HT selective reuptake inhibitors (SSRIs) increase extracellular levels of 5-HT ([5-HT]ext). some also enhance, to a lesser extent, extracellular levels of noradrenaline ([NA]ext). However, the mechanisms by which SSRIs activate noradrenergic transmission in the brain remain to be determined. EXPERIMENTAL APPROACH This study examined the effects of escitalopram, on both [5-HT]ext and [NA]ext in the frontal cortex (FCx) of freely moving wild-type (WT) and mutant mice lacking the 5-HT transporter (SERT−/−) by using intracerebral microdialysis. We explored the possibilities that escitalopram enhances [NA]ext, either by a direct mechanism involving the inhibition of the low- or high-affinity noradrenaline transporters, or by an indirect mechanism promoted by [5-HT]ext elevation. The forced swim test (FST) was used to investigate whether enhancing cortical [5-HT]ext and/or [NA]ext affected the antidepressant-like activity of escitalopram. KEY RESULTS In WT mice, a single systemic administration of escitalopram produced a significant increase in cortical [5-HT]ext and [NA]ext. As expected, escitalopram failed to increase cortical [5-HT]ext in SERT−/− mice, whereas its neurochemical effects on [NA]ext persisted in these mutants. In WT mice subjected to the FST, escitalopram increased swimming parameters without affecting climbing behaviour. Finally, escitalopram, at relevant concentrations, failed to inhibit cortical noradrenaline and 5-HT uptake mediated by low-affinity monoamine transporters. CONCLUSIONS AND IMPLICATIONS These experiments suggest that escitalopram enhances, although moderately, cortical [NA]extin vivo by a direct mechanism involving the inhibition of the high-affinity noradrenaline transporter (NET). PMID:22233336
Plasma cytokine profiles in depressed patients who fail to respond to selective serotonin reuptake inhibitor therapy.

LENUS (Irish Health Repository)

O'Brien, Sinead M

2012-02-03

OBJECTIVE: Approximately 30% of patients with depression fail to respond to a selective serotonin reuptake inhibitor (SSRI). Few studies have attempted to define these patients from a biological perspective. Studies suggest that overall patients with depression show increased production of proinflammatory cytokines. We examined pro- and anti-inflammatory cytokine levels in patients who were SSRI resistant. METHODS: Plasma concentrations of IL-6, IL-8, IL-10, TNF-alpha and sIL-6R were measured with enzyme linked immunosorbent assays (ELISA) in DSM-1V major depressives who were SSRI resistant, in formerly SSRI resistant patients currently euthymic and in healthy controls. RESULTS: Patients with SSRI-resistant depression had significantly higher production of the pro-inflammatory cytokines IL-6 (p=0.01) and TNF-alpha (p=0.004) compared to normal controls. Euthymic patients who were formerly SSRI resistant had proinflammatory cytokine levels which were similar to the healthy subject group. Anti-inflammatory cytokine levels did not differ across the 3 groups. CONCLUSION: Suppression of proinflammatory cytokines does not occur in depressed patients who fail to respond to SSRIs and is necessary for clinical recovery.
Hanford Site Development Plan

International Nuclear Information System (INIS)

Hathaway, H.B.; Daly, K.S.; Rinne, C.A.; Seiler, S.W.

1993-05-01

The Hanford Site Development Plan (HSDP) provides an overview of land use, infrastructure, and facility requirements to support US Department of Energy (DOE) programs at the Hanford Site. The HSDP's primary purpose is to inform senior managers and interested parties of development activities and issues that require a commitment of resources to support the Hanford Site. The HSDP provides an existing and future land use plan for the Hanford Site. The HSDP is updated annually in accordance with DOE Order 4320.1B, Site Development Planning, to reflect the mission and overall site development process. Further details about Hanford Site development are defined in individual area development plans
Radiological characteristics and radiation protection requirements in the remediation of uranium mining and milling sites in Hungary

International Nuclear Information System (INIS)

Juhasz, L.; Szerbin, P.; Lendvai, Z.; Csoevari, M.; Benkovics, I.; Varhegyi, A.

2002-01-01

After more than 35 years of operation the uranium mining and milling facilities located near the city of Pecs in the south of Hungary were finally shut down by the end of 1997. Appropriate strategies and complex plans have been prepared for the implementation of remedial action. The main principle involved in the planning of site restoration work is the application of a step-by-step approach, taking into account local conditions in the given area to the maximum extent possible. As every site considered for restoration has its own particular specifications, different solutions are, in effect, needed for each individual mining and milling site. Due to the lack of approved national regulations, a written authorisation must be obtained in relation to specific issues affecting remedial action. The radiological requirements affecting both the reuse and restoration of affected areas call for the establishment of radiation limits. (orig.)
The SWAMI inspection robot: Fernald site requirements

International Nuclear Information System (INIS)

Hazen, F.B.

1993-01-01

The purpose of this document is to introduce and describe the Stored Waste Autonomous Mobile Inspector (SWAMI) robot project and to identify issues that will need to be addressed prior to its field demonstration at Fernald in mid-1995. SWAMI is a mobile robotic vehicle that will perform mandated weekly inspections of waste containers. Fernald has a large inventory of these containers and a need to protect workers from radiation hazards while enhancing the efficiency and effectiveness of the inspections. Fernald's role in this project is to supply the demonstration site and make all necessary preparations. This includes identification of the test areas and plans, and identification and compliance to Federal, State, DOE, and Site regulations on system safety and quality. In addition, Fernald will link SWAMI output images to off-line mass data storage, and also to an on-line ORACLE database. The authors shall initiate a dialog with State and Federal regulators towards the near term goal of acceptance of the SWAMI test plan and a longer term goal of acceptance of SWAMI as a supplement and improvement to present mandated RCRA inspections
Siting guidelines and their role in repository site selection

International Nuclear Information System (INIS)

Hanlon, C.L.

1985-01-01

The first requirement of the Nuclear Waste Policy Act was for the Secretary of Energy to issue general guidelines for siting repositories. The guidelines were to specify detailed geologic considerations that would be the primary criteria for the selection of sites in various host rocks, as well as factors that would qualify or disqualify any site from development as a repository. These guidelines were clearly intended to provide not only the framework for the siting program but also the stimulus for establishing effective communication and consultation among the parties involved in the program. The Act further required that the guidelines be a factor in the development of all future decision documents of the Office of Civilian Radioactive Waste Management, including the environmental assessments that would accompany the nomination of sites for characterization, the site-characterization plans that are to be prepared before the sinking of exploratory shafts at any candidate site, and the environmental impact statement that is to support the recommendation of a site for development as a repository. More than two years after its passage, the intention of the Act for the guidelines has been realized. Concurred in by the Nuclear Regulatory Commission on June 22, 1984, and issued by the Department in November 1984, the guidelines include postclosure technical guidelines that apply to conditions governing the long-term performance of the repository system; preclosure technical guidelines that apply to conditions governing the siting, construction, operation, and closure of the repository; and system guidelines whose objective is to ensure that the regulatory requirements of the Environmental Protection Agency and the Nuclear Regulatory Commission are met
Site selection handbook: Workshop on site selection for low-level radioactive waste disposal facilities

International Nuclear Information System (INIS)

1987-10-01

The Low-Level Radioactive Waste Policy Amendments Act of 1985 (LLRWPAA) requires the Department of Energy (DOE) to provide technical assistance to ''...those compact regions, host States and nonmember States determined by the Secretary to require assistance.'' Technical assistance has been defined to include, but not be limited to, ''technical guidelines for site selection.'' This site selection workshop was developed to assist States and Compacts in developing new low-level radioactive waste (LLW) disposal sites in accordance with the requirements of the LLRWPAA. The workshop comprises a series of lectures, discussion topics, and exercises, supported by this Site Selection Workshop Handbook, designed to examine various aspects of a comprehensive site selection program. It is not an exhaustive treatment of all aspects of site selection, nor is it prescriptive. The workshop focuses on the major elements of site selection and the tools that can be used to implement the site selection program
Serotonin and noradrenaline reuptake inhibitors (SNRIs) for fibromyalgia.

Science.gov (United States)

Welsch, Patrick; Üçeyler, Nurcan; Klose, Petra; Walitt, Brian; Häuser, Winfried

2018-02-28

Fibromyalgia is a clinically defined chronic condition of unknown etiology characterized by chronic widespread pain that often co-exists with sleep disturbances, cognitive dysfunction and fatigue. People with fibromyalgia often report high disability levels and poor quality of life. Drug therapy, for example, with serotonin and noradrenaline reuptake inhibitors (SNRIs), focuses on reducing key symptoms and improving quality of life. This review updates and extends the 2013 version of this systematic review. To assess the efficacy, tolerability and safety of serotonin and noradrenaline reuptake inhibitors (SNRIs) compared with placebo or other active drug(s) in the treatment of fibromyalgia in adults. For this update we searched CENTRAL, MEDLINE, Embase, the US National Institutes of Health and the World Health Organization (WHO) International Clinical Trials Registry Platform for published and ongoing trials and examined the reference lists of reviewed articles, to 8 August 2017. We selected randomized, controlled trials of any formulation of SNRIs against placebo or any other active treatment of fibromyalgia in adults. Three review authors independently extracted data, examined study quality, and assessed risk of bias. For efficacy, we calculated the number needed to treat for an additional beneficial outcome (NNTB) for pain relief of 50% or greater and of 30% or greater, patient's global impression to be much or very much improved, dropout rates due to lack of efficacy, and the standardized mean differences (SMD) for fatigue, sleep problems, health-related quality of life, mean pain intensity, depression, anxiety, disability, sexual function, cognitive disturbances and tenderness. For tolerability we calculated number needed to treat for an additional harmful outcome (NNTH) for withdrawals due to adverse events and for nausea, insomnia and somnolence as specific adverse events. For safety we calculated NNTH for serious adverse events. We undertook meta
Selective serotonin reuptake inhibitors and the risk of hepatocellular carcinoma in hepatitis B virus-infected patients

Directory of Open Access Journals (Sweden)

Chang CM

2017-11-01

Full Text Available Chia-Ming Chang,1–3 Ming-Shun Hsieh,1–4 Tsung-Chieh Yang,3,5 Vivian Chia-Rong Hsieh,6 Jen-Huai Chiang,7 Hsien-Hao Huang,1,3 Chorng-Kuang How,1,3 Sung-Yuan Hu,8 David Hung-Tsang Yen1,3 1Department of Emergency Medicine, Taipei Veterans General Hospital, 2Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, 3College of Medicine, National Yang-Ming University, Taipei, 4Department of Emergency Medicine, 5Division of Gastroenterology, Department of Internal Medicine, Taipei Veterans General Hospital, Taoyuan Branch, Taoyuan, 6Department of Health Services Administration, 7Management Office for Health Data, China Medical University, 8Department of Emergency Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China Background: This study aimed to investigate the association between the use of selective serotonin reuptake inhibitors (SSRIs and the risk of hepatocellular carcinoma (HCC in patients with chronic hepatitis B virus (HBV infection.Methods: We conducted a population-based cohort study by using claims data from the Taiwan National Health Insurance Research Database (NHIRD. The study cohort comprised 1380 newly diagnosed HBV-infected patients with SSRI use who were frequency matched by age, sex, liver cirrhosis, and index year with HBV-infected patients without SSRI use in the comparison cohort. Each patient case was followed from 2000 to 2012 to identify incident HCC cases. Cox proportional hazards regression was performed to evaluate the association between SSRI use and HCC risk. The further sensitivity analysis used case-control study design. A total of 9070 HCC subjects retrieved from NHIRD, and equal non-HCC subjects were analyzed after matching for age and sex.Results: We identified 9 and 24 HCC cases in the study and comparison cohorts during the follow-up period of 7056 and 6845 person-years, respectively. The incidence rate of HCC was 1.28 and 3
Site characterization criteria (DOE-STD-1022-94) for natural phenomena hazards at DOE sites

International Nuclear Information System (INIS)

Chen, J.C.; Ueng, T.S.; Boissonnade, A.C.

1995-12-01

This paper briefly summarizes requirements of site characterization for Natural Phenomena Hazards (NPH) at DOE sites. In order to comply with DOE Order 5480.28, site characterization criteria has been developed to provide site-specific information needed for development of NPH assessment criteria. Appropriate approaches are outlined to ensure that the current state-of-the-art methodologies and procedures are used in the site characterization. General and detailed site characterization requirements are provided in the areas of meteorology, hydrology, geology, seismology and geotechnical studies
Effect of proton pump inhibitors on the serum concentrations of the selective serotonin reuptake inhibitors citalopram, escitalopram, and sertraline.

Science.gov (United States)

Gjestad, Caroline; Westin, Andreas A; Skogvoll, Eirik; Spigset, Olav

2015-02-01

The selective serotonin reuptake inhibitors (SSRIs) citalopram, escitalopram, and sertraline are all metabolized by the cytochrome P-450 isoenzyme CYP2C19, which is inhibited by the proton pump inhibitors (PPIs) omeprazole, esomeprazole, lansoprazole, and pantoprazole. The aim of the present study was to evaluate the effect of these PPIs on the serum concentrations of citalopram, escitalopram, and sertraline. Serum concentrations from patients treated with citalopram, escitalopram, or sertraline were obtained from a routine therapeutic drug monitoring database, and samples from subjects concomitantly using PPIs were identified. Dose-adjusted SSRI serum concentrations were calculated to compare data from those treated and those not treated with PPIs. Citalopram concentrations were significantly higher in patients treated with omeprazole (+35.3%; P Escitalopram concentrations were significantly higher in patients treated with omeprazole (+93.9%; P escitalopram is affected to a greater extent than are citalopram and sertraline. When omeprazole or esomeprazole are used in combination with escitalopram, a 50% dose reduction of the latter should be considered.
Regulatory requirements for groundwater monitoring networks at hazardous waste sites

International Nuclear Information System (INIS)

Keller, J.F.

1989-10-01

In the absence of an explicit national mandate to protect groundwater quality, operators of active and inactive hazardous waste sites must use a number of statutes and regulations as guidance for detecting, correcting, and preventing groundwater contamination. The objective of this paper is to provide a framework of the technical and regulatory considerations that are important to the development of groundwater monitoring programs at hazardous waste sites. The technical site-specific needs and regulatory considerations, including existing groundwater standards and classifications, will be presented. 14 refs., 2 tabs
The six most widely used selective serotonin reuptake inhibitors decrease androgens and increase estrogens in the H295R cell line

DEFF Research Database (Denmark)

Hansen, Cecilie Hurup; Larsen, Lizette Weber; Sørensen, Amalie Møller

2017-01-01

Selective serotonin reuptake inhibitors (SSRIs) used as first line of treatment in major depressive disorder (MDD) are known to exert negative effects on the endocrine system and fertility. The aim of the present study was to investigate the possible endocrine disrupting effect of six SSRIs...... in the pathway. Furthermore, all SSRIs relatively increased the estrogen/androgen ratio, indicating stimulating effects on the aromatase. Our study demonstrates the potential of SSRIs to interfere with steroid production in the H295R cells around Cmax levels and indicates that these drugs should be investigated...... validated LC-MS/MS method. All 6 SSRIs were found to exert endocrine disrupting effects on steroid hormone synthesis at concentrations just around Cmax. Although the mechanisms of disruption were all different, they all resulted in decreased testosterone levels, some due to effects on CYP17, some earlier...
Site characterization requirements for nuclear-cratering design

International Nuclear Information System (INIS)

Terhune, R.W.; Carlson, R.C.

1977-01-01

A material properties measurement program for the design of large engineering nuclear-excavation projects by computer calculation is presented. Material properties of the site and their relative effect on crater size are analyzed and ordered in relation to their importance in determining the overall cratering efficiency. The measurement program includes both in situ logging and laboratory measurement of core samples, together with the reason for each measurement and its use in the calculations
Fluoxetine: a case history of its discovery and preclinical development

OpenAIRE

Perez-Caballero, Laura; Torres-Sanchez, Sonia; Bravo, Lidia; Mico, Juan A.; Berrocoso, Esther

2014-01-01

Introduction: Depression is a multifactorial mood disorder with a high prevalence worldwide. Until now, treatments for depression have focused on the inhibition of monoaminergic reuptake sites, which augment the bioavailability of monoamines in the CNS. Advances in drug discovery have widened the therapeutic options with the synthesis of so-called selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine. Areas covered: The aim of this case history is to describe and discuss the ...

Selective serotonin reuptake inhibitors and venlafaxine in pregnancy: Changes in drug disposition.

Directory of Open Access Journals (Sweden)

Andreas Austgulen Westin

Full Text Available Pregnancy may cause changes in drug disposition. The clinical consequences may be profound and even counterintuitive; in some cases pregnant women may need more than twice their usual drug dose in order to maintain therapeutic drug levels. For antidepressants, evidence on drug disposition in pregnancy is scarce. The aim of this study was to determine the effects of pregnancy on serum levels of selective serotonin reuptake inhibitors (SSRIs and venlafaxine in a large and naturalistic patient material, in order to provide tentative dose recommendations for pregnant women.Using patient data from two routine therapeutic drug monitoring (TDM services in Norway with linkage to the national birth registry, dose-adjusted serum drug concentrations of SSRIs and venlafaxine during pregnancy were compared to the women's own baseline (non-pregnant values, using a linear mixed model.Overall, the TDM databases contained 196,726 serum concentration measurements from 54,393 women. After data linkage and drug selection (SSRIs or venlafaxine only, we identified 367 analyses obtained from a total of 290 pregnancies in 281 women, and 420 baseline observations from the same women. Serum concentrations in the third trimester were significantly lower than baseline for paroxetine (-51%; 95% confidence interval [CI], -66%, -30%; p<0.001, fluvoxamine (-56%; CI, -75%, -23%; p = 0.004 and citalopram (-24%; CI, -38%, -7%; p = 0,007, and higher than baseline for sertraline (+68%; CI, +37%, +106%; p<0.001. For escitalopram, fluoxetine and venlafaxine concentrations did not change significantly.For paroxetine and fluvoxamine the pronounced decline in maternal drug serum concentrations in pregnancy may necessitate a dose increase of about 100% during the third trimester in order to maintain stable concentrations. For fluoxetine, venlafaxine, citalopram, escitalopram and sertraline, the present study indicates that dose adjustments are generally not necessary during pregnancy.
Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and Trial Sequential Analysis

DEFF Research Database (Denmark)

Jakobsen, Janus Christian; Katakam, Kiran Kumar; Schou, Anne

2017-01-01

-term effects. Conclusions: SSRIs might have statistically significant effects on depressive symptoms, but all trials were at high risk of bias and the clinical significance seems questionable. SSRIs significantly increase the risk of both serious and non-serious adverse events. The potential small beneficial......Background: The evidence on selective serotonin reuptake inhibitors (SSRIs) for major depressive disorder is unclear. Methods: Our objective was to conduct a systematic review assessing the effects of SSRIs versus placebo, 'active' placebo, or no intervention in adult participants with major...... depressive disorder. We searched for eligible randomised clinical trials in The Cochrane Library's CENTRAL, PubMed, EMBASE, PsycLIT, PsycINFO, Science Citation Index Expanded, clinical trial registers of Europe and USA, websites of pharmaceutical companies, the U.S. Food and Drug Administration (FDA...
Hanford Site Development Plan

International Nuclear Information System (INIS)

Hathaway, H.B.; Daly, K.S.; Rinne, C.A.; Seiler, S.W.

1992-05-01

The Hanford Site Development Plan (HSDP) provides an overview of land use, infrastructure, and facility requirements to support US Department of Energy (DOE) programs at the Hanford Site. The HSDP's primary purpose is to inform senior managers and interested parties of development activities and issues that require a commitment of resources to support the Hanford Site. The HSDP provides a land use plan for the Hanford Site and presents a picture of what is currently known and anticipated in accordance with DOE Order 4320.1B. Site Development Planning. The HSDP wig be updated annually as future decisions further shape the mission and overall site development process. Further details about Hanford Site development are defined in individual area development plans
Facility siting as a decision process at the Savannah River Site

International Nuclear Information System (INIS)

Wike, L.D.

1995-01-01

Site selection for new facilities at Savannah River Site (SRS) historically has been a process dependent only upon specific requirements of the facility. While this approach is normally well suited to engineering and operational concerns, it can have serious deficiencies in the modern era of regulatory oversight and compliance requirements. There are many issues related to the site selection for a facility that are not directly related to engineering or operational requirements; such environmental concerns can cause large schedule delays and budget impact,s thereby slowing or stopping the progress of a project. Some of the many concerns in locating a facility include: waste site avoidance, National Environmental Policy Act requirements, Clean Water Act, Clean Air Act, wetlands conservation, US Army Corps of Engineers considerations, US Fish and Wildlife Service statutes including threatened and endangered species issues, and State of South Carolina regulations, especially those of the Department of Health and Environmental Control. In addition, there are SRS restrictions on research areas set aside for National Environmental Research Park (NERP), Savannah River Ecology Laboratory, Savannah River Forest Station, University of South Carolina Institute of Archaeology and Anthropology, Southeastern Forest Experimental Station, and Savannah River Technology Center (SRTC) programs. As with facility operational needs, all of these siting considerations do not have equal importance. The purpose of this document is to review recent site selection exercises conducted for a variety of proposed facilities, develop the logic and basis for the methods employed, and standardize the process and terminology for future site selection efforts
Recruitment of Mcm10 to Sites of Replication Initiation Requires Direct Binding to the Minichromosome Maintenance (MCM) Complex*

Science.gov (United States)

Douglas, Max E.

2016-01-01

Mcm10 is required for the initiation of eukaryotic DNA replication and contributes in some unknown way to the activation of the Cdc45-MCM-GINS (CMG) helicase. How Mcm10 is localized to sites of replication initiation is unclear, as current models indicate that direct binding to minichromosome maintenance (MCM) plays a role, but the details and functional importance of this interaction have not been determined. Here, we show that purified Mcm10 can bind both DNA-bound double hexamers and soluble single hexamers of MCM. The binding of Mcm10 to MCM requires the Mcm10 C terminus. Moreover, the binding site for Mcm10 on MCM includes the Mcm2 and Mcm6 subunits and overlaps that for the loading factor Cdt1. Whether Mcm10 recruitment to replication origins depends on CMG helicase assembly has been unclear. We show that Mcm10 recruitment occurs via two modes: low affinity recruitment in the absence of CMG assembly (“G1-like”) and high affinity recruitment when CMG assembly takes place (“S-phase-like”). Mcm10 that cannot bind directly to MCM is defective in both modes of recruitment and is unable to support DNA replication. These findings indicate that Mcm10 is localized to replication initiation sites by directly binding MCM through the Mcm10 C terminus. PMID:26719337
Recruitment of Mcm10 to Sites of Replication Initiation Requires Direct Binding to the Minichromosome Maintenance (MCM) Complex.

Science.gov (United States)

Douglas, Max E; Diffley, John F X

2016-03-11

Mcm10 is required for the initiation of eukaryotic DNA replication and contributes in some unknown way to the activation of the Cdc45-MCM-GINS (CMG) helicase. How Mcm10 is localized to sites of replication initiation is unclear, as current models indicate that direct binding to minichromosome maintenance (MCM) plays a role, but the details and functional importance of this interaction have not been determined. Here, we show that purified Mcm10 can bind both DNA-bound double hexamers and soluble single hexamers of MCM. The binding of Mcm10 to MCM requires the Mcm10 C terminus. Moreover, the binding site for Mcm10 on MCM includes the Mcm2 and Mcm6 subunits and overlaps that for the loading factor Cdt1. Whether Mcm10 recruitment to replication origins depends on CMG helicase assembly has been unclear. We show that Mcm10 recruitment occurs via two modes: low affinity recruitment in the absence of CMG assembly ("G1-like") and high affinity recruitment when CMG assembly takes place ("S-phase-like"). Mcm10 that cannot bind directly to MCM is defective in both modes of recruitment and is unable to support DNA replication. These findings indicate that Mcm10 is localized to replication initiation sites by directly binding MCM through the Mcm10 C terminus. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
Dimerization site 2 of the bacterial DNA-binding protein H-NS is required for gene silencing and stiffened nucleoprotein filament formation.

Science.gov (United States)

Yamanaka, Yuki; Winardhi, Ricksen S; Yamauchi, Erika; Nishiyama, So-Ichiro; Sowa, Yoshiyuki; Yan, Jie; Kawagishi, Ikuro; Ishihama, Akira; Yamamoto, Kaneyoshi

2018-06-15

The bacterial nucleoid-associated protein H-NS is a DNA-binding protein, playing a major role in gene regulation. To regulate transcription, H-NS silences genes, including horizontally acquired foreign genes. Escherichia coli H-NS is 137 residues long and consists of two discrete and independent structural domains: an N-terminal oligomerization domain and a C-terminal DNA-binding domain, joined by a flexible linker. The N-terminal oligomerization domain is composed of two dimerization sites, dimerization sites 1 and 2, which are both required for H-NS oligomerization, but the exact role of dimerization site 2 in gene silencing is unclear. To this end, we constructed a whole set of single amino acid substitution variants spanning residues 2 to 137. Using a well-characterized H-NS target, the slp promoter of the glutamic acid-dependent acid resistance (GAD) cluster promoters, we screened for any variants defective in gene silencing. Focusing on the function of dimerization site 2, we analyzed four variants, I70C/I70A and L75C/L75A, which all could actively bind DNA but are defective in gene silencing. Atomic force microscopy analysis of DNA-H-NS complexes revealed that all of these four variants formed condensed complexes on DNA, whereas WT H-NS formed rigid and extended nucleoprotein filaments, a conformation required for gene silencing. Single-molecule stretching experiments confirmed that the four variants had lost the ability to form stiffened filaments. We conclude that dimerization site 2 of H-NS plays a key role in the formation of rigid H-NS nucleoprotein filament structures required for gene silencing. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.
Pharmacokinetics and tolerability of DA-8031, a novel selective serotonin reuptake inhibitor for premature ejaculation in healthy male subjects

Directory of Open Access Journals (Sweden)

Shin D

2017-03-01

Full Text Available Dongseong Shin,1 SeungHwan Lee,2 Sojeong Yi,2 Seo Hyun Yoon,2 Joo-Youn Cho,2 Mi Young Bahng,3 In-Jin Jang,2 Kyung-Sang Yu2 1Clinical Trials Center, Gachon University Gil Medical Center, Incheon, 2Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 3Department of Product Development, Dong-A ST, Seoul, Korea Objective: DA-8031 is a selective serotonin reuptake inhibitor under development for the treatment of premature ejaculation. This is the first-in-human study aimed at evaluating the pharmacokinetics and tolerability of DA-8031 and its metabolites (M1, M2, M4, and M5 in the plasma and urine after administration of a single oral dose in healthy male subjects.Methods: A dose block-randomized, double-blind, placebo-controlled, single ascending dose study was conducted. Subjects received either placebo or a single dose of DA-8031 at 5, 10, 20, 40, 60, 80, or 120 mg. DA-8031 and its four metabolites were analyzed in the plasma and urine for pharmacokinetic evaluation. The effect of genetic polymorphisms of cytochrome-P450 (CYP enzymes on the pharmacokinetics of DA-8031 was evaluated.Results: After a single dose, plasma DA-8031 reached the maximum concentration at a median of 2–3 h and was eliminated with terminal elimination half-life of 17.9–28.7 h. The mean renal clearance was 3.7–5.6 L/h. Dose-proportional pharmacokinetics was observed over the dose range of 20–80 mg. Among the metabolites, M4 had the greatest plasma concentration, followed by M5 and M1. Subjects with CYP2D6 intermediate metabolizer had significantly greater dose-normalized Cmax and AUC0–t of DA-8031 as well as smaller metabolic ratios than those subjects with CYP2D6 extensive metabolizer. The most common adverse events were nausea, dizziness, and headache, and no serious adverse events were reported.Conclusion: In conclusion, the systemic exposure of DA-8031 was increased proportionally to the dose within 20
Comparison of paroxetine and dapoxetine, a novel selective serotonin reuptake inhibitor in the treatment of premature ejaculation

Directory of Open Access Journals (Sweden)

Abdulmuttalip Simsek

2014-10-01

Full Text Available Dapoxetine hydrochloride is a selective serotonin reuptake inhibitor and the first drug approved for the on-demand treatment of premature ejaculation (PE. Our objective in this study was to characterize the efficacy of on-demand dapoxetine (30 and 60 mg and daily paroxetine (20 mg usage in treating PE. We conducted a 1 month study involving a total of 150 patients. Patients were divided into three groups of 50. Group 1 were treated with on-demand dapoxetine (30 mg, Group 2 with on-demand dapoxetine (60 mg and Group 3 with daily paroxetine (20 mg. Our outcome measurement was increased from baseline intravaginal ejaculatory latency time (IELT after treatment. The IELT increased from baseline to posttreatment by 117%, 117% and 170% in the paroxetine group (P 0.05, while the 60 mg dapoxetine group had a larger posttreatment IELT increase compared with the 30 mg dapoxetine (P < 0.05 and paroxetine (P < 0.01 groups. Dapoxetine (60 mg 1-3 h before planned intercourse is a very effective treatment modality for PE. However, an on-demand dose of 30 mg dapoxetine is no more effective than the currently prescribed paroxetine treatment.
Development of transportation operations requirements

International Nuclear Information System (INIS)

Grady, S.T.; Best, R.E.; Danese, F.L.; Peterson, R.W.; Pope, R.B.

1990-01-01

Transport conditions at various utility sties vary dramatically in terms of characteristics at and near the site, requirements, administrative procedures, and other factors. Continuation of design efforts for the OCRWM transportation operations system requires that the operating requirements for the transportation system -- quantity of fuel per unit time per site -- be identified so that the effect the variations have on the system can be accommodated. The approach outlined in this paper provides for an identification of specific sites, evaluation of shipment capabilities at each site, and integration of the sites into multi-site shipping campaigns to scope the logistics management problem for the transportation operations system. 1 fig., 1 tab
Transcriptional activation of transforming growth factor alpha by estradiol: requirement for both a GC-rich site and an estrogen response element half-site.

Science.gov (United States)

Vyhlidal, C; Samudio, I; Kladde, M P; Safe, S

2000-06-01

17beta-Estradiol (E2) induces transforming growth factor alpha (TGFalpha) gene expression in MCF-7 cells and previous studies have identified a 53 bp (-252 to -200) sequence containing two imperfect estrogen responsive elements (EREs) that contribute to E2 responsiveness. Deletion analysis of the TGFalpha gene promoter in this study identified a second upstream region of the promoter (-623 to -549) that is also E2 responsive. This sequence contains three GC-rich sites and an imperfect ERE half-site, and the specific cis-elements and trans-acting factors were determined by promoter analysis in transient transfection experiments, gel mobility shift assays and in vitro DNA footprinting. The results are consistent with an estrogen receptor alpha (ERalpha)/Sp1 complex interacting with an Sp1(N)(30) ERE half-site ((1/2)) motif in which both ERalpha and Sp1 bind promoter DNA. The ER/Sp1-DNA complex is formed using nuclear extracts from MCF-7 cells but not with recombinant human ERalpha or Sp1 proteins, suggesting that other nuclear factor(s) are required for complex stabilization. The E2-responsive Sp1(N)(x)ERE(1/2) motif identified in the TGFalpha gene promoter has also been characterized in the cathepsin D and heat shock protein 27 gene promoters; however, in the latter two promoters the numbers of intervening nucleotides are 23 and 10 respectively.
Reduction of intraspecific aggression in adult rats by neonatal treatment with a selective serotonin reuptake inhibitor

Directory of Open Access Journals (Sweden)

Manhães de Castro R.

2001-01-01

Full Text Available Most studies suggest that serotonin exerts an inhibitory control on the aggression process. According to experimental evidence, this amine also influences growth and development of the nervous tissue including serotoninergic neurons. Thus, the possibility exists that increased serotonin availability in young animals facilitates a long-lasting effect on aggressive responses. The present study aimed to investigate the aggressive behavior of adult rats (90-120 days treated from the 1st to the 19th postnatal day with citalopram (CIT, a selective serotonin reuptake inhibitor (20 mg/kg, sc, every 3 days. Aggressive behavior was induced by placing a pair of rats (matched by weight in a box (20 x 20 x 20 cm, and submitting them to a 20-min session of electric footshocks (five 1.6-mA - 2-s current pulses, separated by a 4-min intershock interval. When compared to the control group (rats treated for the same period with equivalent volumes of saline solution, the CIT group presented a 41.4% reduction in the duration of aggressive response. The results indicate that the repeated administration of CIT early in life reduces the aggressive behavior in adulthood and suggest that the increased brain serotoninergic activity could play a role in this effect.
Transportation System Requirements Document

International Nuclear Information System (INIS)

1993-09-01

This Transportation System Requirements Document (Trans-SRD) describes the functions to be performed by and the technical requirements for the Transportation System to transport spent nuclear fuel (SNF) and high-level radioactive waste (HLW) from Purchaser and Producer sites to a Civilian Radioactive Waste Management System (CRWMS) site, and between CRWMS sites. The purpose of this document is to define the system-level requirements for Transportation consistent with the CRWMS Requirement Document (CRD). These requirements include design and operations requirements to the extent they impact on the development of the physical segments of Transportation. The document also presents an overall description of Transportation, its functions, its segments, and the requirements allocated to the segments and the system-level interfaces with Transportation. The interface identification and description are published in the CRWMS Interface Specification
Requirements and criteria for choosing sites suitable for the construction of nuclear installations and power stations

International Nuclear Information System (INIS)

1978-05-01

The present document explains the selection criteria for areas in Italy suitable for the installation of nuclear power stations to be included in the 'National Site Map' provided for in Section 23 of Act No 393 of 2 August 1975. It represents the results of a thorough investigation into the various aspects of the problem of siting nuclear power stations, at the present stage of technology, taking into account the effect of the installations on the environment and the effect of the environment on the installations. The essential aim is to demonstrate that the requirements derived from these analyses, and on which there was full consultation with the other controlling bodies of European countries (in particular, France, Great Britain and West Germany) ensure the optimum choice of areas from the point of view of safety and public health. (author)
The effects of prolonged administration of norepinephrine reuptake inhibitors on long-term potentiation in dentate gyrus, and on tests of spatial and object recognition memory in rats.

Science.gov (United States)

Walling, Susan G; Milway, J Stephen; Ingram, Matthew; Lau, Catherine; Morrison, Gillian; Martin, Gerard M

2016-02-01

Phasic norepinephrine (NE) release events are involved in arousal, novelty detection and in plasticity processes underlying learning and memory in mammalian systems. Although the effects of phasic NE release events on plasticity and memory are prevalently documented, it is less understood what effects chronic NE reuptake inhibition and sustained increases in noradrenergic tone, might have on plasticity and cognitive processes in rodent models of learning and memory. This study investigates the effects of chronic NE reuptake inhibition on hippocampal plasticity and memory in rats. Rats were administered NE reuptake inhibitors (NRIs) desipramine (DMI; 0, 3, or 7.5mg/kg/day) or nortriptyline (NTP; 0, 10 or 20mg/kg/day) in drinking water. Long-term potentiation (LTP; 200 Hz) of the perforant path-dentate gyrus evoked potential was examined in urethane anesthetized rats after 30-32 days of DMI treatment. Short- (4-h) and long-term (24-h) spatial memory was tested in separate rats administered 0 or 7.5mg/kg/day DMI (25-30 days) using a two-trial spatial memory test. Additionally, the effects of chronically administered DMI and NTP were tested in rats using a two-trial, Object Recognition Test (ORT) at 2- and 24-h after 45 and 60 days of drug administration. Rats administered 3 or 7.5mg/kg/day DMI had attenuated LTP of the EPSP slope but not the population spike at the perforant path-dentate gyrus synapse. Short- and long-term memory for objects is differentially disrupted in rats after prolonged administration of DMI and NTP. Rats that were administered 7.5mg/kg/day DMI showed decreased memory for a two-trial spatial task when tested at 4-h. In the novel ORT, rats receiving 0 or 7.5mg/kg/day DMI showed a preference for the arm containing a Novel object when tested at both 2- and 24-h demonstrating both short- and long-term memory retention of the Familiar object. Rats that received either dose of NTP or 3mg/kg/day DMI showed impaired memory at 2-h, however this
The Contribution of Environmental Siting and Permitting Requirements to the Cost of Energy for Wave Energy Devices

Energy Technology Data Exchange (ETDEWEB)

Copping, Andrea E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Geerlofs, Simon H. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hanna, Luke A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

2014-06-01

Responsible deployment of marine and hydrokinetic (MHK) devices in estuaries, coastal areas, and major rivers requires that biological resources and ecosystems be protected through siting and permitting (consenting) processes. Scoping appropriate deployment locations, collecting pre-installation (baseline) and post-installation data all add to the cost of developing MHK projects, and hence to the cost of energy. Under the direction of the U.S. Department of Energy, Pacific Northwest National Laboratory scientists have developed logic models that describe studies and processes for environmental siting and permitting. Each study and environmental permitting process has been assigned a cost derived from existing and proposed tidal, wave, and riverine MHK projects. Costs have been developed at the pilot scale and for commercial arrays for a surge wave energy converter
The use of LeuT as a model in elucidating binding sites for substrates and inhibitors in neurotransmitter transporters

DEFF Research Database (Denmark)

Løland, Claus Juul

2015-01-01

Background: The mammalian neurotransmitter transporters are complex proteins playing a central role in synaptic transmission between neurons by rapid reuptake of neurotransmitters. The proteins which transport dopamine, noradrenaline and serotonin belong to the Neurotransmitter:Sodium Symporters...... (NSS). Due to their important role, dysfunctions are associated with several psychiatric and neurological diseases and they also serve as targets for a wide range of therapeutic and illicit drugs. Despite the central physiological and pharmacological importance, direct evidence on structure......–function relationships on mammalian NSS proteins has so far been unsuccessful. The crystal structure of the bacterial NSS protein, LeuT, has been a turning point in structural investigations. Scope of review: To provide an update on what is known about the binding sites for substrates and inhibitors in the Leu...
Normal Bone Microstructure and Density But Worse Physical Function in Older Women Treated with Selective Serotonin Reuptake Inhibitors, a Cross-Sectional Population-Based Study.

Science.gov (United States)

Larsson, Berit; Mellström, Dan; Johansson, Lisa; Nilsson, Anna G; Lorentzon, Mattias; Sundh, Daniel

2018-05-05

Depression in the elderly is today often treated with selective serotonin reuptake inhibitors (SSRIs) because of their favorable adverse effect profile. However, treatment with SSRIs is associated with increased risk of fractures. Whether this increased risk depends on reduced bone strength or increased fall risk due to reduced physical function is not certain. The aim was therefore to investigate if treatment with SSRIs is associated with impaired bone microstructure, bone density, or physical function in older women. From an ongoing population-based study, 1057 women (77.7 ± 1.5 years) were included. Validated questionnaires were used to assess information regarding medical history, medications, smoking, mental and physical health, and physical activity. Physical function was measured using clinically used tests: timed up and go, walking speed, grip strength, chair stand test, and one leg standing. Bone mineral density (BMD) was measured at the hip and spine with dual-energy X-ray absorptiometry (Hologic Discovery A). Bone geometry and microstructure were measured at the ultradistal and distal (14%) site of radius and tibia using high-resolution peripheral quantitative computed tomography (HR-pQCT; XtremeCT). Treatment with SSRIs was associated with higher BMD at the femoral neck, total hip, and lumbar spine, whereas no associations were found for any HR-pQCT-derived measurements. The use of SSRIs was associated with lower grip strength, walking speed, and fewer chair stand rises. These associations were valid also after adjustments for known risk factors for falls. Treatment with SSRIs was, independently of covariates, associated with worse physical function without any signs of inferior bone geometry and microstructure.
Site environmental report summary

International Nuclear Information System (INIS)

1992-01-01

In this summary of the Fernald 1992 Site Environmental Report the authors will describe the impact of the Fernald site on man and the environment and provide results from the ongoing Environmental Monitoring Program. Also included is a summary of the data obtained from sampling conducted to determine if the site complies with DOE, US Environmental Protection Agency (USEPA), and Ohio EPA (OEPA) requirements. These requirements are set to protect both man and the environment
Caveolin-1-mediated apolipoprotein A-I membrane binding sites are not required for cholesterol efflux.

Directory of Open Access Journals (Sweden)

Soazig Le Lay

Full Text Available Caveolin-1 (Cav1, a structural protein required for the formation of invaginated membrane domains known as caveolae, has been implicated in cholesterol trafficking and homeostasis. Here we investigated the contribution of Cav1 to apolipoprotein A-I (apoA-I cell surface binding and intracellular processing using mouse embryonic fibroblasts (MEFs derived from wild type (WT or Cav1-deficient (Cav1(-/- animals. We found that cells expressing Cav1 have 2.6-fold more apoA-I binding sites than Cav1(-/- cells although these additional binding sites are not associated with detergent-free lipid rafts. Further, Cav1-mediated binding targets apoA-I for internalization and degradation and these processes are not correlated to cholesterol efflux. Despite lower apoA-I binding, cholesterol efflux from Cav1(-/- MEFs is 1.7-fold higher than from WT MEFs. Stimulation of ABCA1 expression with an LXR agonist enhances cholesterol efflux from both WT and Cav1(-/- cells without increasing apoA-I surface binding or affecting apoA-I processing. Our results indicate that there are at least two independent lipid binding sites for apoA-I; Cav1-mediated apoA-I surface binding and uptake is not linked to cholesterol efflux, indicating that membrane domains other than caveolae regulate ABCA1-mediated cholesterol efflux.

What requirements does the KBS-3 repository make on the host rock? Geoscientific suitability indicators and criteria for siting and site evaluation

Energy Technology Data Exchange (ETDEWEB)

Andersson, Johan [Golder Grundteknik AB (Sweden); Stroem, Anders; Svemar, Christer [Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden); Almen, Karl-Erik [KEA Geo-Konsult AB, Naessjoe (Sweden); Ericsson, Lars O. [Chalmers University of Technology, Goeteborg (Sweden)

2000-04-01

This report gives an account of what requirements are made on the rock, what conditions in the rock are advantageous and how the fulfilment of requirements and preferences is to be judged prior to the selection of sites for a site investigation and during a site investigation. The conclusions and results of the report are based on the knowledge and experience acquired by SKB over many years of research and development. The results, and particularly the stipulated criteria, apply to a repository for spent fuel of the KBS-3 type, i.e. a repository where the fuel is contained in copper canisters embedded in bentonite clay at a depth of 400 - 700 m in the Swedish crystalline basement. The report analyzes how the rock's different geological conditions, mechanical, thermal, hydrogeological, chemical and transport properties influence the functions of the deep repository, and whether it is possible to determine requirements and preferences regarding the influence of these properties. Where possible, these requirements or preferences have then been translated into requirements or preferences regarding the individual properties. Criteria are formulated that are based on the quantities that can be measured or estimated at the relevant stage of the investigation. The following requirements are made on the rock: The rock in the repository's deposition zone may not have any ore potential. Regional plastic shear zones shall be avoided if it cannot be demonstrated that the properties of the zone do not deviate from those of the rest of the rock. There may, however, be so-called 'tectonic lenses' near regional plastic shear zones where the bedrock is homogeneous and relatively unaffected. Deposition tunnels and deposition holes for canisters may not pass through or be positioned too close to major regional and major local fracture zones. Deposition holes may not intersect identified local minor fracture zones. The rock's strength, fracture geometry and
The influence of μ-opioid and noradrenaline reuptake inhibition in the modulation of pain responsive neurones in the central amygdala by tapentadol in rats with neuropathy

Science.gov (United States)

Gonçalves, Leonor; Friend, Lauren V.; Dickenson, Anthony H.

2015-01-01

Treatments for neuropathic pain are either not fully effective or have problematic side effects. Combinations of drugs are often used. Tapentadol is a newer molecule that produces analgesia in various pain models through two inhibitory mechanisms, namely central μ-opioid receptor (MOR) agonism and noradrenaline reuptake inhibition. These two components interact synergistically, resulting in levels of analgesia similar to opioid analgesics such as oxycodone and morphine, but with more tolerable side effects. The right central nucleus of the amygdala (CeA) is critical for the lateral spinal ascending pain pathway, regulates descending pain pathways and is key in the emotional-affective components of pain. Few studies have investigated the pharmacology of limbic brain areas in pain models. Here we determined the actions of systemic tapentadol on right CeA neurones of animals with neuropathy and which component of tapentadol contributes to its effect. Neuronal responses to multimodal peripheral stimulation of animals with spinal nerve ligation or sham surgery were recorded before and after two doses of tapentadol. After the higher dose of tapentadol either naloxone or yohimbine were administered. Systemic tapentadol resulted in dose-dependent decrease in right CeA neuronal activity only in neuropathy. Both naloxone and yohimbine reversed this effect to an extent that was modality selective. The interactions of the components of tapentadol are not limited to the synergy between the MOR and α2-adrenoceptors seen at spinal levels, but are seen at this supraspinal site where suppression of responses may relate to the ability of the drug to alter affective components of pain. PMID:25576174
Site characterization criteria (DOE-STD-1022-94) for natural phenomena hazards at DOE sites. Revision 1

International Nuclear Information System (INIS)

Chen, J.C.; Ueng, Tzou-Shin; Boissonnade, A.C.

1995-01-01

This paper briefly summarizes requirements of site characterization for Natural Phenomena Hazards (NPH) at DOE sites. In order to comply with DOE Order 5480.28, site characterization criteria has been developed to provide site-specific information needed for development of NPH assessment criteria. Appropriate approaches are outlined to ensure that the current state-of-the-art methodologies and procedures are used in the site characterization. General and detailed site characterization requirements are provided in the areas of meteorology, hydrology, geology, seismology and geotechnical studies
Site decommissioning management plan

International Nuclear Information System (INIS)

Fauver, D.N.; Austin, J.H.; Johnson, T.C.; Weber, M.F.; Cardile, F.P.; Martin, D.E.; Caniano, R.J.; Kinneman, J.D.

1993-10-01

The Nuclear Regulatory Commission (NRC) staff has identified 48 sites contaminated with radioactive material that require special attention to ensure timely decommissioning. While none of these sites represent an immediate threat to public health and safety they have contamination that exceeds existing NRC criteria for unrestricted use. All of these sites require some degree of remediation, and several involve regulatory issues that must be addressed by the Commission before they can be released for unrestricted use and the applicable licenses terminated. This report contains the NRC staff's strategy for addressing the technical, legal, and policy issues affecting the timely decommissioning of the 48 sites and describes the status of decommissioning activities at the sites
Site decommissioning management plan

Energy Technology Data Exchange (ETDEWEB)

Fauver, D.N.; Austin, J.H.; Johnson, T.C.; Weber, M.F.; Cardile, F.P.; Martin, D.E.; Caniano, R.J.; Kinneman, J.D.

1993-10-01

The Nuclear Regulatory Commission (NRC) staff has identified 48 sites contaminated with radioactive material that require special attention to ensure timely decommissioning. While none of these sites represent an immediate threat to public health and safety they have contamination that exceeds existing NRC criteria for unrestricted use. All of these sites require some degree of remediation, and several involve regulatory issues that must be addressed by the Commission before they can be released for unrestricted use and the applicable licenses terminated. This report contains the NRC staff`s strategy for addressing the technical, legal, and policy issues affecting the timely decommissioning of the 48 sites and describes the status of decommissioning activities at the sites.
Geoscientific evaluation factors and criteria for siting and site evaluation. Progress report

International Nuclear Information System (INIS)

Stroem, A.; Ericsson, Lars O.; Svemar, C.; Almen, K.E.; Andersson, Johan

1999-03-01

The purposes of the present report are to: present the work that has been done to identify the parameters that need to be determined in a geoscientific site investigation and that serve as the basis for the work with geoscientific evaluation factors; give a progress report from the project that was initiated in 1997 named Siting Factors and Criteria for Site Evaluation, with an emphasis on definitions, outline and structure for the execution of the work; present geoscientific requirements on function both general and in detail in the form of an example for the discipline rock mechanics; present geoscientific evaluation factors associated with different stages in the siting work in the form of an example for the discipline hydrogeochemical composition; present plans for further work as regards criteria for site evaluation in different siting stages. The project is under way, and this is to be regarded as a progress report since e.g. criteria for site evaluation will be presented at a later date. The long-term performance and safety of the deep repository must always be evaluated by means of an integrated safety assessment. The work with factors and criteria can never take the place of such an assessment, but can provide guidance regarding its outcome. Requirements and preferences regarding the function of the rock in the deep repository have been clarified in this progress report. What is new here is the structuring that has been carried out, with a classification into different geoscientific disciplines, and the formalism that has been given to the terms requirement, preference and function. Based on fundamental safety and construction functions, requirements on function have been specified for the disciplines geology, thermal properties, hydro-geology, rock mechanics, chemistry and transport properties. Furthermore, function analyses have been identified by means of which it is possible to concretize requirements on function and which geoscientific parameters are
Geoscientific evaluation factors and criteria for siting and site evaluation. Progress report

Energy Technology Data Exchange (ETDEWEB)

Stroem, A.; Ericsson, Lars O.; Svemar, C. [Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden); Almen, K.E. [KEA GEO-konsult AB (Sweden); Andersson, Johan [Golder Grundteknik KB (Sweden)

1999-03-01

The purposes of the present report are to: present the work that has been done to identify the parameters that need to be determined in a geoscientific site investigation and that serve as the basis for the work with geoscientific evaluation factors; give a progress report from the project that was initiated in 1997 named Siting Factors and Criteria for Site Evaluation, with an emphasis on definitions, outline and structure for the execution of the work; present geoscientific requirements on function both general and in detail in the form of an example for the discipline rock mechanics; present geoscientific evaluation factors associated with different stages in the siting work in the form of an example for the discipline hydrogeochemical composition; present plans for further work as regards criteria for site evaluation in different siting stages. The project is under way, and this is to be regarded as a progress report since e.g. criteria for site evaluation will be presented at a later date. The long-term performance and safety of the deep repository must always be evaluated by means of an integrated safety assessment. The work with factors and criteria can never take the place of such an assessment, but can provide guidance regarding its outcome. Requirements and preferences regarding the function of the rock in the deep repository have been clarified in this progress report. What is new here is the structuring that has been carried out, with a classification into different geoscientific disciplines, and the formalism that has been given to the terms requirement, preference and function. Based on fundamental safety and construction functions, requirements on function have been specified for the disciplines geology, thermal properties, hydro-geology, rock mechanics, chemistry and transport properties. Furthermore, function analyses have been identified by means of which it is possible to concretize requirements on function and which geoscientific parameters are
Site characterization quality assurance for the California LLRW Disposal Site Project

International Nuclear Information System (INIS)

Hanrahan, T.P.; Ench, J.E.; Serlin, C.L.; Bennett, C.B.

1988-01-01

In December of 1985 US Ecology was chosen as the license designee for the State of California's low-level radioactive waste disposal facility. In early 1987, three candidate sites were selected for characterization studies in preparation for identifying the preferred site. The geotechnical characterization activities along with studies of the ecological and archaeological attributes, as well as assessments of the socio-economic impacts and cultural resources all provide input towards selection of the proposed site. These technical studies in conjunction with comments from local citizen committees and other interested parties are used as a basis for determining the proposed site for which full site characterization as required by California licensing requirements are undertaken. The purpose of this paper is to present an overview of the program for Quality Assurance and Quality Control for the site characterization activities on the California LLRW Disposal Site Project. The focus is on three major perspectives: The composite QA Program and two of the primary characterization activities, the geotechnical and the meteorological investigations
Evaluation of olive flowering at low latitude sites in Argentina using a chilling requirement model

Energy Technology Data Exchange (ETDEWEB)

Aybar, V.E.; Melo-Abreu, J.P. de; Searles, P.S.; Matias, A.G.; Del Rio, C.; Caballero, C. M.; Rousseaux, M.C.

2015-07-01

Olive production has expanded significantly from the Mediterranean Basin into the New World over the last two decades. In some cases, cultivars of European origin have been introduced at a large commercial scale with little previous evaluation of potential productivity. The objective of this study was to evaluate whether a temperature-driven simulation model developed in the Mediterranean Basin to predict normal flowering occurrence and flowering date using cultivar-specific thermal requirements was suitable for the low latitude areas of Northwest Argentina. The model was validated at eight sites over several years and a wide elevation range (350–1200 m above mean sea level) for three cultivars (‘Arbequina’, ‘Frantoio’, ‘Leccino’) with potentially different chilling requirements. In ‘Arbequina’, normal flowering was observed at almost all sites and in all years, while normal flowering events in ‘Frantoio’ and ‘Leccino’ were uncommon. The model successfully predicted if flowering would be normal in 92% and 83% of the cases in ‘Arbequina’ and ‘Frantoio’, respectively, but was somewhat less successful in ‘Leccino’ (61%). When flowering occurred, the predicted flowering date was within ± 7 days of the observed date in 71% of the cases. Overall, the model results indicate that cultivar-specific simulation models may be used as an approximate tool to predict whether individual cultivars will be successful in new growing areas. In Northwest Argentina, the model could be used to identify cultivars to replace ‘Frantoio’ and ‘Leccino’ and to simulate global warming scenarios. (Author)
National Ignition Facility Project Site Safety Program

International Nuclear Information System (INIS)

Dun, C

2003-01-01

This Safety Program for the National Ignition Facility (NIF) presents safety protocols and requirements that management and workers shall follow to assure a safe and healthful work environment during activities performed on the NIF Project site. The NIF Project Site Safety Program (NPSSP) requires that activities at the NIF Project site be performed in accordance with the ''LLNL ES and H Manual'' and the augmented set of controls and processes described in this NIF Project Site Safety Program. Specifically, this document: (1) Defines the fundamental NIF site safety philosophy. (2) Defines the areas covered by this safety program (see Appendix B). (3) Identifies management roles and responsibilities. (4) Defines core safety management processes. (5) Identifies NIF site-specific safety requirements. This NPSSP sets forth the responsibilities, requirements, rules, policies, and regulations for workers involved in work activities performed on the NIF Project site. Workers are required to implement measures to create a universal awareness that promotes safe practice at the work site and will achieve NIF management objectives in preventing accidents and illnesses. ES and H requirements are consistent with the ''LLNL ES and H Manual''. This NPSSP and implementing procedures (e.g., Management Walkabout, special work procedures, etc.,) are a comprehensive safety program that applies to NIF workers on the NIF Project site. The NIF Project site includes the B581/B681 site and support areas shown in Appendix B
Hanford site transuranic waste sampling plan

International Nuclear Information System (INIS)

GREAGER, T.M.

1999-01-01

This sampling plan (SP) describes the selection of containers for sampling of homogeneous solids and soil/gravel and for visual examination of transuranic and mixed transuranic (collectively referred to as TRU) waste generated at the U.S. Department of Energy (DOE) Hanford Site. The activities described in this SP will be conducted under the Hanford Site TRU Waste Certification Program. This SP is designed to meet the requirements of the Transuranic Waste Characterization Quality Assurance Program Plan (CAO-94-1010) (DOE 1996a) (QAPP), site-specific implementation of which is described in the Hanford Site Transuranic Waste Characterization Program Quality Assurance Project Plan (HNF-2599) (Hanford 1998b) (QAPP). The QAPP defines the quality assurance (QA) requirements and protocols for TRU waste characterization activities at the Hanford Site. In addition, the QAPP identifies responsible organizations, describes required program activities, outlines sampling and analysis strategies, and identifies procedures for characterization activities. The QAPP identifies specific requirements for TRU waste sampling plans. Table 1-1 presents these requirements and indicates sections in this SP where these requirements are addressed
Site decontamination

International Nuclear Information System (INIS)

Bicker, A.E.

1981-01-01

Among the several DOE sites that have been radiologically decontaminated under the auspices of the Nevada Operations Office are three whose physical characteristics are unique. These are the Tatum Dome Test Site (TDTS) near Hattiesburg, Mississippi; a location of mountainous terrain (Pahute Mesa) on the Nevada Test Site; and the GNOME site near Carlsbad, New Mexico. In each case the contamination, the terrain, and the climate conditions were different. This presentation includes a brief description of each site, the methods used to perform radiological surveys, the logistics required to support the decontamination (including health physics and sample analysis), and the specific techniques used to reduce or remove the contamination
The effects of maternal depression and maternal selective serotonin reuptake inhibitor exposure on the offspring

Directory of Open Access Journals (Sweden)

Jocelien DA Olivier

2013-05-01

Full Text Available It has been estimated that 20% of pregnant women suffer from depression and it is well documented that maternal depression can have long-lasting effects on the child. Currently, common treatment for maternal depression has been the selective serotonin reuptake inhibitor medications (SSRIs which are used by 2-3% of pregnant women in the Nordic countries and by up to 10% of pregnant women in the United States. Antidepressants cross the placenta and are transferred to the fetus, thus, the question arises as to whether children of women taking antidepressants are at risk for altered neurodevelopmental outcomes and, if so, whether the risks are due to SSRI medication exposure or to the underlying maternal depression. This review considers the effects of maternal depression and SSRI exposure on offspring development in both clinical and preclinical populations. As it is impossible in humans to study the effects of SSRIs without taking into account the possible underlying effects of maternal depression (healthy pregnant women do not take SSRIs, animal models are of great value. For example, rodents can be used to determine the effects of maternal depression and/or perinatal SSRI exposure on offspring outcomes. Unraveling the joint (or separate effects of maternal depression and SSRI exposure will provide more insights into the risks or benefits of SSRI exposure during gestation and will help women make informed decisions about using SSRIs during pregnancy.
Integration of CERCLA and RCRA requirements at the Radioactive Waste Burial Grounds, Savannah River Site, Aiken, South Carolina

International Nuclear Information System (INIS)

Hoffman, W.D.; Wyatt, D.E.

1992-01-01

The purpose of this paper to is present the comprehensive approach being taken at the Savannah River Site (SRS) to consolidate regulatory documents, characterization and assessment activities for 3 contiguous waste management facilities. These facilities cover 7.12 x 10 5 m 2 (194 acres) and include an Old Radioactive Waste Burial Ground, a Low Level Radioactive Waste Disposal Facility, and a closed Mixed Waste Management Facility. Each of these facilities include one or more operable units including solvent tanks, transuranic waste storage pads, research lysimeters and experimental confinement disposal vaults. All of these facilities have differing submittal dates for regulatory documents but similar and continuous environmental problems. The characterization and risk assessment require simultaneous efforts for all facilities to adequately define the nature and extent of past, present and future environmental impact. Current data indicates that contaminant plumes in both soil and water are comingled, interspersed and possibly exist internally within the contiguous facilities, requiring a combined investigative effort. This paper describes the combination of regulatory documents leading to this comprehensive and integrative approach for burial ground characterization at the Savannah River Site
Single photon emission computed tomography before and after treatment of anxiety using a selective serotonin reuptake inhibitor

International Nuclear Information System (INIS)

Warwick, J.M.; Heerden, B.B. van; Stein, D.J.; Niehaus, D.J.H.; Seedat, S.; Linden, G. van der; Harvey, B.A.

2002-01-01

Background: The selective serotonin reuptake inhibitors (SSRIs) are currently recommended as first line medications for a number of different anxiety disorders, including obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), and social anxiety disorder (social phobia) (SAD). This raises the question of what effects these agents have on the functional neuroanatomy of anxiety disorders. Methods: Single photon emission computed tomography (SPECT) brain scanning was undertaken in patients with OCD, PTSD, and SAD before and after treatment with citalopram, the most selective of the SSRIs. Statistical parametric mapping (SPM) was used to compare scans (pre- vs post-medication, and responders vs nonresponders) in the combined group of subjects. Results: Citalopram pharmacotherapy resulted in significant deactivation within anterior and superior cingulate and left hippocampus. Deactivation within the anterior cingulate, left paracingular cortex, and right inferior frontal cortex was more marked in treatment responders. Baseline activation did not, however, predict response to pharmacotherapy. Conclusion: Although each of the anxiety disorders may be mediated by different neurocircuits, there are some overlaps in the functional neuroanatomy of their response to SSRI treatment. The current data is consistent with previous work demonstrating the importance of limbic circuits in this spectrum of disorders. These play a crucial role in cognitive-affective processing, and are innervated by serotonergic neurons
Dopamine/noradrenaline reuptake inhibition in women improves endurance exercise performance in the heat.

Science.gov (United States)

Cordery, P; Peirce, N; Maughan, R J; Watson, P

2017-11-01

Catecholamine reuptake inhibition improves the performance of male volunteers exercising in warm conditions, but sex differences in thermoregulation, circulating hormones, and central neurotransmission may alter this response. With local ethics committee approval, nine physically active women (mean ± SD age 21 ± 2 years; height 1.68 ± 0.08 m; body mass 64.1 ± 6.0 kg; VO 2peak 51 ± 7 mL/kg/min) were recruited to examine the effect of pre-exercise administration of Bupropion (BUP; 4 × 150 mg) on prolonged exercise performance in a warm environment. Participants completed a VO 2peak test, two familiarization trials, and two randomized, double-blind experimental trials. All trials took place during the first 10 days of the follicular phase of the menstrual cycle. Participants cycled for 1 h at 60% VO 2peak followed by a 30-min performance test. Total work done was greater during the BUP trial (291 ± 48 kJ) than the placebo trial (269 ± 46 kJ, P = 0.042, d = 0.497). At the end of the performance test, core temperature was higher on the BUP trial (39.5 ± 0.4 °C) than on the placebo trial (39.2 ± 0.6 °C, P = 0.021; d = 0.588), as was heart rate (185 ± 9 vs 179 ± 13, P = 0.043; d = 0.537). The results indicate that during the follicular phase of the menstrual cycle, an acute dosing protocol of BUP can improve self-regulated performance in warm conditions. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
On multi-site damage identification using single-site training data

Science.gov (United States)

Barthorpe, R. J.; Manson, G.; Worden, K.

2017-11-01

This paper proposes a methodology for developing multi-site damage location systems for engineering structures that can be trained using single-site damaged state data only. The methodology involves training a sequence of binary classifiers based upon single-site damage data and combining the developed classifiers into a robust multi-class damage locator. In this way, the multi-site damage identification problem may be decomposed into a sequence of binary decisions. In this paper Support Vector Classifiers are adopted as the means of making these binary decisions. The proposed methodology represents an advancement on the state of the art in the field of multi-site damage identification which require either: (1) full damaged state data from single- and multi-site damage cases or (2) the development of a physics-based model to make multi-site model predictions. The potential benefit of the proposed methodology is that a significantly reduced number of recorded damage states may be required in order to train a multi-site damage locator without recourse to physics-based model predictions. In this paper it is first demonstrated that Support Vector Classification represents an appropriate approach to the multi-site damage location problem, with methods for combining binary classifiers discussed. Next, the proposed methodology is demonstrated and evaluated through application to a real engineering structure - a Piper Tomahawk trainer aircraft wing - with its performance compared to classifiers trained using the full damaged-state dataset.
Site study plan for geochemical analytical requirements and methodologies: Revision 1

International Nuclear Information System (INIS)

1987-12-01

This site study plan documents the analytical methodologies and procedures that will be used to analyze geochemically the rock and fluid samples collected during Site Characterization. Information relating to the quality aspects of these analyses is also provided, where available. Most of the proposed analytical procedures have been used previously on the program and are sufficiently sensitive to yield high-quality analyses. In a few cases improvements in analytical methodology (e.g., greater sensitivity, fewer interferences) are desired. Suggested improvements to these methodologies are discussed. In most cases these method-development activities have already been initiated. The primary source of rock and fluid samples for geochemical analysis during Site Characterization will be the drilling program, as described in various SRP Site Study Plans. The Salt Repository Project (SRP) Networks specify the schedule under which the program will operate. Drilling will not begin until after site ground water baseline conditions have been established. The Technical Field Services Contractor (TFSC) is responsible for conducting the field program of drilling and testing. Samples and data will be handled and reported in accordance with established SRP procedures. A quality assurance program will be utilized to assure that activities affecting quality are performed correctly and that the appropriate documentation is maintained. 28 refs., 9 figs., 14 tabs
The effect of selective serotonin reuptake inhibitors in healthy first-degree relatives of patients with major depressive disorder - an experimental medicine blinded controlled trial

DEFF Research Database (Denmark)

Knorr, Ulla Benedichte

2012-01-01

.37). In univariate analyses, no statistically significant correlations were found between change in the primary and secondary outcomes, respectively, and the covariates age, sex, Hamilton depression score 17-items, and plasma escitalopram levels. In conclusion, the present trial does not support an effect......The mechanisms of action for selective serotonin re-uptake in-hibitors (SSRI) in depressed patients remain widely unknown. The serotonergic neurotransmitter system and the hypothalamic-pituitary-adrenal (HPA) system may interact. Further, the serotonergic neurotransmitter system seems closely...... linked to personality and cognition. It is not known if SSRIs have a direct effect on the HPA system, personality or cognition that is independent of their effect on depression. Thus, healthy individuals with a genetic liability for depression represent a group of particular interest when investigating...
Site Rehabilitation Completion Report with No Further Action Proposal for the Northeast Site

Energy Technology Data Exchange (ETDEWEB)

Daniel, Joe [Stoller Newport News Technology, Inc., Grand Junction, CO (United States); Tabor, Charles [Stoller Newport News Technology, Inc., Grand Junction, CO (United States); Survochak, Scott [U.S. Department of Energy, Office of Legacy Management, Grand Junction, CO (United States)

2013-05-01

The purpose of this Site Rehabilitation Completion Report is to present the post-active-remediation monitoring results for the Northeast Site and to propose No Further Action with Controls. This document includes information required by Chapter 62-780.750(4)(d), 62-780.750(6), and 62-780.600(8)(a)27 Florida Administrative Code (F.A.C.). The Closure Monitoring Plan for the Northeast Site and 4.5 Acre Site (DOE 2009a) describes the approach for post-active-remediation monitoring. The Young - Rainey Science, Technology, and Research Center (STAR Center) is a former U.S. Department of Energy (DOE) facility constructed in the mid-1950s. The 99-acre STAR Center is located in Largo, Florida. The Northeast Site is located in the northeast corner of the STAR Center. The Northeast Site meets all the requirements for an RMO II closure—No Further Action with Controls. DOE is nearing completion of a restrictive covenant for the Northeast Site. DOE has completed post-active-remediation monitoring at the Northeast Site as of September 2012. No additional monitoring will be conducted.

Japanese site for ITER: Rokkasho

International Nuclear Information System (INIS)

Kishimoto, Hiroshi

2003-01-01

This paper describes the status of Japanese efforts for hosting ITER in Japan. In May 2002, Japanese Government decided to propose an ITER site, Rokkasho in Aomori Prefecture, a Northern part of the main island, based on the comprehensive/intensive assessments by the Site Selection Committee established by Japanese Government. ITER is designed basically with a potential flexibility beyond the detailed technical objectives to have more clear scope for developing technical key elements in a future power plant. Various flexibilities in the construction, operation and decommissioning of ITER are totally assessed. Consequently the Japanese site has been chosen and it satisfies sufficiently not only the Site Requirements and the Site Design Assumptions but also the further extension and flexibilities. In particular the potential for more flexible construction schedule and operations is technically described as well as the fulfillment of the site requirements and its assumptions as the minimum requirements in this paper. The socio-cultural environment is also described briefly because of a key aspect for the scientists and engineers who will participate in the project
Selective serotonin reuptake inhibitors for fibromyalgia syndrome

Directory of Open Access Journals (Sweden)

Brian Walitt

Full Text Available ABSTRACT BACKGROUND: Fibromyalgia is a clinically well-defined chronic condition with a biopsychosocial aetiology. Fibromyalgia is characterized by chronic widespread musculoskeletal pain, sleep problems, cognitive dysfunction, and fatigue. Patients often report high disability levels and poor quality of life. Since there is no specific treatment that alters the pathogenesis of fibromyalgia, drug therapy focuses on pain reduction and improvement of other aversive symptoms. OBJECTIVES: To assess the benefits and harms of selective serotonin reuptake inhibitors (SSRIs in the treatment of fibromyalgia. METHODS: Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 5, MEDLINE (1966 to June 2014, EMBASE (1946 to June 2014, and the reference lists of reviewed articles. Selection criteria: We selected all randomized, double-blind trials of SSRIs used for the treatment of fibromyalgia symptoms in adult participants. We considered the following SSRIs in this review: citalopram, fluoxetine, escitalopram, fluvoxamine, paroxetine, and sertraline. Data collection and analysis: Three authors extracted the data of all included studies and assessed the risks of bias of the studies. We resolved discrepancies by discussion. MAIN RESULTS: The quality of evidence was very low for each outcome. We downgraded the quality of evidence to very low due to concerns about risk of bias and studies with few participants. We included seven placebo-controlled studies, two with citalopram, three with fluoxetine and two with paroxetine, with a median study duration of eight weeks (4 to 16 weeks and 383 participants, who were pooled together. All studies had one or more sources of potential major bias. There was a small (10% difference in patients who reported a 30% pain reduction between SSRIs (56/172 (32.6% and placebo (39/171 (22.8% risk difference (RD 0.10, 95% confidence interval (CI 0.01 to 0.20; number needed to treat for an
Selective serotonin reuptake inhibitors for fibromyalgia syndrome

Science.gov (United States)

Walitt, Brian; Urrútia, Gerard; Nishishinya, María Betina; Cantrell, Sarah E; Häuser, Winfried

2016-01-01

Background Fibromyalgia is a clinically well-defined chronic condition with a biopsychosocial aetiology. Fibromyalgia is characterized by chronic widespread musculoskeletal pain, sleep problems, cognitive dysfunction, and fatigue. Patients often report high disability levels and poor quality of life. Since there is no specific treatment that alters the pathogenesis of fibromyalgia, drug therapy focuses on pain reduction and improvement of other aversive symptoms. Objectives The objective was to assess the benefits and harms of selective serotonin reuptake inhibitors (SSRIs) in the treatment of fibromyalgia. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 5), MEDLINE (1966 to June 2014), EMBASE (1946 to June 2014), and the reference lists of reviewed articles. Selection criteria We selected all randomized, double-blind trials of SSRIs used for the treatment of fibromyalgia symptoms in adult participants. We considered the following SSRIs in this review: citalopram, fluoxetine, escitalopram, fluvoxamine, paroxetine, and sertraline. Data collection and analysis Three authors extracted the data of all included studies and assessed the risks of bias of the studies. We resolved discrepancies by discussion. Main results The quality of evidence was very low for each outcome. We downgraded the quality of evidence to very low due to concerns about risk of bias and studies with few participants. We included seven placebo-controlled studies, two with citalopram, three with fluoxetine and two with paroxetine, with a median study duration of eight weeks (4 to 16 weeks) and 383 participants, who were pooled together. All studies had one or more sources of potential major bias. There was a small (10%) difference in patients who reported a 30% pain reduction between SSRIs (56/172 (32.6%)) and placebo (39/171 (22.8%)) risk difference (RD) 0.10, 95% confidence interval (CI) 0.01 to 0.20; number needed to treat for an additional
Data requirement comparison between the fixed site upgrade rule guidance compendium and the Structured Assessment Approach Licensee Submittal Document

Energy Technology Data Exchange (ETDEWEB)

Parziale, A.A.; Sacks, I.J.

1980-12-01

We compared the Structured Assessment Approach's (SAA) Licensee Submittal Document (LSD) with the Fixed Site Physical Protection Upgrade Rule Guidance Compendium Standard Format and Content (SFC) Guide using correlation matrices to see how well the data requirements of the SFC Guide coincided with those of a specific automated vulnerability assessment technique for fixed-site nuclear fuel cycle facilities, namely, SAA. We found that a limited SAA assessment is possible using the SFC Guide, but significant and critical safeguards vulnerabilities might be missed. Also, it was found that in some cases the organization and format of the SFC Guide input data and information made the preparation of data for the SAA somewhat awkward. 2 refs., 2 tabs.
Escitalopram, an antidepressant with an allosteric effect at the serotonin transporter--a review of current understanding of its mechanism of action.

Science.gov (United States)

Zhong, Huailing; Haddjeri, Nasser; Sánchez, Connie

2012-01-01

Escitalopram is a widely used antidepressant for the treatment of patients with major depression. It is the pure S-enantiomer of racemic citalopram. Several clinical trials and meta-analyses indicate that escitalopram is quantitatively more efficacious than many other antidepressants with a faster onset of action. This paper reviews current knowledge about the mechanism of action of escitalopram. The primary target for escitalopram is the serotonin transporter (SERT), which is responsible for serotonin (or 5-hydroxytryptamine [5-HT]) reuptake at the terminals and cell bodies of serotonergic neurons. Escitalopram and selective serotonin reuptake inhibitors bind with high affinity to the 5-HT binding site (orthosteric site) on the transporter. This leads to antidepressant effects by increasing extracellular 5-HT levels which enhance 5-HT neurotransmission. SERT also has one or more allosteric sites, binding to which modulates activity at the orthosteric binding site but does not directly affect 5-HT reuptake by the transporter. In vitro studies have shown that through allosteric binding, escitalopram decreases its own dissociation rate from the orthosteric site on the SERT. R-citalopram, the nontherapeutic enantiomer in citalopram, is also an allosteric modulator of SERT but can inhibit the actions of escitalopram by interfering negatively with its binding. Both nonclinical studies and some clinical investigations have demonstrated the cellular, neurochemical, neuroadaptive, and neuroplastic changes induced by escitalopram with acute and chronic administration. The findings from binding, neurochemical, and neurophysiological studies may provide a mechanistic rationale for the clinical difference observed with escitalopram compared to other antidepressant therapies.
The commissioning of CMS sites: Improving the site reliability

International Nuclear Information System (INIS)

Belforte, S; Fisk, I; Flix, J; Hernandez, J M; Klem, J; Letts, J; Magini, N; Saiz, P; Sciaba, A

2010-01-01

The computing system of the CMS experiment works using distributed resources from more than 60 computing centres worldwide. These centres, located in Europe, America and Asia are interconnected by the Worldwide LHC Computing Grid. The operation of the system requires a stable and reliable behaviour of the underlying infrastructure. CMS has established a procedure to extensively test all relevant aspects of a Grid site, such as the ability to efficiently use their network to transfer data, the functionality of all the site services relevant for CMS and the capability to sustain the various CMS computing workflows at the required scale. This contribution describes in detail the procedure to rate CMS sites depending on their performance, including the complete automation of the program, the description of monitoring tools, and its impact in improving the overall reliability of the Grid from the point of view of the CMS computing system.
Subsurface Contamination Focus Area technical requirements. Volume 1: Requirements summary

International Nuclear Information System (INIS)

Nickelson, D.; Nonte, J.; Richardson, J.

1996-10-01

This document summarizes functions and requirements for remediation of source term and plume sites identified by the Subsurface Contamination Focus Area. Included are detailed requirements and supporting information for source term and plume containment, stabilization, retrieval, and selective retrieval remedial activities. This information will be useful both to the decision-makers within the Subsurface Contamination Focus Area (SCFA) and to the technology providers who are developing and demonstrating technologies and systems. Requirements are often expressed as graphs or charts, which reflect the site-specific nature of the functions that must be performed. Many of the tradeoff studies associated with cost savings are identified in the text
Pharmacological Characterization of H05, a Novel Serotonin and Noradrenaline Reuptake Inhibitor with Moderate 5-HT2A Antagonist Activity for the Treatment of Depression.

Science.gov (United States)

Xu, Xiangqing; Wei, Yaqin; Guo, Qiang; Zhao, Song; Liu, Zhiqiang; Xiao, Ting; Liu, Yani; Qiu, Yinli; Hou, Yuanyuan; Zhang, Guisen; Wang, KeWei

2018-06-01

Multitarget antidepressants selectively inhibiting monoaminergic transporters and 5-hydroxytryptamine (5-HT) 2A receptor have demonstrated higher efficacy and fewer side effects than selective serotonin reuptake inhibitors. In the present study, we synthesized a series of novel 3-(benzo[d][1,3]dioxol-4-yloxy)-3-arylpropyl amine derivatives, among which compound H05 was identified as a lead, exhibiting potent inhibitory effects on both serotonin ( K i = 4.81 nM) and norepinephrine (NE) ( K i = 6.72 nM) transporters and moderate 5-HT 2A antagonist activity (IC 50 = 60.37 nM). H05 was able to dose-dependently reduce the immobility duration in mouse forced swimming test and tail suspension test, with the minimal effective doses lower than those of duloxetine, and showed no stimulatory effect on locomotor activity. The administration of H05 (5, 10, and 20 mg/kg, by mouth) significantly shortened the immobility time of adrenocorticotropin-treated rats that serve as a model of treatment-resistant depression, whereas imipramine (30 mg/kg, by mouth) and duloxetine (30 mg/kg, by mouth) showed no obvious effects. Chronic treatment with H05 reversed the depressive-like behaviors in a rat model of chronic unpredictable mild stress and a mouse model of corticosterone-induced depression. Microdialysis analysis revealed that the administration of H05 at either 10 or 20 mg/kg increased the release of 5-HT and NE from the frontal cortex. The pharmacokinetic (PK) and brain penetration analyses suggest that H05 has favorable PK properties with good blood-brain penetration ability. Therefore, it can be concluded that H05, a novel serotonin and NE reuptake inhibitor with 5-HT 2A antagonist activity, possesses efficacious activity in the preclinical models of depression and treatment-resistant depression, and it may warrant further evaluation for clinical development. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.
78 FR 14088 - Environmental Management Site-Specific Advisory Board, Savannah River Site

Science.gov (United States)

2013-03-04

...This notice announces a meeting of the Environmental Management Site-Specific Advisory Board (EM SSAB), Savannah River Site. The Federal Advisory Committee Act requires that public notice of this meeting be announced in the Federal Register.
Hanford analytical services quality assurance requirements documents. Volume 1: Administrative Requirements

International Nuclear Information System (INIS)

Hyatt, J.E.

1997-01-01

Hanford Analytical Services Quality Assurance Requirements Document (HASQARD) is issued by the Analytical Services, Program of the Waste Management Division, US Department of Energy (US DOE), Richland Operations Office (DOE-RL). The HASQARD establishes quality requirements in response to DOE Order 5700.6C (DOE 1991b). The HASQARD is designed to meet the needs of DOE-RL for maintaining a consistent level of quality for sampling and field and laboratory analytical services provided by contractor and commercial field and laboratory analytical operations. The HASQARD serves as the quality basis for all sampling and field/laboratory analytical services provided to DOE-RL through the Analytical Services Program of the Waste Management Division in support of Hanford Site environmental cleanup efforts. This includes work performed by contractor and commercial laboratories and covers radiological and nonradiological analyses. The HASQARD applies to field sampling, field analysis, and research and development activities that support work conducted under the Hanford Federal Facility Agreement and Consent Order Tri-Party Agreement and regulatory permit applications and applicable permit requirements described in subsections of this volume. The HASQARD applies to work done to support process chemistry analysis (e.g., ongoing site waste treatment and characterization operations) and research and development projects related to Hanford Site environmental cleanup activities. This ensures a uniform quality umbrella to analytical site activities predicated on the concepts contained in the HASQARD. Using HASQARD will ensure data of known quality and technical defensibility of the methods used to obtain that data. The HASQARD is made up of four volumes: Volume 1, Administrative Requirements; Volume 2, Sampling Technical Requirements; Volume 3, Field Analytical Technical Requirements; and Volume 4, Laboratory Technical Requirements. Volume 1 describes the administrative requirements
Environmental assessment, Richton Dome site, Mississippi

International Nuclear Information System (INIS)

1986-05-01

The Nuclear Waste Policy Act of 1982 (42 USC Sections 10101-10226) requires the environmental assessment of a potential site to include a statement of the basis for the nomination of a site as suitable for characterization. Volume 2 of this environmental assessment provides a detailed evaluation of the Richton Dome Site and its suitability as the site for a radioactive waste disposal facility under DOE siting guidelines, as well as a comparison of the Richton Dome site with other proposed sites. Evaluation of the Richton Dome site is based on the reference repository design, but the evaluation will not change if based on the Mission Plan repository concept. The comparative evaluation of proposed sites is required under DOE guidelines, but is not intended to directly support the subsequent recommendation of three sites for characterization as candidate sites. 428 refs., 24 figs., 62 tabs
Increasing the risk of spontaneous abortion and major malformations in newborns following use of serotonin reuptake inhibitors during pregnancy: A systematic review and updated meta-analysis

Directory of Open Access Journals (Sweden)

Nikfar Shekoufeh

2012-11-01

Full Text Available Abstract Selective serotonin reuptake inhibitors (SSRIs are the most frequently used antidepressants during pregnancy. There are conflicting results about their influence on pregnancy outcomes. The goal of this study was to update our previous meta-analysis about pregnancy outcomes following exposure to SSRIs. For this purpose, all relevant databases were searched from 1990 to March 2012 for studies investigating the pregnancy outcomes following exposure to any therapeutic dosage of any SSRI (fluoxetine, paroxetine, citalopram, escitalopram, sertraline, fluvoxamine during pregnancy. Types of outcome investigated were spontaneous abortion, major malformations, cardiovascular malformations, and minor malformations. A total of 25 studies met our criteria and were included in the meta-analysis. The odds ratio (OD values are 1.87 (95% CI: 1.5 to 2.33, P
Siting Practices and Site Licensing Process for New Reactors in Canada

International Nuclear Information System (INIS)

Vos, Marcel de

2011-01-01

'Siting' in Canada is composed of Site Evaluation and Site Selection. As outlined in CNSC Regulatory Document RD-346 Site Evaluation for New Nuclear Power Plants (based on IAEA NS-R-3), prior to the triggering of the Environmental Assessment (EA) and licensing processes, the proponent is expected to use a robust process to characterize proposed sites over the full life cycle of the facility, and then develop a fully documented defense of the site selection case. This case forms the backbone for submissions in support of the EA and the application for a License to Prepare Site which will be reviewed by the CNSC and other applicable federal authorities. The Environmental Assessment process and License to Prepare Site in Canada do not require a proponent to select a specific design; however, CNSC does not accept a 'black box' approach to siting. CNSC balances the level of design information required with the extent of safety assurance desired for any designs being contemplated for the proposed site. Nevertheless, the design information submitted must be sufficient to justify the site as suitable for all future licensing stages. The depth of plant design information contributes significantly to the credibility of the applicant's case for both the EA and application for License to Prepare Site. The review process utilizes an assessment plan with defined review stages and timelines. The outcome of these reviews is a series of recommendations to a federal government appointed Joint Review Panel (which also serves as a panel of the 'Commission') which, following public hearings, renders a decision regarding the EA, and subsequently, the application for a License to Prepare Site. (author)
Geohydrology of industrial waste disposal site

International Nuclear Information System (INIS)

Gaynor, R.K.

1984-01-01

An existing desert site for hazardous chemical and low-level radioactive waste disposal is evaluated for suitability. This site is characterized using geologic, geohydrologic, geochemical, and other considerations. Design and operation of the disposal facility is considered. Site characteristics are also evaluated with respect to new and proposed regulatory requirements under the Resource Conservation and Recovery Act (1976) regulations, 40 CFR Part 264, and the ''Licensing Requirements for Landfill Disposal of Radioactive Waste,'' 10 CRF Part 61. The advantages and disadvantages of siting new disposal facilities in similar desert areas are reviewed and contrasted to siting in humid locations
Hanford Site Environmental Management Specification

International Nuclear Information System (INIS)

DAILY, J.L.

2001-01-01

The US Department of Energy, Richland Operations Office (RL) has established a document hierarchy as part of its integrated management system. The Strategic Plan defines the vision, values, missions, strategic goals, high-level outcomes, and the basic strategies in achieving those outcomes. As shown in Figure 1-1, the Site Specification derives requirements from the Strategic Plan and documents the top-level mission technical requirements for the work involved in the RL Hanford Site cleanup and infrastructure activities under the responsibility of the U.S. Department of Energy, Office of Environmental Management (EM). It also provides the basis for all contract technical requirements. Since this is limited to the EM work, neither the Fast Flux Test Facility (FFTF) nor the Pacific Northwest National Laboratory (PNNL) non-EM science activities are included. Figure 1-1 also shows the relationship between this Site Specification and the other Site management and planning documents. Similarly, the documents, orders, and laws referenced in this document represent only the most salient sources of requirements. Current and contractual reference data contain a complete set of source documents
The serotonin transporter in rhesus monkey brain: comparison of DASB and citalopram binding sites

International Nuclear Information System (INIS)

Zeng Zhizhen; Chen, T.-B.; Miller, Patricia J.; Dean, Dennis; Tang, Y.S.; Sur, Cyrille; Williams, David L.

2006-01-01

We have characterized the interaction of the serotonin transporter ligand [ 3 H]-N,N-dimethyl-2-(2-amino-4-cyanophenylthio)-benzylamine (DASB) with rhesus monkey brain in vitro using tissue homogenate binding and autoradiographic mapping. [ 3 H]-DASB, a tritiated version of the widely used [ 11 C] positron emission tomography tracer, was found to selectively bind to a single population of sites with high affinity (K d =0.20±0.04 nM). The serotonin transporter density (B max ) obtained for rhesus frontal cortex was found to be 66±8 fmol/mg protein using [ 3 H]-DASB, similar to the B max value obtained using the reference radioligand [ 3 H]-citalopram, a well-characterized and highly selective serotonin reuptake inhibitor (83±22 fmol/mg protein). Specific binding sites of both [ 3 H]-DASB and [ 3 H]-citalopram were similarly and nonuniformly distributed throughout the rhesus central nervous system, in a pattern consistent with serotonin transporter localization reported for human brain. Regional serotonin transporter densities, estimated from optical densities of the autoradiographic images, were well correlated between the two radioligands. Finally, DASB and fluoxetine showed dose-dependent full inhibition of [ 3 H]-citalopram binding in a competition autoradiographic study, with K i values in close agreement with those obtained from rhesus brain homogenates. This side-by-side comparison of [ 3 H]-DASB and [ 3 H]-citalopram binding sites in rhesus tissue homogenates and in adjacent rhesus brain slices provides additional support for the use of [ 11 C]-DASB to assess the availability and distribution of serotonin transporters in nonhuman primates
Site Selection for the Salt Disposition Facility at the Savannah River Site

International Nuclear Information System (INIS)

Gladden, J.B.; Rueter, K.J.; Morin, J.P.

2000-01-01

A site selection study was conducted to identify a suitable location for the construction and operation of a new Salt Disposition Facility (SDF) at the Savannah River Site (SRS). The facility to be sited is a single processing facility and support buildings that could house either of three technology alternatives being developed by the High Level Waste Systems Engineering Team: Small Tank Tetraphenylborate Precipitation, Crystalline Silicotitanate Non-Elutable Ion Exchange or Caustic Side Solvent Extraction. A fourth alternative, Direct Disposal in grout, is not part of the site selection study because a location has been identified that is unique to this technology (i.e., Z-Area). Facility site selection at SRS is a formal, documented process that seeks to optimize siting of new facilities with respect to facility-specific engineering requirements, sensitive environmental resources, and applicable regulatory requirements. In this manner, the prime objectives of cost minimization, environmental protection, and regulatory compliance are achieved. The results from this geotechnical characterization indicated that continued consideration be given to Site B for the proposed SDF. Suitable topography, the lack of surface hydrology and floodplain issues, no significant groundwater contamination, the presence of minor soft zones along the northeast portion of footprint, and no apparent geological structure in the Gordon Aquitard support this recommendation
Bald eagle site management plan for the Hanford Site, south-central Washington

International Nuclear Information System (INIS)

Fitzner, R.F.; Weiss, S.G.

1994-12-01

The CERCLA remedial investigations of waste sites on the Hanford Site will involve lands containing or adjacent to a bald eagle nest, winter concentration areas, or communal night roost. Because these CERCLA investigations may affect bald eagles, the DOE has prepared this Bald Eagle Site Management Plan (BESMP). However, it is intended that this BESMP be used or updated so as to be also applicable to future activities that affect bald eagles on the Hanford Site. Bald eagles regularly use the US Department of Energy's (DOE) Hanford Site in south-central Washington State during winter months for roosting, perching, and foraging. Each of these activities requires buffer zones to protect eagles from human disturbances. Buffer zones developed in this plan follow recommended guidelines and are intended to be used in planning. If Hanford Site activities in the vicinity of identified bald eagle use areas are carried out in accordance with this plan, such actions are not likely to adversely affect the eagles or their habitat. Activities that may be exceptions will involve informal or formal (whichever is appropriate) consultation with the US Fish and Wildlife Service as required by the Endangered Species Act
5-HT2C receptors in the BNST are necessary for the enhancement of fear learning by selective serotonin reuptake inhibitors.

Science.gov (United States)

Pelrine, Eliza; Pasik, Sara Diana; Bayat, Leyla; Goldschmiedt, Debora; Bauer, Elizabeth P

2016-12-01

Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed to treat anxiety and depression, yet they paradoxically increase anxiety during initial treatment. Acute administration of these drugs prior to learning can also enhance Pavlovian cued fear conditioning. This potentiation has been previously reported to depend upon the bed nucleus of the stria terminalis (BNST). Here, using temporary inactivation, we confirmed that the BNST is not necessary for the acquisition of cued or contextual fear memory. Systemic administration of the SSRI citalopram prior to fear conditioning led to an upregulation of the immediate early gene Arc (activity-regulated cytoskeleton-associated protein) in the oval nucleus of the BNST, and a majority of these neurons expressed the 5-HT2C receptor. Finally, local infusions of a 5-HT2C receptor antagonist directly into the oval nucleus of the BNST prevented the fear memory-enhancing effects of citalopram. These findings highlight the ability of the BNST circuitry to be recruited into gating fear and anxiety-like behaviors. Copyright Â© 2016 Elsevier Inc. All rights reserved.
78 FR 26005 - Environmental Management Site-Specific Advisory Board, Savannah River Site

Science.gov (United States)

2013-05-03

...This notice announces a meeting of the Environmental Management Site-Specific Advisory Board (EM SSAB), Savannah River Site. The Federal Advisory Committee Act (Pub. L. 92-463, 86 Stat. 770) requires that public notice of this meeting be announced in the Federal Register.

78 FR 65979 - Environmental Management Site-Specific Advisory Board, Savannah River Site

Science.gov (United States)

2013-11-04

...This notice announces a meeting of the Environmental Management Site-Specific Advisory Board (EM SSAB), Savannah River Site. The Federal Advisory Committee Act (Pub. L. 92-463, 86 Stat. 770) requires that public notice of this meeting be announced in the Federal Register.
77 FR 24695 - Environmental Management Site-Specific Advisory Board, Savannah River Site

Science.gov (United States)

2012-04-25

...This notice announces a meeting of the Environmental Management Site-Specific Advisory Board (EM SSAB), Savannah River Site. The Federal Advisory Committee Act (Pub. L. . 92-463, 86 Stat. 770) requires that public notice of this meeting be announced in the Federal Register.
77 FR 60688 - Environmental Management Site-Specific Advisory Board, Savannah River Site

Science.gov (United States)

2012-10-04

...This notice announces a meeting of the Environmental Management Site-Specific Advisory Board (EM SSAB), Savannah River Site. The Federal Advisory Committee Act (Pub. L. 92-463, 86 Stat. 770) requires that public notice of this meeting be announced in the Federal Register.
77 FR 13104 - Environmental Management Site-Specific Advisory Board, Savannah River Site

Science.gov (United States)

2012-03-05

...This notice announces a meeting of the Environmental Management Site-Specific Advisory Board (EM SSAB), Savannah River Site. The Federal Advisory Committee Act (Pub. L. 92-463, 86 Stat. 770) requires that public notice of this meeting be announced in the Federal Register.
77 FR 39235 - Environmental Management Site-Specific Advisory Board, Savannah River Site

Science.gov (United States)

2012-07-02

...This notice announces a meeting of the Environmental Management Site-Specific Advisory Board (EM SSAB), Savannah River Site. The Federal Advisory Committee Act (Pub. L. 92-463, 86 Stat. 770) requires that public notice of this meeting be announced in the Federal Register.
78 FR 716 - Environmental Management Site-Specific Advisory Board, Savannah River Site

Science.gov (United States)

2013-01-04

...This notice announces a meeting of the Environmental Management Site-Specific Advisory Board (EM SSAB), Savannah River Site. The Federal Advisory Committee Act (Pub. L. 92-463, 86 Stat. 770) requires that public notice of this meeting be announced in the Federal Register.
78 FR 54461 - Environmental Management Site-Specific Advisory Board, Savannah River Site

Science.gov (United States)

2013-09-04

...This notice announces a meeting of the Environmental Management Site-Specific Advisory Board (EM SSAB), Savannah River Site. The Federal Advisory Committee Act (Pub. L. 92-463, 86 Stat. 770) requires that public notice of this meeting be announced in the Federal Register.
77 FR 53193 - Environmental Management Site-Specific Advisory Board, Savannah River Site

Science.gov (United States)

2012-08-31

...This notice announces a meeting of the Environmental Management Site-Specific Advisory Board (EM SSAB), Savannah River Site. The Federal Advisory Committee Act (Pub. L. 92-463, 86 Stat. 770) requires that public notice of this meeting be announced in the Federal Register.
Subsurface characterization and geohydrologic site evaluation West Chestnut Ridge site

International Nuclear Information System (INIS)

1984-01-01

The West Chestnut Ridge Site at the Oak Ridge National Laboratory is being considered for use as a repository for low-level radioactive waste. The purposes of this study were to provide a geohydrological characterization of the site for use in pathways analysis, and to provide preliminary geotechnical recommendations that would be used for development of a site utilization plan. Subsurface conditions were investigated at twenty locations and observation wells were installed. Field testing at each location included the Standard Penetration Test and permeability tests in soil and rock. A well pumping test was ocmpleted at one site. Laboratory testing included permeability, deformability, strength and compaction tests, as well as index and physical property tests. The field investigations showed that the subsurface conditions include residual soil overlying a weathered zone of dolomite which grades into relatively unweathered dolomite at depth. The thickness of residual soil is typically 80 ft (24 m) on the ridges, but can be as little as 10 ft (3 m) in the valleys. Trench excavations to depths of 30 ft (9 m) should not present serious slope stability problems above the water table. On-site soils can be used for liners or trench backfill but these soils may require moisture conditioning to achieve required densities. 19 figures, 8 tables
Proposed radioactive liquid effluent monitoring requirements at the Savannah River Site

International Nuclear Information System (INIS)

Jannik, G.T.; Carlton, W.H.; Blunt, B.C.

1994-01-01

Clear regulatory guidance exists for structuring a radiological air monitoring program, however, there is no parallel guidance for radiological liquid monitoring. For Department of Energy (DOE) facilities, there are no existing applicable federal regulations, DOE orders, or DOE guidance documents that specify at what levels continuous monitoring, continuous sampling, or periodic confirmatory measurements of radioactive liquid effluents must be made. In order to bridge this gap and to technically justify and document liquid effluent monitoring decisions at DOE's Savannah River Site, Westinghouse Savannah River Company has proposed that a graded, dose-based approach be established, in conjunction with limits on facility radionuclide inventories, to determine the monitoring and sampling criteria to be applied at each potential liquid radioactive effluent point. The graded approach would be similar to--and a conservative extension of--the existing, agreed-upon SRS/EPA-IV airborne effluent monitoring approach documented in WSRC's NESHAP Quality Assurance Project Plan. The limits on facility radionuclide inventories are based on--and are a conservative extension of--the 10 CFR 834, 10 CFR 20, and SCR 61-63 annual limits on discharges to sanitary sewers. Used in conjunction with each other, the recommended source category criteria levels and facility radionuclide inventories would allow for the best utilization of resources and provide consistent, technically justifiable determinations of radioactive liquid effluent monitoring requirements
Site Support Program Plan Infrastructure Program

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-09-26

The Fiscal Year 1996 Infrastructure Program Site Support Program Plan addresses the mission objectives, workscope, work breakdown structures (WBS), management approach, and resource requirements for the Infrastructure Program. Attached to the plan are appendices that provide more detailed information associated with scope definition. The Hanford Site`s infrastructure has served the Site for nearly 50 years during defense materials production. Now with the challenges of the new environmental cleanup mission, Hanford`s infrastructure must meet current and future mission needs in a constrained budget environment, while complying with more stringent environmental, safety, and health regulations. The infrastructure requires upgrading, streamlining, and enhancement in order to successfully support the site mission of cleaning up the Site, research and development, and economic transition.
Neurodevelopment of children prenatally exposed to selective reuptake inhibitor antidepressants: Toronto sibling study.

Science.gov (United States)

Nulman, Irena; Koren, Gideon; Rovet, Joanne; Barrera, Maru; Streiner, David L; Feldman, Brian M

2015-07-01

The reproductive safety of selective reuptake inhibitor (SRI) antidepressants needs to be established to provide optimal control of maternal depression while protecting the fetus. To define a child's neurodevelopment following prenatal exposure to SRIs and to account for genetic and environmental confounders in a sibling design using the Toronto Motherisk prospective database. Intelligence and behavior of siblings prenatally exposed and unexposed to SRIs were assessed by using the Wechsler Preschool and Primary Scale of Intelligence-Third Edition, Child Behavior Checklist, and Conners Parent Rating Scale-Revised and subsequently compared. Mothers, diagnosed with depression using DSM-IV, were assessed for intelligence quotient (IQ) and for severity of depressive symptoms with the Center for Epidemiologic Studies Depression scale. Prenatal drug doses and durations of exposure, child's age, child's sex, birth order, severity of maternal depression symptoms, and Full Scale IQ, the primary outcome measure, of both the mother and the child were considered in the analyses. Forty-five sibling pairs (ages 3 years to 6 years 11 months, prenatally exposed and unexposed to SRIs) did not differ in their mean ± SD Full Scale IQs (103 ± 13 vs 106 ± 12; P = .30; 95% CI, -7.06 to 2.21) or rates of problematic behaviors. Significant predictor of children's intelligence was maternal IQ (P = .043, β = 0.306). Severity of maternal depression was a significant predictor of Child Behavior Checklist Internalizing (P = .019, β = 0.366), Externalizing (P = .003, β = 0.457), and Total scores (P = .001, β = 0.494). Drug doses and durations of exposure during pregnancy did not predict any outcomes of interest in the exposed siblings. SRI antidepressants were not found to be neurotoxic. Maternal depression may risk the child's future psychopathology. The sibling design in behavioral teratology aids in separating the effects of maternal depression from those of SRIs, providing stronger
Are selective serotonin reuptake inhibitors safe for drivers? What is the evidence?

Science.gov (United States)

Ravera, Silvia; Ramaekers, Johannes G; de Jong-van den Berg, Lolkje T W; de Gier, Johan J

2012-05-01

Selective serotonin reuptake inhibitors (SSRIs) are widely used medications to treat several psychiatric diseases and, above all, depression. They seem to be as effective as older antidepressants but have a different adverse effect profile. Despite their favorable safety profile, little is known about their influence on traffic safety. To conduct a literature review to summarize the current evidence on the role of SSRIs in traffic safety, particularly concerning undesirable effects that could potentially impair fitness to drive, experimental and pharmacoepidemiologic studies on driving impairment, 2 existing categorization systems for driving-impairing medications, and the European legislative procedures for assessing fitness to drive before issuing a driver's license and driving under the influence of medicines. The article search was performed in the following electronic databases: MEDLINE, PsycINFO, ScienceDirect, and SafetyLit. The English-language scientific literature was searched using key words such as SSRIs and psychomotor performance, car crash or traffic accident, and adverse effects. For inclusion in this review, papers had to be full-text articles, refer to possible driving-related adverse effects, and be experimental or pharmacoepidemiologic studies on SSRIs and traffic accident risks. No restrictions concerning publication year were applied. Ten articles were selected as background information on driving-related adverse effects, and 15 articles were selected regarding experimental and pharmacoepidemiologic work. Regarding SSRI adverse effects, the most reported undesirable effects referring to driving impairment were anxiety, agitation, sleep disturbances, headache, increased risk of suicidal behavior, and deliberate self-harm. Regarding the remaining issues addressed in this article, inconsistencies were found between the outcomes of the selected experimental and epidemiologic studies and between the 2 existing categorization systems under
CERCLA and RCRA requirements affecting cleanup of a hazardous waste management unit at a Superfund site: A case study

International Nuclear Information System (INIS)

Walsh, T.J.

1995-03-01

The Fernald Environmental Management Project (FEMP) attempted to address both RCRA and CERCLA requirements at the fire training facility (FTF) by integrating a CERCLA removal action work plan with a RCRA closure plan. While the regulatory agencies involved with the FTF cleanup agreed the integrated document was a good idea, implementation proved complicated, owing to disposition of clean debris from a Superfund site, treatment of contaminated media, duration of cleanup activities, and cleanup certification. While all the complications have not been resolved, solutions to all have been proposed to Ohio EPA and U.S. EPA. Both agencies have worked closely with FEMP to find the most effective fulfillment of RCRA and CERCLA requirements
Site operations

International Nuclear Information System (INIS)

House, W.B.; Ebenhack, D.G.

1989-01-01

This chapter is a discussion of the management and operations practices used at the Barnwell Waste Management Facility in Barnwell, SC. The following topics are discussed: (1) Waste receiving and inspection, including manifest and certificates of compliance, radiological surveys, disposition of nonconforming items, and decontamination and disposition of secondary waste streams; (2) Waste disposal, including Title 10 CFR 61 requirements, disposal area evaluations, shipment offloading, container emplacement, and radiation protection; (3) Trench closure, including trench backfilling, trench capping, and permanent markers; (4) Site maintenance and stabilization, including trench maintenance, surface water management, and site closure activities; (5) Site monitoring programs, including operational monitoring, and environmental monitoring program; (6) Personnel training and qualifications, including basic training program, safety training program, special skills training, and physical qualifications; (7) Records management, including waste records, personnel training records, personnel dosimetry records, site monitoring records, trench qualification and construction records, and site drawings and stabilization records; (8) Site security; (9) Emergency response plans; and (10) Quality assurance
Construction plant requirements for nuclear sites

International Nuclear Information System (INIS)

Tatum, C.B.; Harris, J.A.

1981-01-01

Planning and developing the temporary construction plant facilities for a nuclear project is equivalent to providing utility services for a small city. Provision of adequate facilities is an important factor in the productivity of both the manual and non-manual work force. This paper summarizes construction facility requirements for a two unit (1300 MWe each) nuclear project. Civil, mechanical and electrical facilities are described, including design, installation and operation. Assignment of responsibility for specific work tasks regarding the construction plant is also discussed. In presenting this data, the authors seek to transfer experience and assist in the provision of adequate facilities on future projects
78 FR 40130 - Environmental Management Site-Specific Advisory Board, Savannah River Site

Science.gov (United States)

2013-07-03

...This notice announces a meeting of the Environmental Management Site-Specific Advisory Board (EM SSAB), Savannah River Site. The Federal Advisory Committee Act (Pub. L. No. 92-463, 86 Stat. 770) requires that public notice of this meeting be announced in the Federal Register.
Structuring a cost-effective site characterization

International Nuclear Information System (INIS)

Berven, B.A.; Little, C.A.; Swaja, R.E.

1990-01-01

Successful chemical and radiological site characterizations are complex activities which require meticulously detailed planning. Each layer of investigation is based upon previously generated information about the site. Baseline historical, physical, geological, and regulatory information is prerequisite for preliminary studies at a site. Preliminary studies then provide samples and measurements which define the identity of potential contaminants and define boundaries around the area to be investigated. The goal of a full site characterization is to accurately determine the extent and magnitude of contaminants and carefully define the site conditions such that the future movements of site contaminants can be assessed for potential exposure to human occupants and/or environmental impacts. Critical to this process is the selection of appropriate measurement and sampling methodology, selection and use of appropriate instrumentation and management/interpretation of site information. Site investigations require optimization between the need of information to maximize the understanding of site conditions and the cost of acquiring that information. 5 refs., 1 tab
Synthesis and binding to striatal membranes of non carrier added I-123 labeled 4'-iodococaine

International Nuclear Information System (INIS)

Metwally, S.A.M.; Gatley, S.J.; Wolf, A.P.; Yu, D.-W.

1992-01-01

An 123 I labeled cocaine analog, 4'-[ 123 I]iodococaine, has been prepared by oxidative destannylation of the tributyltin analog and shown to interact with cocaine binding sites in rat brain striatal membranes. It may thus be a suitable SPECT radiotracer for studies of the dopamine reuptake site in neurodegenerative diseases. (Author)
Web sites that work secrets from winning web sites

CERN Document Server

Smith, Jon

2012-01-01

Leading web site entrepreneur Jon Smith has condensed the secrets of his success into 52 inspiring ideas that even the most hopeless technophobe can implement. The brilliant tips and practical advice in Web sites that work will uplift and transform any website, from the simplest to the most complicated. It deals with everything from fundamentals such as how to assess the effectiveness of a website and how to get a site listed on the most popular search engines to more sophisticated challenges like creating a community and dealing with legal requirements. Straight-talking, practical and humorou

Efficacy of bupropion and the selective serotonin reuptake inhibitors in the treatment of major depressive disorder with high levels of anxiety (anxious depression): a pooled analysis of 10 studies.

Science.gov (United States)

Papakostas, George I; Stahl, Stephen M; Krishen, Alok; Seifert, Cheryl A; Tucker, Vivian L; Goodale, Elizabeth P; Fava, Maurizio

2008-08-01

The goal of this work was to compare the efficacy of the norepinephrine and dopamine reuptake inhibitor bupropion with the selective serotonin reuptake inhibitors (SSRIs) in the treatment of major depressive disorder with high levels of anxiety (anxious depression). Ten double-blind, randomized studies from 1991 through 2006 were combined (N = 2122). Anxious depression was defined as a 17-item Hamilton Rating Scale for Depression (HAM-D-17) anxiety-somatization factor score >or= 7. Among patients with anxious depression (N = 1275), response rates were greater following SSRI than bupropion treatment according to the HAM-D-17 (65.4% vs. 59.4%, p = .03) and the Hamilton Rating Scale for Anxiety (61.5% vs. 54.5%, p = .03). There was also a greater reduction in HAM-D-17 mean +/- SD scores (-14.1 +/- 7.6 vs. -13.2 +/- 7.9, p = .03) and a trend toward statistical significance for a greater reduction in HAM-A mean +/- SD scores (-10.5 +/- 7.4 vs. -9.6 +/- 7.6, p = .05) in favor of SSRI treatment among patients with anxious depression. There was no statistically significant difference in efficacy between bupropion and the SSRIs among patients with moderate/low levels of anxiety. There appears to be a modest advantage for the SSRIs compared to bupropion in the treatment of anxious depression (6% difference in response rates). Using the number-needed-to-treat (NNT) statistic as 1 indicator of clinical significance, nearly 17 patients would need to be treated with an SSRI than with bupropion in order to obtain 1 additional responder. This difference falls well above the limit of NNT = 10, which was suggested by the United Kingdom's National Institute of Clinical Excellence. Nevertheless, the present work is of theoretical interest because it provides preliminary evidence suggesting a central role for serotonin in the regulation of symptoms of negative affect such as anxiety.
Site Support Program Plan Infrastructure Program

International Nuclear Information System (INIS)

1995-01-01

The Fiscal Year 1996 Infrastructure Program Site Support Program Plan addresses the mission objectives, workscope, work breakdown structures (WBS), management approach, and resource requirements for the Infrastructure Program. Attached to the plan are appendices that provide more detailed information associated with scope definition. The Hanford Site's infrastructure has served the Site for nearly 50 years during defense materials production. Now with the challenges of the new environmental cleanup mission, Hanford's infrastructure must meet current and future mission needs in a constrained budget environment, while complying with more stringent environmental, safety, and health regulations. The infrastructure requires upgrading, streamlining, and enhancement in order to successfully support the site mission of cleaning up the Site, research and development, and economic transition
2013 Annual Site Inspection and Monitoring Report for Uranium Mill Tailings Radiation Control Act Title I Disposal Sites

Energy Technology Data Exchange (ETDEWEB)

None, None

2014-03-01

This report, in fulfillment of a license requirement, presents the results of long-term surveillance and maintenance activities conducted by the U.S. Department of Energy (DOE) Office of Legacy Management (LM) in 2013 at 19 uranium mill tailings disposal sites established under Title I of the Uranium Mill Tailings Radiation Control Act (UMTRCA) of 1978.1 These activities verified that the UMTRCA Title I disposal sites remain in compliance with license requirements. DOE operates 18 UMTRCA Title I sites under a general license granted by the U.S. Nuclear Regulatory Commission (NRC) in accordance with Title 10 Code of Federal Regulations Part 40.27 (10 CFR 40.27). As required under the general license, a long-term surveillance plan (LTSP) for each site was prepared by DOE and accepted by NRC. The Grand Junction, Colorado, Disposal Site, one of the 19 Title I sites, will not be included under the general license until the open, operating portion of the cell is closed. The open portion will be closed either when it is filled or in 2023. This site is inspected in accordance with an interim LTSP. Long-term surveillance and maintenance services for these disposal sites include inspecting and maintaining the sites; monitoring environmental media and institutional controls; conducting any necessary corrective actions; and performing administrative, records, stakeholder relations, and other regulatory stewardship functions. Annual site inspections and monitoring are conducted in accordance with site-specific LTSPs and procedures established by DOE to comply with license requirements. Each site inspection is performed to verify the integrity of visible features at the site; to identify changes or new conditions that may affect the long-term performance of the site; and to determine the need, if any, for maintenance, follow-up or contingency inspections, or corrective action in accordance with the LTSP. LTSPs and site compliance reports are available on the Internet at http://www.lm.doe.gov/.
Hanford Site Solid Waste Acceptance Criteria

Energy Technology Data Exchange (ETDEWEB)

1993-11-17

This manual defines the Hanford Site radioactive, hazardous, and sanitary solid waste acceptance criteria. Criteria in the manual represent a guide for meeting state and federal regulations; DOE Orders; Hanford Site requirements; and other rules, regulations, guidelines, and standards as they apply to acceptance of radioactive and hazardous solid waste at the Hanford Site. It is not the intent of this manual to be all inclusive of the regulations; rather, it is intended that the manual provide the waste generator with only the requirements that waste must meet in order to be accepted at Hanford Site TSD facilities.
Hanford Site Solid Waste Acceptance Criteria

International Nuclear Information System (INIS)

1993-01-01

This manual defines the Hanford Site radioactive, hazardous, and sanitary solid waste acceptance criteria. Criteria in the manual represent a guide for meeting state and federal regulations; DOE Orders; Hanford Site requirements; and other rules, regulations, guidelines, and standards as they apply to acceptance of radioactive and hazardous solid waste at the Hanford Site. It is not the intent of this manual to be all inclusive of the regulations; rather, it is intended that the manual provide the waste generator with only the requirements that waste must meet in order to be accepted at Hanford Site TSD facilities
NEVADA TEST SITE WASTE ACCEPTANCE CRITERIA

International Nuclear Information System (INIS)

U.S. DEPARTMENT OF ENERGY, NATIONAL NUCLEAR SECURITY ADMINISTRATION, NEVADA SITE OFFICE

2005-01-01

This document establishes the U. S. Department of Energy, National Nuclear Security Administration Nevada Site Office (NNSA/NSO) waste acceptance criteria (WAC). The WAC provides the requirements, terms, and conditions under which the Nevada Test Site will accept low-level radioactive and mixed waste for disposal. Mixed waste generated within the State of Nevada by NNSA/NSO activities is accepted for disposal. It includes requirements for the generator waste certification program, characterization, traceability, waste form, packaging, and transfer. The criteria apply to radioactive waste received at the Nevada Test Site Area 3 and Area 5 Radioactive Waste Management Site for storage or disposal
Radiation legacy of nuclear tests at the Semipalatinsk test site in the light of requirements ensuring radiation safety performance

International Nuclear Information System (INIS)

Logachev, V.A.; Logacheva, L.A.

2005-01-01

Peculiarities of nuclear tests radiation legacy at the Semipalatinsk test site (STS) are shown in the light of performance of requirements ensuring radiation safety, decrease radiation contamination levels in environment and minimize exposure of radiation for population residing contaminated areas by radioactive fallout. The paper provides data on characterization of peculiarities of the STS operation legacy based on review of archival data of the former 3-d General Administration under USSR Ministry of Health. (author)
Environmental assessment, Richton Dome site, Mississippi (US)

Energy Technology Data Exchange (ETDEWEB)

none,

1986-05-01

The Nuclear Waste Policy Act of 1982 (42 USC Sections 10101-10226) requires the environmental assessment of a potential site to include a statement of the basis for the nomination of a site as suitable for characterization. Volume 2 of this environmental assessment provides a detailed evaluation of the Richton Dome Site and its suitability as the site for a radioactive waste disposal facility under DOE siting guidelines, as well as a comparison of the Richton Dome site with other proposed sites. Evaluation of the Richton Dome site is based on the reference repository design, but the evaluation will not change if based on the Mission Plan repository concept. The comparative evaluation of proposed sites is required under DOE guidelines, but is not intended to directly support the subsequent recommendation of three sites for characterization as candidate sites. 428 refs., 24 figs., 62 tabs. (MHB)
Feedback from performance assessment to site characterisation. The SITE-94 example

International Nuclear Information System (INIS)

Dverstorp, B.; Geier, J.

1999-01-01

Interaction and information exchange between site characterisation and performance assessment are key features of any successful radioactive waste management programme. Some examples are presented of the types of feedback that can be offered from performance assessment to site characterisation, based on SKI's most recent performance assessment project, SITE-94. SITE-94 in Sweden was an assessment of a hypothetical repository for spent nuclear fuel, based on real data gathered in the surface-based investigation of the Aespoe Hard Rock Laboratory site. Examples of feedback are given concerning quality control of data and site investigation procedures, identification of key parameters for the performance assessment, use of models for planning and evaluation of a site investigation, data sampling strategies, and guidance on future priorities for further development of site investigation methods. Because site characterisation serves multiple purposes, including provision of data for repository design and construction, it must account for and compromise among requirements from several lines of analyses in the performance assessment. (author)
Some Examples of the Relationship Between Containment and Other Engineered Safeguard Requirements, Accident Analyses and Site Conditions

Energy Technology Data Exchange (ETDEWEB)

Vinck, W. F.; Maurer, H. [EURATOM, Brussels (Belgium)

1967-09-15

The paper refers primarily to nuclear power reactors for which EURATOM has performed safety reviews in co-operation with national technical advisory organizations concerned in the licensing procedures. Comparative data are tabulated on a number of containment concepts and other engineered safeguards to protect against or to limit the consequences of major hypothetical accidents for a number of power reactors. Main environmental data, such as magnitudes of exclusion areas and population densities, are also presented. A number of topics of particular interest which were encountered during the safety analysis and which find widespread application in the assessment of the siting conditions and emergency planning are discussed. In this discussion, emphasis is placed on containment, engineered safeguards and emergency equipment. These items are considered in general with emphasis on: (a ) the importance of meeting operability and high efficiency requirements (reliability ) when needed through design and layout; (b) periodic testing and/or inspection possibilities and requirements in order to maintain high availability standards. Attention is drawn to some difficulties which have arisen in connection with design, material choice and construction of steel containment structures and which in the interests of safety as well as of economic optimization justify in the future more care in the use of possibly uniform or single-code requirements. Examples of uncertainties encountered in some accident analyses and their influence on siting considerations are discussed, with emphasis on safeguards intended to retain radioactive material in the plant, such as extent of core damage, iodine plate-out, filtering efficiency, wash-out effects. The means by which some of the main uncertainties have been or can in the future be eliminated through appropriate experimental programmes performed throughout the world are discussed. Some examples are also given of the influence of factors which
2013 Annual Site Inspection and Monitoring Report for Uranium Mill Tailings Radiation Control Act Title II Disposal Sites

International Nuclear Information System (INIS)

2013-01-01

This report, in fulfillment of a license requirement, presents the results of long-term surveillance and maintenance activities conducted by the U.S. Department of Energy (DOE) Office of Legacy Management in 2013 at six uranium mill tailings disposal sites reclaimed under Title II of the Uranium Mill Tailings Radiation Control Act (UMTRCA) of 1978. These activities verified that the UMTRCA Title II disposal sites remain in compliance with license requirements. DOE manages six UMTRCA Title II disposal sites under a general license granted by the U.S. Nuclear Regulatory Commission (NRC) established at Title 10 Code of Federal Regulations Part 40.28. Reclamation and site transition activities continue at other sites, and DOE ultimately expects to manage approximately 27 Title II disposal sites. Long-term surveillance and maintenance activities and services for these disposal sites include inspecting and maintaining the sites; monitoring environmental media and institutional controls; conducting any necessary corrective action; and performing administrative, records, stakeholder services, and other regulatory functions. Annual site inspections and monitoring are conducted in accordance with site-specific long-term surveillance plans (LTSPs) and procedures established by DOE to comply with license requirements. Each site inspection is performed to verify the integrity of visible features at the site; to identify changes or new conditions that may affect the long-term performance of the site; and to determine the need, if any, for maintenance, follow-up inspections, or corrective action. LTSPs and site compliance reports are available online at http://www.lm.doe.gov
2013 Annual Site Inspection and Monitoring Report for Uranium Mill Tailings Radiation Control Act Title II Disposal Sites

Energy Technology Data Exchange (ETDEWEB)

None

2013-11-01

This report, in fulfillment of a license requirement, presents the results of long-term surveillance and maintenance activities conducted by the U.S. Department of Energy (DOE) Office of Legacy Management in 2013 at six uranium mill tailings disposal sites reclaimed under Title II of the Uranium Mill Tailings Radiation Control Act (UMTRCA) of 1978. These activities verified that the UMTRCA Title II disposal sites remain in compliance with license requirements. DOE manages six UMTRCA Title II disposal sites under a general license granted by the U.S. Nuclear Regulatory Commission (NRC) established at Title 10 Code of Federal Regulations Part 40.28. Reclamation and site transition activities continue at other sites, and DOE ultimately expects to manage approximately 27 Title II disposal sites. Long-term surveillance and maintenance activities and services for these disposal sites include inspecting and maintaining the sites; monitoring environmental media and institutional controls; conducting any necessary corrective action; and performing administrative, records, stakeholder services, and other regulatory functions. Annual site inspections and monitoring are conducted in accordance with site-specific long-term surveillance plans (LTSPs) and procedures established by DOE to comply with license requirements. Each site inspection is performed to verify the integrity of visible features at the site; to identify changes or new conditions that may affect the long-term performance of the site; and to determine the need, if any, for maintenance, follow-up inspections, or corrective action. LTSPs and site compliance reports are available online at http://www.lm.doe.gov
Site study plan for Transportation, Deaf Smith County Site, Texas: Preliminary draft

International Nuclear Information System (INIS)

1987-06-01

This site study plan describes transportation field studies to be conducted during the characterization of the Deaf Smith County, Texas, site for the US Department of Energy's Salt Repository Project. The studies are needed to identify and assess potential project impacts to transportation infrastructure and systems in the project vicinity and along potential transportation routes to the site across the State of Texas. The studies are also needed to locate and design project transportation facilities, and to evaluate and design impact mitigation. After identifying the transportation information requirements needed to comply with Federal, State, and local regulations and repository program requirements, the site study plan describes the study design and rationale, the field data collection procedures and equipment, the data analysis methods and application of results, the data management strategy, the schedule of field activities, the management of the study, and the study's quality assurance program. The field data collection activities are organized into programs for the characterization of site vicinity rail corridors and highway corridors, characterization of alternative statewide transportation routes, monitoring of site characterization effects on transportation, characterization of aircraft overflight patterns and hazardous material transportation patterns, and assessment of emergency response preparedness along alternative statewide transportation routes. 34 refs., 10 figs., 2 tabs
Rapid Onset of the Effects of Combined Selective Serotonin Reuptake Inhibitors and Electroacupuncture on Primary Depression: A Meta-Analysis.

Science.gov (United States)

Zhang, Yue; Qu, Shan-shan; Zhang, Ji-ping; Sun, Ya-ling; Liu, Wei-lu; Xie, Ling; Huang, Yong; Chen, Jun-qi

2016-01-01

To evaluate the efficacy and safety of combined selective serotonin reuptake inhibitors (SSRIs) and electroacupuncture therapies for the early treatment of primary depression. Randomized controlled trials (RCTs) were analyzed to compare therapy combining SSRIs and electroacupuncture to SSRI therapy alone. The RCTs were identified by searching, among others, PubMed, the Cochrane Library, the Chinese National Knowledge Infrastructure, the Chongqing VIP database for Chinese Technical Periodicals, WANFANG DATA, and the Chinese Biological Medical Literature Database. Scores from Self-Rated Depression Scale (SDS), the Hamilton Depression Scale (HAMD), the Side Effect Rating Scale (SERS), and the Treatment Emergent Symptom Scale (TESS) were analyzed and coded by two independent investigators and used to evaluate the safety and efficacy of treatment. Statistical analyses were performed using RevMan 5.2 software. Six RCTs were analyzed. The meta-analysis revealed that the combined therapy of SSRIs and electroacupuncture were associated with superior scores on the HAMD, SDS, and SERS measures compared with SSRIs alone after 1-4 weeks of treatment: HAMD scores, mean difference (MD)(1 week), 2.32 (95% confidence interval [CI](1 week), 1.47-3.16, p(1 week)electroacupuncture therapies is more efficient than treatments with SSRIs alone and leads to a better and earlier control of depressive symptoms.
Drupal 7 Multilingual Sites

CERN Document Server

Pol, Kristen

2012-01-01

A practical book with plenty of screenshots to guide you through the many features of multilingual Drupal. A demo ecommerce site is provided if you want to practice on a sample site, although you can apply the techniques learnt in the book directly to your site too. Any Drupal users who know the basics of building a Drupal site and are familiar with the Drupal UI, will benefit from this book. No previous knowledge of localization or internationalization is required.
Hanford Site Infrastructure Plan

International Nuclear Information System (INIS)

1990-01-01

The Hanford Site Infrastructure Plan (HIP) has been prepared as an overview of the facilities, utilities, systems, and services that support all activities on the Hanford Site. Its purpose is three-fold: to examine in detail the existing condition of the Hanford Site's aging utility systems, transportation systems, Site services and general-purpose facilities; to evaluate the ability of these systems to meet present and forecasted Site missions; to identify maintenance and upgrade projects necessary to ensure continued safe and cost-effective support to Hanford Site programs well into the twenty-first century. The HIP is intended to be a dynamic document that will be updated accordingly as Site activities, conditions, and requirements change. 35 figs., 25 tabs
Synthesis and binding to striatal membranes of non carrier added I-123 labeled 4'-iodococaine

Energy Technology Data Exchange (ETDEWEB)

Metwally, S.A.M.; Gatley, S.J.; Wolf, A.P.; Yu, D.-W. (Brookhaven National Lab., Upton, NY (United States))

1992-03-01

An {sup 123}I labeled cocaine analog, 4'-({sup 123}I)iodococaine, has been prepared by oxidative destannylation of the tributyltin analog and shown to interact with cocaine binding sites in rat brain striatal membranes. It may thus be a suitable SPECT radiotracer for studies of the dopamine reuptake site in neurodegenerative diseases. (Author).
One-site versus two-site phacotrabeculectomy: a prospective randomized study

Directory of Open Access Journals (Sweden)

Moschos MM

2015-08-01

Full Text Available Marilita M Moschos,1 Irini P Chatziralli,2 Michael Tsatsos3 1First Department of Ophthalmology, University of Athens, 2Second Department of Ophthalmology, Ophthalmiatrion Athinon, Athens, Greece; 3Department of Ophthalmology, Cambridge University Hospital NHS, Cambridge, UK Purpose: The purpose of this study is to compare the efficacy and safety of one-site and two-site combined phacotrabeculectomy with foldable posterior chamber intraocular lens implantation.Methods: Thirty-four patients (41 eyes with glaucoma and cataract were randomly assigned to undergo either a one-site (22 eyes or a two-site (19 eyes combined procedure. One-site approach consisted of a standard superior phacotrabeculectomy with a limbus-based conjunctival flap, while two-site approach consisted of a clear cornea phacoemulsification and a separate superior trabeculectomy with a limbus-based conjunctival flap.Results: Mean follow-up period was 54 months (standard deviation [SD] 2.3. Mean preoperative intraocular pressure (IOP in the one-site group was 21.3 mmHg (SD 2.8 and in the two-site group was 21.8 mmHg (SD 3.0 (P>0.1. Mean postoperative IOP significantly decreased in both groups compared to the preoperative level and was 15.6 mmHg (SD 3.5 in the one-site group and 14.9 mmHg (SD 2.7 in the two-site group. Three months later, the difference between the two groups was not statistically significant (P=0.058. The one-site group required significantly more medications than the two-site group (P=0.03. Best-corrected visual acuity (BCVA improved similarly in both groups, but there was less postoperative (induced astigmatism in the two-site group in a marginal statistical level (P=0.058. Intra- and postoperative complications were comparable in the two groups.Conclusion: Both techniques yielded similar results concerning final BCVA and IOP reduction. However, the two-site group had less induced astigmatism and a better postoperative IOP control with less required
The evolutionary origin of the need to sleep: an inevitable consequence of synaptic neurotransmission?

Science.gov (United States)

Cantor, Robert S

2015-01-01

It is proposed that the evolutionary origin of the need to sleep is the removal of neurotransmitters (NTs) that escape reuptake and accumulate in brain interstitial fluid (ISF). Recent work suggests that the activity of ionotropic postsynaptic receptors, rapidly initiated by binding of NTs to extracellular sites, is modulated over longer times by adsorption of these NTs to the lipid bilayers in which the receptors are embedded. This bilayer-mediated mechanism is far less molecularly specific than binding, so bilayer adsorption of NTs that have diffused into synapses for other receptors would modulate their activity as well. Although NTs are recycled by membrane protein reuptake, the process is less than 100% efficient; a fraction escapes the region in which these specific reuptake proteins are localized and eventually diffuses throughout the ISF. It is estimated that even if only 0.1% of NTs escape reuptake, they would accumulate and adsorb to bilayers in synapses of other receptors sufficiently to affect receptor activity, the harmful consequences of which are avoided by sleep: a period of efficient convective clearance of solutes together with greatly reduced synaptic activity.
The evolutionary origin of the need to sleep: An inevitable consequence of synaptic neurotransmission?

Directory of Open Access Journals (Sweden)

Robert S. Cantor

2015-09-01

Full Text Available It is proposed that the evolutionary origin of the need to sleep is the removal of neurotransmitters (NTs that escape reuptake and accumulate in brain interstitial fluid. Recent work suggests that the activity of ionotropic postsynaptic receptors, rapidly initiated by binding of NTs to extracellular sites, is modulated over longer times by adsorption of these NTs to the lipid bilayers in which the receptors are embedded. This bilayer-mediated mechanism is far less molecularly specific than binding, so bilayer adsorption of NTs that have diffused into synapses for other receptors would modulate their activity as well. Although NTs are recycled by membrane protein reuptake, the process is less than 100% efficient; a fraction escapes the region in which these specific reuptake proteins are localized and eventually diffuses throughout the interstitial fluid. It is estimated that even if only 0.1% of NTs escape reuptake, they would accumulate and adsorb to bilayers in synapses of other receptors sufficiently to affect receptor activity, the harmful consequences of which are avoided by sleep: a period of efficient convective clearance of solutes together with greatly reduced synaptic activity.

10 CFR 72.96 - Siting limitations.

Science.gov (United States)

2010-01-01

... REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR THE INDEPENDENT STORAGE OF SPENT NUCLEAR FUEL... site within which there is a candidate site for a HLW repository. This limitation shall apply until such time as DOE decides that such candidate site is no longer a candidate site under consideration for...
Tratamento farmacológico do transtorno obsessivo-compulsivo

Directory of Open Access Journals (Sweden)

Carla Marques

2001-10-01

Full Text Available The pharmacotherapy for obsessive-compulsive disorder (OCD has started with clomipramine, a potent non-selective serotonin reuptake inhibitor. Newer drugs that selectively inhibit serotonin reuptake (SSRIs such as fluvoxamine, fluoxetine, paroxetine, and sertraline are also effective and well-tolerated by OCD patients, even in high doses. Efficacy of venlafaxine and citalopram for OCD are under investigation. Randomized controlled trials of OCD pharmacotherapy, as well as positive results found in open trials and case reports are reviewed in this paper. Potent selective serotonin reuptake inhibitors are the pharmacotherapy of choice for OCD. If one SSRI is ineffective, others may be beneficial. OCD is frequently a chronic condition that requires long-term treatment.
On-site meteorological instrumentation requirements to characterize diffusion from point sources: workshop report. Final report Sep 79-Sep 80

International Nuclear Information System (INIS)

Strimaitis, D.; Hoffnagle, G.; Bass, A.

1981-04-01

Results of a workshop entitled 'On-Site Meteorological Instrumentation Requirements to Characterize Diffusion from Point Sources' are summarized and reported. The workshop was sponsored by the U.S. Environmental Protection Agency in Raleigh, North Carolina, on January 15-17, 1980. Its purpose was to provide EPA with a thorough examination of the meteorological instrumentation and data collection requirements needed to characterize airborne dispersion of air contaminants from point sources and to recommend, based on an expert consensus, specific measurement technique and accuracies. Secondary purposes of the workshop were to (1) make recommendations to the National Weather Service (NWS) about collecting and archiving meteorological data that would best support air quality dispersion modeling objectives and (2) make recommendations on standardization of meteorological data reporting and quality assurance programs
Environmental assessment, Deaf Smith County site, Texas

Energy Technology Data Exchange (ETDEWEB)

1986-05-01

The Nuclear Waste Policy Act of 1982 (42 USC sections 10101-10226) requires the environmental assessment of a proposed site to include a statement of the basis for nominating a site as suitable for characterization. Volume 2 provides a detailed statement evaluating the site suitability of the Deaf Smith County Site under DOE siting guidelines, as well as a comparison of the Deaf Smith County Site to the other sites under consideration. The evaluation of the Deaf Smith County Site is based on the impacts associated with the reference repository design, but the evaluation will not change if based on the Mission Plan repository concept. The second part of this document compares the Deaf Smith County Site to Davis Canyon, Hanford, Richton Dome and Yucca Mountain. This comparison is required under DOE guidelines and is not intended to directly support subsequent recommendation of three sites for characterization as candidate sites. 259 refs., 29 figs., 66 refs. (MHB)
Environmental assessment, Deaf Smith County site, Texas

International Nuclear Information System (INIS)

1986-05-01

The Nuclear Waste Policy Act of 1982 (42 USC sections 10101-10226) requires the environmental assessment of a proposed site to include a statement of the basis for nominating a site as suitable for characterization. Volume 2 provides a detailed statement evaluating the site suitability of the Deaf Smith County Site under DOE siting guidelines, as well as a comparison of the Deaf Smith County Site to the other sites under consideration. The evaluation of the Deaf Smith County Site is based on the impacts associated with the reference repository design, but the evaluation will not change if based on the Mission Plan repository concept. The second part of this document compares the Deaf Smith County Site to Davis Canyon, Hanford, Richton Dome and Yucca Mountain. This comparison is required under DOE guidelines and is not intended to directly support subsequent recommendation of three sites for characterization as candidate sites. 259 refs., 29 figs., 66 refs
Decommissioning of commercial shallow-land burial sites

International Nuclear Information System (INIS)

Murphy, E.S.; Holter, G.M.

1979-01-01

Estimated costs and safety considerations for decommissioning LLW burial grounds have been evaluated. Calculations are based on a generic burial ground assumed to be located at a western and an eastern site. Decommissioning modes include: (1) site stabilization followed by long-term care of the site; and (2) waste relocation. Site stabilization is estimated to cost from $0.4 million to $7.5 million, depending on the site and the stabilization option chosen. Long-term care is estimated to cost about $100,000 annually, with somewhat higher costs during early years because of increased site maintenance and environmental monitoring requirements. Long-term care is required until the site is released for unrestricted public use. Occupational and public safety impacts of site stabilization and long-term care are estimated to be small. Relocation of all the waste from a reference burial ground is estimated to cost more than $1.4 billion and to require more than 20 years for completion. Over 90% of the cost is associated with packaging, transportation, and offsite disposal of the exhumed waste. Waste relocation results in significant radiation exposure to decommissioning workers
Hanford site transuranic waste certification plan

International Nuclear Information System (INIS)

GREAGER, T.M.

1999-01-01

As a generator of transuranic (TRU) and TRU mixed waste destined for disposal at the Waste Isolation Pilot Plant (WIPP), the Hanford Site must ensure that its TRU waste meets the requirements of U.S. Department of Energy (DOE) Order 5820.2A, ''Radioactive Waste Management, and the Waste Acceptance Criteria for the Waste Isolation Pilot Plant' (DOE 1996d) (WIPP WAC). The WIPP WAC establishes the specific physical, chemical, radiological, and packaging criteria for acceptance of defense TRU waste shipments at WIPP. The WIPP WAC also requires that participating DOE TRU waste generator/treatment/storage sites produce site-specific documents, including a certification plan, that describe their management of TRU waste and TRU waste shipments before transferring waste to WIPP. The Hanford Site must also ensure that its TRU waste destined for disposal at WIPP meets requirements for transport in the Transuranic Package Transporter41 (TRUPACT-11). The U.S. Nuclear Regulatory Commission (NRC) establishes the TRUPACT-I1 requirements in the ''Safety Analysis Report for the TRUPACT-II Shipping Package'' (NRC 1997) (TRUPACT-I1 SARP)
Five Patients With Burning Mouth Syndrome in Whom an Antidepressant (Serotonin-Noradrenaline Reuptake Inhibitor) Was Not Effective, but Pregabalin Markedly Relieved Pain.

Science.gov (United States)

Ito, Mikiko; Tokura, Tatsuya; Yoshida, Keizo; Nagashima, Wataru; Kimura, Hiroyuki; Umemura, Eri; Tachibana, Masako; Miyauchi, Tomoya; Kobayashi, Yuka; Arao, Munetaka; Ozaki, Norio; Kurita, Kenichi

2015-01-01

Burning mouth syndrome (BMS) causes idiopathic pain or a burning sensation in clinically normal oral mucosa. Burning mouth syndrome is a chronic disease with an unknown etiology. Burning mouth syndrome is also idiopathic, and a consensus regarding diagnosis/treatment has not been reached yet. Recent studies have supported the suggestion that BMS is a neuropathic pain disorder in which both the peripheral and central nervous systems are involved. Tricyclic antidepressants (nortriptyline and amitriptyline), serotonin-noradrenaline reuptake inhibitors (SNRIs) (duloxetine and milnacipran), and antiepileptic drugs, potential-dependent calcium channel α2δ subunit ligands (gabapentine and pregabalin), are currently recommended as the first-choice drugs for neuropathic pain. In this study, we report 5 patients with BMS in whom there was no response to SNRI (milnacipran or duloxetine), or administration was discontinued because of adverse reactions, but in whom pregabalin therapy markedly reduced or led to the disappearance of pain in a short period. Pregabalin, whose mechanism of action differs from that of SNRIs, may become a treatment option for BMS patients who are not responsive to or are resistant to SNRIs.
The serotonin transporter in rhesus monkey brain: comparison of DASB and citalopram binding sites

Energy Technology Data Exchange (ETDEWEB)

Zeng Zhizhen [Imaging Department, Merck Research Laboratories, West Point, PA 19486 (United States)]. E-mail: zhizhen_zeng@merck.com; Chen, T.-B. [Imaging Department, Merck Research Laboratories, West Point, PA 19486 (United States); Miller, Patricia J. [Imaging Department, Merck Research Laboratories, West Point, PA 19486 (United States); Dean, Dennis [Labeled Compound Synthesis Group, Drug Metabolism, Merck Research Laboratories, Rahway, NJ 07065-0900 (United States); Tang, Y.S. [Labeled Compound Synthesis Group, Drug Metabolism, Merck Research Laboratories, Rahway, NJ 07065-0900 (United States); Sur, Cyrille [Imaging Department, Merck Research Laboratories, West Point, PA 19486 (United States); Williams, David L. [Imaging Department, Merck Research Laboratories, West Point, PA 19486 (United States)

2006-05-15

We have characterized the interaction of the serotonin transporter ligand [{sup 3}H]-N,N-dimethyl-2-(2-amino-4-cyanophenylthio)-benzylamine (DASB) with rhesus monkey brain in vitro using tissue homogenate binding and autoradiographic mapping. [{sup 3}H]-DASB, a tritiated version of the widely used [{sup 11}C] positron emission tomography tracer, was found to selectively bind to a single population of sites with high affinity (K {sub d}=0.20{+-}0.04 nM). The serotonin transporter density (B {sub max}) obtained for rhesus frontal cortex was found to be 66{+-}8 fmol/mg protein using [{sup 3}H]-DASB, similar to the B {sub max} value obtained using the reference radioligand [{sup 3}H]-citalopram, a well-characterized and highly selective serotonin reuptake inhibitor (83{+-}22 fmol/mg protein). Specific binding sites of both [{sup 3}H]-DASB and [{sup 3}H]-citalopram were similarly and nonuniformly distributed throughout the rhesus central nervous system, in a pattern consistent with serotonin transporter localization reported for human brain. Regional serotonin transporter densities, estimated from optical densities of the autoradiographic images, were well correlated between the two radioligands. Finally, DASB and fluoxetine showed dose-dependent full inhibition of [{sup 3}H]-citalopram binding in a competition autoradiographic study, with K {sub i} values in close agreement with those obtained from rhesus brain homogenates. This side-by-side comparison of [{sup 3}H]-DASB and [{sup 3}H]-citalopram binding sites in rhesus tissue homogenates and in adjacent rhesus brain slices provides additional support for the use of [{sup 11}C]-DASB to assess the availability and distribution of serotonin transporters in nonhuman primates.
Piv site-specific invertase requires a DEDD motif analogous to the catalytic center of the RuvC Holliday junction resolvases.

Science.gov (United States)

Buchner, John M; Robertson, Anne E; Poynter, David J; Denniston, Shelby S; Karls, Anna C

2005-05-01

Piv, a unique prokaryotic site-specific DNA invertase, is related to transposases of the insertion elements from the IS110/IS492 family and shows no similarity to the site-specific recombinases of the tyrosine- or serine-recombinase families. Piv tertiary structure is predicted to include the RNase H-like fold that typically encompasses the catalytic site of the recombinases or nucleases of the retroviral integrase superfamily, including transposases and RuvC-like Holliday junction resolvases. Analogous to the DDE and DEDD catalytic motifs of transposases and RuvC, respectively, four Piv acidic residues D9, E59, D101, and D104 appear to be positioned appropriately within the RNase H fold to coordinate two divalent metal cations. This suggests mechanistic similarity between site-specific inversion mediated by Piv and transposition or endonucleolytic reactions catalyzed by enzymes of the retroviral integrase superfamily. The role of the DEDD motif in Piv catalytic activity was addressed using Piv variants that are substituted individually or multiply at these acidic residues and assaying for in vivo inversion, intermolecular recombination, and DNA binding activities. The results indicate that all four residues of the DEDD motif are required for Piv catalytic activity. The DEDD residues are not essential for inv recombination site recognition and binding, but this acidic tetrad does appear to contribute to the stability of Piv-inv interactions. On the basis of these results, a working model for Piv-mediated inversion that includes resolution of a Holliday junction is presented.
Siting factors for the Swedish deep repository for spent fuel

International Nuclear Information System (INIS)

Stroem, A.; Ericsson, Lars O.; Svemar, C.; Almen, K.E.; Andersson, Johan

1998-01-01

A project entitled Siting factors and criteria for site evaluation was initiated at the SKB in 1997. The project comprises an important part of the work of siting and site selection that is being pursued within SKB. The purpose of the project is to create a logical structure for the continued siting work, and its results should also be able to be used to assist in evaluating sites. The project will thereby also provide a means - in accordance with the Government's decision regarding Research Programme 95 - to obtain more detailed and quantified siting factors and criteria than those previously presented in the supplement to Research Programme 92. The overall goals of the project are to identify and quantify requirements and preferences regarding the properties of the rock and the soil from the perspectives of long-term safety, performance and planning and design of the rock works, and to identify siting factors and criteria. The latter should be able to be used to determine whether requirements and preferences are satisfied, both when screening sites for site investigation and after completed site investigation. Presented requirements, preferences, factors and criteria must be acceptable to national and municipal authorities or others with influence over the siting work. To start with, requirements and preferences regarding the performance of the rock in a deep repository have been clarified. These requirements and preferences are based on many years of experience of safety assessments and construction analyses within SKB. What is new here is the structuring that has been done, where a classification is made into different geoscientific disciplines, and the formalism that has been developed for the concepts requirements, preferences and performance. This is a prerequisite for a consistent and hopefully comprehensive set of requirements from a functional perspective. Work has continued on siting factors with reference to a coming site investigation programme. A
Implications of NGA for NEHRP site coefficients

Science.gov (United States)

Borcherdt, Roger D.

2012-01-01

Three proposals are provided to update tables 11.4-1 and 11.4-2 of Minimum Design Loads for Buildings and Other Structures (7-10), by the American Society of Civil Engineers (2010) (ASCE/SEI 7-10), with site coefficients implied directly by NGA (Next Generation Attenuation) ground motion prediction equations (GMPEs). Proposals include a recommendation to use straight-line interpolation to infer site coefficients at intermediate values of ̅vs (average shear velocity). Site coefficients are recommended to ensure consistency with ASCE/SEI 7-10 MCER (Maximum Considered Earthquake) seismic-design maps and simplified site-specific design spectra procedures requiring site classes with associated tabulated site coefficients and a reference site class with unity site coefficients. Recommended site coefficients are confirmed by independent observations of average site amplification coefficients inferred with respect to an average ground condition consistent with that used for the MCER maps. The NGA coefficients recommended for consideration are implied directly by the NGA GMPEs and do not require introduction of additional models.
Proposal for geological site selection for L/ILW and HLW repositories. Statement of requirements, procedure and results. Technical report 08-03

International Nuclear Information System (INIS)

2008-10-01

Important steps in the process of managing radioactive wastes have already been implemented in Switzerland. These include the handing and packaging of the waste, waste characterisation and documentation of waste inventories and interim storage along with associated transport. In terms of preparing for deep geological disposal, the necessary scientific and technical work is well advanced and the feasibility of constructing geological repositories that provide the required long-term safety has been successfully demonstrated for all waste types arising in Switzerland. Sufficient knowledge is available to allow the next steps in the selection of repository sites to be defined. The legal framework is also in place and organisational measures have been provided that will allow the tasks to be performed in the coming years to be implemented efficiently. The selection of geological siting regions and sites for repositories in Switzerland will be conducted in three stages. Stage 1 ends with the definition of geological siting regions within which the repository projects will be elaborated in more detail in stages 2 and 3. This report documents and justifies the siting proposals prepared by Nagra for the repositories for low- and intermediate-level waste (L/ILW) and high-level waste (HLW). Formulation of these proposals is conducted in five steps: 1) The waste inventory, which includes reserves for future developments, is allocated to the L/ILW and HLW repositories; 2) Based on this waste allocation, the second step involves defining the barrier and safety concepts for the two repositories. With a view to evaluating the geological siting possibilities, quantitative and qualitative guidelines and requirements on the geology are derived on the basis of these concepts. These relate to the time period to be considered, the space requirements for the repository, the properties of the host rock (depth, thickness, lateral extent, hydraulic conductivity), long-term stability
Site investigations: Strategy for rock mechanics site descriptive model

International Nuclear Information System (INIS)

Andersson, Johan; Christiansson, Rolf; Hudson, John

2002-05-01

As a part of the planning work for the Site Investigations, SKB has developed a Rock Mechanics Site Descriptive Modelling Strategy. Similar strategies are being developed for other disciplines. The objective of the strategy is that it should guide the practical implementation of evaluating site specific data during the Site Investigations. It is also understood that further development may be needed. This methodology enables the crystalline rock mass to be characterised in terms of the quality at different sites, for considering rock engineering constructability, and for providing the input to numerical models and performance assessment calculations. The model describes the initial stresses and the distribution of deformation and strength properties of the intact rock, of fractures and fracture zones, and of the rock mass. The rock mass mechanical properties are estimated by empirical relations and by numerical simulations. The methodology is based on estimation of mechanical properties using both empirical and heroretical/numerical approaches; and estimation of in situ rock stress using judgement and numerical modelling, including the influence of fracture zones. These approaches are initially used separately, and then combined to produce the required characterisation estimates. The methodology was evaluated with a Test Case at the Aespoe Hard Rock Laboratory in Sweden. The quality control aspects are an important feature of the methodology: these include Protocols to ensure the structure and coherence of the procedures used, regular meetings to enhance communication, feedback from internal and external reviewing, plus the recording of an audit trail of the development steps and decisions made. The strategy will be reviewed and, if required, updated as appropriate
Site investigations: Strategy for rock mechanics site descriptive model

Energy Technology Data Exchange (ETDEWEB)

Andersson, Johan [JA Streamflow AB, Aelvsjoe (Sweden); Christiansson, Rolf [Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden); Hudson, John [Rock Engineering Consultants, Welwyn Garden City (United Kingdom)

2002-05-01

As a part of the planning work for the Site Investigations, SKB has developed a Rock Mechanics Site Descriptive Modelling Strategy. Similar strategies are being developed for other disciplines. The objective of the strategy is that it should guide the practical implementation of evaluating site specific data during the Site Investigations. It is also understood that further development may be needed. This methodology enables the crystalline rock mass to be characterised in terms of the quality at different sites, for considering rock engineering constructability, and for providing the input to numerical models and performance assessment calculations. The model describes the initial stresses and the distribution of deformation and strength properties of the intact rock, of fractures and fracture zones, and of the rock mass. The rock mass mechanical properties are estimated by empirical relations and by numerical simulations. The methodology is based on estimation of mechanical properties using both empirical and heroretical/numerical approaches; and estimation of in situ rock stress using judgement and numerical modelling, including the influence of fracture zones. These approaches are initially used separately, and then combined to produce the required characterisation estimates. The methodology was evaluated with a Test Case at the Aespoe Hard Rock Laboratory in Sweden. The quality control aspects are an important feature of the methodology: these include Protocols to ensure the structure and coherence of the procedures used, regular meetings to enhance communication, feedback from internal and external reviewing, plus the recording of an audit trail of the development steps and decisions made. The strategy will be reviewed and, if required, updated as appropriate.
Savannah River Site computing architecture

Energy Technology Data Exchange (ETDEWEB)

1991-03-29

A computing architecture is a framework for making decisions about the implementation of computer technology and the supporting infrastructure. Because of the size, diversity, and amount of resources dedicated to computing at the Savannah River Site (SRS), there must be an overall strategic plan that can be followed by the thousands of site personnel who make decisions daily that directly affect the SRS computing environment and impact the site`s production and business systems. This plan must address the following requirements: There must be SRS-wide standards for procurement or development of computing systems (hardware and software). The site computing organizations must develop systems that end users find easy to use. Systems must be put in place to support the primary function of site information workers. The developers of computer systems must be given tools that automate and speed up the development of information systems and applications based on computer technology. This document describes a proposal for a site-wide computing architecture that addresses the above requirements. In summary, this architecture is standards-based data-driven, and workstation-oriented with larger systems being utilized for the delivery of needed information to users in a client-server relationship.
Meteorology in site operations

International Nuclear Information System (INIS)

Anon.

1986-01-01

During the site selection and design phases of a plant, meteorological assistance must be based on past records, usually accumulated at stations not actually on the site. These preliminary atadvices will be averages and extremes that might be expected. After a location has been chosen and work has begun, current and forecast weather conditions become of immediate concern. On-site meteorological observations and forecasts have many applications to the operating program of an atomic energy site. Requirements may range from observations of the daily minimum temperatures to forecasts of radiation dosages from airborne clouds
Site Decommissioning Management Plan. Supplement 1

International Nuclear Information System (INIS)

Fauver, D.N.; Weber, M.F.; Johnson, T.C.; Kinneman, J.D.

1995-11-01

The Nuclear Regulatory Commission (NRC) staff has identified 51 sites contaminated with radioactive material that require special attention to ensure timely decommissioning. While none of these sites represent an immediate threat to public health and safety, they have contamination that exceeds existing NRC criteria for unrestricted use. All of these sites require some degree of remediation, and several involve regulatory issues that must be addressed by the Commission before they can be released for unrestricted use and the applicable licenses terminated. This report contains the NRC stairs strategy for addressing the technical, legal, and policy issues affecting the timely decommissioning of the 51 sites and describes the status of decommissioning activities at the sites. This is supplement number one to NUREG-1444, which was published in October 1993
Bedrock hydrogeology Forsmark. Site descriptive modelling, SDM-Site Forsmark

Energy Technology Data Exchange (ETDEWEB)

Follin, Sven (SF GeoLogic AB, Taeby (Sweden))

2008-12-15

The Swedish Nuclear Fuel and Waste Management Company (SKB) has conducted site investigations at two different locations, the Forsmark and Laxemar-Simpevarp areas, with the objective of siting a final repository for spent nuclear fuel according to the KBS-3 concept. Site characterisation should provide all data required for an integrated evaluation of the suitability of the investigated site and an important component in the characterisation work is the development of a hydrogeological model. The hydrogeological model is used by repository engineering to design the underground facility and to develop a repository layout adapted to the site. It also provides input to the safety assessment. Another important use of the hydrogeological model is in the environmental impact assessment. This report presents the understanding of the hydrogeological conditions of the bedrock at Forsmark reached following the completion of the surface-based investigations and provides a summary of the bedrock hydrogeological model and the underlying data supporting its development. It constitutes the main reference on bedrock hydrogeology for the site descriptive model concluding the surface-based investigations at Forsmark, SDM-site, and is intended to describe the hydraulic properties and hydrogeological conditions of the bedrock at the site and to give the information essential for demonstrating understanding
Antenatal exposure to the selective serotonin reuptake inhibitor fluoxetine leads to postnatal metabolic and endocrine changes associated with type 2 diabetes in Wistar rats

Energy Technology Data Exchange (ETDEWEB)

De Long, Nicole E.; Barry, Eric J. [Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON L8S 4K1 (Canada); Pinelli, Christopher; Wood, Geoffrey A. [Department of Pathobiology, University of Guelph, Guelph, ON N1G 2W1 (Canada); Hardy, Daniel B. [Department of Obstetrics and Gynecology, Physiology and Pharmacology, University of Western, London, ON N6A 3K6 (Canada); Morrison, Katherine M. [Department of Pediatrics, McMaster University, Hamilton, ON L8S 4K1 (Canada); Taylor, Valerie H. [Department of Psychiatry, University of Toronto, Toronto, ON M5S 1A1 (Canada); Gerstein, Hertzel C. [Department of Medicine, McMaster University, Hamilton, ON L8S 4K1 (Canada); Holloway, Alison C., E-mail: hollow@mcmaster.ca [Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON L8S 4K1 (Canada)

2015-05-15

Hypothesis: 10–15% of women take antidepressant medications during pregnancy. A recent clinical study reported that the use of selective serotonin reuptake inhibitor antidepressants during pregnancy is linked with an increased risk of postnatal obesity. While obesity is often associated with fatty liver, dyslipidemia and inflammation, to date, the effects of perinatal exposure to SSRIs on these outcomes are unknown. Methods: Female nulliparous Wistar rats were given vehicle (N = 15) or fluoxetine hydrochloride (FLX 10 mg/kg/d; N = 15) orally for 2 weeks prior to mating until weaning. We assessed glucometabolic changes and hepatic pathophysiology in the offspring. Results: Fluoxetine exposed offspring demonstrated altered glucose homeostasis without any alterations to beta cell mass. FLX-exposed offspring had a significant increase in the number of offspring with mild to moderate NASH and dyslipidemia. There was also increased inflammation of the liver in FLX-exposed offspring; males had significant elevations in TNFα, IL6 and monocyte chemoattractant protein 1 (MCP1), while female offspring had higher expression of TNFα, and increased macrophage infiltration (MCP1). Limitations: This is an animal study. Further research examining the metabolic outcomes of children exposed to antidepressants in utero are required, given the increase in childhood obesity and psychiatric medication use during pregnancy. Conclusion: These data demonstrate that fetal and neonatal exposure to FLX results in evidence of increased adiposity, fatty liver and abnormal glycemic control. Since these are all hallmarks of the metabolic syndrome, this raises concerns regarding the long term metabolic sequelae of fetal exposure to SSRIs in human populations. - Highlights: • Antenatal exposure to fluoxetine results in postnatal adiposity in the offspring. • Offspring exposed to fluoxetine have abnormal glycemic control in adulthood. • Maternal exposure to fluoxetine causes fatty liver in

Antenatal exposure to the selective serotonin reuptake inhibitor fluoxetine leads to postnatal metabolic and endocrine changes associated with type 2 diabetes in Wistar rats

International Nuclear Information System (INIS)

De Long, Nicole E.; Barry, Eric J.; Pinelli, Christopher; Wood, Geoffrey A.; Hardy, Daniel B.; Morrison, Katherine M.; Taylor, Valerie H.; Gerstein, Hertzel C.; Holloway, Alison C.

2015-01-01

Hypothesis: 10–15% of women take antidepressant medications during pregnancy. A recent clinical study reported that the use of selective serotonin reuptake inhibitor antidepressants during pregnancy is linked with an increased risk of postnatal obesity. While obesity is often associated with fatty liver, dyslipidemia and inflammation, to date, the effects of perinatal exposure to SSRIs on these outcomes are unknown. Methods: Female nulliparous Wistar rats were given vehicle (N = 15) or fluoxetine hydrochloride (FLX 10 mg/kg/d; N = 15) orally for 2 weeks prior to mating until weaning. We assessed glucometabolic changes and hepatic pathophysiology in the offspring. Results: Fluoxetine exposed offspring demonstrated altered glucose homeostasis without any alterations to beta cell mass. FLX-exposed offspring had a significant increase in the number of offspring with mild to moderate NASH and dyslipidemia. There was also increased inflammation of the liver in FLX-exposed offspring; males had significant elevations in TNFα, IL6 and monocyte chemoattractant protein 1 (MCP1), while female offspring had higher expression of TNFα, and increased macrophage infiltration (MCP1). Limitations: This is an animal study. Further research examining the metabolic outcomes of children exposed to antidepressants in utero are required, given the increase in childhood obesity and psychiatric medication use during pregnancy. Conclusion: These data demonstrate that fetal and neonatal exposure to FLX results in evidence of increased adiposity, fatty liver and abnormal glycemic control. Since these are all hallmarks of the metabolic syndrome, this raises concerns regarding the long term metabolic sequelae of fetal exposure to SSRIs in human populations. - Highlights: • Antenatal exposure to fluoxetine results in postnatal adiposity in the offspring. • Offspring exposed to fluoxetine have abnormal glycemic control in adulthood. • Maternal exposure to fluoxetine causes fatty liver in
Site Environmental Report, 1993

Energy Technology Data Exchange (ETDEWEB)

1994-06-01

The Site Environmental Report (SER) is prepared annually in accordance with DOE Order 5400.1, ``General Environmental Protection Program.`` This 1993 SER provides the general public as well as scientists and engineers with the results from the site`s ongoing Environmental Monitoring Program. Also included in this report is information concerning the site`s progress toward achieving full compliance with requirements set forth by DOE, US Environmental Protection Agency (USEPA), and Ohio EPA (OEPA). For some readers, the highlights provided in the Executive Summary may provide sufficient information. Many readers, however, may wish to read more detailed descriptions of the information than those which are presented here.
A single nucleotide polymorphism in the human serotonin transporter introduces a new site for N-linked glycosylation

DEFF Research Database (Denmark)

Rasmussen, Trine Nygaard; Plenge, Per; Bay, Tina

2009-01-01

The human serotonin transporter (hSERT) is responsible for reuptake of serotonin (5-HT) from the synaptic cleft and is target for antidepressant medicine. Differential hSERT activity caused by genetic polymorphisms is believed to affect the risk of developing depression and, moreover, to affect t...
Hanford Site environmental management specification

Energy Technology Data Exchange (ETDEWEB)

Grygiel, M.L.

1998-06-10

The US Department of Energy, Richland Operations Office (RL) uses this Hanford Site Environmental Management Specification (Specification) to document top-level mission requirements and planning assumptions for the prime contractors involved in Hanford Site cleanup and infrastructure activities under the responsibility of the US Department of Energy, Office of Environmental Management. This Specification describes at a top level the activities, facilities, and infrastructure necessary to accomplish the cleanup of the Hanford Site and assigns this scope to Site contractors and their respective projects. This Specification also references the key National Environmental Policy Act of 1969 (NEPA), Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA), and safety documentation necessary to accurately describe the cleanup at a summary level. The information contained in this document reflects RL`s application of values, priorities, and critical success factors expressed by those involved with and affected by the Hanford Site project. The prime contractors and their projects develop complete baselines and work plans to implement this Specification. These lower-level documents and the data that support them, together with this Specification, represent the full set of requirements applicable to the contractors and their projects. Figure 1-1 shows the relationship of this Specification to the other basic Site documents. Similarly, the documents, orders, and laws referenced in this specification represent only the most salient sources of requirements. Current and contractual reference data contain a complete set of source documents.
Hanford Site environmental management specification

International Nuclear Information System (INIS)

Grygiel, M.L.

1998-01-01

The US Department of Energy, Richland Operations Office (RL) uses this Hanford Site Environmental Management Specification (Specification) to document top-level mission requirements and planning assumptions for the prime contractors involved in Hanford Site cleanup and infrastructure activities under the responsibility of the US Department of Energy, Office of Environmental Management. This Specification describes at a top level the activities, facilities, and infrastructure necessary to accomplish the cleanup of the Hanford Site and assigns this scope to Site contractors and their respective projects. This Specification also references the key National Environmental Policy Act of 1969 (NEPA), Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA), and safety documentation necessary to accurately describe the cleanup at a summary level. The information contained in this document reflects RL's application of values, priorities, and critical success factors expressed by those involved with and affected by the Hanford Site project. The prime contractors and their projects develop complete baselines and work plans to implement this Specification. These lower-level documents and the data that support them, together with this Specification, represent the full set of requirements applicable to the contractors and their projects. Figure 1-1 shows the relationship of this Specification to the other basic Site documents. Similarly, the documents, orders, and laws referenced in this specification represent only the most salient sources of requirements. Current and contractual reference data contain a complete set of source documents
Antidepressant stimulation of CDP-diacylglycerol synthesis does not require monoamine reuptake inhibition

Directory of Open Access Journals (Sweden)

Aboukhatwa Marwa A

2010-01-01

Full Text Available Abstract Background Recent studies demonstrate that diverse antidepressant agents increase the cellular production of the nucleolipid CDP-diacylglycerol and its synthetic derivative, phosphatidylinositol, in depression-relevant brain regions. Pharmacological blockade of downstream phosphatidylinositide signaling disrupted the behavioral antidepressant effects in rats. However, the nucleolipid responses were resistant to inhibition by serotonin receptor antagonists, even though antidepressant-facilitated inositol phosphate accumulation was blocked. Could the neurochemical effects be additional to the known effects of the drugs on monoamine transmitter transporters? To examine this question, we tested selected agents in serotonin-depleted brain tissues, in PC12 cells devoid of serotonin transporters, and on the enzymatic activity of brain CDP-diacylglycerol synthase - the enzyme that catalyzes the physiological synthesis of CDP-diacylglycerol. Results Imipramine, paroxetine, and maprotiline concentration-dependently increased the levels of CDP-diacylglycerol and phosphatidylinositides in PC12 cells. Rat forebrain tissues depleted of serotonin by pretreatment with p-chlorophenylalanine showed responses to imipramine or maprotiline that were comparable to respective responses from saline-injected controls. With fluoxetine, nucleolipid responses in the serotonin-depleted cortex or hippocampus were significantly reduced, but not abolished. Each drug significantly increased the enzymatic activity of CDP-diacylglycerol synthase following incubations with cortical or hippocampal brain tissues. Conclusion Antidepressants probably induce the activity of CDP-diacylglycerol synthase leading to increased production of CDP-diacylglycerol and facilitation of downstream phosphatidylinositol synthesis. Phosphatidylinositol-dependent signaling cascades exert diverse salutary effects in neural cells, including facilitation of BDNF signaling and neurogenesis. Hence, the present findings should strengthen the notion that modulation of brain phosphatidylinositide signaling probably contributes to the molecular mechanism of diverse antidepressant medications.
16 CFR 1130.8 - Requirements for Web site registration or alternative e-mail registration.

Science.gov (United States)

2010-01-01

... registration. (a) Link to registration page. The manufacturer's Web site, or other Web site established for the... web page that goes directly to “Product Registration.” (b) Purpose statement. The registration page... registration page. The Web site registration page shall request only the consumer's name, address, telephone...
Umatilla Satellite and Release Sites Project : Final Siting Report.

Energy Technology Data Exchange (ETDEWEB)

Montgomery, James M.

1992-04-01

This report presents the results of site analysis for the Umatilla Satellite and Release Sites Project. The purpose of this project is to provide engineering services for the siting and conceptual design of satellite and release facilities for the Umatilla Basin hatchery program. The Umatilla Basin hatchery program consists of artificial production facilities for salmon and steelhead to enhance production in the Umatilla River as defined in the Umatilla master plan approved in 1989 by the Northwest Power Planning Council. Facilities identified in the master plan include adult salmon broodstock holding and spawning facilities, facilities for recovery, acclimation, and/or extended rearing of salmon juveniles, and development of river sites for release of hatchery salmon and steelhead. The historic and current distribution of fall chinook, summer chinook, and coho salmon and steelhead trout was summarized for the Umatilla River basin. Current and future production and release objectives were reviewed. Twenty seven sites were evaluated for the potential and development of facilities. Engineering and environmental attributes of the sites were evaluated and compared to facility requirements for water and space. Site screening was conducted to identify the sites with the most potential for facility development. Alternative sites were selected for conceptual design of each facility type. A proposed program for adult holding facilities, final rearing/acclimation, and direct release facilities was developed.
Final vegetative cover for closed waste sites

International Nuclear Information System (INIS)

Cook, J.R.; Salvo, S.K.

1993-01-01

Low-level, hazardous, and mixed waste disposal sites normally require some form of plant material to prevent erosion of the final closure cap. Waste disposal sites are closed and capped in a complex scientific manner to minimize water infiltration and percolation into and through the waste material. Turf type grasses are currently being used as an interim vegetative cover for most sites. This coverage allows for required monitoring of the closure cap for settlement and maintenance activities. The purpose of this five year study was to evaluate plant materials for use on wastes sites after the post-closure care period that are quickly and easily established and economically maintained, retard water infiltration, provide maximum year-round evapotranspiration, are ecologically acceptable and do not harm the closure cap. The results of the study suggest that two species of bamboo (Phyllostachys (P.) bissetii and P. rubromarginata) can be utilized to provide long lived, low maintenance, climax vegetation for the waste sites after surveillance and maintenance requirements have ceased
Improved preclinical cardiovascular therapeutic indices with long-term inhibition of norepinephrine reuptake using reboxetine

International Nuclear Information System (INIS)

Fossa, Anthony A.; Wisialowski, Todd A.; Cremers, Thomas; Hart, Marieke van der; Tseng, Elaine; Deng, Shibing; Rollema, Hans; Wang, Ellen Q.

2012-01-01

Norepinephrine reuptake inhibitors (NRIs) acutely increase norepinephrine (NE) levels, but therapeutic antidepressant activity is only observed after weeks of treatment because central NE levels progressively increase during continued drug exposure. Similarly, while NRIs acutely increase blood pressure (BP) and heart rate (HR) due to enhanced sympathetic neurotransmission, chronic treatment changes the responsiveness of the central noradrenergic system and suppresses these effects via autonomic regulation. To better understand the relationship between NE increases and cardiovascular safety, we investigated acute and chronic effects of the NRI reboxetine on central NE release and on BP and HR and electrical alternans, a measure of arrhythmia liability, in guinea pigs. NE release was assessed by microdialysis in medial prefrontal cortex (mPFC) and hypothalamic paraventricular nucleus (PVN); BP and HR were measured by telemetry. Animals were treated for 28 days with 15 mg/kg/day of reboxetine or vehicle via an osmotic minipump and then challenged with acute intravenous doses of reboxetine. Animals chronically treated with reboxetine had 2-fold higher extracellular basal NE levels in mPFC and PVN compared to basal levels after chronic vehicle treatment. BP was significantly increased after the first day of treatment, and gradually returned to vehicle levels by day 21. These data indicate that chronic NRI treatment may lead to an increase in central NE levels and a concomitant reduction in BP based on exposure–response curves compared to vehicle treatment, suggesting a larger separation between preclinical estimates of efficacy vs. safety compared to acute NRI treatment. -- Highlights: ► Acute RBX produces blood pressure increases acutely that decrease with chronic RBX ► Chronic RBX increases brain NE levels, a preclinical surrogate of improved efficacy ► Short-term screening of NRI often underestimates the chronic therapeutic index ► Chronic cardiovascular
Improved preclinical cardiovascular therapeutic indices with long-term inhibition of norepinephrine reuptake using reboxetine

Energy Technology Data Exchange (ETDEWEB)

Fossa, Anthony A., E-mail: anthony.fossa@icardiac.com [Department of Global Safety Pharmacology, Department of Pharmacokinetics, Dynamics and Metabolism, and Neuroscience, Pfizer Global Research and Development Eastern Point Road, Groton, CT 06340 (United States); Wisialowski, Todd A. [Department of Global Safety Pharmacology, Department of Pharmacokinetics, Dynamics and Metabolism, and Neuroscience, Pfizer Global Research and Development Eastern Point Road, Groton, CT 06340 (United States); Cremers, Thomas; Hart, Marieke van der [Brains On-Line B.V., University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen (Netherlands); Tseng, Elaine; Deng, Shibing; Rollema, Hans; Wang, Ellen Q. [Department of Global Safety Pharmacology, Department of Pharmacokinetics, Dynamics and Metabolism, and Neuroscience, Pfizer Global Research and Development Eastern Point Road, Groton, CT 06340 (United States)

2012-11-01

Norepinephrine reuptake inhibitors (NRIs) acutely increase norepinephrine (NE) levels, but therapeutic antidepressant activity is only observed after weeks of treatment because central NE levels progressively increase during continued drug exposure. Similarly, while NRIs acutely increase blood pressure (BP) and heart rate (HR) due to enhanced sympathetic neurotransmission, chronic treatment changes the responsiveness of the central noradrenergic system and suppresses these effects via autonomic regulation. To better understand the relationship between NE increases and cardiovascular safety, we investigated acute and chronic effects of the NRI reboxetine on central NE release and on BP and HR and electrical alternans, a measure of arrhythmia liability, in guinea pigs. NE release was assessed by microdialysis in medial prefrontal cortex (mPFC) and hypothalamic paraventricular nucleus (PVN); BP and HR were measured by telemetry. Animals were treated for 28 days with 15 mg/kg/day of reboxetine or vehicle via an osmotic minipump and then challenged with acute intravenous doses of reboxetine. Animals chronically treated with reboxetine had 2-fold higher extracellular basal NE levels in mPFC and PVN compared to basal levels after chronic vehicle treatment. BP was significantly increased after the first day of treatment, and gradually returned to vehicle levels by day 21. These data indicate that chronic NRI treatment may lead to an increase in central NE levels and a concomitant reduction in BP based on exposure–response curves compared to vehicle treatment, suggesting a larger separation between preclinical estimates of efficacy vs. safety compared to acute NRI treatment. -- Highlights: ► Acute RBX produces blood pressure increases acutely that decrease with chronic RBX ► Chronic RBX increases brain NE levels, a preclinical surrogate of improved efficacy ► Short-term screening of NRI often underestimates the chronic therapeutic index ► Chronic cardiovascular
Tracer measured substrate turnover requires arterial sampling downstream of infusion site

International Nuclear Information System (INIS)

Stanley, W.C.; Neese, R.A.; Gertz, E.W.; Wisneski, J.A.; Morris, D.L.; Brooks, G.A.

1986-01-01

Measurement of metabolite turnover (Rt) with radioactive tracers is done by either infusing tracer venously and sampling specific activity (SA) arterially (V-A modes), or by infusing into the aorta and sampling venous blood (A-V mode). Using the Fick principle, the necessity for using the V-A mode can be demonstrated. If tracer is infused into the left ventricle, in a steady state the Rt is the product of arterial trace concentration, the cardiac output, and the tracer extraction ratio for the whole body. This is expressed as: Rt = Ca x Qx ((*Ca - *Cv)/*Ca) (Eq1) where C=trace concentration (μmol/ml), *C=tracer conc. (dpm/ml), a=arterial, v-=mixed venous, and Q=cardiac output (ml/min). Rearranging the equation: Rt = Qx(*Ca - *Cv)/SAa = F/SAa (Eq2) where SAa is *Ca/Ca, and Qx (*Ca-*Cv) equals the infusion rate (F). The authors compared Eqs1 and 2 (Rt = F/SAa) in 3 anesthetized dogs in which [1- 14 C] lactate was infused into the left ventricle, and blood was sampled arterially downstream from the infusion site and in the pulmonary artery. Eqs 1 and 2 gave similar results for Rt (45.9 vs. 43.9 μmol/kg min), while substituting SAv for SAa (A-V mode) into Eq 2 gave a higher Rt (53.6). When SAv (A-V mode) is used, the specific activity seen by the tissues (SAa) is not considered in the calculation of Rt. Therefore, only the V-A mode meets the requirements for tracer measured metabolite turnover
An analysis of psychotropic drug sales. Increasing sales of selective serotonin reuptake inhibitors are closely related to number of products.

Science.gov (United States)

Nielsen, Margrethe; Gøtzsche, Peter

2011-01-01

Prescribing of selective serotonin reuptake inhibitors (SSRIs) has increased dramatically. To compare the sales of benzodiazepines and SSRIs within the primary care sector in Denmark and relate changes in usage to number of indications and products on the market. We used data from various sources to establish the sales curves of psychotropic drugs in the period 1970 to 2007, based on the Anatomic Therapeutic Classification system and Defined Daily Doses. Fluctuations in sales of psychotropic drugs that cannot be explained by disease prevalence were caused by changes in sales of the benzodiazepines and SSRIs. We found a decline in the sales of benzodiazepines after a peak in 1986, likely due to the recognition that they cause dependence. From a low level in 1992, we found that the sales of SSRIs increased almost linearly by a factor of 18, up to 44 DDD per 1000 inhabitants, which was closely related to the number of products on the market that increased by a factor of 16. Sales of antidepressant drugs are mainly determined by market availability of products indicating that marketing pressures are playing an important role. Thus the current level of use of SSRIs may not be evidence-based, which is supported by studies showing that the effect of SSRIs has been overestimated.
Serotonin reuptake inhibitors and mortality in epilepsy: A linked primary-care cohort study.

Science.gov (United States)

Josephson, Colin B; Gonzalez-Izquierdo, Arturo; Denaxas, Spiros; Fitzpatrick, Natalie K; Sajobi, Tolulope T; Engbers, Jordan D T; Patten, Scott; Jette, Nathalie; Wiebe, Samuel

2017-11-01

Preliminary evidence suggests that serotonin reuptake inhibitor (SRI) use may increase postictal respiratory drive and prevent death. We sought to determine whether SRIs are associated with improved all-cause and possible seizure-specific mortality in patients with epilepsy. Patients with epilepsy and a random 10:1 sample without epilepsy were extracted from The ClinicAl research using LInked Bespoke studies and Electronic health Records (CALIBER) resource. The hazard ratio (HR) of all-cause and possible seizure-specific mortality, treating SRI use as a time-varying covariate, was determined using the date of a second SRI prescription as exposure and in discrete 6-month periods over the entire duration of follow-up. We used Cox regression and competing risk models with Firth correction to calculate the HR. We controlled for age, sex, depression, comorbidity, (Charlson comorbidity index) and socioeconomic status (Index of Multiple Deprivation). We identified 2,718,952 eligible patients in CALIBER, of whom 16,379 (0.60%) had epilepsy. Median age and follow-up were 44 (interquartile range [IQR] 29-61]) and 6.4 years (IQR 2.4-10.4 years), respectively, and 53% were female. A total of 2,178 patients (13%) had at least two SRI prescriptions. Hazard of all-cause mortality was significantly elevated following a second prescription for an SRI (HR 1.64 95% confidence interval [95% CI] 1.44-1.86; p < 0.001). The HR was similar in 163,778 age, sex, and general practitioner (GP) practice-matched controls without epilepsy. Exposure to an SRI was not associated with seizure-related death (HR 1.08, 95% CI 0.59-1.97; 0.796). There is no evidence in this large population-based cohort that SRIs protect against all-cause mortality or seizure-specific mortality. Rather, SRI use was associated with increased mortality, irrespective of epilepsy, which is probably due to various factors associated with the use of antidepressants. Larger studies with systematically collected clinical
Site Maintenance Plan: Part 2, Site Maintenance Action Plan for FY 1994

Energy Technology Data Exchange (ETDEWEB)

Fisk, E.L.

1994-06-01

This Fiscal Year (FY) 1994 Site Maintenance Action Plan (SMAP) is Part II of the Site Maintenance Plan, and has been written by Westinghouse Hanford Company (WHC) to outline the requirements stated in DOE Order 4330.4B, Maintenance Management Program, Chapter 1, Paragraph 3.3.1. The SMAP provides an annual status of maintenance initiatives completed and planned, a summary of performance indicators, a summary of maintenance backlog, a listing of real property and capital equipment maintenance cost estimates that were used to create the FY 1996 infrastructure and maintenance budget input, and a listing of proposed line item and general plant projects. Additionally, assumptions for various Site programs are listed to bring the Site Maintenance Plan into focus with overall Site activities. The primary mission at Hanford is to clean up the Site. In this cleanup process WHC will provide scientific and technological expertise to meet global needs, and partnership with stakeholders in the region to develop regional economic diversification. Other missions at the Hanford Site include energy research and development, and waste management and disposal activities. Their primary mission has a 30-year projected life span and will direct the shutting down and cleanup of defense production facilities and the Fast Flux Test Facility. This long-term mission requires continuous maintenance and in many instances, replacement of existing basic infrastructure, support facilities, and utilities. Without adequate maintenance and capital funding these infrastructure, support facilities, and utilities will continue to deteriorate causing an increase in backlogged work.
Site Maintenance Plan: Part 2, Site Maintenance Action Plan for FY 1994

International Nuclear Information System (INIS)

Fisk, E.L.

1994-06-01

This Fiscal Year (FY) 1994 Site Maintenance Action Plan (SMAP) is Part II of the Site Maintenance Plan, and has been written by Westinghouse Hanford Company (WHC) to outline the requirements stated in DOE Order 4330.4B, Maintenance Management Program, Chapter 1, Paragraph 3.3.1. The SMAP provides an annual status of maintenance initiatives completed and planned, a summary of performance indicators, a summary of maintenance backlog, a listing of real property and capital equipment maintenance cost estimates that were used to create the FY 1996 infrastructure and maintenance budget input, and a listing of proposed line item and general plant projects. Additionally, assumptions for various Site programs are listed to bring the Site Maintenance Plan into focus with overall Site activities. The primary mission at Hanford is to clean up the Site. In this cleanup process WHC will provide scientific and technological expertise to meet global needs, and partnership with stakeholders in the region to develop regional economic diversification. Other missions at the Hanford Site include energy research and development, and waste management and disposal activities. Their primary mission has a 30-year projected life span and will direct the shutting down and cleanup of defense production facilities and the Fast Flux Test Facility. This long-term mission requires continuous maintenance and in many instances, replacement of existing basic infrastructure, support facilities, and utilities. Without adequate maintenance and capital funding these infrastructure, support facilities, and utilities will continue to deteriorate causing an increase in backlogged work
Paraho oil shale module. Site development plan, Task 4

Energy Technology Data Exchange (ETDEWEB)

1981-10-01

A management plan and schedule which covers all requirements for gaining access to the site and for conducting a Paraho Process demonstration program have been prepared. The oil shale available should represent a regional resource of suitable size and quality for commercial development. Discussed in this report are: proof of ownership; requirements for rights-of-way for access to the site; local zoning restrictions; water rights; site availability verification; and other legal requirements. (DMC)
Site Study Plan for land use, Deaf Smith County site, Texas: Environmental Field Program: Preliminary draft

International Nuclear Information System (INIS)

1987-06-01

The Land Use Site Study Plan describes a field program consisting of characterization of the site; seismic survey rights-of-way and transportation and utility corridors, the vicinity, the region, future land use, and monitoring land-use change. Aerial photography will be used to characterize the site, seismic rows and transportation and utility corridors, and the vicinity. The resulting land-use maps and overlays will then be verified in the field. Interviews with farm managers and local experts will provide additional information. A Geographic Information System (GIS) and satellite imagery will be used to characterize the region, monitor land-use change, and provide information to assist with the future land use study. The site study plan describes the study design and rationale, the filed data collection procedures and equipment, the data analysis methods and application of results, the data management strategy, the schedule of field activities, the personnel requirements and management of the study, and the study's quality assurance program. The directives and requirements that drive these studies are derived from the Salt Repository Project Requirements Document. 51 refs; 6 figs; 3 tabs
Selective serotonin reuptake inhibitors (SSRIs) for post-partum depression (PPD): a systematic review of randomized clinical trials.

Science.gov (United States)

De Crescenzo, Franco; Perelli, Federica; Armando, Marco; Vicari, Stefano

2014-01-01

The treatment of postpartum depression with selective serotonin reuptake inhibitors (SSRIs) has been claimed to be both efficacious and well tolerated, but no recent systematic reviews have been conducted. A qualitative systematic review of randomized clinical trials on women with postpartum depression comparing SSRIs to placebo and/or other treatments was performed. A comprehensive literature search of online databases, the bibliographies of published articles and grey literature were conducted. Data on efficacy, acceptability and tolerability were extracted and the quality of the trials was assessed. Six randomised clinical trials, comprising 595 patients, met quality criteria for inclusion in the analysis. Cognitive-behavioural intervention, psychosocial community-based intervention, psychodynamic therapy, cognitive behavioural therapy, a second-generation tricyclic antidepressant and placebo were used as comparisons. All studies demonstrated higher response and remission rates among those treated with SSRIs and greater mean changes on depression scales, although findings were not always statistically significant. Dropout rates were high in three of the trials but similar among treatment and comparison groups. In general, SSRIs were well tolerated and trial quality was good. There are few trials, patients included in the trials were not representative of all patients with postpartum depression, dropout rates in three trials were high, and long-term efficacy and tolerability were assessed in only two trials. SSRIs appear to be efficacious and well tolerated in the treatment of postpartum depression, but the available evidence fails to demonstrate a clear superiority over other treatments. © 2013 Elsevier B.V. All rights reserved.
Comparison of the neurobiological effects of attribution retraining group therapy with those of selective serotonin reuptake inhibitors

Directory of Open Access Journals (Sweden)

C. Wang

2013-03-01

Full Text Available The aim of this study was to compare the effectiveness of attribution retraining group therapy (ARGT with selective serotonin reuptake inhibitors (SSRIs in the treatment of major depressive disorder (MDD, generalized anxiety disorder (GAD, and obsessive-compulsive disorder (OCD. Subjects were sequentially recruited and randomized into two groups, one receiving ARGT (n = 63 and the other SSRIs (n = 66 for 8 weeks. Fifty-four ARGT outpatients with MDD (n = 19, GAD (n = 19, and OCD (n = 16 and 55 SSRI outpatients with MDD (n = 19, GAD (n = 19, and OCD (n = 17 completed the study. All subjects were assessed using the Hamilton Depression Scale and Hamilton Anxiety Scale before and after treatment. The 10-item Yale-Brown Obsessive Compulsive Scale was employed only for OCD subjects. Plasma levels of serotonin, norepinephrine, cortisol, and adrenocorticotropic hormone were also measured at baseline and 8 weeks after completion of treatment. Symptom scores were significantly reduced (P < 0.001 in both the ARGT and SSRI groups at the end of treatment. However, MDD, GAD and OCD patients in the ARGT group had significantly lower plasma cortisol concentrations compared to baseline (P < 0.05, whereas MDD and OCD patients receiving SSRIs showed significantly increased plasma levels of serotonin (P < 0.05. These findings suggest that ARGT may modulate plasma cortisol levels and affect the hypothalamus-pituitary-adrenal axis as opposed to SSRIs, which may up-regulate plasma serotonin levels via a different pathway to produce an overall improvement in the clinical condition of the patients.

Comparison of the neurobiological effects of attribution retraining group therapy with those of selective serotonin reuptake inhibitors

Directory of Open Access Journals (Sweden)

C. Wang

Full Text Available The aim of this study was to compare the effectiveness of attribution retraining group therapy (ARGT with selective serotonin reuptake inhibitors (SSRIs in the treatment of major depressive disorder (MDD, generalized anxiety disorder (GAD, and obsessive-compulsive disorder (OCD. Subjects were sequentially recruited and randomized into two groups, one receiving ARGT (n = 63 and the other SSRIs (n = 66 for 8 weeks. Fifty-four ARGT outpatients with MDD (n = 19, GAD (n = 19, and OCD (n = 16 and 55 SSRI outpatients with MDD (n = 19, GAD (n = 19, and OCD (n = 17 completed the study. All subjects were assessed using the Hamilton Depression Scale and Hamilton Anxiety Scale before and after treatment. The 10-item Yale-Brown Obsessive Compulsive Scale was employed only for OCD subjects. Plasma levels of serotonin, norepinephrine, cortisol, and adrenocorticotropic hormone were also measured at baseline and 8 weeks after completion of treatment. Symptom scores were significantly reduced (P < 0.001 in both the ARGT and SSRI groups at the end of treatment. However, MDD, GAD and OCD patients in the ARGT group had significantly lower plasma cortisol concentrations compared to baseline (P < 0.05, whereas MDD and OCD patients receiving SSRIs showed significantly increased plasma levels of serotonin (P < 0.05. These findings suggest that ARGT may modulate plasma cortisol levels and affect the hypothalamus-pituitary-adrenal axis as opposed to SSRIs, which may up-regulate plasma serotonin levels via a different pathway to produce an overall improvement in the clinical condition of the patients.
24 CFR 583.320 - Site control.

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false Site control. 583.320 Section 583... DEVELOPMENT COMMUNITY FACILITIES SUPPORTIVE HOUSING PROGRAM Program Requirements § 583.320 Site control. (a) Site control. (1) Where grant funds will be used for acquisition, rehabilitation, or new construction...
Savannah River Site computing architecture

Energy Technology Data Exchange (ETDEWEB)

1991-03-29

A computing architecture is a framework for making decisions about the implementation of computer technology and the supporting infrastructure. Because of the size, diversity, and amount of resources dedicated to computing at the Savannah River Site (SRS), there must be an overall strategic plan that can be followed by the thousands of site personnel who make decisions daily that directly affect the SRS computing environment and impact the site's production and business systems. This plan must address the following requirements: There must be SRS-wide standards for procurement or development of computing systems (hardware and software). The site computing organizations must develop systems that end users find easy to use. Systems must be put in place to support the primary function of site information workers. The developers of computer systems must be given tools that automate and speed up the development of information systems and applications based on computer technology. This document describes a proposal for a site-wide computing architecture that addresses the above requirements. In summary, this architecture is standards-based data-driven, and workstation-oriented with larger systems being utilized for the delivery of needed information to users in a client-server relationship.
Impact of liability and site closure and long-term care issues on future siting efforts

International Nuclear Information System (INIS)

Carlin, E.M.; Hana, S.L.A.

1988-01-01

Washington's research in the area of financial responsibility for liability and cleanup for radioactive materials licensees and low-level radioactive waste permittees is offered to assist unsited states and regions in their planning and development of new low-level waste disposal capacity. The state considered the need for third party bodily injury and property damage financial responsibility and determined that the USDOT requirements comprehensively cover transport of wastes. In regard to licensees' facilities, it is the state's opinion that an adequate technical basis for third party requirements has not yet been developed. Also considered was the need for financial assurance for cleanup, which is covered for transportation, but generally not available for facilities. Three options are examined to provide such coverage, and the economic impact on licensees assessed. Finally, the current low-level waste disposal site operator's insurance coverage is analyzed and deficiencies are identified. Washington is also conducting research into site closure and perpetual care and maintenance requirements for the commercial low-level radioactive waste disposal facility located on the Hanford reservation near Richland, Washington. This research includes a site assessment and identification and formulation of site-specific design elements for closure and long-term care
Two-week administration of the combined serotonin-noradrenaline reuptake inhibitor duloxetine augments functioning of mesolimbic incentive processing circuits.

Science.gov (United States)

Ossewaarde, Lindsey; Verkes, Robbert J; Hermans, Erno J; Kooijman, Sabine C; Urner, Maren; Tendolkar, Indira; van Wingen, Guido A; Fernández, Guillén

2011-09-15

Anhedonia and lack of motivation are core symptoms of major depressive disorder (MDD). Neuroimaging studies in MDD patients have shown reductions in reward-related activity in terminal regions of the mesolimbic dopamine (DA) system, such as the ventral striatum. Monoamines have been implicated in both mesolimbic incentive processing and the mechanism of action of antidepressant drugs. However, not much is known about antidepressant effects on mesolimbic incentive processing in humans, which might be related to the effects on anhedonia. To investigate the short-term effects of antidepressants on reward-related activity in the ventral striatum, we investigated the effect of the combined serotonin-norepinephrine reuptake inhibitor duloxetine. Healthy volunteers underwent functional magnetic resonance imaging in a randomized, double-blind, placebo-controlled, crossover study. After taking duloxetine (60 mg once a day) or placebo for 14 days, participants completed a monetary incentive delay task that activates the ventral striatum during reward anticipation. Our results (n = 19) show enhanced ventral striatal responses after duloxetine administration compared with placebo. Moreover, this increase in ventral striatal activity was positively correlated with duloxetine plasma levels. This is the first study to demonstrate that antidepressants augment neural activity in mesolimbic DA incentive processing circuits in healthy volunteers. These effects are likely caused by the increase in monoamine neurotransmission in the ventral striatum. Our findings suggest that antidepressants may alleviate anhedonia by stimulating incentive processing. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Atomoxetine, a selective norepinephrine reuptake inhibitor, improves short-term histological outcomes after hypoxic-ischemic brain injury in the neonatal male rat.

Science.gov (United States)

Toshimitsu, Masatake; Kamei, Yoshimasa; Ichinose, Mari; Seyama, Takahiro; Imada, Shinya; Iriyama, Takayuki; Fujii, Tomoyuki

2018-03-30

Despite the recent progress of perinatal medicine, perinatal hypoxic-ischemic (HI) insult remains an important cause of brain injury in neonates, and is pathologically characterized by neuronal loss and the presence of microglia. Neurotransmitters, such as norepinephrine (NE) and glutamate, are involved in the pathogenesis of hypoxic-ischemic encephalopathy via the interaction between neurons and microglia. Although it is well known that the monoamine neurotransmitter NE acts as an anti-inflammatory agent in the brain under pathological conditions, its effects on perinatal HI insult remains elusive. Atomoxetine, a selective NE reuptake inhibitor, has been used clinically for the treatment of attention-deficit hyperactivity disorder in children. Here, we investigated whether the enhancement of endogenous NE by administration of atomoxetine could protect neonates against HI insult by using the neonatal male rat model. We also examined the involvement of microglia in this process. Unilateral HI brain injury was induced by the combination of left carotid artery dissection followed by ligation and hypoxia (8% O 2 , 2 h) in postnatal day 7 (P7) male rat pups. The pups were randomized into three groups: the atomoxetine treatment immediately after HI insult, the atomoxetine treatment at 3 h after HI insult, or the vehicle treatment group. The pups were euthanized on P8 and P14, and the brain regions including the cortex, striatum, hippocampus, and thalamus were evaluated by immunohistochemistry. HI insult resulted in severe brain damage in the ipsilateral hemisphere at P14. Atomoxetine treatment immediately after HI insult significantly increased NE levels in the ipsilateral hemisphere at 1 h after HI insult and reduced the neuronal damage via the increased phosphorylation of cAMP response element-binding protein (pCREB) in all brain regions examined. In addition, the number of microglia was maintained under atomoxetine treatment compared with that of the vehicle
Site characterization plan:

International Nuclear Information System (INIS)

1988-01-01

The Yucca Mountain site in Nevada is one of three candidate sites for the first geologic repository for radioactive waste. On May 28, 1986, it was recommended for detailed study in a program of site characterization. This site characterization plan (SCP) has been prepared in accordance with the requirements of the Nuclear Waste Policy Act to summarize the information collected to date about the geologic conditions at the site;to describe the conceptual designs for the repository and the waste package;and to present the plans for obtaining the geologic information necessary to demonstrate the suitability of the site for repository, to design the repository and the waste package, to prepare an environmental impact statement, and to obtain from the US Nuclear Regulatory Commission (NRC) an authorization to construct the repository. This introduction begins with a brief section on the process for siting and developing a repository, followed by a discussion of the pertinent legislation and regulations. A description of site characterization is presented next;it describes the facilities to be constructed for the site characterization program and explains the principal activities to be conducted during the program. Finally, the purpose, content, organizing principles, and organization of this site characterization plan are outlined, and compliance with applicable regulations is discussed
The novel triple monoamine reuptake inhibitor tesofensine induces sustained weight loss and improves glycemic control in the diet-induced obese rat: comparison to sibutramine and rimonabant

DEFF Research Database (Denmark)

Hansen, Henrik H; Hansen, Gitte; Tang-Christensen, Mads

2010-01-01

Tesofensine, a novel triple monoamine reuptake inhibitor, produces a significant weight loss in humans. The present study aimed at characterizing the weight-reducing effects of tesofensine in a rat model of diet-induced obesity. Sibutramine and rimonabant were used as reference comparators....... Compared to baseline, long-term treatment with tesofensine (28 days, 1.0 or 2.5mg/kg, p.o.) resulted in a significant, dose-dependent and sustained weight loss of 5.7 and 9.9%, respectively. Sibutramine (7.5mg/kg, p.o.) treatment caused a sustained weight loss of 7.6%, whereas the employed dose...... of rimonabant (10mg/kg, p.o.) only produced a transient weight reduction. While all compounds exhibited a significant inhibitory effect on food intake which gradually wore off, the hypophagic effect of tesofensine was longer lasting than sibutramine and rimonabant. In contrast to tesofensine, the body weight...
Environmental compliance at U.S. Department of Energy FUSRAP (Formerly Utilized Sites Remedial Action Program) sites

International Nuclear Information System (INIS)

Liedle, S.D.; Clemens, B.W.

1988-01-01

With the promulgation of the Superfund Amendments and Reauthorization Act (SARA), federal facilities were required to comply with the Comprehensive Environmental Response Compensation and Liability Act (CERCLA) in the same manner as any non-government entity. This presented challenges for the Department of Energy (DOE) and other federal agencies involved in remedial action work because there are many requirements under SARA that overlap other laws requiring DOE compliance, e.g., the National Environmental Policy Act (NEPA). This paper outlines the options developed to comply with CERCLA and NEPA as part of active, multi-site remedial action program. The program, the Formerly Utilized Sites Remedial Action Program (FUSRAP), was developed to identify, clean up, or control sites containing residual radioactive or chemical contamination as a result of the nation's early development of nuclear power. During the Manhattan Project, uranium was extracted from ores and resulted in mill concentrates, purified metals, and waste products that were transported for use or disposal at other locations. Figure 1 shows the steps for producing uranium metal during the Manhattan Project. As a result of these activities materials, equipment, buildings, and land became contaminated, primarily with naturally occurring radionuclides. Currently, FUSRAP includes 29 sites; three are on the Environmental Protection Agency's (EPA's) National Priorities List (NPL) of hazardous waste sites
SITE: a methodology for assessment of energy facility siting patterns. Regional studies program

International Nuclear Information System (INIS)

Frigerio, N.A.; Habegger, L.J.; King, R.F.; Hoover, L.J.; Clark, N.A.; Cobian, J.M.

1975-08-01

The timely development of the nation's energy production capacity in a manner that minimizes potential adverse local and regional impacts associated with energy facilities requires the use of sophisticated techniques for evaluation of siting alternatives and fuel cycle options. This report is a documentation of the computerized SITE methodology that has been developed for evaluating health, environmental, and socioeconomic impacts related to utilization of alternate sites for energy production within a region of interest. The cost, impact, and attribute vectors, which are generated and displayed on density maps, can be used in a multiparameter overlay process to identify preferable siting areas. The assessment of clustered facilities in energy centers is also possible within the SITE analysis framework. An application of the SITE methodology to Northern Illinois is presented. Also included is a description of the ongoing extension of SITE for the accumulative evaluation of alternative regional energy siting patterns and fuel cycle options. An appendix provides documentation and user information for the SITE computer program
Site observational work plan for the UMTRA Project Site at Riverton, Wyoming. Revision 3/95

International Nuclear Information System (INIS)

1995-03-01

Ground water compliance for the Uranium Mill Tailings Remedial Action (UMTRA) Project sites, including the Riverton, Wyoming, site, is governed by the Uranium Mill Tailings Radiation Control Act and the US Environmental Protection Agency's Health and Environmental Protection Standards for Uranium and Thorium Mill Tailings. The compliance strategy proposed for this site is natural flushing in conjunction with institutional controls. The essential premise of natural flushing is that ground water movement and natural attenuation processes will reduce the detected contamination to background levels or alternate concentration limits that do not pose a risk to human health or the environment within 100 years. This document contains the following sections. Section 2.0 of this SOWP describes the requirements for meeting standards at UMTRA Project sites. Section 3.0 provides site-specific data and the related conceptual model. Section 4.0 provides the justification for the recommended ground water compliance strategy for the Riverton site. Section 5.0 provides the justification and process for collection and assessment of additional required data. Section 6.0 provides a list of the references cited. The appendixes include data on monitor wells and lithography, ground water, surface water, and sediment quality
Socioeconomic Site Study Plan: Draft

International Nuclear Information System (INIS)

1987-07-01

Social and economic issues and concerns of the Deak Smith County site area will be evaluated during site characterization. Effects that the area could experience from a repository project include demographic, economic, community service, fiscal, and social impacts. The Socioeconomic Site Study Plan is designed to provide a strategy to assess the potential for those impacts. The Socioeconomic Site Study Plan is structured to provide an overview of the socioeconomic program requirements, objectives, and activities to be conducted during site characterization. This report will describe the study design and its rationale; data collection, management, and reporting; program schedules and milestones; site study organization and management; and quality assurance issues. 43 refs
Nuclear Energy Center Site Survey, 1975. Part V. Resource availability and site screening

International Nuclear Information System (INIS)

1976-01-01

Resource requirements for nuclear energy centers are discussed and the large land areas which meet these requirements and may contain potential sites for a nuclear energy center (NEC) are identified. Maps of the areas are included that identify seismic zones, river flow rates, and population density
Site observational work plan for the UMTRA Project site at Spook, Wyoming

International Nuclear Information System (INIS)

1995-05-01

The Spook, Wyoming, site observational work plan proposes site-specific activities to achieve compliance with Subpart B of 40 CFR Part 192 (1994) of the final US Environmental Protection Agency (EPA) ground water protection standards 60 FR 2854 (1995) at this Uranium Mill Tailing Remedial Action (UMTRA) Project site. This draft SOWP presents a comprehensive summary of existing site characterization data, a conceptual site model of the nature and extent of ground water contamination, exposure pathways, and potential impact to human health and the environment. Section 2.0 describes the requirements for meeting ground water standards at UMTRA Project sites. Section 3.0 defines past and current conditions, describes potential environmental and human health risks, and provides site-specific data that supports the selection of a proposed ground water compliance strategy. Section 4.0 provides the justification for selecting the proposed ground water compliance strategy based on the framework defined in the ground water programmatic environmental impact statement (PEIS)
Organizational requirements of the SaeR binding sites for a functional P1 promoter of the sae operon in Staphylococcus aureus.

Science.gov (United States)

Cho, Hoonsik; Jeong, Do-Won; Li, Chunling; Bae, Taeok

2012-06-01

In Staphylococcus aureus, the SaeRS two-component system controls the expression of multiple virulence factors. Of the two promoters in the sae operon, P1 is autoinduced and has two binding sites for the response regulator SaeR. In this study, we examined the organizational requirements of the SaeR binding sites in P1 for transcription activation. Mutational studies showed that both binding sites are essential for binding to phosphorylated SaeR (P-SaeR) and transcription activation. When the 21-bp distance between the centers of the two SaeR binding sites was altered to 26 bp, 31 bp, 36 bp, or 41 bp, only the 31-bp mutant retained approximately 40% of the original promoter activity. When the -1-bp spacing (i.e.,1-bp overlap) between the primary SaeR binding site and the -35 promoter region was altered, all mutant P1 promoters failed to initiate transcription; however, when the first nucleotide of the -35 region was changed from A to T, the mutants with 0-bp or 22-bp spacing showed detectable promoter activity. Although P-SaeR was essential for the binding of RNA polymerase to P1, it was not essential for the binding of the enzyme to the alpha-hemolysin promoter. When the nonoptimal spacing between promoter elements in P1 or the coagulase promoter was altered to the optimal spacing of 17 bp, both promoters failed to initiate transcription. These results suggest that SaeR binding sites are under rather strict organizational restrictions and provide clues for understanding the molecular mechanism of sae-mediated transcription activation.
Fermilab Security Site Access Request Database

Science.gov (United States)

Fermilab Security Site Access Request Database Use of the online version of the Fermilab Security Site Access Request Database requires that you login into the ESH&Q Web Site. Note: Only Fermilab generated from the ESH&Q Section's Oracle database on May 27, 2018 05:48 AM. If you have a question
Safety of Research Reactors. Safety Requirements

International Nuclear Information System (INIS)

2010-01-01

The main objective of this Safety Requirements publication is to provide a basis for safety and a basis for safety assessment for all stages in the lifetime of a research reactor. Another objective is to establish requirements on aspects relating to regulatory control, the management of safety, site evaluation, design, operation and decommissioning. Technical and administrative requirements for the safety of research reactors are established in accordance with these objectives. This Safety Requirements publication is intended for use by organizations engaged in the site evaluation, design, manufacturing, construction, operation and decommissioning of research reactors as well as by regulatory bodies
Risk management at hazardous waste sites

International Nuclear Information System (INIS)

Travis, C.C.; Doty, C.B.

1990-01-01

The Superfund Amendments and Reauthorization Act of 1986 (SARA) provided the Environmental Protection Agency (EPA) with additional resources and direction for the identification, evaluation, and remediation of hazardous waste sites in the United States. SARA established more stringent requirements for the Superfund program, both in terms of the pace of the program and the types of remedial alternatives selected. The central requirement is that remedial alternatives be ''protective of public health and the environment'' and ''significantly and permanently'' reduce the toxicity, mobility, or volume of contaminants. The mandate also requires that potential risk be considered in the decision-making process. This document discusses risk management at hazardous waste sites. Topics include selection of sites for placement on the National Priority List, risk assessment and the decision process, risk reduction and remedial alternative selection, and aquifer restoration. 10 refs., 2 figs
2011 ANNUAL SITE ENVIRONMENTAL REPORT

Energy Technology Data Exchange (ETDEWEB)

Meyer, A.; Eddy, T.; Jannik, T.; Terry, B.; Cauthen, K.; Coward, L.; Dunaway-Ackerman, J.; Wilson, M.; Hutchison, J.; O' Quinn, S.

2012-10-01

The Savannah River Site Environmental Report for 2011 (SRNS-STI-2012-00200) is prepared for the U.S. Department of Energy (DOE) according to requirements of DOE Order 231.1 B, “Environment, Safety and Health Reporting." The annual SRS Environmental Report has been produced for more than 50 years. Several hundred copies are and interested individuals. The report’s purpose is to: present summary environmental data that characterize site environmental management performance; describe compliance status with respect to environmental standards and requirements; highlight significant programs and efforts.
Site Study Plan for meteorology/air quality, Deaf Smith County site, Texas: Environmental Field Program: Preliminary draft

International Nuclear Information System (INIS)

1987-06-01

The Meteorological/Air Quality Site Study Plan describes a field program consisting of continuous measurements of surface (10-meter) wind speed and direction, temperature, humidity, dew point, pressure, and sensible heat flux (vertical). Air quality measurements will be limited to suspended particulate matter. After the first year of measurements, a 60-meter tower will be added to incorporate measurements needed for later modeling and dose calculations; these will include upper level winds, vertical temperature structure, and vertical wind speed. All of these measurements will be made at a site located within the 9-mi 2 site area but remote from the ESF. A second site, located near and downwind from the ESF, will monitor only particulate matter. The SSP describes the need for each study; its design and design rationale; analysis, management, and use of data, schedule of field activities, organization of field personnel and sample management, and quality assurance requirements. These studies will provide data needed to satisfy requirements contained in, or derived from the Salt Repository Project Requirements Document. 38 refs., 8 figs., 3 tabs

Hanford Site solid waste acceptance criteria

International Nuclear Information System (INIS)

Willis, N.P.; Triner, G.C.

1991-09-01

Westinghouse Hanford Company manages the Hanford Site solid waste treatment, storage, and disposal facilities for the US Department of Energy Field Office, Richland under contract DE-AC06-87RL10930. These facilities include radioactive solid waste disposal sites, radioactive solid waste storage areas and hazardous waste treatment, storage, and/or disposal facilities. This manual defines the criteria that must be met by waste generators for solid waste to be accepted by Westinghouse Hanford Company for treatment, storage and/or disposal facilities. It is to be used by all waste generators preparing radioactive solid waste for storage or disposal at the Hanford Site facilities and for all Hanford Site generators of hazardous waste. This manual is also intended for use by Westinghouse Hanford Company solid waste technical staff involved with approval and acceptance of solid waste. The criteria in this manual represent a compilation of state and federal regulations; US Department of Energy orders; Hanford Site requirements; and other rules, regulations, guidelines, and standards as they apply to management of solid waste. Where appropriate, these requirements are included in the manual by reference. It is the intent of this manual to provide guidance to the waste generator in meeting the applicable requirements
Hanford Site Transuranic (TRU) Waste Certification Plan

International Nuclear Information System (INIS)

GREAGER, T.M.

2000-01-01

As a generator of transuranic (TRU) and TRU mixed waste destined for disposal at the Waste Isolation Pilot Plant (WIPP), the Hanford Site must ensure that its TRU waste meets the requirements of US. Department of Energy (DOE) 0 435.1, ''Radioactive Waste Management,'' and the Contact-Handled (CH) Transuranic Waste Acceptance Criteria for the Waste Isolation Pilot Plant (WIPP-WAC). WIPP-WAC requirements are derived from the WIPP Technical Safety Requirements, WIPP Safety Analysis Report, TRUPACT-II SARP, WIPP Land Withdrawal Act, WIPP Hazardous Waste Facility Permit, and Title 40 Code of Federal Regulations (CFR) 191/194 Compliance Certification Decision. The WIPP-WAC establishes the specific physical, chemical, radiological, and packaging criteria for acceptance of defense TRU waste shipments at WIPP. The WPP-WAC also requires that participating DOE TRU waste generator/treatment/storage sites produce site-specific documents, including a certification plan, that describe their program for managing TRU waste and TRU waste shipments before transferring waste to WIPP. Waste characterization activities provide much of the data upon which certification decisions are based. Waste characterization requirements for TRU waste and TRU mixed waste that contains constituents regulated under the Resource Conservation and Recovery Act (RCRA) are established in the WIPP Hazardous Waste Facility Permit Waste Analysis Plan (WAP). The Hanford Site Quality Assurance Project Plan (QAPjP) (HNF-2599) implements the applicable requirements in the WAP and includes the qualitative and quantitative criteria for making hazardous waste determinations. The Hanford Site must also ensure that its TRU waste destined for disposal at WPP meets requirements for transport in the Transuranic Package Transporter-11 (TRUPACT-11). The US. Nuclear Regulatory Commission (NRC) establishes the TRUPACT-11 requirements in the Safety Analysis Report for the TRUPACT-II Shipping Package (TRUPACT-11 SARP). In
ITER site selection studies in Spain

International Nuclear Information System (INIS)

Medrano, M.; Alejaldre, C.; Doncel, J.; Garcia, A.; Ibarra, A.; Jimenez, J.A.; Sanchez de Mora, M.A.; Alcala, F.; Diez, J.E.; Dominguez, M.; Albisu, F.

2003-01-01

The studies carried out to evaluate and select a candidate site for International Thermonuclear Experimental Reactor (ITER) construction in Spain are presented in this paper. The ITER design, completed in July 2001, considered a number of technical requirements that must be fulfilled by the selected site. Several assumptions concerning the ITER site were made in order to carry on the design before final site selection. In the studies undertaken for ITER site selection in Spain, the referred technical requirements and assumptions were applied across the whole of Spain and two areas were identified as being preferential. These areas are on the Mediterranean coast and are situated in the Catalan and Valencian regions. A comparative evaluation based on technical characteristics for the concrete plots, proposed within the preferential areas, has been done. The result of these studies was the selection of a site that was deemed to be the most competitive--Vandellos (Tarragona)--and it was proposed to the European Commission for detailed studies in order to be considered as a possible European site for ITER construction. Another key factor for hosting ITER in Spain, is the licensing process. The present status is summarised in this paper
Site characterization plan:

International Nuclear Information System (INIS)

1988-01-01

The Yucca Mountain site in Nevada is one of three candidate sites for the first geologic repository for radioactive waste. On May 28, 1986, it was recommended for detailed study in a program of site characterization. This site characterization plan (SCP) has been prepared in acordance with the requirements of the Nuclear Waste Policy Act to summarize the information collected to date about the geologic conditions at the site;to describe the conceptual designs for the repository and the waste package and to present the plans for obtaining the geologic information necessary to demonstrate the suitability of the site for a repository, to design the repository and the waste package, to prepare an environmental impact statement, and to obtain from the US Nuclear Regulatory Commission (NRC) an authorization to construct the repository. This introduction begins with a brief section on the process for siting and eveloping a repository, followed by a discussion of the pertinent legislation and regulations. A description of site characterization is presented next;it describes the facilities to be constructed for the site characterization program and explains the principal activities to be conducted during the program. Finally, the purpose, content, organizing prinicples, and organization of this site characterization plan are outlined, and compliance with applicable regulations is discussed. 880 refs., 130 figs., 25 tabs
Building arrangement and site layout design guides for on site low level radioactive waste storage facilities

International Nuclear Information System (INIS)

McMullen, J.W.; Feehan, M.J.

1986-01-01

Many papers have been written by AE's and utilities describing their onsite storage facilities, why they are needed, NRC regulations, and disposal site requirements. This paper discusses a typical storage facility and address the design considerations and operational aspects that are generally overlooked when designing and siting a low level radioactive waste storage facility. Some topics to be addressed are: 1. Container flexibility; 2. Modular expansion capabilities; 3. DOT regulations; 4. Meterological requirements; 5. OSHA; 6. Fire protection; 7. Floods; 8. ALARA
US Department of Energy wind turbine candidate site program: the regulatory process

Energy Technology Data Exchange (ETDEWEB)

Greene, M.R.; York, K.R.

1982-06-01

Sites selected in 1979 as tentative sites for installation of a demonstration MOD-2 turbine are emphasized. Selection as a candidate site in this program meant that the US Department of Energy (DOE) designated the site as eligible for a DOE-purchased and installed meteorological tower. The regulatory procedures involved in the siting and installation of these meteorological towers at the majority of the candidate sites are examined. An attempt is also made, in a preliminary fashion, to identify the legal and regulatory procedures that would be required to put up a turbine at each of these candidate sites. The information provided on each of these sites comes primarily from utility representatives, supplemented by conversations with state and local officials. The major findings are summarized on the following: federal requirements, state requirements, local requirements, land ownership, wind rights, and public attitudes.
Selection and cultivation of final vegetative cover for closed waste sites at the Savannah River Site, SC

International Nuclear Information System (INIS)

Cook, J.R.; Salvo, S.K.

1992-01-01

Low-level, hazardous, and mixed waste disposal sites normally require some form of plant material to prevent erosion of the final closure cap. Waste disposal sites are closed and capped in a complex scientific manner to minimize water infiltration and percolation into and through the waste material. Turf type grasses are currently being used as a vegetative cover for most sites. Consequently, the sites require periodic mowing and other expensive annual maintenance practices. The purpose of this five year study was to evaluate alternative plant material for use on wastes sites that is quickly and easily established and economically maintained, retards water infiltration, provides maximum year-round evapotranspiration, is ecologically acceptable and does not harm the closure cap. The results of the study are described in this report and suggest that two species of bamboo (Phyllostachys bissetii and P. rubromarainata) can be utilized to provide long lived, low maintenance, climax vegetation for the waste sites. These large species of bamboo will also reduce the probability of intrusion by humans, animals and deeply rooted plant species
Report of the Siting Policy Task Force

International Nuclear Information System (INIS)

1979-08-01

In August 1978, the Nuclear Regulatory Commission directed the staff to develop a general policy statement on nuclear power reactor siting. A Task Force was formed for that purpose and has prepared a statement of current NRC policy and practice and has recommended a number of changes to current policy. Recommendations were made to accomplish the following goals: (1) To strengthen siting as a factor in defense in depth by establishing requirements for site approval that are independent of plant design consideration. The present policy of permitting plant design features to compensate for unfavorable site characteristics has resulted in improved designs but has tended to deemphasize site isolation. (2) To take into consideration in siting the risk associated with accidents beyond the design basis (Class 9) by establishing population density and distribution criteria. Plant design improvements have reduced the probability and consequences of design basis accidents, but there remains the residual risk from accidents not considered in the design basis. Although this risk cannot be completely reduced to zero, it can be significantly reduced by selective siting. (3) To require that sites selected will minimize the risk from energy generation. The selected sites should be among the best available in the region where new generating capacity is needed. Siting requirements should be stringent enough to limit the residual risk of reactor operation but not so stringent as to eliminate the nuclear option from large regions of the country. This is because energy generation from any source has its associated risk, with risks from some energy sources being greater than that of the nuclear option
Steroidogenic disruptive effects of the serotonin-noradrenaline reuptake inhibitors duloxetine, venlafaxine and tramadol in the H295R cell assay and in a recombinant CYP17 assay

DEFF Research Database (Denmark)

Islin, Julie; Munkboel, Cecilie Hurup; Styrishave, Bjarne

2018-01-01

The aim of this study was to determine the steroidogenic endocrine disrupting effect of the three most widely used serotonin-noradrenaline reuptake inhibitors duloxetine, venlafaxine and tramadol, using two in vitro models, the H295R assay and a recombinant CYP17 enzyme assay. Steroid hormones were...... quantified using LC-MS/MS. Duloxetine showed endocrine disrupting effects at 5-20μM with CYP17 being the main target. Venlafaxine also affected the steroidogenesis, mainly by affecting the CYP17 lyase reaction, although at much higher concentrations i.e. 100μM. Tramadol only exerted minor effects...... on the steroidogenesis with the lowest observed effect at 314μM. Based on the H295R results, the inhibition of CYP17 by duloxetine and venlafaxine was investigated in a recombinant CYP17 assay with the use of the 4 major CYP17 substrates pregnenolone, progesterone, 17α-hydroxypregnenolone and 17α...
Air quality measurements for site characterization

International Nuclear Information System (INIS)

Carter, M.W.; Conklin, W.C.

1982-01-01

Effective and timely site characterization is an important part of selecting a site for low-level waste disposal. Parameters measured can be compared with pertinent regulatory requirements, used for a reference base, helpful in evaluating environmental impacts, utilized in documenting changes in control programs, of value in modeling studies and other data uses, and beneficial in providing relevant sampling and methodology training. This paper will focus on specific air quality measurements which should be an inherent part of the site characterization program. The program is designed to measure, quantify, and identify contributions from site uses (operational procedures), atmospheric fallout, natural radioactivity, and vicinity and regional applications of radionuclides. The recommended air quality measurements program will be described in association with a reference site developd by the US Nuclear Regulatory Commission. Particular attention will be devoted to the type and quality of information which is needed, the scope of sampling and measurements, the frequency of measurements, locations and numbers of sampling stations, the period of time needed for site characterization, and the proper uses of the information once it has been obtained. Adequate characterization of the site will be most important in final site selection and in the operation of the site as to periodically assessing environmental impacts and helping guide any remedial control efforts designed to meet regulatory requirements
Nevada Test Site Waste Acceptance Criteria

International Nuclear Information System (INIS)

U.S. Department of Energy, Nevada Operations Office, Waste Acceptance Criteria

1999-01-01

This document provides the requirements, terms, and conditions under which the Nevada Test Site will accept low-level radioactive and mixed waste for disposal; and transuranic and transuranic mixed waste for interim storage at the Nevada Test Site
Comparative efficacy of selective serotonin reuptake inhibitors (SSRI) in treating major depressive disorder: a protocol for network meta-analysis of randomised controlled trials.

Science.gov (United States)

Jia, Yongliang; Zhu, Hongmei; Leung, Siu-Wai

2016-06-07

There have been inconsistent findings from randomised controlled trials (RCTs) and systematic reviews on the efficacies of selective serotonin reuptake inhibitors (SSRIs) as the first-line treatment of major depressive disorder (MDD). Besides inconsistencies among randomised controlled trials (RCTs), their risks of bias and evidence grading have seldom been evaluated in meta-analysis. This study aims to compare the efficacy of SSRIs by conducting a Bayesian network meta-analysis, which will be the most comprehensive evaluation of evidence to resolve the inconsistency among previous studies. SSRIs including citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline and vilazodone have been selected. Systematic database searching and screening will be conducted for the RCTs on drug treatment of patients with MDD according to pre-specified search strategies and selection criteria. PubMed, the Cochrane Library, EMBASE, ScienceDirect, the US Food and Drug Administration Website, ClinicalTrial.gov and WHO Clinical Trials will be searched. Outcome data including Hamilton Depression Rating Scale (HDRS), Montgomery-Åsberg Depression Rating Scale (MADRS) and Clinical Global Impression (CGI) from eligible RCTs will be extracted. The outcomes will be analysed as ORs and mean differences under a random-effects model. A Bayesian network meta-analysis will be conducted with WinBUGS software, to compare the efficacies of SSRIs. Subgroup and sensitivity analysis will be performed to explain the study heterogeneity and evaluate the robustness of the results. Meta-regression analysis will be conducted to determine the possible factors affecting the efficacy outcomes. The Cochrane risk of bias assessment tool will be used to assess the RCT quality, and the Grading of Recommendation, Assessment, Development and Evaluation will be used to assess the strength of evidence from the meta-analysis. No ethical approval is required because this study includes neither
Middlesex FUSRAP Site - A Path to Site-Wide Closure - 13416

Energy Technology Data Exchange (ETDEWEB)

Miller, David M. [ECC, 110 Fieldcrest Ave, Ste 31, Edison, NJ, 08837 (United States); Edge, Helen [US Army Corps of Engineers - NYD, 26 Federal Plaza, Room 1811, New York, NY, 10278 (United States)

2013-07-01

The road-map to obtaining closure of the Middlesex Sampling Plant FUSRAP site in Middlesex, New Jersey (NJ) has required a multi-faceted approach, following the CERCLA Process. Since 1998, the US ACE, ECC, and other contractors have completed much of the work required for regulatory acceptance of site closure with unrestricted use. To date, three buildings have been decontaminated, demolished, and disposed of. Two interim storage piles have been removed and disposed of, followed by the additional removal and disposal of over 87,000 tons of radiologically and chemically-impacted subsurface soils by the summer of 2008. The US ACE received a determination from the EPA for the soils Operable Unit, (OU)-1, in September 2010 that the remedial excavations were acceptable, and meet the criteria for unrestricted use as required by the 2004 Record of Decision (ROD) for OU-1. Following the completion of OU-1, the project delivery team performed additional field investigation of the final Operable Unit for Middlesex, OU-2, Groundwater. As of December 2012, the project delivery team has completed a Supplemental Remedial Investigation, which will be followed with a streamlined Feasibility Study, Proposed Plan, and ROD. Several years of historical groundwater data was available from previous investigations and the FUSRAP Environmental Surveillance Program. Historical data indicated sporadic detections of Volatile Organic Compounds (VOCs), primarily trichloroethylene (TCE), carbon tetrachloride (CT), and methyl tert-butyl ether (MTBE), with no apparent trend or pattern indicating extent or source of the VOC impact. In 2008, the project delivery team initiated efforts to re-assess the Conceptual Site Model (CSM) for groundwater. The bedrock was re-evaluated as a leaky multi-unit aquifer, and a plan was developed for additional investigations for adequate bedrock characterization and delineation of groundwater contaminated primarily by CT, TCE, and tetrachloroethene (PCE). The
Post-Closure Strategy for Use-Restricted Sites on the Nevada National Security Site, Nevada Test and Training Range, and Tonopah Test Range, Nevada

International Nuclear Information System (INIS)

Silvas, A. J.

2014-01-01

The purpose of this Post-Closure Strategy is to provide a consistent methodology for continual evaluation of post-closure requirements for use-restricted areas on the Nevada National Security Site (NNSS), Nevada Test and Training Range (NTTR), and Tonopah Test Range (TTR) to consolidate, modify, or streamline the program. In addition, this document stipulates the creation of a single consolidated Post-Closure Plan that will detail the current post-closure requirements for all active use restrictions (URs) and outlines its implementation and subsequent revision. This strategy will ensure effective management and control of the post-closure sites. There are currently over 200 URs located on the NNSS, NTTR, and TTR. Post-closure requirements were initially established in the Closure Report for each site. In some cases, changes to the post-closure requirements have been implemented through addenda, errata sheets, records of technical change, or letters. Post-closure requirements have been collected from these multiple sources and consolidated into several formats, such as summaries and databases. This structure increases the possibility of inconsistencies and uncertainty. As more URs are established and the post-closure program is expanded, the need for a comprehensive approach for managing the program will increase. Not only should the current requirements be obtainable from a single source that supersedes all previous requirements, but the strategy for modifying the requirements should be standardized. This will enable more effective management of the program into the future. This strategy document and the subsequent comprehensive plan are to be implemented under the assumption that the NNSS and outlying sites will be under the purview of the U.S. Department of Energy, National Nuclear Security Administration for the foreseeable future. This strategy was also developed assuming that regulatory control of the sites remains static. The comprehensive plan is not
WAG 2 remedial investigation and site investigation site-specific work plan/health and safety checklist for the soil and sediment task

International Nuclear Information System (INIS)

Holt, V.L.; Burgoa, B.B.

1993-12-01

This document is a site-specific work plan/health and safety checklist (WP/HSC) for a task of the Waste Area Grouping 2 Remedial Investigation and Site Investigation (WAG 2 RI ampersand SI). Title 29 CFR Part 1910.120 requires that a health and safety program plan that includes site- and task-specific information be completed to ensure conformance with health- and safety-related requirements. To meet this requirement, the health and safety program plan for each WAG 2 RI ampersand SI field task must include (1) the general health and safety program plan for all WAG 2 RI ampersand SI field activities and (2) a WP/HSC for that particular field task. These two components, along with all applicable referenced procedures, must be kept together at the work site and distributed to field personnel as required. The general health and safety program plan is the Health and Safety Plan for the Remedial Investigation and Site Investigation of Waste Area Grouping 2 at the Oak Ridge National Laboratory, Oak Ridge, Tennessee (ORNL/ER-169). The WP/HSCs are being issued as supplements to ORNL/ER-169
The effects of compound stimulus extinction and inhibition of noradrenaline reuptake on the renewal of alcohol seeking

Science.gov (United States)

Furlong, T M; Pan, M J; Corbit, L H

2015-01-01

Alcohol-related stimuli can trigger relapse of alcohol-seeking behaviors even after extended periods of abstinence. Extinction of such stimuli can reduce their impact on relapse; however, the expression of extinction can be disrupted when testing occurs outside the context where extinction learning took place, an effect termed renewal. Behavioral and pharmacological methods have recently been shown to augment extinction learning; yet, it is not known whether the improved expression of extinction following these treatments remains context-dependent. Here we examined whether two methods, compound–stimulus extinction and treatment with the noradrenaline reuptake inhibitor atomoxetine, would reduce the vulnerability of extinction to a change in context. Following alcohol self-administration, responding was extinguished in a distinct context. After initial extinction, further extinction was given to a target stimulus presented in compound with another alcohol-predictive stimulus intended to augment prediction error (Experiment 1) or after a systemic injection of atomoxetine (1.0 mg kg−1; Experiment 2). A stimulus extinguished as part of a compound elicited less responding than a stimulus receiving equal extinction alone regardless of whether animals were tested in the training or extinction context; however, reliable renewal was not observed in this paradigm. Importantly, atomoxetine enhanced extinction relative to controls even in the presence of a reliable renewal effect. Thus, extinction of alcohol-seeking behavior can be improved by extinguishing multiple alcohol-predictive stimuli or enhancing noradrenaline neurotransmission during extinction training. Importantly, both methods improve extinction even when the context is changed between extinction training and test, and thus could be utilized to enhance the outcome of extinction-based treatments for alcohol-use disorders. PMID:26327688
Site 300 SPCC Plan

Energy Technology Data Exchange (ETDEWEB)

Griffin, D. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2016-11-23

This Spill Prevention, Control, and Countermeasure (SPCC) Plan describes the measures that are taken at Lawrence Livermore National Laboratory’s (LLNL) Experimental Test Site (Site 300) near Tracy, California, to prevent, control, and handle potential spills from aboveground containers that can contain 55 gallons or more of oil. This SPCC Plan complies with the Oil Pollution Prevention regulation in Title 40 of the Code of Federal Regulations, Part 112 (40 CFR 112) and with 40 CFR 761.65(b) and (c), which regulates the temporary storage of polychlorinated biphenyls (PCBs). This Plan has also been prepared in accordance with Division 20, Chapter 6.67 of the California Health and Safety Code (HSC 6.67) requirements for oil pollution prevention (referred to as the Aboveground Petroleum Storage Act [APSA]), and the United States Department of Energy (DOE) Order No. 436.1. This SPCC Plan establishes procedures, methods, equipment, and other requirements to prevent the discharge of oil into or upon the navigable waters of the United States or adjoining shorelines for aboveground oil storage and use at Site 300. This SPCC Plan has been prepared for the entire Site 300 facility and replaces the three previous plans prepared for Site 300: LLNL SPCC for Electrical Substations Near Buildings 846 and 865 (LLNL 2015), LLNL SPCC for Building 883 (LLNL 2015), and LLNL SPCC for Building 801 (LLNL 2014).
Nevada Test Site Environmental Report 2006 and Site Description (Volume 1)

Energy Technology Data Exchange (ETDEWEB)

Cathy Wills

2007-10-01

The Nevada Test Site Environmental Report 2006 (NTSER) was prepared to meet the information needs of the public and the requirements and guidelines of the U.S. Department of Energy (DOE) for annual site environmental reports. It was prepared by National Security Technologies, LLC (NSTec). This Executive Summary presents the purpose of the document, the major programs conducted at the Nevada Test Site (NTS), NTS key environmental initiatives, radiological releases and potential doses to the public resulting from site operations, a summary of nonradiological releases, implementation status of the NTS Environmental Management System, a summary of compliance with environmental regulations, pollution prevention and waste minimization accomplishments, and significant environmental accomplishments. Much of the content of this Executive Summary is also presented in a separate stand-alone pamphlet titled Nevada Test Site Environmental Report Summary 2006 produced to be a more cost-effective means of distributing information contained in the NTSER to interested DOE stakeholders.
Nevada Test Site Environmental Report 2006 and Site Description (Volume 1)

International Nuclear Information System (INIS)

Cathy Wills

2007-01-01

The Nevada Test Site Environmental Report 2006 (NTSER) was prepared to meet the information needs of the public and the requirements and guidelines of the U.S. Department of Energy (DOE) for annual site environmental reports. It was prepared by National Security Technologies, LLC (NSTec). This Executive Summary presents the purpose of the document, the major programs conducted at the Nevada Test Site (NTS), NTS key environmental initiatives, radiological releases and potential doses to the public resulting from site operations, a summary of nonradiological releases, implementation status of the NTS Environmental Management System, a summary of compliance with environmental regulations, pollution prevention and waste minimization accomplishments, and significant environmental accomplishments. Much of the content of this Executive Summary is also presented in a separate stand-alone pamphlet titled Nevada Test Site Environmental Report Summary 2006 produced to be a more cost-effective means of distributing information contained in the NTSER to interested DOE stakeholders
Intra-site Secure Transport Vehicle test and evaluation

International Nuclear Information System (INIS)

Scott, S.

1995-01-01

In the past many DOE and DoD facilities involved in handling nuclear material realized a need to enhance the safely and security for movement of sensitive materials within their facility, or ''intra-site''. There have been prior efforts to improve on-site transportation; however, there remains a requirement for enhanced on-site transportation at a number of facilities. The requirements for on-site transportation are driven by security, safety, and operational concerns. The Intra-site Secure Transport Vehicle (ISTV) was designed to address these concerns specifically for DOE site applications with a standardized vehicle design. This paper briefly reviews the ISTV design features providing significant enhancement of onsite transportation safety and security, and also describes the test and evaluation activities either complete of underway to validate the vehicle design and operation

New Reactor Siting in Finland, Hanhikivi Site in Pyhaejoki - STUK preliminary safety assessment

International Nuclear Information System (INIS)

Nevalainen, Janne

2013-01-01

STUK has performed a preliminary assessment of the Decision-in-Principle on the Fennovoima application. A variety of factors must be considered in the selection of a site, including effects of the site on the plant design and the effects of the plant on the site environment. These include external hazards, both natural and human-induced. Since this is a new site, an extensive siting process is followed, that can include an EIA. A site survey is performed to identify candidate sites, after investigating a large region and rejecting unsuitable sites. The remaining sites are then screened and compared on the basis of safety and other considerations to select one or more preferred sites. Natural hazards include geology, seismology, hydrology and meteorology. Offshore ice will be a particular hazard for this plant, since the site is on average only 1.5 m above sea level. The design basis earthquake corresponds to a return frequency of 100,000 years, with 50 % confidence. The existing sites in southern Finland used a design peak ground acceleration of 0.1 g with the ground response spectrum maximum at 10 Hz. The candidate sites in northern Finland will require a peak ground acceleration of 0.2 g with the ground response spectrum maximum at 25 Hz
Quality assurance during site construction. Pt. 1

International Nuclear Information System (INIS)

Mueller, J.

1980-01-01

The first part of the lecture deals with the Quality Assurance system on the construction site in general. Basic site-related problems during contract implementation and the QA system requirements resulting from them are presented. The compilation of these requirements in a QA program and its inclusion in the site manual in written form are explained. Site organization, personnel qualification and procedures are referred to. Whereas the first part shows what is to be done, the second part shows how it can be put into practice on the site. All the essential points for the assurance of quality are addressed. They include, e.g., review of documents, incoming goods control, in-process surveillance, store controls, identification of components and systems, dealing with changes and deviations, documentation control and audits. By means of examples taken form practice the necessity of a well-functioning QA system, and the importance of quality-assuring measures on the site are pointed out. (orig.)
The Contribution of Environmental Siting and Permitting Requirements to the Cost of Energy for Oscillating Water Column Wave Energy Devices

Energy Technology Data Exchange (ETDEWEB)

Copping, Andrea E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Geerlofs, Simon H. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hanna, Luke A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

2013-09-01

Responsible deployment of marine and hydrokinetic (MHK) devices in estuaries, coastal areas, and major rivers requires that biological resources and ecosystems be protected through siting and permitting (consenting) processes. Scoping appropriate deployment locations, collecting pre-installation (baseline) and post-installation data all add to the cost of developing MHK projects, and hence to the cost of energy. Under the direction of the U.S. Department of Energy, Pacific Northwest National Laboratory scientists have developed logic models that describe studies and processes for environmental siting and permitting. Each study and environmental permitting process has been assigned a cost derived from existing and proposed tidal, wave, and riverine MHK projects, as well as expert opinion of marine environmental research professionals. Cost estimates have been developed at the pilot and commercial scale. The reference model described in this document is an oscillating water column device deployed in Northern California at approximately 50 meters water depth.
Location of the Antidepressant Binding Site in the Serotonin Transporter IMPORTANCE OF SER-438 IN RECOGNITION OF CITALOPRAM AND TRICYCLIC ANTIDEPRESSANTS

DEFF Research Database (Denmark)

Andersen, Jacob; Taboureau, Olivier; Hansen, Kasper B.

2009-01-01

antidepressants, including the selective serotonin reuptake inhibitor citalopram and the tricyclic antidepressants imipramine, clomipramine, and amitriptyline. A conservative mutation of Ser-438 to threonine (S438T) selectively increased the K-i values for these antidepressants up to 175-fold. The effects...
Intruder scenarios for site-specific waste classification

International Nuclear Information System (INIS)

Kennedy, W.E. Jr.

1988-01-01

The US Department of Energy (DOE) is currently revising its low-level radioactive waste (LLW) management requirements and guidelines for waste generated at its facilities that support defense missions. Specifically, draft DOE 5820.2A, Chapter 3, describes the purpose, policy, and requirements necessary for the management of defense LLW. The draft DOE policy calls for DOE LLW operations to be managed to protect the health and safety of the public, preserve the environment, and ensure that no remedial action will be necessary after termination of operations. The requirements and guidelines apply to radioactive wastes but are also intended to apply to mixed hazardous and radioactive wastes as defined in draft DOE 5400.5, Hazardous and Radioactive Mixed Waste. The basic approach used by DOE is to establish overall performance objectives in terms of ground-water protection and public radiation dose limits and to require site-specific performance assessments to determine compliance. As a result of these performance assessments, each site shall develop waste acceptance criteria that define the allowable quantities and concentrations of specific radioisotopes. Additional limitations on waste disposal design, waste form, and waste treatment shall also be developed on a site-specific basis. As a key step in the site-specific performance assessments, an evaluation must be conducted of potential radiation doses to intruders who may inadvertently move onto a closed DOE LLW disposal site after loss of institutional controls must be conducted. This paper describes the types of intruder scenarios that should be considered when performing this step of the site-specific performance assessment
Selective serotonin reuptake inhibitors potentiate the rapid antidepressant-like effects of serotonin4 receptor agonists in the rat.

Directory of Open Access Journals (Sweden)

Guillaume Lucas

2010-02-01

Full Text Available We have recently reported that serotonin(4 (5-HT(4 receptor agonists have a promising potential as fast-acting antidepressants. Here, we assess the extent to which this property may be optimized by the concomitant use of conventional antidepressants.We found that, in acute conditions, the 5-HT(4 agonist prucalopride was able to counteract the inhibitory effect of the selective serotonin reuptake inhibitors (SSRI fluvoxamine and citalopram on 5-HT neuron impulse flow, in Dorsal Raphé Nucleus (DRN cells selected for their high (>1.8 Hz basal discharge. The co-administration of both prucalopride and RS 67333 with citalopram for 3 days elicited an enhancement of DRN 5-HT neuron average firing rate, very similar to what was observed with either 5-HT(4 agonist alone. At the postsynaptic level, this translated into the manifestation of a tonus on hippocampal postsynaptic 5-HT(1A receptors, that was two to three times stronger when the 5-HT(4 agonist was combined with citalopram. Similarly, co-administration of citalopram synergistically potentiated the enhancing effect of RS 67333 on CREB protein phosphorylation within the hippocampus. Finally, in the Forced Swimming Test, the combination of RS 67333 with various SSRIs (fluvoxamine, citalopram and fluoxetine was more effective to reduce time of immobility than the separate administration of each compound.These findings strongly suggest that the adjunction of an SSRI to a 5-HT(4 agonist may help to optimize the fast-acting antidepressant efficacy of the latter.
Ecstasy use and serotonin syndrome: a neglected danger to adolescents and young adults prescribed selective serotonin reuptake inhibitors.

Science.gov (United States)

Dobry, Yuriy; Rice, Timothy; Sher, Leo

2013-01-01

At present, there are scarce clinical and basic lab data concerning the risk of acute serotonin toxicity from selective serotonin reuptake inhibitors (SSRIs) and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) co-administration. The health care community can strongly benefit from efforts to address the high risks associated with serotonin syndrome from this specific drug combination. The aim of this work is to review the risk of serotonin syndrome in adolescents and young adults prescribed with SSRIs and are concurrently using ecstasy. An electronic search of the major behavioral science bibliographic databases (Pubmed, PsycINFO, Medline) was conducted to retrieve peer-reviewed articles, which detail the clinical characteristics, biological mechanisms and social implications of SSRIs, MDMA, and their potential synergism in causing serotonin syndrome in the pediatric and young adult population. Search terms included "serotonin syndrome", "ecstasy", "MDMA", "pediatric", and "SSRI". Additional references were incorporated from the bibliographies of these retrieved articles. MDMA, in combination with the widely-prescribed SSRI antidepressant class, can lead to rapid, synergistic rise of serotonin (5-HT) concentration in the central nervous system, leading to the acute medical emergency known as serotonin syndrome. This review addresses such complication through an exploration of the theoretical mechanisms and clinical manifestations of this life-threatening pharmacological interaction. The increasing incidences of recreational ecstasy use and SSRI pharmacotherapy among multiple psychiatric disorders in the adolescent population have made this an overlooked yet increasingly relevant danger, which poses a threat to public health. This can be curbed through further research, as well as greater health care provision and attention from a regulatory body owing.
Radiosynthesis of [F-18]fluoxetine as a potential radiotracer for serotonin reuptake sites

International Nuclear Information System (INIS)

Das, M.K.; Mukherjee, Jogeshwar

1993-01-01

Synthesis of 4-nitro-α-bromo-α,α-difluorotoluene was accomplished in two steps starting from 4-nitrobenzaldehyde, with a 30% overall yield. Radiolabeling of 4-nitro-α-bromo-α, α-difluorotoluene with no-carrier-added [ 18 F]fluoride provided 4-nitro-α,α-difluoro-α-[ 18 F] fluorotoluene in 2-4% yields with a specific activity of 2590 GBq/mmol (70 Ci/mmol). The effect of the reaction temperature on the radiochemical yield and specific activity of the radiolabeling reaction was studied. Radiochemical yields increased, whereas specific activity decreased, with increasing temperature. Radiosynthesis of [ 18 F] fluoxetine involved coupling of 4-nitro-α,α-difluoro-α-[ 18 F]fluorotoluene with the sodium alkoxide of (S)-3-(methylamino)-1-phenyl-1-propanol. The overall yield of HPLC purified [ 18 F]fluoxetine was 1-2% (decay-corrected; total radiosynthesis time, 150-180 min). The specific activity of the product was 1480 GBq/mmol (40 Ci/mmol). (Author)
Radiosynthesis of [F-18]fluoxetine as a potential radiotracer for serotonin reuptake sites

Energy Technology Data Exchange (ETDEWEB)

Das, M.K.; Mukherjee, Jogeshwar (Chicago Univ., IL (United States). Dept. of Radiology)

1993-05-01

Synthesis of 4-nitro-[alpha]-bromo-[alpha],[alpha]-difluorotoluene was accomplished in two steps starting from 4-nitrobenzaldehyde, with a 30% overall yield. Radiolabeling of 4-nitro-[alpha]-bromo-[alpha], [alpha]-difluorotoluene with no-carrier-added [[sup 18]F]fluoride provided 4-nitro-[alpha],[alpha]-difluoro-[alpha]-[[sup 18]F] fluorotoluene in 2-4% yields with a specific activity of 2590 GBq/mmol (70 Ci/mmol). The effect of the reaction temperature on the radiochemical yield and specific activity of the radiolabeling reaction was studied. Radiochemical yields increased, whereas specific activity decreased, with increasing temperature. Radiosynthesis of [[sup 18]F] fluoxetine involved coupling of 4-nitro-[alpha],[alpha]-difluoro-[alpha]-[[sup 18]F]fluorotoluene with the sodium alkoxide of (S)-3-(methylamino)-1-phenyl-1-propanol. The overall yield of HPLC purified [[sup 18]F]fluoxetine was 1-2% (decay-corrected; total radiosynthesis time, 150-180 min). The specific activity of the product was 1480 GBq/mmol (40 Ci/mmol). (Author).
Report of early site suitability evaluation of the potential repository site at Yucca Mountain, Nevada; Yucca Mountain Site Characterization Project

Energy Technology Data Exchange (ETDEWEB)

Younker, J.L.; Andrews, W.B.; Fasano, G.A.; Herrington, C.C.; Mattson, S.R.; Murray, R.C. [Science Applications International Corp., Las Vegas, NV (United States); Ballou, L.B.; Revelli, M.A. [Lawrence Livermore National Lab., CA (United States); Ducharme, A.R.; Shephard, L.E. [Sandia National Labs., Albuquerque, NM (United States); Dudley, W.W.; Hoxie, D.T. [Geological Survey, Denver, CO (United States); Herbst, R.J.; Patera, E.A. [Los Alamos National Lab., NM (United States); Judd, B.R. [Decision Analysis Co., Portola Valley, CA (United States); Docka, J.A.; Rickertsen, L.D. [Weston Technical Associates, Washington, DC (United States)

1992-01-01

This study evaluated the technical suitability of Yucca Mountain, Nevada, as a potential site for a mined geologic repository for the permanent disposal of radioactive waste. The evaluation was conducted primarily to determine early in the site characterization program if there are any features or conditions at the site that indicate it is unsuitable for repository development. A secondary purpose was to determine the status of knowledge in the major technical areas that affect the suitability of the site. This early site suitability evaluation (ESSE) was conducted by a team of technical personnel at the request of the Associate Director of the US Department of Energy (DOE) Office of Geologic Disposal, a unit within the DOE`s Office of Civilian Radioactive Waste Management. The Yucca Mountain site has been the subject of such evaluations for over a decade. In 1983, the site was evaluated as part of a screening process to identify potentially acceptable sites. The site was evaluated in greater detail and found suitable for site characterization as part of the Environmental Assessment (EA) (DOE, 1986) required by the Nuclear Waste Policy Act of 1982 (NWPA). Additional site data were compiled during the preparation of the Site Characterization Plan (SCP) (DOE, 1988a). This early site suitability evaluation has considered information that was used in preparing both-documents, along with recent information obtained since the EA and SCP were published. This body of information is referred to in this report as ``current information`` or ``available evidence.``
Pharmacology of morphine and morphine-3-glucuronide at opioid, excitatory amino acid, GABA and glycine binding sites

Energy Technology Data Exchange (ETDEWEB)

Bartlett, S.E.; Smith, M.T. (Department of Pharmacy, The University of Queensland (Australia)); Dood, P.R. (Clinical Research Centre, Royal Brisbane Hospital Foundation, Brisbane (Australia))

1994-07-01

Morphine in high doses and its major metabolite, morphine-3-glucuronide, cause CNS excitation following intrathecal and intracerebroventricular administration by an unknown mechanism. This study investigated whether morphine and morphine-3-glucuronide interact at major excitatory (glutamate), major inhibitory (GABA or glycine), or opioid binding sites. Homogenate binding assays were performed using specific radioligands. At opioid receptors, morphine-3-glucuronide and morphine caused an equipotent sodium shift, consistent with morphine-3-glucuronide behaving as an agonist. This suggests that morphine-3-glucuronide-mediated excitation is not caused by an interaction at opioid receptors. Morphine-3-glucuronide and morphine caused a weak inhibition of the binding of [sup 3]H-MK801 (non-competitive antagonist) and [sup 125]I-ifenprodil (polyamine site antagonist), but at unphysiologically high concentrations. This suggests that CNS excitation would not result from an interaction of morphine-3-glucuronide and high-dose morphine with these sites on the NMDA receptor. Morphine-3-glucuronide and morphine inhibited the binding of [sup 3]H-muscimol (GABA receptor agonist), [sup 3]H-diazepam and [sup 3]H-flunitraxepam (benzodiazepine agonists) binding very weakly, suggesting the excitatory effects of morphine-3-glucuronide and high-dose morphine are not elicited through GABA[sub A] receptors. Morphine-3-glucuronide and high-dose morphine did not prevent re-uptake of glutamate into presynaptic nerve terminals. In addition, morphine-3-glucuronide and morphine did not inhibit the binding of [sup 3]H-strychnine (glycine receptor antagonist) to synaptic membranes prepared from bovine spinal cord. It is concluded that excitation caused by high-dose morphine and morphine-3-glucuronide is not mediated by an interaction with postsynaptic amino acid receptors. (au) (30 refs.).
Drupal 7 Multi Sites Configuration

CERN Document Server

Butcher, Matt

2012-01-01

Follow the creation of a multi-site instance with Drupal. The practical examples and accompanying screenshots will help you to get multiple Drupal sites set up in no time. This book is for Drupal site builders. It is assumed that readers are familiar with Drupal already, with a basic grasp of its concepts and components. System administration concepts, such as configuring Apache, MySQL, and Vagrant are covered but no previous knowledge of these tools is required.
Nevada Test Site Waste Acceptance Criteria, December 2000

Energy Technology Data Exchange (ETDEWEB)

NONE

2000-12-01

This document establishes the US Department of Energy, Nevada Operations Office waste acceptance criteria. The waste acceptance criteria provides the requirements, terms, and conditions under which the Nevada Test Site will accept low-level radioactive waste and mixed waste for disposal. It includes requirements for the generator waste certification program, characterization, traceability, waste form, packaging, and transfer. The criteria apply to radioactive waste received at the Nevada Test Site Area 3 and Area 5 Radioactive Waste Management Sites for storage or disposal.
Nevada Test Site Waste Acceptance Criteria, December 2000

International Nuclear Information System (INIS)

2000-01-01

This document establishes the US Department of Energy, Nevada Operations Office waste acceptance criteria. The waste acceptance criteria provides the requirements, terms, and conditions under which the Nevada Test Site will accept low-level radioactive waste and mixed waste for disposal. It includes requirements for the generator waste certification program, characterization, traceability, waste form, packaging, and transfer. The criteria apply to radioactive waste received at the Nevada Test Site Area 3 and Area 5 Radioactive Waste Management Sites for storage or disposal
Transportation system requirements document. Revision 1 DCN01. Supplement

International Nuclear Information System (INIS)

1995-05-01

The original Transportation System Requirements Document described the functions to be performed by and the technical requirements for the Transportation System to transport spent nuclear fuel (SNF) and high-level radioactive waste (HLW) from Purchaser and Producer sites to a Civilian Radioactive Waste Management System (CRWMS) site, and between CRWMS sites. The purpose of that document was to define the system-level requirements. These requirements include design and operations requirements to the extent they impact on the development of the physical segments of Transportation. The document also presented an overall description of Transportation, its functions, its segments, and the requirements allocated to the segments and the system-level interfaces with Transportation. This revision of the document contains only the pages that have been modified
The role of a fertilizer trial in reconciling agricultural expectations and landscape ecology requirements on an opencast coal site in South Wales, United Kingdom

International Nuclear Information System (INIS)

Humphries, C.E.L.; Humphries, R.N.; Wesemann, H.

1999-01-01

Since the 1940s the restoration of opencast coal sites in the UK has been predominantly to productive agriculture and forestry. With new UK government policies on sustainability and biodiversity such land uses may be no longer be acceptable or appropriate in the upland areas of South Wales. A scheme was prepared for the upland Nant Helen site with the objective of restoring the landscape ecology of the site; it included acid grassland to provide the landscape setting and for grazing. The scheme met with the approval of the planning authority. An initial forty hectares (about 13% of the site) was restored between 1993 and 1996. While the approved low intensity grazing and low fertilizer regime met the requirements of the planning authority and the statutory agencies, it was not meeting the expectations of the grazers who had grazing rights to the land. To help reconcile the apparent conflict a fertilizer trial was set up. The trial demonstrated that additional fertilizer and intensive grazing was required to meet the nutritional needs of sheep. It also showed typical upland stocking densities of sheep could be achieved with the acid grassland without the need for reseeding with lowland types. However this was not acceptable to the authority and agencies as such fertilizer and grazing regimes would be detrimental to the landscape and ecological objectives of the restoration scheme. A compromise was agreed whereby grazing intensity and additional fertilizer have been zoned. This has been implemented and is working to the satisfaction of all parties. Without the fertilizer trial it is unlikely that the different interests could have been reconciled
40 CFR Table C-5 to Subpart C of... - Summary of Comparability Field Testing Campaign Site and Seasonal Requirements for Class II and...

Science.gov (United States)

2010-07-01

... Campaign Site and Seasonal Requirements for Class II and III FEMs for PM10â2.5 and PM2.5 C Table C-5 to Subpart C of Part 53 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... Between Candidate Methods and Reference Methods Pt. 53, Subpt. C, Table C-5 Table C-5 to Subpart C of Part...
Searching your site`s management information systems

Energy Technology Data Exchange (ETDEWEB)

Marquez, W.; Rollin, C. [S.M. Stoller Corp., Boulder, CO (United States)

1994-12-31

The Department of Energy`s guidelines for the Baseline Environmental Management Report (BEMR) encourage the use of existing data when compiling information. Specific systems mentioned include the Progress Tracking System, the Mixed-Waste Inventory Report, the Waste Management Information System, DOE 4700.1-related systems, Programmatic Environmental Impact Statement (PEIS) data, and existing Work Breakdown Structures. In addition to these DOE-Headquarters tracking and reporting systems, there are a number of site systems that will be relied upon to produce the BEMR, including: (1) site management control and cost tracking systems; (2) commitment/issues tracking systems; (3) program-specific internal tracking systems; (4) Site material/equipment inventory systems. New requirements have often prompted the creation of new, customized tracking systems. This is a very time and money consuming process. As the BEMR Management Plan emphasizes, an effort should be made to use the information in existing tracking systems. Because of the wealth of information currently available from in-place systems, development of a new tracking system should be a last resort.
1994 Site environmental report

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-07-01

The Fernald site is a Department of Energy (DOE)-owned facility that produced high-quality uranium metals for military defense for nearly 40 years. DOE suspended production at the site in 1989 and formally ended production in 1991. Although production activities have ceased, the site continues to examine the air and liquid pathways as possible routes through which pollutants from past operations and current remedial activities may leave the site. The Site Environmental Report (SER) is prepared annually in accordance with DOE Order 5400.1, General Environmental Protection Program. This 1994 SER provides the general public as well as scientists and engineers with the results from the site`s ongoing Environmental Monitoring Program. Also included in this report is information concerning the site`s progress toward achieving full compliance with requirements set forth by DOE, U.S. Environmental Protection Agency (USEPA), and Ohio EPA (OEPA). For some readers, the highlights provided in this Executive Summary may provide sufficient information. Many readers, however, may wish to read more detailed descriptions of the information than those which are presented here. All information presented in this summary is discussed more fully in the main body of this report.
Site transition framework for long-term surveillance and maintenance

International Nuclear Information System (INIS)

2014-01-01

This document provides a framework for all U.S. Department of Energy (DOE) facilities and sites where DOE may have anticipated long-term surveillance and maintenance (LTSM) responsibilities. It is a tool to help facilitate a smooth transition from remediation to LTSM, providing a systematic process for affected parties to utilize in analyzing the baseline to understand and manage the actions from EM mission completion through a site's transition into LTSM. The framework is not meant to provide an exhaustive list of the specific requirement and information that are needed. Sites will have unique considerations that may not be adequately addressed by this tool, and it is anticipated that a team comprised of the transferring and receiving organization will use judgment in utilizing this augmenting with other DOE guidance. However the framework should be followed to the extent possible at each site; and adapted to accommodate unique site-specific requirements, needs, and documents. Since the objective of the tool is facilitate better understanding of the conditions of the site and the actions required for transfer, the transition team utilizing the checklist is expected to consult with management of both the receiving and transferring organization to verify that major concerns are addressed. Ideally, this framework should be used as early in the remediation process as possible. Subsequent applications of the Site Transition Framework (STF) to the site should be conducted periodically and used to verify that all appropriate steps have been or will be taken to close-out the site and that actions by both organization are identified to transfer the site to LTSM. The requirements are provided herein

Nevada Test Site Waste Acceptance Criteria (NTSWAC)

Energy Technology Data Exchange (ETDEWEB)

NNSA/NSO Waste Management Project

2008-06-01

This document establishes the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office, Nevada Test Site Waste Acceptance Criteria (NTSWAC). The NTSWAC provides the requirements, terms, and conditions under which the Nevada Test Site will accept low-level radioactive (LLW) and LLW Mixed Waste (MW) for disposal.
Nevada Test Site Waste Acceptance Criteria (NTSWAC)

International Nuclear Information System (INIS)

NNSA/NSO Waste Management Project

2008-01-01

This document establishes the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office, Nevada Test Site Waste Acceptance Criteria (NTSWAC). The NTSWAC provides the requirements, terms, and conditions under which the Nevada Test Site will accept low-level radioactive (LLW) and LLW Mixed Waste (MW) for disposal
Lawrence Berkeley Laboratory 1993 Site Environmental Report

Energy Technology Data Exchange (ETDEWEB)

1994-05-01

This annual Site Environmental Report summarizes Lawrence Berkeley Laboratory`s (LBL`s) environmental activities in calendar year (CY) 1993. The purpose of this report is to characterize site environmental management performance, confirm compliance status with environmental standards and requirements, and highlight significant programs and efforts. Its format and content are consistent with the requirements of the US Department of Energy (DOE) Order 5400.1, General Environmental Protection Program.
Site study plan for cultural resources, Deaf Smith County site, Texas: Environmental Field Program: Preliminary draft

International Nuclear Information System (INIS)

1987-06-01

The Cultural Resources Site Study Plan describes a field program to identify and evaluate the archaeological, historical, and Native American Indian resources of the site on local and regional perspectives; monitor and manage discovered cultural resources; and establish a worker education program. The archaeological field program consists of three pedestrian surveys: Survey 1 includes two EDBH seismic survey lines and the area within the exploratory shaft facility (ESF); Survey 2 includes the remainder of the site plus a 1/4 to 3/4-mi border area; and Survey 3 includes an assortment of offsite areas. The historical studies will identify and evaluate known and discovered historical sites and structures and the Native American Indian will identify and evaluate cultural and religious concerns expressed by Indian tribal groups. Prehistoric and historic sites will be evaluated to determine if they meet eligibility criteria for listing on the National Register of Historic Places. This site study plan describes the need for each study; its design and design rationale; analysis, management, and use of data; schedule of field activities; organization of field personnel and sample management; and quality assurance requirements. The cultural resource studies will provide data for satisfying the Programmatic Agreement, engineering design needs, and SRP requirements for permits and approvals, and for minimizing effects to any cultural properties discovered during site characterization. 75 refs., 10 figs., 2 tabs
Case studies of community relations on DOE's Formerly Utilized Sites Remedial Action Program as models for Superfund sites

International Nuclear Information System (INIS)

Plant, S.W.; Adler, D.G.

1995-01-01

Ever since the US Department of Energy (DOE) created its Formerly Utilized Sites Remedial Action Program (FUSRAP) in 1974, there has been a community relations program. The community relations effort has grown as FUSRAP has grown. With 20 of 46 sites now cleaned up, considerable experience in working with FUSRAP stakeholders has been gained. Why not share that experience with others who labor on the Superfund sites? Many similarities exist between the Superfund sites and FUSRAP. FUSRAP is a large, multiple-site environmental restoration program. The challenges range from small sites requiring remedial actions measurable in weeks to major sites requiring the full remedial investigation/feasibility study process. The numerous Superfund sites throughout the United States offer the same diversity, both geographically and technically. But before DOE offers FUSRAP's community relations experience as a model, it needs to make clear that this will be a realistic model. As experiences are shared, DOE will certainly speak of the efforts that achieved its goals. But many of the problems that DOE encountered along the way will also be related. FUSRAP relies on a variety of one- and two-way communication techniques for involving stakeholders in the DOE decision-making process. Some of the techniques and experiences from the case studies are presented
Site Response Analysis Using DeepSoil: Case Study of Bangka Site, Indonesia

Energy Technology Data Exchange (ETDEWEB)

Iswanto, Eko Rudi; Yee, Eric [KEPCO International Nuclear Graduate School, Ulsan (Korea, Republic of)

2015-10-15

Indonesia government declared through Act No. 17 year 2007 on the National Long-Term Development Plant Year 2005-2025 and Presidential Decree No. 5 year 2006 on the National Energy Policy (Indonesia 2007; Indonesia 2006), that nuclear energy is stated as a part of the national energy system. In order to undertake the above national policy, National Nuclear Energy Agency of Indonesia, as the promotor for the utilization of nuclear energy will conduct site study, which is a part of infrastructure preparation for NPP construction. Thorough preparation and steps are needed to operate an NPP and it takes between 10 to 15 years from the preliminary study (site selection, financial study, etc.) up to project implementation (manufacturing, construction, commissioning). During project implementation, it is necessary to prepare various documents relevant for permit application such as Safety Evaluation Report for site permit, Preliminary Safety Analysis Report and Environment Impact Assessment Report for construction permit. Considering the continuously increasing electricity energy demand, it is necessary to prepare for alternative NPP sites. The safety requirements of NPP's are stringent; amongst the various requirements is the ability to safely shut down in the wake of a possible earthquake. Ground response analysis of a potential site therefore needs to be carried out, parameter that affect the resistance of an NPP to earthquakes such as peak strain profiles is analysed. The objective of this paper is to analyse the ground response of the selected site for a NPP, using The Mw 7.9 in Sikuai Island, West Sumatra on September 12, 2007 as present input motion. This analysis will be carried out using a ground response analysis program, DeepSoil. In addition to this, an attempt was made to define the site specific input motion characteristics of the selected site for use in DeepSoil (DeepSoil 5.0). A site investigation at the WB site was performed primarily on the PS
Nevada National Security Site Radiation Protection Program

Energy Technology Data Exchange (ETDEWEB)

none,

2013-04-30

Title 10 Code of Federal Regulations (CFR) Part 835, “Occupational Radiation Protection,” establishes radiation protection standards, limits, and program requirements for protecting individuals from ionizing radiation resulting from the conduct of U.S. Department of Energy (DOE) activities. 10 CFR 835.101(a) mandates that DOE activities be conducted in compliance with a documented Radiation Protection Program (RPP) as approved by DOE. This document promulgates the RPP for the Nevada National Security Site (NNSS), related (on-site or off-site) U.S. Department of Energy, National Nuclear Security Administration Nevada Field Office (NNSA/NFO) operations, and environmental restoration off-site projects. This RPP section consists of general statements that are applicable to the NNSS as a whole. The RPP also includes a series of appendices which provide supporting detail for the associated NNSS Tennant Organizations (TOs). Appendix H, “Compliance Demonstration Table,” contains a cross-walk for the implementation of 10 CFR 835 requirements. This RPP does not contain any exemptions from the established 10 CFR 835 requirements. The RSPC and TOs are fully compliant with 10 CFR 835 and no additional funding is required in order to meet RPP commitments. No new programs or activities are needed to meet 10 CFR 835 requirements and there are no anticipated impacts to programs or activities that are not included in the RPP. There are no known constraints to implementing the RPP. No guides or technical standards are adopted in this RPP as a means to meet the requirements of 10 CFR 835.
Rotation of nucleotide sites is not required for the enzymatic activity of chloroplast coupling factor

Energy Technology Data Exchange (ETDEWEB)

Musier, K.M.; Hammes, G.G.

1987-09-22

New heterobifunctional photoaffinity cross-linking reagents, 6-maleimido-N-(4-benzoylphenyl)hexanamide, 12-maleimido-N-(4-benzoylphenyl)dodecanamide, and 12-(/sup 14/C)maleimido-N-(4-benzoylphenyo)dodecanamide, were synthesized to investigate the mechanism of ATP hydrolysis by chloroplast coupling factor 1. These reagents react with sulfhydryl groups on the ..gamma..-polypeptide. Subsequent photolysis cross-links the ..gamma..-polypeptide covalently to ..cap alpha..- and ..beta..-polypeptides. The cross-linkers prevent major movements of the ..gamma..-polypeptide with respect to the ..cap alpha..- and ..beta..-polypeptides but are sufficiently long to permit some flexibility in the enzyme structure. When approx. 50% of the ..gamma..-polypeptide was cross-linked to a ..cap alpha..- and ..beta..-polypeptides, a 7% loss in ATPase activity was observed for the longer cross-linker and a 12% loss for the shorter. These results indicate that large movements of ..cap alpha..- and ..beta..-polypeptides with respect to the ..gamma..-polypeptide are not essential for catalysis. In particular, rotation of the polypeptide chains to crease structurally equivalent sites during catalysis is not a required feature of the enzyme mechanism.
Quality assurance during site construction

International Nuclear Information System (INIS)

Eymess, K.J.; Haas, R.; Wellnitz, G.

1980-01-01

Quality Assurance for Nuclear Power Plants under consideration of pipe assembling. Flow of Quality Requirements during: - Desing - Construction - Procurement - Prefabrication - Site. Organizational Requirements and Measurements during Erection: - Incoming Control - Material Storage - Surveillance of Tools - Weld Surveillance - Nondestructive Testing - Cleaning - Final Documentation. Qualification and Training of QA Personnel. (orig.)
Hanford Site storm water comprehensive site compliance evaluation report for the reporting period July 1, 1996 through June 30, 1997

International Nuclear Information System (INIS)

Perkins, C.J.

1997-01-01

On September 9, 1992, the US Environmental Protection Agency (EPA) issued General Permit No. WA-R-00-OOOF, Authorization to Discharge Under the National Pollutant Discharge Elimination System (NPDES) for Storm Water Discharges Associated with Industrial Activity to the US Department of Energy, Richland Operations Office (RL). RL submitted a Notice of Intent to comply with this permit to EPA in conformance with the General Permit requirements on October 1, 1992. On February 14, 1994, EPA issued a Storm Water General Permit Coverage Notice and assigned WA-R-00-Al7F as the Hanford Site's National Pollutant Discharge Elimination System (NPDES) storm water permit number. The Hanford Site Storm Water Pollution Prevention Plan (SWPPP) (WHC 1996a) was certified by J. E Rasmussen, Director Environmental Assurance, RL, on September 24, 1996, in compliance with Part IV.B(i) of the General Permit. As required by General Permit No. WA-R-00-OOOF (WA-R-00-Al7F), Section IV, Part D, Section 4.c, an annual report must be developed by RL and retained on site to verify that the requirements listed in the General Permit are being implemented. The previous Hanford Site Storm Plater Comprehensive Site Compliance Evaluation Report (WHC 1996b) addressed the period from July 1995 through June 1996. This document fulfills the requirement to prepare an annual report and contains the results of inspections of the storm water outfalls listed in the SWPPP (WHC 1996a). This report also describes the methods used to conduct the 1100 Storm Plater Comprehensive Site Compliance Evaluation (SWCSCE) as required in Part IV, Section D.4.c in the General Permit; summarizes the results of the compliance evaluation; and documents significant leaks and spills. The reporting year for this SWCSCE report is July 1, 1996 through June 30, 1997
Site Specific Vendor's License

Data.gov (United States)

Montgomery County of Maryland — This dataset contains information of a site-specific vendor's license which is required if an individual sells or offers to sell goods or services from a stationary...
Low-level waste disposal site selection demonstration

International Nuclear Information System (INIS)

Rogers, V.C.

1984-01-01

This paper discusses the results of recent studies undertaken at EPRI related to low-level waste disposal technology. The initial work provided an overview of the state of the art including an assessment of its influence upon transportation costs and waste form requirements. The paper discusses work done on the overall system design aspects and computer modeling of disposal site performance characteristics. The results of this analysis are presented and provide a relative ranking of the importance of disposal parameters. This allows trade-off evaluations to be made of factors important in the design of a shallow land burial facility. To help minimize the impact of a shortage of low-level radioactive waste disposal sites, EPRI is closely observing the development of bellweather projects for developing new sites. The purpose of this activity is to provide information about lessons learned in those projects in order to expedite the development of additional disposal facilities. This paper describes most of the major stems in selecting a low-level radioactive waste disposal site in Texas. It shows how the Texas Low-Level Radioactive Waste Disposal Authority started with a wide range of potential siting areas in Texas and narrowed its attention down to a few preferred sites. The parameters used to discriminate between large areas of Texas and, eventually, 50 candidate disposal sites are described, along with the steps in the process. The Texas process is compared to those described in DOE and EPRI handbooks on site selection and to pertinent NRC requirements. The paper also describes how an inventory of low-level waste specific to Texas was developed and applied in preliminary performance assessments of two candidate sites. Finally, generic closure requirements and closure operations for low-level waste facilities in arid regions are given
On-site cell field test support program

Science.gov (United States)

Staniunas, J. W.; Merten, G. P.

1982-09-01

Utility sites for data monitoring were reviewed and selected. Each of these sites will be instrumented and its energy requirements monitored and analyzed for one year prior to the selection of 40 Kilowatt fuel cell field test sites. Analyses in support of the selection of sites for instrumentation shows that many building sectors offered considerable market potential. These sectors include nursing home, health club, restaurant, industrial, hotel/motel and apartment.
Requirements on information of the site of the European Union from member states within the area of the environment

International Nuclear Information System (INIS)

Virgovic, R.; Grofova, R; Sochorova, O.

2005-01-01

In this presentation authors deal with requirements on information of the site of the European Union from member states within the area of the environment. As of May 1, 2004 with entrance into the European Union for the Slovak Republic results the responsibility feeding reports about the environment. Reports about the environment (State of the environment Report - Slovak Republic) deal with the following areas: (A) Horizontally measures; (B) Air protection; (C) Waste management; (D) Water protection; (E) Nature protection; (F) Inspection of industrial pollution and risk management; (G) Chemical agents and genetically modified organisms; (H) Noise from motor-cars and machines; (I) Nuclear safety; (J) Civil protection
Monitored Retrievable Storage System Requirements Document

International Nuclear Information System (INIS)

1994-03-01

This Monitored Retrievable Storage System Requirements Document (MRS-SRD) describes the functions to be performed and technical requirements for a Monitored Retrievable Storage (MRS) facility subelement and the On-Site Transfer and Storage (OSTS) subelement. The MRS facility subelement provides for temporary storage, at a Civilian Radioactive Waste Management System (CRWMS) operated site, of spent nuclear fuel (SNF) contained in an NRC-approved Multi-Purpose Canister (MPC) storage mode, or other NRC-approved storage modes. The OSTS subelement provides for transfer and storage, at Purchaser sites, of spent nuclear fuel (SNF) contained in MPCs. Both the MRS facility subelement and the OSTS subelement are in support of the CRWMS. The purpose of the MRS-SRD is to define the top-level requirements for the development of the MRS facility and the OSTS. These requirements include design, operation, and decommissioning requirements to the extent they impact on the physical development of the MRS facility and the OSTS. The document also presents an overall description of the MRS facility and the OSTS, their functions (derived by extending the functional analysis documented by the Physical System Requirements (PSR) Store Waste Document), their segments, and the requirements allocated to the segments. In addition, the top-level interface requirements of the MRS facility and the OSTS are included. As such, the MRS-SRD provides the technical baseline for the MRS Safety Analysis Report (SAR) design and the OSTS Safety Analysis Report design
Expedited Site Characterization: A rapid, cost-effective process for preremedial site characterization

International Nuclear Information System (INIS)

Burton, J.C.; Walker, J.L.; Jennings, T.V.; Aggarwal, P.K.; Hastings, B.; Meyer, W.T.; Rose, C.M.; Rosignolo, C.L.

1993-01-01

Argonne National Laboratory has developed a unique, cost- and time-effective, technically innovative process for preremedial site characterization, referred to as Expedited Site Characterization (ESC). The cost of the ESC field sampling process ranges from 1/10 to 1/5 of the cost of traditional site characterization. The time required for this ESC field activity is approximately 1/30 of that for current methods. Argonne's preremedial site investigations based on this approach have been accepted by the appropriate regulatory agencies. The ESC process is flexible and neither site nor contaminant dependent. The process has been successfully tested and applied in site investigations of multiple contaminated landfills in New Mexico (for the US Department of the Interior's Bureau of Land Management [BLM]) and at former grain storage facilities in Nebraska and Kansas, contaminated with carbon tetrachloride (for the Department of Agriculture's Commodity Credit Corporation [CCC/USDA]). A working demonstration of this process was sponsored by the US Department of Energy (DOE) Office of Technology Development as a model of the methodology needed to accelerate site characterizations at DOE facilities. This report describes the application of the process in New Mexico, Nebraska and Kansas
Evolutionary optimization technique for site layout planning

KAUST Repository

El Ansary, Ayman M.

2014-02-01

Solving the site layout planning problem is a challenging task. It requires an iterative approach to satisfy design requirements (e.g. energy efficiency, skyview, daylight, roads network, visual privacy, and clear access to favorite views). These design requirements vary from one project to another based on location and client preferences. In the Gulf region, the most important socio-cultural factor is the visual privacy in indoor space. Hence, most of the residential houses in this region are surrounded by high fences to provide privacy, which has a direct impact on other requirements (e.g. daylight and direction to a favorite view). This paper introduces a novel technique to optimally locate and orient residential buildings to satisfy a set of design requirements. The developed technique is based on genetic algorithm which explores the search space for possible solutions. This study considers two dimensional site planning problems. However, it can be extended to solve three dimensional cases. A case study is presented to demonstrate the efficiency of this technique in solving the site layout planning of simple residential dwellings. © 2013 Elsevier B.V. All rights reserved.
Remediation management of complex sites using an adaptive site management approach.

Science.gov (United States)

Price, John; Spreng, Carl; Hawley, Elisabeth L; Deeb, Rula

2017-12-15

Complex sites require a disproportionate amount of resources for environmental remediation and long timeframes to achieve remediation objectives, due to their complex geologic conditions, hydrogeologic conditions, geochemical conditions, contaminant-related conditions, large scale of contamination, and/or non-technical challenges. A recent team of state and federal environmental regulators, federal agency representatives, industry experts, community stakeholders, and academia worked together as an Interstate Technology & Regulatory Council (ITRC) team to compile resources and create new guidance on the remediation management of complex sites. This article summarizes the ITRC team's recommended process for addressing complex sites through an adaptive site management approach. The team provided guidance for site managers and other stakeholders to evaluate site complexities and determine site remediation potential, i.e., whether an adaptive site management approach is warranted. Adaptive site management was described as a comprehensive, flexible approach to iteratively evaluate and adjust the remedial strategy in response to remedy performance. Key aspects of adaptive site management were described, including tools for revising and updating the conceptual site model (CSM), the importance of setting interim objectives to define short-term milestones on the journey to achieving site objectives, establishing a performance model and metrics to evaluate progress towards meeting interim objectives, and comparing actual with predicted progress during scheduled periodic evaluations, and establishing decision criteria for when and how to adapt/modify/revise the remedial strategy in response to remedy performance. Key findings will be published in an ITRC Technical and Regulatory guidance document in 2017 and free training webinars will be conducted. More information is available at www.itrc-web.org. Copyright © 2017 Elsevier Ltd. All rights reserved.
Site transition framework for long-term surveillance and maintenance

Energy Technology Data Exchange (ETDEWEB)

None

2014-04-01

This document provides a framework for all U.S. Department of Energy (DOE) facilities and sites where DOE may have anticipated long-term surveillance and maintenance (LTSM) responsibilities. It is a tool to help facilitate a smooth transition from remediation to LTSM, providing a systematic process for affected parties to utilize in analyzing the baseline to understand and manage the actions from EM mission completion through a site’s transition into LTSM. The framework is not meant to provide an exhaustive list of the specific requirement and information that are needed. Sites will have unique considerations that may not be adequately addressed by this tool, and it is anticipated that a team comprised of the transferring and receiving organization will use judgment in utilizing this augmenting with other DOE guidance. However the framework should be followed to the extent possible at each site; and adapted to accommodate unique site-specific requirements, needs, and documents. Since the objective of the tool is facilitate better understanding of the conditions of the site and the actions required for transfer, the transition team utilizing the checklist is expected to consult with management of both the receiving and transferring organization to verify that major concerns are addressed. Ideally, this framework should be used as early in the remediation process as possible. Subsequent applications of the Site Transition Framework (STF) to the site should be conducted periodically and used to verify that all appropriate steps have been or will be taken to close-out the site and that actions by both organization are identified to transfer the site to LTSM. The requirements are provided herein.
Site study plan for borehole search and characterization, Deaf Smith County Site, Texas: Revision 1

International Nuclear Information System (INIS)

1987-01-01

This site study plan describes the Borehole Search and Characterization field activities to be conducted during the early stages of Site Characterization at the Deaf Smith County site, Texas. The field program has been designed to provide data useful in addressing information/data needs resulting from Federal/State/Local regulatory requirements and repository program requirements. Air and ground surveys, an extensive literature search, and landowner interviews will be conducted to locate wells within and adjacent to the proposed nuclear waste repository site in Deaf Smith County. Initially, the study will center around the planned Exploratory Shaft Facilities location and will expand outward from that location. Findings from this study may lead to preparation of a new site study plan to search suspected borehole locations, and excavate or reenter known boreholes for additional characterization or remedial action. The Salt Repository Project (SRP) Networks specify the schedule under which the program will operate. The Technical Field Services Contractor (TFSC) is responsible for conducting the field program. Data will be handled and reported in accordance with established SRP procedures. A quality assurance program will be utilized to assure that activities affecting quality are performed correctly and that appropriate documentation is maintained. 13 refs., 6 figs., 3 tabs

Nevada Test Site Waste Acceptance Criteria

International Nuclear Information System (INIS)

U. S. Department of Energy, National Nuclear Security Administration Nevada Site Office

2005-01-01

This document establishes the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Site Office (NNSA/NSO) waste acceptance criteria (WAC). The WAC provides the requirements, terms, and conditions under which the Nevada Test Site (NTS) will accept low-level radioactive (LLW) and mixed waste (MW) for disposal. It includes requirements for the generator waste certification program, characterization, traceability, waste form, packaging, and transfer. The criteria apply to radioactive waste received at the NTS Area 3 and Area 5 Radioactive Waste Management Complex (RWMC) for storage or disposal
The Current and Historical Distribution of Special Status Amphibians at the Livermore Site and Site 300

Energy Technology Data Exchange (ETDEWEB)

Hattem, M V; Paterson, L; Woollett, J

2008-08-20

65 surveys were completed in 2002 to assess the current distribution of special status amphibians at the Lawrence Livermore National Laboratory's (LLNL) Livermore Site and Site 300. Combined with historical information from previous years, the information presented herein illustrates the dynamic and probable risk that amphibian populations face at both sites. The Livermore Site is developed and in stark contrast to the mostly undeveloped Site 300. Yet both sites have significant issues threatening the long-term sustainability of their respective amphibian populations. Livermore Site amphibians are presented with a suite of challenges inherent of urban interfaces, most predictably the bullfrog (Rana catesbeiana), while Site 300's erosion issues and periodic feral pig (Sus scrofa) infestations reduce and threaten populations. The long-term sustainability of LLNL's special status amphibians will require active management and resource commitment to maintain and restore amphibian habitat at both sites.
DOE site performance assessment activities

International Nuclear Information System (INIS)

1990-07-01

Information on performance assessment capabilities and activities was collected from eight DOE sites. All eight sites either currently dispose of low-level radioactive waste (LLW) or plan to dispose of LLW in the near future. A survey questionnaire was developed and sent to key individuals involved in DOE Order 5820.2A performance assessment activities at each site. The sites surveyed included: Hanford Site (Hanford), Idaho National Engineering Laboratory (INEL), Los Alamos National Laboratory (LANL), Nevada Test Site (NTS), Oak Ridge National Laboratory (ORNL), Paducah Gaseous Diffusion Plant (Paducah), Portsmouth Gaseous Diffusion Plant (Portsmouth), and Savannah River Site (SRS). The questionnaire addressed all aspects of the performance assessment process; from waste source term to dose conversion factors. This report presents the information developed from the site questionnaire and provides a comparison of site-specific performance assessment approaches, data needs, and ongoing and planned activities. All sites are engaged in completing the radioactive waste disposal facility performance assessment required by DOE Order 5820.2A. Each site has achieved various degrees of progress and have identified a set of critical needs. Within several areas, however, the sites identified common needs and questions
Preschool outcomes following prenatal serotonin reuptake inhibitor exposure: differences in language and behavior, but not cognitive function.

Science.gov (United States)

Johnson, Katrina C; Smith, Alicia K; Stowe, Zachary N; Newport, D Jeffrey; Brennan, Patricia A

2016-02-01

To test the hypothesis that prenatal exposure to serotonin reuptake inhibitors (SRIs) is associated with language and behavioral outcomes in preschool-aged children, while accounting for confounds such as concomitant exposures and maternal mental illness. An observational, prospective, longitudinal study of mental illness in pregnancy was conducted at a university-based women's mental health clinic (April 2010-November 2012). A sample of 178 mother-child dyads participated in a laboratory visit at preschool age (2.5-5.5 years). The majority of women (87%) received psychotropic medication during pregnancy. Psychiatric status (based on DSM-IV), other medication use, and substance use were serially assessed and tested as confounds. Primary outcome measures included standardized measures of expressive language and cognitive function and mother and alternate caregiver ratings of child behavior problems, including the Pervasive Developmental Disorders (PDD) subscale of the Child Behavior Checklist. Linear regression analyses revealed that, after controlling for relevant covariates, expressive language scores from the Test of Early Language Development, 3rd edition, were negatively associated with prenatal SRI exposure (β = -0.15, t = -2.41), while the PDD behavioral problems subscales completed by alternate caregivers and mothers were positively associated with prenatal SRI exposure (β = 0.17, t = 2.01; β = 0.16, t = 2.00, respectively). Cognitive function, measured using the Differential Ability Scales, 2nd edition, was not associated with any medication exposures. The current data suggest a small but significant association between prenatal SRI exposure and preschool outcomes, including expressive language and behavior problems. These data corroborate data from recent, population-based studies, although overall, published findings are mixed. Replication and identification of moderating risk factors are needed to understand potential clinical implications. �
ITER plant layout and site services

International Nuclear Information System (INIS)

Chuyanov, V.A.

2000-01-01

The ITER site has not yet been determined. Nevertheless, to develop a construction plan and a cost estimate, it is necessary to have a detailed layout of the buildings, structures and outdoor equipment integrated with the balance of plant service systems prototypical of large fusion power plants. These services include electrical power for magnet feeds and plasma heating systems, cryogenic and conventional cooling systems, compressed air, gas supplies, demineralized water, steam and drainage. Nuclear grade facilities are provided to handle tritium fuel and activated waste, as well as to prevent radiation exposure of workers and the public. To prevent interference between services of different types and for efficient arrangement of buildings, structures and equipment within the site area, a plan was developed which segregated different classes of services to four quadrants surrounding the tokamak building, placed at the approximate geographical centre of the site. The locations of the buildings on the generic site were selected to meet all design requirements at minimum total project cost. A similar approach was used to determine the locations of services above, at and below grade. The generic site plan can be adapted to the site selected for ITER without significant changes to the buildings or equipment. Some rearrangements may be required by site topography, resulting primarily in changes to the length of services that link the buildings and equipment. (author)
Site Environmental Report, 1993

International Nuclear Information System (INIS)

1994-06-01

The Site Environmental Report (SER) is prepared annually in accordance with DOE Order 5400.1, ''General Environmental Protection Program.'' This 1993 SER provides the general public as well as scientists and engineers with the results from the site's ongoing Environmental Monitoring Program. Also included in this report is information concerning the site's progress toward achieving full compliance with requirements set forth by DOE, US Environmental Protection Agency (USEPA), and Ohio EPA (OEPA). For some readers, the highlights provided in the Executive Summary may provide sufficient information. Many readers, however, may wish to read more detailed descriptions of the information than those which are presented here
Executive summary: Weldon Spring Site Environmental Report for calendar year 1992. Weldon Spring Site Remedial Action Project, Weldon Spring, Missouri

Energy Technology Data Exchange (ETDEWEB)

1993-06-01

This report has been prepared to provide information about the public safety and environmental protection programs conducted by the Weldon Spring Site Remedial Action Project. The Weldon Spring site is located in southern St. Charles County, Missouri, approximately 48 km (30 mi) west of St. Louis. The site consists of two main areas, the Weldon Spring Chemical Plant and raffinate pits and the Weldon Spring Quarry. The objectives of the Site Environmental Report are to present a summary of data from the environmental monitoring program, to characterize trends and environmental conditions at the site, and to confirm compliance with environmental and health protection standards and requirements. The report also presents the status of remedial activities and the results of monitoring these activities to assess their impacts on the public and environment. The scope of the environmental monitoring program at the Weldon Spring site has changed since it was initiated. Previously, the program focused on investigations of the extent and level of contaminants in the groundwater, surface waters, buildings, and air at the site. In 1992, the level of remedial activities required monitoring for potential impacts of those activities, particularly on surface water runoff and airborne effluents. This report includes monitoring data from routine radiological and nonradiological sampling activities. These data include estimates of dose to the public from the Weldon Spring site; estimates of effluent releases; and trends in groundwater contaminant levels. Also, applicable compliance requirements, quality assurance programs, and special studies conducted in 1992 to support environmental protection programs are reviewed.
Potential energy center site investigations

International Nuclear Information System (INIS)

Savage, W.F.

1977-01-01

Past studies by the AEC, NRC, NSF and others have indicated that energy centers have certain advantages over dispersed siting. There is the need, however, to investigate such areas as possible weather modifications due to major heat releases, possible changes in Federal/state/local laws and institutional arrangements to facilitate implementation of energy centers, and to assess methods of easing social and economic pressures on a surrounding community due to center construction. All of these areas are under study by ERDA, but there remains the major requirement for the study of a potential site to yield a true assessment of the energy center concept. In this regard the Division of Nuclear Research and Applications of ERDA is supporting studies by the Southern and Western Interstate Nuclear Boards to establish state and utility interest in the concept and to carry out screening studies of possible sites. After selection of a final site for center study , an analysis will be made of the center including technical areas such as heat dissipation methods, water resource management, transmission methods, construction methods and schedules, co-located fuel cycle facilities, possible mix of reactor types, etc. Additionally, studies of safeguards, the interaction of all effected entities in the siting, construction, licensing and regulation of a center, labor force considerations in terms of local impact, social and economic changes, and financing of a center will be conducted. It is estimated that the potential site study will require approximately two years
Framework for DOE mixed low-level waste disposal: Site fact sheets

Energy Technology Data Exchange (ETDEWEB)

Gruebel, M.M.; Waters, R.D.; Hospelhorn, M.B.; Chu, M.S.Y. [eds.

1994-11-01

The Department of Energy (DOE) is required to prepare and submit Site Treatment Plans (STPS) pursuant to the Federal Facility Compliance Act (FFCAct). Although the FFCAct does not require that disposal be addressed in the STPS, the DOE and the States recognize that treatment of mixed low-level waste will result in residues that will require disposal in either low-level waste or mixed low-level waste disposal facilities. As a result, the DOE is working with the States to define and develop a process for evaluating disposal-site suitability in concert with the FFCAct and development of the STPS. Forty-nine potential disposal sites were screened; preliminary screening criteria reduced the number of sites for consideration to twenty-six. The DOE then prepared fact sheets for the remaining sites. These fact sheets provided additional site-specific information for understanding the strengths and weaknesses of the twenty-six sites as potential disposal sites. The information also provided the basis for discussion among affected States and the DOE in recommending sites for more detailed evaluation.
OSU TOMF Program Site Selection and Preliminary Concept Design Report

Energy Technology Data Exchange (ETDEWEB)

Spadling, Steve [Oklahoma State Univ., Stillwater, OK (United States)

2012-05-10

The purpose of this report is to confirm the programmatic requirements for the new facilities, identify the most appropriate project site, and develop preliminary site and building concepts that successfully address the overall project goals and site issues. These new facilities will be designed to accommodate the staff, drivers and maintenance requirements for the future mixed fleet of passenger vehicles, Transit Style Buses and School Buses.
Inhibition of G-Protein-Activated Inwardly Rectifying K+ Channels by the Selective Norepinephrine Reuptake Inhibitors Atomoxetine and Reboxetine

Science.gov (United States)

Kobayashi, Toru; Washiyama, Kazuo; Ikeda, Kazutaka

2010-01-01

Atomoxetine and reboxetine are commonly used as selective norepinephrine reuptake inhibitors (NRIs) for the treatment of attention-deficit/hyperactivity disorder and depression, respectively. Furthermore, recent studies have suggested that NRIs may be useful for the treatment of several other psychiatric disorders. However, the molecular mechanisms underlying the various effects of NRIs have not yet been sufficiently clarified. G-protein-activated inwardly rectifying K+ (GIRK or Kir3) channels have an important function in regulating neuronal excitability and heart rate, and GIRK channel modulation has been suggested to be a potential treatment for several neuropsychiatric disorders and cardiac arrhythmias. In this study, we investigated the effects of atomoxetine and reboxetine on GIRK channels using the Xenopus oocyte expression assay. In oocytes injected with mRNA for GIRK1/GIRK2, GIRK2, or GIRK1/GIRK4 subunits, extracellular application of atomoxetine or reboxetine reversibly reduced GIRK currents. The inhibitory effects were concentration-dependent, but voltage-independent, and time-independent during each voltage pulse. However, Kir1.1 and Kir2.1 channels were insensitive to atomoxetine and reboxetine. Atomoxetine and reboxetine also inhibited GIRK currents induced by activation of cloned A1 adenosine receptors or by intracellularly applied GTPγS, a nonhydrolyzable GTP analogue. Furthermore, the GIRK currents induced by ethanol were concentration-dependently inhibited by extracellularly applied atomoxetine but not by intracellularly applied atomoxetine. The present results suggest that atomoxetine and reboxetine inhibit brain- and cardiac-type GIRK channels, revealing a novel characteristic of clinically used NRIs. GIRK channel inhibition may contribute to some of the therapeutic effects of NRIs and adverse side effects related to nervous system and heart function. PMID:20393461
An association between initiation of selective serotonin reuptake inhibitors and suicide - a nationwide register-based case-crossover study.

Directory of Open Access Journals (Sweden)

Charlotte Björkenstam

Full Text Available BACKGROUND: Treatment with selective serotonin reuptake inhibitors (SSRI is one of the most common treatments for depression. It is however not clear whether or not there is an increased short-term suicide risk during initiation with SSRI. METHODS: A register-based nationwide case-crossover study including 5,866 suicides, 1,698 women and 4,168 men, from the Death Register 2007-2010 in Sweden. SSRI initiation was defined as a dispensed prescription of SSRI within 28 days prior to the date of suicide with no previous dispensed prescription of SSRI within 4 months prior that prescription. The control period took place one year earlier. Odds ratio (OR was estimated using conditional logistic regression. RESULT: During the 28 day period prior to suicide 48 women and 138 men were exposed to SSRI initiation (while not being exposed in the control period and 22 women and 43 men were exposed in the control period (while not being exposed in the case period. The OR for suicide after initiation with SSRI was 2.7 (95% CI: 1.6-44 for women, and 4.3 (95% CI: 3.0-6.1 for men. The highest OR was found 8-11 days after initiation with SSRI 9.7 (95% CI: 3.0-31.7 for women and men combined. CONCLUSION: The main limitation in this study is confounding by indication, but the descriptive question is however not confounded by indication. Together with plausible biological mechanisms and previous clinical and epidemiological observations our findings, linking initiation of SSRI to increased short-term suicide risk, deserve further attention specifically in the clinical setting.
Fernald Environmental Management Project 1995 site environmental report

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-06-01

The Fernald site continues to examine the air and liquid pathways as possible routes through which pollutants from past operations and current remedial activities may leave the site. This 1995 Site Environmental Report provides the general public as well as scientists and engineers with the results from the site`s ongoing Environmental Monitoring Program. Also included in this report is information concerning the site`s progress toward achieving full compliance with requirements set forth by DOE, US Environmental Protection Agency (USEPA), and Ohio EPA.
Site environmental report for calendar year 1996: Yucca Mountain site, Nye County, Nevada

International Nuclear Information System (INIS)

1997-11-01

The environmental program established by the Yucca Mountain Site Characterization Office (YMSCO) has been designed and implemented to protect, maintain, and restore environmental quality, minimize potential threats to the environment and the public, and comply with environmental policies and US Department of Energy (DOE) Orders. In accordance with DOE Order 5400.1, General Environmental Protection Program (DOE, 1990a), to be superseded by DOE Order 231.1 (under review), the status of the Yucca Mountain Site Characterization Project (YMP) environmental program has been summarized in this annual Site Environmental Report (SER) to characterize performance, document compliance with environmental requirements, and highlight significant programs and efforts during calendar year 1996
Closure Strategy Nevada Test Site Area 5 Radioactive Waste Management Site

Energy Technology Data Exchange (ETDEWEB)

NSTec Environmental Management

2007-03-01

This paper presents an overview of the strategy for closure of part of the Area 5 Radioactive Waste Management Site (RWMS) at the Nevada Test Site (NTS), which is about 65 miles northwest of Las Vegas, Nevada (Figure 1). The Area 5 RWMS is in the northern part of Frenchman Flat, approximately 14 miles north of Mercury. The Area 5 RWMS encompasses 732 acres subdivided into quadrants, and is bounded by a 1,000-foot (ft)-wide buffer zone. The northwest and southwest quadrants have not been developed. The northeast and southeast quadrants have been used for disposal of unclassified low-level radioactive waste (LLW) and indefinite storage of classified materials. This paper focuses on closure of the 38 waste disposal and classified material storage units within the southeast quadrant of the Area 5 RWMS, called the ''92-Acre Area''. The U.S Department of Energy (DOE), National Nuclear Security Administration Nevada Site Office (NNSA/NSO) is currently planning to close the 92-Acre Area by 2011. Closure planning for this site must take into account the regulatory requirements for a diversity of waste streams, disposal and storage configurations, disposal history, and site conditions. For ease of discussion, the 92-Acre Area has been subdivided into six closure units defined by waste type, location, and similarity in regulatory requirements. Each of the closure units contains one or more waste disposal units; waste disposal units are also called waste disposal cells. The paper provides a brief background of the Area 5 RWMS, identifies key closure issues for the 92-Acre Area, recommends actions to address the issues, and provides the National Security Technologies, LLC (NSTec), schedule for closure.
Aggravation by paroxetine, a selective serotonin reuptake inhibitor, of antral lesions generated by nonsteroidal anti-inflammatory drugs in rats.

Science.gov (United States)

Takeuchi, Koji; Tanaka, Akiko; Nukui, Kazuo; Kojo, Azusa; Gyenge, Melinda; Amagase, Kikuko

2011-09-01

Recent clinical studies have suggested a risk of adverse gastric reactions from the concomitant use of selective serotonin (5-HT) reuptake inhibitors (SSRIs) with nonsteroidal anti-inflammatory drugs (NSAIDs). We examined the adverse effects of SSRIs on antral lesions produced by indomethacin in rats. Rats fasted for 24 h were refed for 1 h, then administered indomethacin (30 mg/kg s.c.) 1 h after the refeeding and killed 6 h later. Paroxetine (1-10 mg/kg) was given orally 30 min before indomethacin. Indomethacin caused antral lesions in refed rats. Paroxetine dose-dependently aggravated these lesions, despite provoking no damage by itself. Similar results were obtained when other NSAIDs such as diclofenac, flurbiprofen, and loxoprofen were coadministered with paroxetine or when indomethacin was coadministered with other antidepressants such as fluvoxamine and milnacipran, but not imipramine or maprotiline. Exogenous 5-HT also worsened the indomethacin-induced antral damage, whereas the aggravating effect of paroxetine was attenuated by ondansetron, a selective 5-HT(3) antagonist, but not antagonists for other 5-HT receptor subtypes. Indomethacin plus paroxetine had no effect on gastric secretion but significantly decreased mucosal superoxide dismutase (SOD) activity as well as GSH content. The antral damage induced by indomethacin plus paroxetine was significantly prevented by antisecretory (acid or pepsin) agents and mucosal protective agents as well as SOD and allopurinol. These results suggest that SSRIs aggravate NSAID-induced antral lesions, probably via the activation of 5HT(3) receptors, and the mechanism of aggravation may involve the corrosive action of acid/pepsin as well as an impaired antioxidative system.
Analysis of non-typeable Haemophilous influenzae VapC1 mutations reveals structural features required for toxicity and flexibility in the active site.

Directory of Open Access Journals (Sweden)

Brooke Hamilton

Full Text Available Bacteria have evolved mechanisms that allow them to survive in the face of a variety of stresses including nutrient deprivation, antibiotic challenge and engulfment by predator cells. A switch to dormancy represents one strategy that reduces energy utilization and can render cells resistant to compounds that kill growing bacteria. These persister cells pose a problem during treatment of infections with antibiotics, and dormancy mechanisms may contribute to latent infections. Many bacteria encode toxin-antitoxin (TA gene pairs that play an important role in dormancy and the formation of persisters. VapBC gene pairs comprise the largest of the Type II TA systems in bacteria and they produce a VapC ribonuclease toxin whose activity is inhibited by the VapB antitoxin. Despite the importance of VapBC TA pairs in dormancy and persister formation, little information exists on the structural features of VapC proteins required for their toxic function in vivo. Studies reported here identified 17 single mutations that disrupt the function of VapC1 from non-typeable H. influenzae in vivo. 3-D modeling suggests that side chains affected by many of these mutations sit near the active site of the toxin protein. Phylogenetic comparisons and secondary mutagenesis indicate that VapC1 toxicity requires an alternative active site motif found in many proteobacteria. Expression of the antitoxin VapB1 counteracts the activity of VapC1 mutants partially defective for toxicity, indicating that the antitoxin binds these mutant proteins in vivo. These findings identify critical chemical features required for the biological function of VapC toxins and PIN-domain proteins.
Guideline for environmental site investigations in Manitoba : June 1998

International Nuclear Information System (INIS)

1998-06-01

The procedures for the investigation and characterization of contaminated sites in Manitoba are described in an effort to provide a baseline for developing applicable risk-based remedial action and management plans. This document presents information regarding the methods and protocols for sites where the quality of groundwater, surface water, sediments or soil may have been affected by pollutants as a result of past or present usage of the site. The 1998 document focuses on petroleum impacted sites and also includes the requirements for the investigation of sites potentially impacted by other pollutants. It is based on the principles established by the Canadian Council of Ministers of the Environment for the management of sites in Canada and the requirements of the Manitoba Contaminated Sites Remediation and Consequential Amendments Act. Manitoba's petroleum storage program and the hazardous waste management program, including the disposal or treatment of contaminated soils are also summarized
Strategic plan for Hanford site information management

International Nuclear Information System (INIS)

1994-09-01

The Hanford Site missions are to clean up the Site, to provide scientific knowledge and technology to meet global needs, and to partner in the economic diversification of the region. To achieve these long-term missions and increase confidence in the quality of the Site's decision making process, a dramatically different information management culture is required, consistent with US Department of Energy (DOE) mandates on increased safety, productivity, and openness at its sites. This plan presents a vision and six strategies that will move the Site toward an information management culture that will support the Site missions and address the mandates of DOE
Remote sensing to monitor uranium tailing sites

International Nuclear Information System (INIS)

1992-02-01

This report concerns the feasibility of using remotely-sensed data for long-term monitoring of uranium tailings. Decommissioning of uranium mine tailings sites may require long-term monitoring to confirm that no unanticipated release of contaminants occurs. Traditional ground-based monitoring of specific criteria of concern would be a significant expense depending on the nature and frequency of the monitoring. The objective of this study was to evaluate whether available remote-sensing data and techniques were applicable to the long-term monitoring of tailings sites. This objective was met by evaluating to what extent the data and techniques could be used to identify and discriminate information useful for monitoring tailings sites. The cost associated with obtaining and interpreting this information was also evaluated. Satellite and aircraft remote-sensing-based activities were evaluated. A monitoring programme based on annual coverage of Landsat Thematic Mapper data is recommended. Immediately prior to and for several years after decommissioning of the tailings sites, airborne multispectral and thermal infrared surveys combined with field verification data are required in order to establish a baseline for the long-term satellite-based monitoring programme. More frequent airborne surveys may be required if rapidly changing phenomena require monitoring. The use of a geographic information system is recommended for the effective storage and manipulation of data accumulated over a number of years

Use of DOE site selection criteria for screening low-level waste disposal sites on the Oak Ridge Reservation

International Nuclear Information System (INIS)

Lee, D.W.; Ketelle, R.H.; Stinton, L.H.

1983-09-01

The proposed Department of Energy (DOE) site selection criteria were applied to the Oak Ridge Reservation, and the application was evaluated to determine the criteria's usefulness in the selection of a low-level waste disposal site. The application of the criteria required the development of a methodology to provide a framework for evaluation. The methodology is composed of site screening and site characterization stages. The site screening stage relies on reconnaissance data to identify a preferred site capable of satisfying the site selection criteria. The site characterization stage relies on a detailed site investigation to determine site acceptability. The site selection criteria were applied to the DOE Oak Ridge Reservation through the site screening stage. Results of this application were similar to those of a previous siting study on the Oak Ridge Reservation. The DOE site selection criteria when coupled with the methodology that was developed were easily applied and would be adaptable to any region of interest
1994 Site environmental report

International Nuclear Information System (INIS)

1995-07-01

The Fernald site is a Department of Energy (DOE)-owned facility that produced high-quality uranium metals for military defense for nearly 40 years. DOE suspended production at the site in 1989 and formally ended production in 1991. Although production activities have ceased, the site continues to examine the air and liquid pathways as possible routes through which pollutants from past operations and current remedial activities may leave the site. The Site Environmental Report (SER) is prepared annually in accordance with DOE Order 5400.1, General Environmental Protection Program. This 1994 SER provides the general public as well as scientists and engineers with the results from the site's ongoing Environmental Monitoring Program. Also included in this report is information concerning the site's progress toward achieving full compliance with requirements set forth by DOE, U.S. Environmental Protection Agency (USEPA), and Ohio EPA (OEPA). For some readers, the highlights provided in this Executive Summary may provide sufficient information. Many readers, however, may wish to read more detailed descriptions of the information than those which are presented here. All information presented in this summary is discussed more fully in the main body of this report
LLNL Experimental Test Site (Site 300) Potable Water System Operations Plan

Energy Technology Data Exchange (ETDEWEB)

Ocampo, R. P. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Bellah, W. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2015-09-14

The existing Lawrence Livermore National Laboratory (LLNL) Site 300 drinking water system operation schematic is shown in Figures 1 and 2 below. The sources of water are from two Site 300 wells (Well #18 and Well #20) and San Francisco Public Utilities Commission (SFPUC) Hetch-Hetchy water through the Thomas shaft pumping station. Currently, Well #20 with 300 gallons per minute (gpm) pump capacity is the primary source of well water used during the months of September through July, while Well #18 with 225 gpm pump capacity is the source of well water for the month of August. The well water is chlorinated using sodium hypochlorite to provide required residual chlorine throughout Site 300. Well water chlorination is covered in the Lawrence Livermore National Laboratory Experimental Test Site (Site 300) Chlorination Plan (“the Chlorination Plan”; LLNL-TR-642903; current version dated August 2013). The third source of water is the SFPUC Hetch-Hetchy Water System through the Thomas shaft facility with a 150 gpm pump capacity. At the Thomas shaft station the pumped water is treated through SFPUC-owned and operated ultraviolet (UV) reactor disinfection units on its way to Site 300. The Thomas Shaft Hetch- Hetchy water line is connected to the Site 300 water system through the line common to Well pumps #18 and #20 at valve box #1.
Temelin 3,4 Siting

International Nuclear Information System (INIS)

Kubanova, Iva; Fuzer, Jiri

2011-01-01

In the future the Czech Republic will need new energetic resources in spite of current decrease of electricity consumption due to economical crisis. Nuclear power generation is considered as important part of energetic mix of the Czech Republic and this opinion is newly reflected in new government official statement issued in August 2010. CEZ, a. s. prepares new nuclear power plants projects accordingly governmental expectations. Currently 3 projects are in preparation. Temelin 3, 4 project is in the most advanced status, tender is in progress. Potential construction of Dukovany unit 5 and new Jaslovske Bohunice units are analyzed in feasibility studies. Temelin 3, 4 project activities were started 4 years ago. Preparatory analyses, market investigation, feasibility study including many particular studies were elaborated in years 2006-2008. Later on decision to work on bid invitation specification was done and followed. EIA process was started in July 2008 by Intention Announcement and continues. Public tender for EPC contract was announced in August 2009 and it is in progress accordingly schedule. Siting process is in the initial stage. EIA process started in July 2008 through Intention Announcement in spite of anti - nuclear political climate in the Czech Republic. EIA process is interstate process, Austria and Germany participate. Investigation Process Protocol was issued by Ministry of Environment in February 2009 with 34 main conditions and 165 additional comments, requirements, statements. CEZ, a. s. adopted the positive approach with philosophy to deal with all conditions and requirements properly. Elaboration of EIA documentation took 18 months. In May 2010 CEZ, a. s. handed over the EIA documentation to the Ministry of Environment and consequently all legal steps followed including hand-over of EIA documentation to Austria and Germany. In next weeks and months all comments will be gathered by Ministry of Environment and relevant decisions and legal steps
Site release in the decommissioning of nuclear installations

International Nuclear Information System (INIS)

Revilla, Jose Luis; Sanz, Maria Teresa; Marugan, Inmaculada; Simon, Inmaculada; Martin, Manuel; Solis, Susana; Sterling, Agustina

2008-01-01

Spanish regulatory framework for the decommissioning process of a nuclear facility ends up with a decommission statement, which releases the licence-holder of the facility from its responsibilities as an operator. It also establishes -where a restricted site release applies- the appropriate future use restrictions, and the responsible of both maintaining such restrictions and ensuring their compliance. Releasing a site implies eliminating all radiological monitoring. The Regulations, however, did not specify either the radiological conditions to be met for the site to be released, or the possibility of a partial release -with or without restrictions-. In case of restricted site release, the Regulations did not specify either the required criteria for such a release. This paper presents the main features of the Safety Instruction IS-13 'Radiological criteria for the release of nuclear facilities sites' issued recently by the Spanish Nuclear Safety Council as a new specific regulation. This Safety Instruction establishes the requirements and conditions for the release of nuclear facility sites, that is, radiological criteria on the effective dose to the public, partial release of nuclear facility sites and restricted release of nuclear facility sites. (author).
Software configuration management plan for the Hanford site technical database

International Nuclear Information System (INIS)

GRAVES, N.J.

1999-01-01

The Hanford Site Technical Database (HSTD) is used as the repository/source for the technical requirements baseline and programmatic data input via the Hanford Site and major Hanford Project Systems Engineering (SE) activities. The Hanford Site SE effort has created an integrated technical baseline for the Hanford Site that supports SE processes at the Site and project levels which is captured in the HSTD. The HSTD has been implemented in Ascent Logic Corporation (ALC) Commercial Off-The-Shelf (COTS) package referred to as the Requirements Driven Design (RDD) software. This Software Configuration Management Plan (SCMP) provides a process and means to control and manage software upgrades to the HSTD system
Lessons learned with ISO 14001 at DOE sites

Energy Technology Data Exchange (ETDEWEB)

Wilkinson, C. H., LLNL

1998-03-01

ISO 14001 is the international standard for environmental management systems (EMS). The standard applies the `plan, do, check, act` management system model to assure that the environmental impacts of operations are fully considered in planning and facility operations. ISO 14001 has grown in popularity in both the public and the private sector and has seen increasing utility within the U.S. Department of Energy (DOE). While there is no final DOE policy or requirement for ISO 14001 EMS implementation, ISO 14001 commands an active presence at many DOE sites. In general, the impetus for ISO 14001 in the DOE complex has been either an initiative by site management contractors to improve performance, or an actual requirement in the new management contracts for the sites. Several DOE sites now are committed to implement EMS`s in conformance with ISO 14001: Brookhaven National Laboratory (BNL), Hanford, Idaho National Engineering and Environmental Laboratory (INEEL), Kansas City Plant, Nevada Test Site, Savannah River Site (SRS), Waste Isolation Pilot Project (WIPP), West Valley. Several other DOE sites are expected to proceed in the near future with an EMS consistent with ISO 14001. However, not all sites are proceeding with an ISO 14001 EMS based on individual site business considerations. This paper describes the status of EMS implementation at these sites and identifies lessons learned that may be of use to other DOE sites.
Savannah River Site environmental report for 1993

International Nuclear Information System (INIS)

Arnett, M.W.; Karapatakis, L.K.; Mamatey, A.R.

1994-01-01

Savannah River Site (SRS) conducts effluent monitoring and environmental surveillance to ensure the safety of the public and the well-being of the environment. DOE Order 5400,1, ''General Environmental Protection Program,'' requires the submission of an environmental report that documents the impact of facility operations on the environment and on public health. SRS has had an extensive environmental surveillance program in place since 1951 (before site startup). At that time, data generated by the on-site surveillance program were reported in site documents. Beginning in 1959, data from off-site environmental monitoring activities were presented in reports issued for public dissemination. Separate reporting of SRS's on- and off-site environmental monitoring activities continued until 1985, when data from both surveillance programs were merged into a single public document. The Savannah River Site Environmental Report for 1993 is an overview of effluent monitoring and environmental surveillance activities conducted on and in the vicinity of SRS from January 1 through December 31, 1993. For complete program descriptions, consult the ''SRS Environmental Monitoring Plan'' (WSRC-3Ql-2-1000). It documents the rationale and design criteria for the monitoring program, the frequency of monitoring and analysis, the specific analytical and sampling procedures, and the quality assurance requirements
Savannah River Site environmental report for 1993

Energy Technology Data Exchange (ETDEWEB)

Arnett, M.W.; Karapatakis, L.K.; Mamatey, A.R. [eds.

1994-08-01

Savannah River Site (SRS) conducts effluent monitoring and environmental surveillance to ensure the safety of the public and the well-being of the environment. DOE Order 5400,1, ``General Environmental Protection Program,`` requires the submission of an environmental report that documents the impact of facility operations on the environment and on public health. SRS has had an extensive environmental surveillance program in place since 1951 (before site startup). At that time, data generated by the on-site surveillance program were reported in site documents. Beginning in 1959, data from off-site environmental monitoring activities were presented in reports issued for public dissemination. Separate reporting of SRS`s on- and off-site environmental monitoring activities continued until 1985, when data from both surveillance programs were merged into a single public document. The Savannah River Site Environmental Report for 1993 is an overview of effluent monitoring and environmental surveillance activities conducted on and in the vicinity of SRS from January 1 through December 31, 1993. For complete program descriptions, consult the ``SRS Environmental Monitoring Plan`` (WSRC-3Ql-2-1000). It documents the rationale and design criteria for the monitoring program, the frequency of monitoring and analysis, the specific analytical and sampling procedures, and the quality assurance requirements.
Quebec's new contaminated sites policy : special report

International Nuclear Information System (INIS)

Anon.

1998-01-01

Quebec's new contaminated site policy sets out a broad new set of requirements with which industry will have to comply. The new policy entitled 'Politique de protection des sols et de rehabilitation des terrains contamines' is much more comprehensive and detailed than its 1988 predecessor and contains many new elements. The policy seeks to maintain soil and groundwater quality criteria and focuses on the protection of clean commercial and industrial sites through pollution prevention actions. It also takes into account progress which has been made since the inventory of contaminated sites across Quebec. It considers the characteristics of each site and the problems posed by ongoing disposal of contaminated soils in landfills and advances in treatment technologies. The issue of who is responsible for contaminated sites is addressed and the requirements for responsible parties are described in detail. Risk assessment was also introduced as a tool for remediation planning in some cases. The new policy stresses prevention, and attempts to clearly outline site characterization and remediation duties for new and existing industries that pose potential risk of soil and groundwater contamination. 2 tabs., 2 figs
Closure Plan for the Area 5 Radioactive Waste Management Site at the Nevada Test Site

International Nuclear Information System (INIS)

NSTec Environmental Management

2008-01-01

The Area 5 Radioactive Waste Management Site (RMWS) at the Nevada Test Site (NTS) is managed and operated by National Security Technologies, LLC (NSTec), for the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Site Office (NNSA/NSO). This document is the first update of the preliminary closure plan for the Area 5 RWMS at the NTS that was presented in the Integrated Closure and Monitoring Plan (DOE, 2005a). The major updates to the plan include a new closure schedule, updated closure inventory, updated site and facility characterization data, the Title II engineering cover design, and the closure process for the 92-Acre Area of the RWMS. The format and content of this site-specific plan follows the Format and Content Guide for U.S. Department of Energy Low-Level Waste Disposal Facility Closure Plans (DOE, 1999a). This interim closure plan meets closure and post-closure monitoring requirements of the order DOE O 435.1, manual DOE M 435.1-1, Title 40 Code of Federal Regulations (CFR) Part 191, 40 CFR 265, Nevada Administrative Code (NAC) 444.743, and Resource Conservation and Recovery Act (RCRA) requirements as incorporated into NAC 444.8632. The Area 5 RWMS accepts primarily packaged low-level waste (LLW), low-level mixed waste (LLMW), and asbestiform low-level waste (ALLW) for disposal in excavated disposal cells
Closure Plan for the Area 5 Radioactive Waste Management Site at the Nevada Test Site

Energy Technology Data Exchange (ETDEWEB)

NSTec Environmental Management

2008-09-01

The Area 5 Radioactive Waste Management Site (RMWS) at the Nevada Test Site (NTS) is managed and operated by National Security Technologies, LLC (NSTec), for the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Site Office (NNSA/NSO). This document is the first update of the preliminary closure plan for the Area 5 RWMS at the NTS that was presented in the Integrated Closure and Monitoring Plan (DOE, 2005a). The major updates to the plan include a new closure schedule, updated closure inventory, updated site and facility characterization data, the Title II engineering cover design, and the closure process for the 92-Acre Area of the RWMS. The format and content of this site-specific plan follows the Format and Content Guide for U.S. Department of Energy Low-Level Waste Disposal Facility Closure Plans (DOE, 1999a). This interim closure plan meets closure and post-closure monitoring requirements of the order DOE O 435.1, manual DOE M 435.1-1, Title 40 Code of Federal Regulations (CFR) Part 191, 40 CFR 265, Nevada Administrative Code (NAC) 444.743, and Resource Conservation and Recovery Act (RCRA) requirements as incorporated into NAC 444.8632. The Area 5 RWMS accepts primarily packaged low-level waste (LLW), low-level mixed waste (LLMW), and asbestiform low-level waste (ALLW) for disposal in excavated disposal cells.
Environmental audit of the Maywood Site: Formerly Utilized Sites Remedial Action Program, Maywood Interim Storage Site vicinity properties

Energy Technology Data Exchange (ETDEWEB)

1990-12-01

This report presents the results of the Environmental Audit of the Maywood Site managed by the Formerly Utilized Sites Remedial Action Program (FUSRAP). The Audit was carried out from November 7 through 16, 1990. The Audit Team found overall technical competence and knowledge of management and staff to be excellent. This applies to DOE as well as to Bechtel National, Incorporated (BNI). In particular, there was excellent knowledge of federal, state, and local environmental regulations, as well as analysis for applicability of these regulations to FUSRAP. Project management of the Maywood Site is also excellent. BNI and DOE project staff have made frequent contact with members of the community, and all removal actions and remedial investigation activities have been planned, scheduled, and accomplished with competence and attention to total quality principles. To date, all actions taken for the Maywood Site cleanup have been completed ahead of schedule and on or under budget. Weakness noted include self-assessment efforts by DOE, failure to fully implement DOE Order requirements throughout the program, and some discrepancies in formally documenting and reviewing procedures. 7 figs., 10 tabs.
Site Study Plan for salt, Deaf Smith County site, Texas: Environmental Field Program: Preliminary draft

International Nuclear Information System (INIS)

1987-06-01

The Salt Site Study Plan (SSP) describes a program for characterizing the existing salt environment in the site vicinity. A step-by-step approach is described which proceeds from published data and planned theoretical studies, to planned laboratory studies, and finally to planned field studies, to provide the necessary data to meet program requirements contained in the Salt Repository Project - Requirements Document (SRP-RD). The plan also draws on the results of other SSP's for certain data; for example, soil salinity data are to be provided under the Soils SSP. The salt studies consist of evaluation of control and mitigation measures, salt monitoring studies, emission factors development, air models development and validation, and risk assessment. For each study, its design and design rationale; analysis, management, and use of data; schedule of activities; organization of personnel and sample management; and quality assurance requirements are described. 90 refs., 9 figs., 7 tabs
Site Study Plan for Acoustics, Deaf Smith County Site, Texas: Environmental Field Program: Preliminary draft

International Nuclear Information System (INIS)

1987-06-01

The Acoustics site study plan describes a field program which characterizes existing sound levels, determines the area's sound propagation characteristics, and monitors the project-related sound emissions. The plan describes for each study: the need for the study, study design, data management and use, schedule, and quality assurance requirements. These studies will provide data needed to satisfy requirements contained in, or derived from, the Salt Repository Requirements Document. 37 refs., 9 figs., 3 tabs
7 CFR 1948.96 - Audit requirements.

Science.gov (United States)

2010-01-01

... Program § 1948.96 Audit requirements. (a) Audit requirements for Site Development and Acquisition Grants will be made in accordance with FmHA Instruction 1942-G. (b) Audits for planning grants made in... 7 Agriculture 13 2010-01-01 2009-01-01 true Audit requirements. 1948.96 Section 1948.96...
Review of underground siting of nuclear power plants

International Nuclear Information System (INIS)

1974-01-01

A review of the potential for the underground siting of nuclear power generating plants has been undertaken. The review comprised a survey and assessment of relevant published documents currently available, together with discussions with Government sponsored agencies and other bodies, to evaluate the current status of technology related to the design and construction of underground nuclear power plants. It includes a review of previous work related to the underground siting of power plants and other facilities; a preliminary evaluation of the relative merits of the various concepts of undergrounding which have been proposed or constructed; a review of current technology as it relates to the requirements for the design, construction and operation of underground nuclear power plants; an examination of the safety and environmental aspects; and the identification of areas of further study which will be required if the underground is to be established as a fully viable alternative to surface siting. No attempt has been made to draw final conclusions at this stage. Nothing has been found to suggest that the underground siting concept could not provide a viable alternative to the surface concept. It is also apparent that no major technological developments are required. It is not clear, however, whether the improvements in safety and containment postulated for the underground can be realized at an economic cost; or even whether any additional cost is in fact involved. The problem is essentially site dependent and requires further study for which recommendations are made. (auth)
Site environmental report for calendar year 1996

International Nuclear Information System (INIS)

1997-06-01

This Annual Site Environmental Report presents information pertaining to environmental activities conducted during calendar year 1996 at the U.S. Department of Energy (DOE) Grand Junction Office (GJO) facility in Grand Junction, Colorado. WASTREN-Grand Junction, the Facility Operations and Support contractor for the GJO, prepared this report in accordance with the requirements of DOE Order 5400.1, General Environmental Protection Program, and supplemental guidance from DOE Headquarters. This report applies specifically to the GJO facility; the Monticello Mill Tailings Site Environmental Summary for Calendar Year 1996 was prepared as a separate document. Primary GJO activities involve laboratory analysis of environmental samples from GJO and other DOE sites and site remediation of contamination caused by previous uranium mill operations. Activities at the GJO are conducted in compliance with applicable Federal, State, and local regulations and requirements and as directed by applicable DOE orders. Environmental monitoring is performed on air emissions, sewer effluent, surface water and groundwater, and wetlands restoration. Wastes are generated from the Analytical Laboratory, site remediation, and facility operation
Solid waste management complex site development plan

International Nuclear Information System (INIS)

Greager, T.M.

1994-01-01

The main purpose of this Solid Waste Management Complex Site Development Plan is to optimize the location of future solid waste treatment and storage facilities and the infrastructure required to support them. An overall site plan is recommended. Further, a series of layouts are included that depict site conditions as facilities are constructed at the SWMC site. In this respect the report serves not only as the siting basis for future projects, but provides siting guidance for Project W-112, as well. The plan is intended to function as a template for expected growth of the site over the next 30 years so that future facilities and infrastructure will be properly integrated
Solid waste management complex site development plan

Energy Technology Data Exchange (ETDEWEB)

Greager, T.M.

1994-09-30

The main purpose of this Solid Waste Management Complex Site Development Plan is to optimize the location of future solid waste treatment and storage facilities and the infrastructure required to support them. An overall site plan is recommended. Further, a series of layouts are included that depict site conditions as facilities are constructed at the SWMC site. In this respect the report serves not only as the siting basis for future projects, but provides siting guidance for Project W-112, as well. The plan is intended to function as a template for expected growth of the site over the next 30 years so that future facilities and infrastructure will be properly integrated.

Treatment with selective serotonin reuptake inhibitors and mirtapazine results in differential brain activation by visual erotic stimuli in patients with major depressive disorder.

Science.gov (United States)

Kim, Won; Jin, Bo-Ra; Yang, Wan-Seok; Lee, Kyuong-Uk; Juh, Ra-Hyung; Ahn, Kook-Jin; Chung, Yong-An; Chae, Jeong-Ho

2009-06-01

The objective of this study was to identify patterns of brain activation elicited by erotic visual stimuli in patients treated with either Selective Serotonin Reuptake Inhibitors (SSRIs) or mirtazipine. Nine middle-aged men with major depressive disorder treated with an SSRI and ten middle-aged men with major depressive disorder treated with mirtazapine completed the trial. Ten subjects with no psychiatric illness were included as a control group. We conducted functional brain magnetic resonance imaging (fMRI) while a film alternatively played erotic and non-erotic contents for 14 minutes and 9 seconds. The control group showed activation in the occipitotemporal area, anterior cingulate gyrus, insula, orbitofrontal cortex, and caudate nucleus. For subjects treated with SSRIs, the intensity of activity in these regions was much lower compared to the control group. Intensity of activation in the group treated with mirtazapine was less than the control group but grea-ter than those treated with SSRIs. Using subtraction analysis, the SSRI group showed significantly lower activation than the mirtazapine group in the anterior cingulate gyrus and the caudate nucleus. Our study suggests that the different rates of sexual side effects between the patients in the SSRI-treated group and the mirtazapine-treated group may be due to different effects on brain activation.
G. Nuclear power plant siting

International Nuclear Information System (INIS)

1976-01-01

The selection of a site for a nuclear power site is a complex process involving considerations of public health and safety, engineering design, economics, and environmental impact. Although policies adopted in various countries differ in some details, a common philosophy usually underlies the criteria employed. The author discusses the basic requirements, as they relate to New Zealand, under the headings: engineering and economics; health and safety; environmental factors
Radiation safety for site radiography

International Nuclear Information System (INIS)

1986-01-01

This guidance is an update of the 1975 Code of Practice for Site Radiography and is for the use of employers and their radiographers who carry out site work. The subject is discussed under the following headings: Administrative organization, Personnel requirements, Equipment (x-ray and gamma-ray equipment, security, pipeline crawler equipment and safety equipment) Work methods and monitoring, Carriage of sources, Contingency plans, Legal considerations. (U.K.)
Participation of concerned citizens in site selection decisions

International Nuclear Information System (INIS)

Appel, D.

2003-01-01

The contribution presents preliminary results of two international projects aimed at integrating the general public, or parts thereof, in the decision process of selecting ultimate storage sites. The author participated in these projects and is a former member of the task group for selection of ultimate storage sites (Arbeitskreis Auswahlverfahren Endlagerstandorte - AkEnd). The two projects are: Forum on Stakeholder Confidence (FSC) of the Nuclear Energy Agency (NEA) OECD, Project 'COWAM' (Community Waste Management) of the European Commission. The participants, goals and methods of the two projects were different, but they both presented concrete methods of selecting ultimate storage sites from the view of different actors in the form of case studies. The focus was on the participation of the public and its importance for success. Apart from meeting technical requirements the selection process should also take account of the requirements of democracy and citizens' participation in order to gain wide acceptance for its results. Deficiencies and advantages of the proposed selection processes are analyzed, and general requirements on the decision process in site selection are derived. (orig.) [de
Challenges in radiological impact assessment studies at new sites for nuclear facilities and its safety review and assessment for siting consent

International Nuclear Information System (INIS)

Mukherjee Roy, Susmita; Roshan, A.D.; Bishnoi, L.R.

2018-01-01

One of the basic requirement of site evaluation for a Nuclear Facility (NF) is radiological impact assessment (RIA). This involves evaluation of transportation of radioactive materials discharged from a nuclear facility under normal operational or accidental conditions, through different compartments of environment viz. air, land and water, and finally assessment of its consequences. Amongst others, site characteristics and the site related parameters play major role in evaluation of impact of postulated releases from NPPs. Doses to public from both external and internal exposures are computed to assess potential consequences of a radiological release and acceptability of the site-plant pair is established based on the outcome of this assessment. A comprehensive study of the site characteristics including meteorology, hydrology, hydro-geology and demography of the region along with details of land and water use, bioaccumulation, transfer to and from the environmental matrices is required for accomplishing satisfactory RIA
Determination of import process during Yucca Mountain Site characterization

International Nuclear Information System (INIS)

Hastings, P.S.; Gwyn, D.W.; Wemheuer, R.F.

1996-01-01

Construction of an underground Exploratory Studies Facility (ESF) for characterizing the Yucca Mountain site precedes the design of a potential repository, with site characterization testing and ESF construction conducted as parallel activities. As a result of this fact, a program is required to: (1) provide for inclusion of the underground excavation into a potential repository, (2) minimize the potential impact of ESF construction on site characterization test results, and (3) minimize the potential impact of ESF construction and site characterization testing on the waste isolation capabilities of the site. At Yucca Mountain, the Determination of Importance (DI) process fulfills these goals. This paper addresses the evolution of the DI process; describes how the DI process fits into design, testing, and construction programs: and discusses how the process is implemented through specification requirements
Nevada Test Site Environmental Report 2008

Energy Technology Data Exchange (ETDEWEB)

Cathy A. Wills

2009-09-01

The Nevada Test Site Environmental Report (NTSER) 2008 was prepared to meet the information needs of the public and the requirements and guidelines of the U.S. Department of Energy (DOE) for annual site environmental reports. It was prepared by National Security Technologies, LLC (NSTec), for the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office (NNSA/NSO). This and previous years’ NTSERs are posted on the NNSA/NSO website at http://www.nv.doe.gov/library/publications/aser.aspx.
Hanford Site waste minimization and pollution prevention awareness program plan

International Nuclear Information System (INIS)

Place, B.G.

1998-01-01

This plan, which is required by US Department of Energy (DOE) Order 5400. 1, provides waste minimization and pollution prevention guidance for all Hanford Site contractors. The plan is primary in a hierarchical series that includes the Hanford Site Waste Minimization and Pollution Prevention Awareness Program Plan, Prime contractor implementation plans, and the Hanford Site Guide for Preparing and Maintaining Generator Group Pollution Prevention Program Documentation (DOE-RL, 1997a) describing programs required by Resource Conservation and Recovery Act of 1976 (RCRA) 3002(b) and 3005(h) (RCRA and EPA, 1994). Items discussed include the pollution prevention policy and regulatory background, organizational structure, the major objectives and goals of Hanford Site's pollution prevention program, and an itemized description of the Hanford Site pollution prevention program. The document also includes US Department of Energy, Richland Operations Office's (RL's) statement of policy on pollution prevention as well as a listing of regulatory drivers that require a pollution prevention program
Wind turbine siting: A summary of the state of the art

Science.gov (United States)

Hiester, T. R.

1982-01-01

The process of siting large wind turbines may be divided into two broad steps: site selection, and site evaluation. Site selection is the process of locating windy sites where wind energy development shows promise of economic viability. Site evaluation is the process of determining in detail for a given site the economic potential of the site. The state of the art in the first aspect of siting, site selection is emphasized. Several techniques for assessing the wind resource were explored or developed in the Federal Wind Energy Program. Local topography and meteorology will determine which of the techniques should be used in locating potential sites. None of the techniques can do the job alone, none are foolproof, and all require considerable knowledge and experience to apply correctly. Therefore, efficient siting requires a strategy which is founded on broad based application of several techniques without relying solely on one narrow field of expertise.
Long-term surveillance plan for the Maybell, Colorado Disposal Site

International Nuclear Information System (INIS)

1997-09-01

This long-term surveillance plan (LTSP) describes the U.S. Department of Energy's (DOE) long-term care program for the Uranium Mill Tailings Remedial Action (UMTRA) Project Maybell disposal site in Moffat County, Colorado. The U.S. Nuclear Regulatory Commission (NRC) has developed regulations for the issuance of a general license for the custody and long-term care of UMTRA Project disposal sites in 10 CFR Part 40. The purpose of this general license is to ensure that the UMTRA Project disposal sites are cared for in a manner that protects the public health and safety and the environment. Before each disposal site is licensed, the NRC requires the DOE to submit a site-specific LTSP. The DOE prepared this LTSP to meet this requirement for the Maybell disposal site. The general license becomes effective when the NRC concurs with the DOE's determination that remedial action is complete for the Maybell site and the NRC formally accepts this LTSP. This document describes the long-term surveillance program the DOE will implement to ensure the Maybell disposal site performs as designed. The program is based on site inspections to identify threats to disposal cell integrity. The LTSP is based on the UMTRA Project long-term surveillance program guidance document and meets the requirements of 10 CFR section 40.27(b) and 40 CFR section 192.03
24 CFR 1710.15 - Regulatory exemption-multiple site subdivision-determination required.

Science.gov (United States)

2010-04-01

... non-waivable provision in bold face type (which must be distinguished from the type used for the rest... contract or other document by requiring a specific type of notice or by requiring that notice be given at a... font. A copy of the acknowledgement will be maintained by the developer for three years and will be...
Development of a subset of forelimb muscles and their attachment sites requires the ulnar-mammary syndrome gene Tbx3

Directory of Open Access Journals (Sweden)

Mary P. Colasanto

2016-11-01

Full Text Available In the vertebrate limb over 40 muscles are arranged in a precise pattern of attachment via muscle connective tissue and tendon to bone and provide an extensive range of motion. How the development of somite-derived muscle is coordinated with the development of lateral plate-derived muscle connective tissue, tendon and bone to assemble a functional limb musculoskeletal system is a long-standing question. Mutations in the T-box transcription factor, TBX3, have previously been identified as the genetic cause of ulnar-mammary syndrome (UMS, characterized by distinctive defects in posterior forelimb bones. Using conditional mutagenesis in mice, we now show that TBX3 has a broader role in limb musculoskeletal development. TBX3 is not only required for development of posterior forelimb bones (ulna and digits 4 and 5, but also for a subset of posterior muscles (lateral triceps and brachialis and their bone eminence attachment sites. TBX3 specification of origin and insertion sites appears to be tightly linked with whether these particular muscles develop and may represent a newly discovered mechanism for specification of anatomical muscles. Re-examination of an individual with UMS reveals similar previously unrecognized muscle and bone eminence defects and indicates a conserved role for TBX3 in regulating musculoskeletal development.
Antimicrobial Pesticide Use Site Index

Science.gov (United States)

This Use Site Index provides guidance to assist applicants for antimicrobial pesticide registration by helping them identify the data requirements necessary to register a pesticide or support their product registrations.
Description of the Formerly Utilized Sites Remedial Action Program

International Nuclear Information System (INIS)

1980-09-01

The background and the results to date of the Department of Energy program to identify and evaluate the radiological conditions at sites formerly utilized by the Corps of Engineers' Manhattan Engineer District (MED) and the US Atomic Energy Commission (AEC) are summarized. The sites of concern were federally, privately, and institutionally owned and were used primarily for research, processing, and storage of uranium and thorium ores, concentrates, or residues. Some sites were subsequently released for other purposes without radiological restriction. Surveys have been conducted since 1974 to document radiological conditions at such sites. Based on radiological surveys, sites are identified in this document that require, or are projected to require, remedial action to remove potential restrictions on the use of the property due to the presence of residual low-level radioactive contamination. Specific recommendations for each site will result from more detailed environmental and engineering surveys to be conducted at those sites and, if necessary, an environmental impact assessment or environmental impact statement will be prepared. Section 3.0 describes the current standards and guidelines now being used to conduct remedial actions. Current authority of the US Department of Energy (DOE) to proceed with remedial actions and the new authority required are summarized. A plan to implement the Formerly Utilized Sites Remedial Action Program (FUSRAP) in accordance with the new authority is presented, including the objectives, scope, general approach, and a summary schedule. Key issues affecting schedule and cost are discussed
Description of the Formerly Utilized Sites Remedial Action Program

Energy Technology Data Exchange (ETDEWEB)

1980-09-01

The background and the results to date of the Department of Energy program to identify and evaluate the radiological conditions at sites formerly utilized by the Corps of Engineers' Manhattan Engineer District (MED) and the US Atomic Energy Commission (AEC) are summarized. The sites of concern were federally, privately, and institutionally owned and were used primarily for research, processing, and storage of uranium and thorium ores, concentrates, or residues. Some sites were subsequently released for other purposes without radiological restriction. Surveys have been conducted since 1974 to document radiological conditions at such sites. Based on radiological surveys, sites are identified in this document that require, or are projected to require, remedial action to remove potential restrictions on the use of the property due to the presence of residual low-level radioactive contamination. Specific recommendations for each site will result from more detailed environmental and engineering surveys to be conducted at those sites and, if necessary, an environmental impact assessment or environmental impact statement will be prepared. Section 3.0 describes the current standards and guidelines now being used to conduct remedial actions. Current authority of the US Department of Energy (DOE) to proceed with remedial actions and the new authority required are summarized. A plan to implement the Formerly Utilized Sites Remedial Action Program (FUSRAP) in accordance with the new authority is presented, including the objectives, scope, general approach, and a summary schedule. Key issues affecting schedule and cost are discussed.
Fernald Environmental Management Project 1995 site environmental report

International Nuclear Information System (INIS)

1996-06-01

The Fernald site continues to examine the air and liquid pathways as possible routes through which pollutants from past operations and current remedial activities may leave the site. This 1995 Site Environmental Report provides the general public as well as scientists and engineers with the results from the site's ongoing Environmental Monitoring Program. Also included in this report is information concerning the site's progress toward achieving full compliance with requirements set forth by DOE, US Environmental Protection Agency (USEPA), and Ohio EPA
Pharmacokinetics of paroxetine, a selective serotonin reuptake inhibitor, in Grey parrots (Psittacus erithacus erithacus): influence of pharmaceutical formulation and length of dosing.

Science.gov (United States)

van Zeeland, Y R A; Schoemaker, N J; Haritova, A; Smit, J W; van Maarseveen, E M; Lumeij, J T; Fink-Gremmels, J

2013-02-01

Paroxetine, a selective serotonin reuptake inhibitor, may be beneficial in the treatment of behavioural disorders in pet birds. The lack of pharmacokinetic data and clinical trials currently limits the use of this drug in clinical avian practice. This paper evaluates the pharmacokinetic properties and potential side effects of single and repeated dosing of paroxetine in Grey parrots (Psittacus erithacus erithacus). Paroxetine pharmacokinetics were studied after single i.v. and single oral dosing, and after repeated oral administration during 1 month. Plasma paroxetine concentrations were determined by liquid chromatography-tandem mass spectrometry. No undesirable side effects were observed during the study. Pharmacokinetic analysis revealed a quick distribution and rapid elimination after i.v. administration. Oral administration of paroxetine HCl dissolved in water resulted in a relatively slow absorption (T(max)=5.9±2.6 h) and a low bioavailability (31±15%). Repeated administration resulted in higher rate of absorption, most likely due to a saturation of the cytochrome P450-mediated first-pass metabolism. This study shows that oral administration of paroxetine HCl (4 mg/kg twice daily) in parrots results in plasma concentrations within the therapeutic range recommended for the treatment of depressions in humans. Further studies are needed to demonstrate the clinical efficacy of this dosage regimen in parrots with behavioural disorders. © 2012 Blackwell Publishing Ltd.
SAVANNAH RIVER SITE ENVIRONMENTAL REPORT FOR 2007

International Nuclear Information System (INIS)

Mamatey, A

2008-01-01

The Savannah River Site Environmental Report for 2007 (WSRC-STI-2008-00057) prepared for the US Department of Energy (DOE) according to requirements of DOE Order 231.1A, 'Environment, Safety and Health Reporting', and DOE Order 5400.5, 'Radiation Protection of the Public and Environment'. The report's purpose is to: (1) present summary environmental data that characterize site environmental management performance; (2) confirm compliance with environmental standards and requirements; (3) highlight significant programs and efforts; (4) assess the impact of SRS operations on the public and the environment
Savannah River Site Environmental Report for 2004

International Nuclear Information System (INIS)

Mamatey, Albert R.

2005-01-01

The Savannah River Site Environmental Report for 2004 (WSRC-TR-2005-00005) is prepared for the U.S. Department of Energy (DOE) according to requirements of DOE Order 231.1A, ''Environment, Safety and Health Reporting,'' and DOE Order 5400.5, ''Radiation Protection of the Public and Environment''. The report's purpose is to present summary environmental data that characterize site environmental management performance; confirm compliance with environmental standards and requirements; highlight significant programs and efforts; and assess the impact of SRS operations on the public and the environment
SAVANNAH RIVER SITE ENVIRONMENTAL REPORT FOR 2007

Energy Technology Data Exchange (ETDEWEB)

Mamatey, A

2008-08-27

The Savannah River Site Environmental Report for 2007 (WSRC-STI-2008-00057) prepared for the US Department of Energy (DOE) according to requirements of DOE Order 231.1A, 'Environment, Safety and Health Reporting', and DOE Order 5400.5, 'Radiation Protection of the Public and Environment'. The report's purpose is to: (1) present summary environmental data that characterize site environmental management performance; (2) confirm compliance with environmental standards and requirements; (3) highlight significant programs and efforts; (4) assess the impact of SRS operations on the public and the environment.

Double tracks test site characterization report

International Nuclear Information System (INIS)

1996-05-01

This report presents the results of site characterization activities performed at the Double Tracks Test Site, located on Range 71 North, of the Nellis Air Force Range (NAFR) in southern Nevada. Site characterization activities included reviewing historical data from the Double Tracks experiment, previous site investigation efforts, and recent site characterization data. The most recent site characterization activities were conducted in support of an interim corrective action to remediate the Double Tracks Test Site to an acceptable risk to human health and the environment. Site characterization was performed using a phased approach. First, previously collected data and historical records sere compiled and reviewed. Generalized scopes of work were then prepared to fill known data gaps. Field activities were conducted and the collected data were then reviewed to determine whether data gaps were filled and whether other areas needed to be investigated. Additional field efforts were then conducted, as required, to adequately characterize the site. Characterization of the Double Tracks Test Site was conducted in accordance with the US Department of Energy's (DOE) Streamlined Approach for Environmental Restoration (SAFER)
Nevada Test Site Environmental Report 2005

International Nuclear Information System (INIS)

Cathy A. Wills

2006-01-01

The Nevada Test Site Environmental Report 2005 (NTSER) was prepared to meet the information needs of the public and the requirements and guidelines of the U.S. Department of Energy (DOE) for annual site environmental reports. Its purpose is to (1) report compliance status with environmental standards and requirements, (2) present results of environmental monitoring of radiological and nonradiological effluents, (3) report estimated radiological doses to the public from releases of radioactive material, (4) summarize environmental incidents of noncompliance and actions taken in response to them, (5) describe the NTS Environmental Management System and characterize its performance, and (6) highlight significant environmental programs and efforts
Nevada Test Site Environmental Report 2005

Energy Technology Data Exchange (ETDEWEB)

Cathy A. Wills

2006-10-01

The Nevada Test Site Environmental Report 2005 (NTSER) was prepared to meet the information needs of the public and the requirements and guidelines of the U.S. Department of Energy (DOE) for annual site environmental reports. Its purpose is to (1) report compliance status with environmental standards and requirements, (2) present results of environmental monitoring of radiological and nonradiological effluents, (3) report estimated radiological doses to the public from releases of radioactive material, (4) summarize environmental incidents of noncompliance and actions taken in response to them, (5) describe the NTS Environmental Management System and characterize its performance, and (6) highlight significant environmental programs and efforts.
The disposal of Canada's nuclear fuel waste: site screening and site evaluation technology

International Nuclear Information System (INIS)

Davison, C.C.; Brown, A.; Everitt, R.A.; Gascoyne, M.; Kozak, E.T.; Lodha, G.S.; Martin, C.D.; Soonawala, N.M.; Stevenson, D.R.; Thorne, G.A.; Whitaker, S.H.

1994-06-01

carefully characterized to understand the groundwater flow conditions in the rock. This understanding would be used to situate the disposal vault in the rock so as to allow the flow and chemical characteristics of the groundwater to enhance the safety of the disposal system. The geoscience methods for characterizing the conditions within plutonic rocks of the Canadian Shield have been developed and tested by AECL at geologic research areas on the Shield. This report presents examples of the site characterization methods which are drawn from the studies at these research areas. The geoscience work performed at the Whiteshell Research Area (WRA) on the Shield in southeastern Manitoba comes closest to illustrating the spatial coverage of characterization that would be required for siting an actual nuclear fuel waste disposal vault in a candidate area of the Shield. The characterization work done at the site of the Underground Research Laboratory (URL) in the WRA demonstrates how to evaluate the geoscience conditions of the rock at a candidate disposal site, and illustrates how that information would be used to confirm the suitability of the site for disposal. This report presents evidence from case studies at the URL and the geologic research areas that the surface-based, borehole and underground site characterization methods developed by AECL are now sufficiently developed that they can be used to obtain the geoscience information needed for siting a disposal vault in plutonic rock of the Canadian Shield. We expect that these site characterization methods will continue to be improved and that new methods will be developed during the long time period required for implementation of the disposal project. Improvements and new developments are continuing through ongoing research at the site of the URL and at the other geologic research areas on the Shield. However the methods that are currently available are sufficiently well developed to allow siting to commence. (author)
Site Study Plan for Aesthetics, Deaf Smith County Site, Texas: Environmental Field Program: Preliminary draft

International Nuclear Information System (INIS)

1987-06-01

The Aesthetic Site Study Plan describes a field program consisting of identification of the visually affected area; determination of scenic quality, visual sensitivity, and visual management classes of the site and vicinity; and analysis of the level of visual contrast that would be created by the project. Field ratings of scenic quality, visual sensitivity, and visual contrast will be supplemented by a public perception survey designed to incorporate the views of the public. This plan describes the need for the study, the study design, data management and use, schedule for proposed activities, and quality assurance program. This study will provide data needed to satisfy requirements contained in, or derived from, SRPO Requirement Document (SRP-RD). 35 refs., 6 figs., 2 tabs
Environmental Assessment for the construction and operation of the Health Physics Site Support Facility on the Savannah River Site

International Nuclear Information System (INIS)

1995-07-01

DOE has prepared an environmental assessment for the proposed construction and operation of the Health Physics Site Support Facility on the Savannah River Site. This (new) facility would meet requirements of the site radiological protection program and would ensure site compliance with regulations. It was determined that the proposed action is not a major Federal action significantly affecting the quality of the environment within the meaning of NEPA. Therefore, a finding of no significant impact is made, and no environmental impact statement is needed
Hydroelectric generating site signage

Energy Technology Data Exchange (ETDEWEB)

Bentley, K [British Columbia Hydro, Vancouver, BC (Canada)

1997-04-01

Recreational sites have been developed at several BC Hydro reservoirs. These sites are visited by approximately 800,000 people annually and therefore, require consistent control measures to ensure public safety and to restrict public access to hazardous areas. BC Hydro is in the process of establishing a province-wide standard in which layout, colour, description of hazards, BC Hydro identity and sign placement would follow an established set of criteria. Proposed signs would consist of a pictograph and a printed warning below. Preliminary designs for 16 of the signs were presented. 16 figs.
NG09 And CTBT On-Site Inspection Noble Gas Sampling and Analysis Requirements

Science.gov (United States)

Carrigan, Charles R.; Tanaka, Junichi

2010-05-01

A provision of the Comprehensive Test Ban Treaty (CTBT) allows on-site inspections (OSIs) of suspect nuclear sites to determine if the occurrence of a detected event is nuclear in origin. For an underground nuclear explosion (UNE), the potential success of an OSI depends significantly on the containment scenario of the alleged event as well as the application of air and soil-gas radionuclide sampling techniques in a manner that takes into account both the suspect site geology and the gas transport physics. UNE scenarios may be broadly divided into categories involving the level of containment. The simplest to detect is a UNE that vents a significant portion of its radionuclide inventory and is readily detectable at distance by the International Monitoring System (IMS). The most well contained subsurface events will only be detectable during an OSI. In such cases, 37 Ar and radioactive xenon cavity gases may reach the surface through either "micro-seepage" or the barometric pumping process and only the careful siting of sampling locations, timing of sampling and application of the most site-appropriate atmospheric and soil-gas capturing methods will result in a confirmatory signal. The OSI noble gas field tests NG09 was recently held in Stupava, Slovakia to consider, in addition to other field sampling and analysis techniques, drilling and subsurface noble gas extraction methods that might be applied during an OSI. One of the experiments focused on challenges to soil-gas sampling near the soil-atmosphere interface. During withdrawal of soil gas from shallow, subsurface sample points, atmospheric dilution of the sample and the potential for introduction of unwanted atmospheric gases were considered. Tests were designed to evaluate surface infiltration and the ability of inflatable well-packers to seal out atmospheric gases during sample acquisition. We discuss these tests along with some model-based predictions regarding infiltration under different near
Site Characterization Work Plan for Gnome-Coach Site, New Mexico

Energy Technology Data Exchange (ETDEWEB)

DOE/NV

2001-02-13

Project Gnome was the first nuclear experiment conducted under the U.S. Atomic Energy Commission (AEC), predecessor to the U.S. Department of Energy (DOE), Plowshare Program. Gnome was part of a joint government-industry experiment focused on developing nuclear devices exclusively for peaceful purposes. The intent of the Gnome experiment was to evaluate the effects of a nuclear detonation in a salt medium. Historically, Project Gnome consisted of a single detonation of a nuclear device on December 10, 1961. Since the Gnome detonation, the AEC/DOE has conducted surface restoration, site reconnaissance, and decontamination and decommissioning activities at the site. In addition, annual groundwater sampling is performed under a long-term hydrological monitoring program begun in 1980. Coach, an experiment to be located near the Gnome project, was initially scheduled for 1963. Although construction and rehabilitation were completed for Coach, the experiment was canceled and never executed. Known collectively as Project Gnome-Coach, the site is situated within the Salado Formation approximately 25 miles east of Carlsbad, New Mexico, in Eddy County, and is comprised of nearly 680 acres, of which 60 acres are disturbed from the combined AEC/DOE operations. The scope of this work plan is to document the environmental objectives and the proposed technical site investigation strategies that will be utilized for the site characterization of the project. The subsurface at the Gnome-Coach site has two contaminant sources that are fundamentally different in terms of both their stratigraphic location and release mechanism. The goal of this characterization is to collect data of sufficient quantity and quality to establish current site conditions and to use the data to identify and evaluate if further action is required to protect human health and the environment and achieve permanent closure of the site. The results of these activities will be presented in a subsequent corrective
Association of the Polygenic Scores for Personality Traits and Response to Selective Serotonin Reuptake Inhibitors in Patients with Major Depressive Disorder

Science.gov (United States)

Amare, Azmeraw T.; Schubert, Klaus Oliver; Tekola-Ayele, Fasil; Hsu, Yi-Hsiang; Sangkuhl, Katrin; Jenkins, Gregory; Whaley, Ryan M.; Barman, Poulami; Batzler, Anthony; Altman, Russ B.; Arolt, Volker; Brockmöller, Jürgen; Chen, Chia-Hui; Domschke, Katharina; Hall-Flavin, Daniel K.; Hong, Chen-Jee; Illi, Ari; Ji, Yuan; Kampman, Olli; Kinoshita, Toshihiko; Leinonen, Esa; Liou, Ying-Jay; Mushiroda, Taisei; Nonen, Shinpei; Skime, Michelle K.; Wang, Liewei; Kato, Masaki; Liu, Yu-Li; Praphanphoj, Verayuth; Stingl, Julia C.; Bobo, William V.; Tsai, Shih-Jen; Kubo, Michiaki; Klein, Teri E.; Weinshilboum, Richard M.; Biernacka, Joanna M.; Baune, Bernhard T.

2018-01-01

Studies reported a strong genetic correlation between the Big Five personality traits and major depressive disorder (MDD). Moreover, personality traits are thought to be associated with response to antidepressants treatment that might partly be mediated by genetic factors. In this study, we examined whether polygenic scores (PGSs) derived from the Big Five personality traits predict treatment response and remission in patients with MDD who were prescribed selective serotonin reuptake inhibitors (SSRIs). In addition, we performed meta-analyses of genome-wide association studies (GWASs) on these traits to identify genetic variants underpinning the cross-trait polygenic association. The PGS analysis was performed using data from two cohorts: the Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS, n = 529) and the International SSRI Pharmacogenomics Consortium (ISPC, n = 865). The cross-trait GWAS meta-analyses were conducted by combining GWAS summary statistics on SSRIs treatment outcome and on the personality traits. The results showed that the PGS for openness and neuroticism were associated with SSRIs treatment outcomes at p trait GWAS meta-analyses, we identified eight loci associated with (a) SSRIs response and conscientiousness near YEATS4 gene and (b) SSRI remission and neuroticism eight loci near PRAG1, MSRA, XKR6, ELAVL2, PLXNC1, PLEKHM1, and BRUNOL4 genes. An assessment of a polygenic load for personality traits may assist in conjunction with clinical data to predict whether MDD patients might respond favorably to SSRIs. PMID:29559929
Programmatic implications of implementing the relational algebraic capacitated location (RACL algorithm outcomes on the allocation of laboratory sites, test volumes, platform distribution and space requirements

Directory of Open Access Journals (Sweden)

Naseem Cassim

2017-02-01

Full Text Available Introduction: CD4 testing in South Africa is based on an integrated tiered service delivery model that matches testing demand with capacity. The National Health Laboratory Service has predominantly implemented laboratory-based CD4 testing. Coverage gaps, over-/under-capacitation and optimal placement of point-of-care (POC testing sites need investigation. Objectives: We assessed the impact of relational algebraic capacitated location (RACL algorithm outcomes on the allocation of laboratory and POC testing sites. Methods: The RACL algorithm was developed to allocate laboratories and POC sites to ensure coverage using a set coverage approach for a defined travel time (T. The algorithm was repeated for three scenarios (A: T = 4; B: T = 3; C: T = 2 hours. Drive times for a representative sample of health facility clusters were used to approximate T. Outcomes included allocation of testing sites, Euclidian distances and test volumes. Additional analysis included platform distribution and space requirement assessment. Scenarios were reported as fusion table maps. Results: Scenario A would offer a fully-centralised approach with 15 CD4 laboratories without any POC testing. A significant increase in volumes would result in a four-fold increase at busier laboratories. CD4 laboratories would increase to 41 in scenario B and 61 in scenario C. POC testing would be offered at two sites in scenario B and 20 sites in scenario C. Conclusion: The RACL algorithm provides an objective methodology to address coverage gaps through the allocation of CD4 laboratories and POC sites for a given T. The algorithm outcomes need to be assessed in the context of local conditions.
Hanford Site groundwater monitoring: Setting, sources and methods

International Nuclear Information System (INIS)

Hartman, M.J.

2000-01-01

Groundwater monitoring is conducted on the Hanford Site to meet the requirements of the Resource Conservation and Recovery Act of 1976 (RCRA); Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA); U.S. Department of Energy (DOE) orders; and the Washington Administrative Code. Results of monitoring are published annually (e.g., PNNL-11989). To reduce the redundancy of these annual reports, background information that does not change significantly from year to year has been extracted from the annual report and published in this companion volume. This report includes a description of groundwater monitoring requirements, site hydrogeology, and waste sites that have affected groundwater quality or that require groundwater monitoring. Monitoring networks and methods for sampling, analysis, and interpretation are summarized. Vadose zone monitoring methods and statistical methods also are described. Whenever necessary, updates to information contained in this document will be published in future groundwater annual reports
Hanford Site groundwater monitoring: Setting, sources and methods

Energy Technology Data Exchange (ETDEWEB)

M.J. Hartman

2000-04-11

Groundwater monitoring is conducted on the Hanford Site to meet the requirements of the Resource Conservation and Recovery Act of 1976 (RCRA); Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA); U.S. Department of Energy (DOE) orders; and the Washington Administrative Code. Results of monitoring are published annually (e.g., PNNL-11989). To reduce the redundancy of these annual reports, background information that does not change significantly from year to year has been extracted from the annual report and published in this companion volume. This report includes a description of groundwater monitoring requirements, site hydrogeology, and waste sites that have affected groundwater quality or that require groundwater monitoring. Monitoring networks and methods for sampling, analysis, and interpretation are summarized. Vadose zone monitoring methods and statistical methods also are described. Whenever necessary, updates to information contained in this document will be published in future groundwater annual reports.
Department of Energy – Office of Science Pacific Northwest Site Office Environmental Monitoring Plan for the DOE-SC PNNL Site

Energy Technology Data Exchange (ETDEWEB)

Snyder, Sandra F.; Meier, Kirsten M.; Barnett, J. Matthew; Bisping, Lynn E.; Poston, Ted M.; Rhoads, Kathleen

2011-12-21

The Pacific Northwest Site Office (PNSO) manages the contract for operations at the U.S. Depart¬ment of Energy Office of Science (DOE-SC) Pacific Northwest National Laboratory (PNNL) Site in Richland, Washington. Radiological operations at the DOE-SC PNNL Site expanded in 2010 with the completion of facilities at the Physical Sciences Facility. As a result of the expanded radiological work at the site, the Washington State Department of Health (WDOH) has required that offsite environmental surveillance be conducted as part of the PNNL Site Radioactive Air Emissions License. The environ¬mental monitoring and surveillance requirements of various orders, regulations, and guidance documents consider emission levels and subsequent risk of negative human and environmental impacts. This Environmental Monitoring Plan (EMP) describes air surveillance activities at the DOE-SC PNNL Site. The determination of offsite environmental surveillance needs evolved out of a Data Quality Objectives process (Barnett et al. 2010) and Implementation Plan (Snyder et al. 2010). The entire EMP is a compilation of several documents, which include the Main Document (this text), Attachment 1: Sampling and Analysis Plan, Attachment 2: Data Management Plan, and Attachment 3: Dose Assessment Guidance.
State of Nevada comments on the US Department of Energy site characterization plan, Yucca Mountain site, Nevada

International Nuclear Information System (INIS)

1989-09-01

In December 1988, the US Department of Energy issued a Site Characterization Plan (SCP) for the Yucca Mountain site, as required by Section 113 of the Nuclear Waste Policy Act of 1982 (NWPA). The purpose of site characterization is to develop sufficient information to support a determination of the suitability, or lack of suitability of the site to safely isolate high-level radioactive waste with reasonable certainty for thousands of years. The purpose of the Site Characterization Plan is to describe plans for obtaining sufficient information about the site, plans for mitigation of any adverse impacts occurring from site characterization activities, and plans for decontamination and decommissioning of the site if it is determined not to be suitable for a repository. Part I presents an overview of the State's comments. The overview takes the form of general concerns and comments organized by specific areas of concern. The overview does not follow the format of the SCP
Description of the Northwest hazardous waste site data base and preliminary analysis of site characteristics

International Nuclear Information System (INIS)

Woodruff, D.L.; Hartz, K.E.; Triplett, M.B.

1988-08-01

The Northwest Hazardous Waste RD and D Center (the Center) conducts research, development, and demonstration (RD and D) activities for hazardous and radioactive mixed-waste technologies applicable to remediating sites in the states of Idaho, Montana, Oregon, and Washington. To properly set priorities for these RD and D activities and to target development efforts it is necessary to understand the nature of the sites requiring remediation. A data base of hazardous waste site characteristics has been constructed to facilitate this analysis. The data base used data from EPA's Region X Comprehensive Environmental Response, Compensation, and Liability Information System (CERCLIS) and from Preliminary Assessment/Site Investigation (PA/SI) forms for sites in Montana. The Center's data base focuses on two sets of sites--those on the National Priorities List (NPL) and other sites that are denoted as ''active'' CERCLIS sites. Active CERCLIS sites are those sites that are undergoing active investigation and analysis. The data base contains information for each site covering site identification and location, type of industry associated with the site, waste categories present (e.g., heavy metals, pesticides, etc.), methods of disposal (e.g., tanks, drums, land, etc.), waste forms (e.g., liquid, solid, etc.), and hazard targets (e.g., surface water, groundwater, etc.). As part of this analysis, the Northwest region was divided into three geographic subregions to identify differences in disposal site characteristics within the Northwest. 2 refs., 18 figs., 5 tabs
Burn site groundwater interim measures work plan.

Energy Technology Data Exchange (ETDEWEB)

Witt, Jonathan L. (North Wind, Inc., Idaho Falls, ID); Hall, Kevin A. (North Wind, Inc., Idaho Falls, ID)

2005-05-01

This Work Plan identifies and outlines interim measures to address nitrate contamination in groundwater at the Burn Site, Sandia National Laboratories/New Mexico. The New Mexico Environment Department has required implementation of interim measures for nitrate-contaminated groundwater at the Burn Site. The purpose of interim measures is to prevent human or environmental exposure to nitrate-contaminated groundwater originating from the Burn Site. This Work Plan details a summary of current information about the Burn Site, interim measures activities for stabilization, and project management responsibilities to accomplish this purpose.
On-Site Detection as a Countermeasure to Chemical Warfare/Terrorism.

Science.gov (United States)

Seto, Y

2014-01-01

On-site monitoring and detection are necessary in the crisis and consequence management of wars and terrorism involving chemical warfare agents (CWAs) such as sarin. The analytical performance required for on-site detection is mainly determined by the fatal vapor concentration and volatility of the CWAs involved. The analytical performance for presently available on-site technologies and commercially available on-site equipment for detecting CWAs interpreted and compared in this review include: classical manual methods, photometric methods, ion mobile spectrometry, vibrational spectrometry, gas chromatography, mass spectrometry, sensors, and other methods. Some of the data evaluated were obtained from our experiments using authentic CWAs. We concluded that (a) no technologies perfectly fulfill all of the on-site detection requirements and (b) adequate on-site detection requires (i) a combination of the monitoring-tape method and ion-mobility spectrometry for point detection and (ii) a combination of the monitoring-tape method, atmospheric pressure chemical ionization mass spectrometry with counterflow introduction, and gas chromatography with a trap and special detectors for continuous monitoring. The basic properties of CWAs, the concept of on-site detection, and the sarin gas attacks in Japan as well as the forensic investigations thereof, are also explicated in this article. Copyright © 2014 Central Police University.
Nevada National Security Site Waste Acceptance Criteria

Energy Technology Data Exchange (ETDEWEB)

NSTec Environmental Management

2010-09-03

This document establishes the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office (NNSA/NSO) Nevada National Security Site Waste Acceptance Criteria (NNSSWAC). The NNSSWAC provides the requirements, terms, and conditions under which the Nevada National Security Site (NNSS) will accept low-level radioactive waste and mixed low-level waste for disposal. The NNSSWAC includes requirements for the generator waste certification program, characterization, traceability, waste form, packaging, and transfer. The criteria apply to radioactive waste received at the NNSS Area 3 and Area 5 Radioactive Waste Management Complex for disposal. The NNSA/NSO and support contractors are available to assist you in understanding or interpreting this document. For assistance, please call the NNSA/NSO Waste Management Project at (702) 295-7063 or fax to (702) 295-1153.
Nevada National Security Site Waste Acceptance Criteria

International Nuclear Information System (INIS)

2010-01-01

This document establishes the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office (NNSA/NSO) Nevada National Security Site Waste Acceptance Criteria (NNSSWAC). The NNSSWAC provides the requirements, terms, and conditions under which the Nevada National Security Site (NNSS) will accept low-level radioactive waste and mixed low-level waste for disposal. The NNSSWAC includes requirements for the generator waste certification program, characterization, traceability, waste form, packaging, and transfer. The criteria apply to radioactive waste received at the NNSS Area 3 and Area 5 Radioactive Waste Management Complex for disposal. The NNSA/NSO and support contractors are available to assist you in understanding or interpreting this document. For assistance, please call the NNSA/NSO Waste Management Project at (702) 295-7063 or fax to (702) 295-1153.

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