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Sample records for mediates cerebellar long-term

  1. Propofol effects on cerebellar long-term depression.

    PubMed

    Lee, Kwan Young; Kim, Young Im; Kim, Se Hoon; Park, Hyung Seo; Park, Youn Joon; Ha, Myung Sook; Jin, Yunju; Kim, Dong Kwan

    2015-11-16

    Propofol is an intravenously administered anesthetic that induces γ-aminobutyric acid-mediated inhibition in the central nervous system. It has been implicated in prolonged movement disorders. Since the cerebellum is important for motor coordination and learning, we investigated the potential effects of propofol on cerebellar circuitry. Using the whole-cell patch-clamp technique in Wister rat cerebellar slices, we demonstrated that propofol administration impaired long-term depression from the parallel fiber (PF) to Purkinje cell (PC) synapses (PF-LTD). Also, propofol reduced metabotropic glutamate receptor 1 (mGluR1)-mediated and group I mGluR agonist-induced slow currents in PCs. These results suggest that the propofol-induced PF-LTD impairment may be related to an alteration in mGluR1 signaling, which is essential to motor learning.

  2. Inhibition promotes long-term potentiation at cerebellar excitatory synapses

    PubMed Central

    Binda, F.; Dorgans, K.; Reibel, S.; Sakimura, K.; Kano, M.; Poulain, B.; Isope, P.

    2016-01-01

    The ability of the cerebellar cortex to learn from experience ensures the accuracy of movements and reflex adaptation, processes which require long-term plasticity at granule cell (GC) to Purkinje neuron (PN) excitatory synapses. PNs also receive GABAergic inhibitory inputs via GCs activation of interneurons; despite the involvement of inhibition in motor learning, its role in long-term plasticity is poorly characterized. Here we reveal a functional coupling between ionotropic GABAA receptors and low threshold CaV3 calcium channels in PNs that sustains calcium influx and promotes long-term potentiation (LTP) at GC to PN synapses. High frequency stimulation induces LTP at GC to PN synapses and CaV3-mediated calcium influx provided that inhibition is intact; LTP is mGluR1, intracellular calcium store and CaV3 dependent. LTP is impaired in CaV3.1 knockout mice but it is nevertheless recovered by strengthening inhibitory transmission onto PNs; promoting a stronger hyperpolarization via GABAA receptor activation leads to an enhanced availability of an alternative Purkinje-expressed CaV3 isoform compensating for the lack of CaV3.1 and restoring LTP. Accordingly, a stronger hyperpolarization also restores CaV3-mediated calcium influx in PNs from CaV3.1 knockout mice. We conclude that by favoring CaV3 channels availability inhibition promotes LTP at cerebellar excitatory synapses. PMID:27641070

  3. Inhibition promotes long-term potentiation at cerebellar excitatory synapses.

    PubMed

    Binda, F; Dorgans, K; Reibel, S; Sakimura, K; Kano, M; Poulain, B; Isope, P

    2016-01-01

    The ability of the cerebellar cortex to learn from experience ensures the accuracy of movements and reflex adaptation, processes which require long-term plasticity at granule cell (GC) to Purkinje neuron (PN) excitatory synapses. PNs also receive GABAergic inhibitory inputs via GCs activation of interneurons; despite the involvement of inhibition in motor learning, its role in long-term plasticity is poorly characterized. Here we reveal a functional coupling between ionotropic GABAA receptors and low threshold CaV3 calcium channels in PNs that sustains calcium influx and promotes long-term potentiation (LTP) at GC to PN synapses. High frequency stimulation induces LTP at GC to PN synapses and CaV3-mediated calcium influx provided that inhibition is intact; LTP is mGluR1, intracellular calcium store and CaV3 dependent. LTP is impaired in CaV3.1 knockout mice but it is nevertheless recovered by strengthening inhibitory transmission onto PNs; promoting a stronger hyperpolarization via GABAA receptor activation leads to an enhanced availability of an alternative Purkinje-expressed CaV3 isoform compensating for the lack of CaV3.1 and restoring LTP. Accordingly, a stronger hyperpolarization also restores CaV3-mediated calcium influx in PNs from CaV3.1 knockout mice. We conclude that by favoring CaV3 channels availability inhibition promotes LTP at cerebellar excitatory synapses. PMID:27641070

  4. Inhibition promotes long-term potentiation at cerebellar excitatory synapses.

    PubMed

    Binda, F; Dorgans, K; Reibel, S; Sakimura, K; Kano, M; Poulain, B; Isope, P

    2016-09-19

    The ability of the cerebellar cortex to learn from experience ensures the accuracy of movements and reflex adaptation, processes which require long-term plasticity at granule cell (GC) to Purkinje neuron (PN) excitatory synapses. PNs also receive GABAergic inhibitory inputs via GCs activation of interneurons; despite the involvement of inhibition in motor learning, its role in long-term plasticity is poorly characterized. Here we reveal a functional coupling between ionotropic GABAA receptors and low threshold CaV3 calcium channels in PNs that sustains calcium influx and promotes long-term potentiation (LTP) at GC to PN synapses. High frequency stimulation induces LTP at GC to PN synapses and CaV3-mediated calcium influx provided that inhibition is intact; LTP is mGluR1, intracellular calcium store and CaV3 dependent. LTP is impaired in CaV3.1 knockout mice but it is nevertheless recovered by strengthening inhibitory transmission onto PNs; promoting a stronger hyperpolarization via GABAA receptor activation leads to an enhanced availability of an alternative Purkinje-expressed CaV3 isoform compensating for the lack of CaV3.1 and restoring LTP. Accordingly, a stronger hyperpolarization also restores CaV3-mediated calcium influx in PNs from CaV3.1 knockout mice. We conclude that by favoring CaV3 channels availability inhibition promotes LTP at cerebellar excitatory synapses.

  5. Cannabinoids decrease excitatory synaptic transmission and impair long-term depression in rat cerebellar Purkinje cells.

    PubMed

    Lévénés, C; Daniel, H; Soubrié, P; Crépel, F

    1998-08-01

    1. CB-1 cannabinoid receptors are strongly expressed in the molecular layer of the cerebellar cortex. We have analysed, in patch-clamped Purkinje cells (PCs) in rat cerebellar slices, the effect of the selective CB-1 agonists WIN55,212-2 and CP55,940 and of the selective CB-1 antagonist SR141716-A on excitatory synaptic transmission and synaptic plasticity. 2. Bath application of both agonists markedly depressed parallel fibre (PF) EPSCs. This effect was reversed by SR141716-A. In contrast, responses of PCs to ionophoretic application of glutamate were not affected by WIN55, 212-2. 3. The coefficient of variation and the paired-pulse facilitation of these PF-mediated EPSCs increased in the presence of WIN55,212-2. 4. WIN55,212-2 decreased the frequency of miniature EPSCs and of asynchronous synaptic events evoked in the presence of strontium in the bath, but did not affect their amplitude. 5. WIN55, 212-2 did not change the excitability of PFs. 6. WIN55,212-2 impaired long-term depression induced by pairing protocols in PCs. This effect was antagonized by SR141716-A. The same impairment of LTD was produced by 2-chloroadenosine, a compound that decreases the probability of release of glutamate at PF-PC synapses. 7. The present study demonstrates that cannabinoids inhibit synaptic transmission at PF-PC synapses by decreasing the probability of release of glutamate, and thereby impair LTD. These two effects might represent a plausible cellular mechanism underlying cerebellar dysfunction caused by cannabinoids.

  6. Long-term supratentorial brain structure and cognitive function following cerebellar tumour resections in childhood.

    PubMed

    Moberget, T; Andersson, S; Lundar, T; Due-Tønnessen, B J; Heldal, A; Endestad, T; Westlye, L T

    2015-03-01

    The cerebellum is connected to extensive regions of the cerebrum, and cognitive deficits following cerebellar lesions may thus be related to disrupted cerebello-cerebral connectivity. Moreover, early cerebellar lesions could affect distal brain development, effectively inducing long-term changes in brain structure and cognitive function. Here, we characterize supratentorial brain structure and cognitive function in 20 adult patients treated for cerebellar tumours in childhood (mean age at surgery: 7.1 years) and 26 matched controls. Relative to controls, patients showed reduced cognitive function and increased grey matter density in bilateral cingulum, left orbitofrontal cortex and the left hippocampus. Within the patient group, increased grey matter density in these regions was associated with decreased performance on tests of processing speed and executive function. Further, diffusion tensor imaging revealed widespread alterations in white matter microstructure in patients. While current ventricle volume (an index of previous hydrocephalus severity it patients) was associated with grey matter density and white matter microstructure in patients, this could only partially account for the observed group differences in brain structure and cognitive function. In conclusion, our results show distal effects of cerebellar lesions on cerebral integrity and wiring, likely caused by a combination of neurodegenerative processes and perturbed neurodevelopment.

  7. Involvement of presynaptic N-methyl-D-aspartate receptors in cerebellar long-term depression.

    PubMed

    Casado, Mariano; Isope, Philippe; Ascher, Philippe

    2002-01-01

    At the cerebellar synapses between parallel fibers (PFs) and Purkinje cells (PCs), long-term depression (LTD) of the excitatory synaptic current has been assumed to be independent of the N-methyl-D-aspartate (NMDA) receptor activation because PCs lack NMDA receptors. However, we now report that LTD is suppressed by NMDA receptor antagonists that act on presynaptic NMDA receptors of the PFs. This effect is still observed when the input is restricted to a single fiber. Therefore, LTD does not require the spatial integration of multiple inputs. In contrast, it involves a temporal integration, since reliable LTD induction requires the PFs to fire two action potentials in close succession. This implies that LTD will selectively depress the response to a burst of presynaptic action potentials.

  8. Rabbit cerebellar slice analysis of long-term depression and its role in classical conditioning.

    PubMed

    Schreurs, B G; Alkon, D L

    1993-12-24

    Cerebellar long-term depression (LTD) has been proposed as a mechanism underlying classical conditioning of the rabbit nictitating membrane/eyelid response (NMR). However, LTD has only been obtained reliably when (1) cerebellar slices are bathed in GABA antagonists which abolish disynaptic inhibitory post synaptic potentials, and (2) the temporal sequence of stimulation used in slice or intact preparations is the opposite of that used in classical conditioning. Based on intradendritic Purkinje cell recordings obtained from rabbit cerebellar slices, we report that stimulation of climbing fibers and then parallel fibers in the presence of the GABA antagonist, bicuculline, produced significant depression of parallel fiber excitatory post synaptic potential (epsp) amplitude that continued to increase for at least 20 min after stimulation. However, application of the same stimulation protocol without GABA antagonists produced a brief depression of parallel fiber epsps that disappeared within minutes. Activation of parallel fibers and then climbing fibers in an order opposite to the LTD-producing sequence (i.e. a classical conditioning-like order) produced a brief depression that dissipated quickly. Stimulation of parallel fibers alone produced a small, slowly developing potentiation, but stimulation of parallel fibers during depolarization-induced local dendritic calcium spikes produced significant depression almost immediately which then declined slowly to more modest levels. Finally, stimulation of parallel fibers at frequencies used in in vivo parallel fiber-climbing fiber stimulation experiments (e.g. 100 Hz) produced an immediate and profound long-lasting epsp depression. The depression occurred, however, whether parallel and climbing fibers were stimulated separately (unpaired) or in a classical conditioning-like protocol (paired) where parallel fiber stimulation coterminated with climbing fiber stimulation (10 Hz).(ABSTRACT TRUNCATED AT 250 WORDS)

  9. A Computational Model for the AMPA Receptor Phosphorylation Master Switch Regulating Cerebellar Long-Term Depression.

    PubMed

    Gallimore, Andrew R; Aricescu, A Radu; Yuzaki, Michisuke; Calinescu, Radu

    2016-01-01

    The expression of long-term depression (LTD) in cerebellar Purkinje cells results from the internalisation of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) from the postsynaptic membrane. This process is regulated by a complex signalling pathway involving sustained protein kinase C (PKC) activation, inhibition of serine/threonine phosphatase, and an active protein tyrosine phosphatase, PTPMEG. In addition, two AMPAR-interacting proteins-glutamate receptor-interacting protein (GRIP) and protein interacting with C kinase 1 (PICK1)-regulate the availability of AMPARs for trafficking between the postsynaptic membrane and the endosome. Here we present a new computational model of these overlapping signalling pathways. The model reveals how PTPMEG cooperates with PKC to drive LTD expression by facilitating the effect of PKC on the dissociation of AMPARs from GRIP and thus their availability for trafficking. Model simulations show that LTD expression is increased by serine/threonine phosphatase inhibition, and negatively regulated by Src-family tyrosine kinase activity, which restricts the dissociation of AMPARs from GRIP under basal conditions. We use the model to expose the dynamic balance between AMPAR internalisation and reinsertion, and the phosphorylation switch responsible for the perturbation of this balance and for the rapid plasticity initiation and regulation. Our model advances the understanding of PF-PC LTD regulation and induction, and provides a validated extensible platform for more detailed studies of this fundamental synaptic process. PMID:26807999

  10. Pairing of pre- and postsynaptic activities in cerebellar Purkinje cells induces long-term changes in synaptic efficacy in vitro.

    PubMed

    Crepel, F; Jaillard, D

    1991-01-01

    1. An in vitro slice preparation of rat cerebellar cortex was used to analyse long-lasting modifications of synaptic transmission at parallel fibre (PF)-Purkinje cell (PC) synapses. These use-dependent changes were induced by pairing PF-mediated EPSPs evoked at low frequency (1 Hz) with different levels of membrane polarization (or bioelectrical activities) of PCs for 15 min. 2. Experiments were performed on forty-eight PCs recorded intracellularly in a conventional perfused chamber, and in fifty other cells maintained in a static chamber either in the presence (n = 21) or in the absence (n = 29) of 400 nM-phorbol 12,13-dibutyrate (PDBu). 3. In these three experimental conditions, PF-mediated EPSPs were always measured on PCs maintained at a holding potential of -75 mV, and further hyperpolarized by constant hyperpolarizing pulses. This allowed us both to test the input resistance of PCs and to avoid their firing during PF-mediated EPSPs. 4. In all cells retained for the present study, latencies of PF-mediated EPSPs evoked at 0.2 Hz were stable during the pre-pairing period, and the same was true for their amplitude and time course. 5. In the perfused chamber, pairing of PF-mediated EPSPs with the same hyperpolarization of PCs as that used for measurements of synaptic responses had no effect on these EPSPs in 30% of PCs. It induced long-term depression (LTD) and long-term potentiation (LTP) in 23 and 47% of the tested cells respectively (n = 17). 6. In the perfused chamber, pairing of PF-mediated EPSPs with moderate depolarization of PCs (n = 19) giving rise to a sustained firing of sodium spikes significantly favoured the appearance of LTP as compared to the previous pairing protocol. However, there were still 27 and 15% of cells which showed no modification and LTD respectively. 7. In contrast, pairing of PF-mediated EPSPs with calcium (Ca2+) spikes evoked by strong depolarization of PCs (n = 12) led to LTD of synaptic transmission in nearly half of the tested

  11. Long-term climbing fibre activity induces transcription of microRNAs in cerebellar Purkinje cells.

    PubMed

    Barmack, Neal H; Qian, Zuyuan; Yakhnitsa, Vadim

    2014-09-26

    Synaptic activation of central neurons is often evoked by electrical stimulation leading to post-tetanic potentiation, long-term potentiation or long-term depression. Even a brief electrical tetanus can induce changes in as many as 100 proteins. Since climbing fibre activity is often associated with cerebellar behavioural plasticity, we used horizontal optokinetic stimulation (HOKS) to naturally increase synaptic input to floccular Purkinje cells in mice for hours, not minutes, and investigated how this activity influenced the transcription of microRNAs, small non-coding nucleotides that reduce transcripts of multiple, complementary mRNAs. A single microRNA can reduce the translation of as many as 30 proteins. HOKS evoked increases in 12 microRNA transcripts in floccular Purkinje cells. One of these microRNAs, miR335, increased 18-fold after 24 h of HOKS. After HOKS stopped, miR335 transcripts decayed with a time constant of approximately 2.5 h. HOKS evoked a 28-fold increase in pri-miR335 transcripts compared with an 18-fold increase in mature miR335 transcripts, confirming that climbing fibre-evoked increases in miR335 could be attributed to increases in transcription. We used three screens to identify potential mRNA targets for miR335 transcripts: (i) nucleotide complementarity, (ii) detection of increased mRNAs following microinjection of miR335 inhibitors into the cerebellum, and (iii) detection of decreased mRNAs following HOKS. Two genes, calbindin and 14-3-3-θ, passed these screens. Transfection of N2a cells with miR335 inhibitors or precursors inversely regulated 14-3-3-θ transcripts. Immunoprecipitation of 14-3-3-θ co-immunoprecipitated PKC-γ and GABAAγ2. Knockdown of either 14-3-3-θ or PKC-γ decreased the serine phosphorylation of GABAAγ2, suggesting that 14-3-3-θ and PKC-γ under the control of miR335 homeostatically regulate the phosphorylation and insertion of GABAAγ2 into the Purkinje cell post-synaptic membrane. PMID:25135969

  12. Hippocampal long-term potentiation in adult Lurcher mutant mice: effect of embryonic cerebellar graft and motor training.

    PubMed

    Barcal, J; Cendelín, J; Vozeh, F

    2008-01-01

    Possible effect of trophic factors from embryonic cerebellar graft transplanted in adult Lurcher mutant mice on LTP as electrophysiological marker of learning and memory process was studied. Also the combination of the transplantation and long-term forced motor training was investigated. An evaluation of LTP ability in four animal groups (transplanted, sham-operated, with and without forced motor activity) and comparison among them showed the highest LTP improvement in the group with combination of both influences (ie. transplantation and motor training).

  13. Presynaptic and postsynaptic effects of nitric oxide donors at synapses between parallel fibres and Purkinje cells: involvement in cerebellar long-term depression.

    PubMed

    Blond, O; Daniel, H; Otani, S; Jaillard, D; Crépel, F

    1997-04-01

    The involvement of nitric oxide in cerebellar long-term depression is widely accepted. Nevertheless, its site of action has remained unclear. Using the coefficient of variation method applied to the parallel fibre-mediated excitatory postsynaptic currents recorded in voltage-clamped Purkinje cells. this study shows that nitric oxide donors exert their effects at both presynaptic and postsynaptic sites. The presynaptic depression fades away with washout of nitric oxide donors and is mediated through the potentiation of A1 adenosine receptors. Part of this effect may be due to non-nitric oxide products. In contrast, long-term depression induced by nitric oxide donors is expressed at a postsynaptic site, and is independent of the ADP ribosylation. Long-term depression induced by pairing is also expressed mainly at a postsynaptic level. These results establish that long-term depression at the parallel fibre Purkinje cell synapse induced by pairing of nitric oxide donors is mostly expressed at a postsynaptic site.

  14. Enhanced AMPA Receptor Function Promotes Cerebellar Long-Term Depression Rather than Potentiation

    ERIC Educational Resources Information Center

    van Beugen, Boeke J.; Qiao, Xin; Simmons, Dana H.; De Zeeuw, Chris I.; Hansel, Christian

    2014-01-01

    Ampakines are allosteric modulators of AMPA receptors that facilitate hippocampal long-term potentiation (LTP) and learning, and have been considered for the treatment of cognition and memory deficits. Here, we show that the ampakine CX546 raises the amplitude and slows the decay time of excitatory postsynaptic currents (EPSCs) at cerebellar…

  15. Psychosocial Mediators of Long-Term Abstinence Following Smoking Cessation.

    ERIC Educational Resources Information Center

    Horwitz, Michael B.; And Others

    It is well known that many smokers who quit during cessation programs relapse soon after leaving treatment. To investigate the relationship of health locus of control, social support, nonsmoking areas, and objecting to another person's smoking to relapse and long-term maintenance of nonsmoking, male (N=70) and female (N=149) subjects participated…

  16. The effect of gallium nitride on long-term culture induced aging of neuritic function in cerebellar granule cells.

    PubMed

    Chen, Chi-Ruei; Young, Tai-Horng

    2008-04-01

    Gallium nitride (GaN) has been developed for a variety of microelectronic and optical applications due to its unique electric property and chemical stability. In the present study, n-type and p-type GaN were used as substrates to culture cerebellar granule neurons to examine the effect of GaN on cell response for a long-term culture period. It was found that GaN could rapidly induce cultured neurons to exhibit a high phosphorylated Akt level after 20h of incubation. It was assumed that the anti-apoptotic effect of Akt phosphorylation could be correlated with cell survival, neurite growth and neuronal function for up to 35 days of incubation. Morphological studies showed GaN induced larger neuronal aggregates and neurite fasciculation to exhibit a dense fiber network after 8 days of incubation. Western blot analysis and immunocytochemical characterization showed that GaN still exhibited the expression of neurite growth and function, such as high levels of GAP-43, synapsin I and synaptophysin even after 35 days of incubation. In addition, survival of cerebellar granule neurons on GaN was improved by the analysis of lactate dehydrogenase (LDH) release from damaged cells. These results indicated that neuronal connections were formed on GaN by a gradual process from Akt activation and cell aggregation to develop neurite growth, fasciculation and function. Therefore, GaN offers a good model system to identify a well-characterized pattern of neuronal behavior for a long-term culture period, consistent with the development of a neurochip requiring the integration of biological system and semiconductor material.

  17. Long-term potentiation of inhibitory synaptic transmission onto cerebellar Purkinje neurons contributes to adaptation of vestibulo-ocular reflex.

    PubMed

    Tanaka, Shinsuke; Kawaguchi, Shin-Ya; Shioi, Go; Hirano, Tomoo

    2013-10-23

    Synaptic plasticity in the cerebellum is thought to contribute to motor learning. In particular, long-term depression (LTD) at parallel fiber (PF) to Purkinje neuron (PN) excitatory synapses has attracted much attention of neuroscientists as a primary cellular mechanism for motor learning. In contrast, roles of plasticity at cerebellar inhibitory synapses in vivo remain unknown. Here, we have investigated the roles of long-lasting enhancement of transmission at GABAergic synapses on a PN that is known as rebound potentiation (RP). Previous studies demonstrated that binding of GABAA receptor with GABAA receptor-associated protein (GABARAP) is required for RP, and that a peptide that blocks this binding suppresses RP induction. To address the functional roles of RP, we generated transgenic mice that express this peptide fused to a fluorescent protein selectively in PNs using the PN-specific L7 promoter. These mice failed to show RP, although they showed no changes in the basal amplitude or frequency of miniature IPSCs. The transgenic mice also showed no abnormality in gross cerebellar morphology, LTD, or other excitatory synaptic properties, or intrinsic excitability of PNs. Next, we attempted to evaluate their motor control and learning ability by examining reflex eye movements. The basal dynamic properties of the vestibulo-ocular reflex and optokinetic response, and adaptation of the latter, were normal in the transgenic mice. In contrast, the transgenic mice showed defects in the adaptation of vestibulo-ocular reflex, a model paradigm of cerebellum-dependent motor learning. These results together suggest that RP contributes to a certain type of motor learning.

  18. The Mediating Role of Insight for Long-Term Improvements in Psychodynamic Therapy

    ERIC Educational Resources Information Center

    Johansson, Paul; Hoglend, Per; Ulberg, Randi; Amlo, Svein; Marble, Alice; Bogwald, Kjell-Petter; Sorbye, Oystein; Sjaastad, Mary Cosgrove; Heyerdahl, Oscar

    2010-01-01

    Objective: According to psychoanalytic theory, interpretation of transference leads to increased insight that again leads to improved interpersonal functioning over time. In this study, we performed a full mediational analysis to test whether insight gained during treatment mediates the long-term effects of transference interpretation in dynamic…

  19. Lgr4 protein deficiency induces ataxia-like phenotype in mice and impairs long term depression at cerebellar parallel fiber-Purkinje cell synapses.

    PubMed

    Guan, Xin; Duan, Yanhong; Zeng, Qingwen; Pan, Hongjie; Qian, Yu; Li, Dali; Cao, Xiaohua; Liu, Mingyao

    2014-09-19

    Cerebellar dysfunction causes ataxia characterized by loss of balance and coordination. Until now, the molecular and neuronal mechanisms of several types of inherited cerebellar ataxia have not been completely clarified. Here, we report that leucine-rich G protein-coupled receptor 4 (Lgr4/Gpr48) is highly expressed in Purkinje cells (PCs) in the cerebellum. Deficiency of Lgr4 leads to an ataxia-like phenotype in mice. Histologically, no obvious morphological changes were observed in the cerebellum of Lgr4 mutant mice. However, the number of PCs was slightly but significantly reduced in Lgr4(-/-) mice. In addition, in vitro electrophysiological analysis showed an impaired long term depression (LTD) at parallel fiber-PC (PF-PC) synapses in Lgr4(-/-) mice. Consistently, immunostaining experiments showed that the level of phosphorylated cAMP-responsive element-binding protein (Creb) was significantly decreased in Lgr4(-/-) PCs. Furthermore, treatment with forskolin, an adenylyl cyclase agonist, rescued phospho-Creb in PCs and reversed the impairment in PF-PC LTD in Lgr4(-/-) cerebellar slices, indicating that Lgr4 is an upstream regulator of Creb signaling, which is underlying PF-PC LTD. Together, our findings demonstrate for first time an important role for Lgr4 in motor coordination and cerebellar synaptic plasticity and provide a potential therapeutic target for certain types of inherited cerebellar ataxia. PMID:25063812

  20. Activation of protein kinase C induces a long-term depression of glutamate sensitivity of cerebellar Purkinje cells. An in vitro study.

    PubMed

    Crepel, F; Krupa, M

    1988-08-23

    In immature rat cerebellar slices in vitro, a long term depression (LTD) of the responses of Purkinje cells (PCs) to L-glutamate (Glu) was achieved in 30% of the recorded cells by simultaneous stimulation of the neurones by Glu and by climbing fibres (CFs). This effect was not observed for L-aspartate (Asp)-induced responses. Similarly, selective LTD of Glu-induced responses was obtained in 22% of the cells by pairing Glu applications with direct stimulation of the cells which elicited calcium spikes in these neurones. Finally, bath application of phorbol esters also induced a selective LTD of Glu-induced responses in all cells tested. These results suggest that protein kinase C is involved in cerebellar synaptic plasticity.

  1. Transient inhibition of the ERK pathway prevents cerebellar developmental defects and improves long-term motor functions in murine models of neurofibromatosis type 1

    PubMed Central

    Kim, Edward; Wang, Yuan; Kim, Sun-Jung; Bornhorst, Miriam; Jecrois, Emmanuelle S; Anthony, Todd E; Wang, Chenran; Li, Yi E; Guan, Jun-Lin; Murphy, Geoffrey G; Zhu, Yuan

    2014-01-01

    Individuals with neurofibromatosis type 1 (NF1) frequently exhibit cognitive and motor impairments and characteristics of autism. The cerebellum plays a critical role in motor control, cognition, and social interaction, suggesting that cerebellar defects likely contribute to NF1-associated neurodevelopmental disorders. Here we show that Nf1 inactivation during early, but not late stages of cerebellar development, disrupts neuronal lamination, which is partially caused by overproduction of glia and subsequent disruption of the Bergmann glia (BG) scaffold. Specific Nf1 inactivation in glutamatergic neuronal precursors causes premature differentiation of granule cell (GC) precursors and ectopic production of unipolar brush cells (UBCs), indirectly disrupting neuronal migration. Transient MEK inhibition during a neonatal window prevents cerebellar developmental defects and improves long-term motor performance of Nf1-deficient mice. This study reveals essential roles of Nf1 in GC/UBC migration by generating correct numbers of glia and controlling GC/UBC fate-specification/differentiation, identifying a therapeutic prevention strategy for multiple NF1-associcated developmental abnormalities. DOI: http://dx.doi.org/10.7554/eLife.05151.001 PMID:25535838

  2. Pairing-specific long-term depression of Purkinje cell excitatory postsynaptic potentials results from a classical conditioning procedure in the rabbit cerebellar slice.

    PubMed

    Schreurs, B G; Oh, M M; Alkon, D L

    1996-03-01

    1. Using a rabbit cerebellar slice preparation, we stimulated a classical conditioning procedure by stimulating parallel fiber inputs to Purkinje cells with the use of a brief, high-frequency train of eight constant-current pulses 80 ms before climbing fiber inputs to the same Purkinje cell were stimulated with the use of a brief, lower frequency train of three constant-current pulses. In all experiments, we assessed the effects of stimulation by measuring the peak amplitude of Purkinje cell excitatory postsynaptic potentials (EPSPs) to single parallel fiber test pulses. 2. Intradendritically recorded Purkinje cell EPSPs underwent a long-term (> 20 min) reduction in peak amplitude (30%) after paired stimulation of the parallel and climbing fibers but not after unpaired or parallel fiber alone stimulation. We call this phenomenon pairing-specific long-term depression (PSD). 3. Facilitation of the peak amplitude of a second EPSP elicited by a parallel fiber train occurred both before and after paired stimulation suggesting that the locus of depression was not presynaptic. Depression of the peak amplitude of a depolarizing response to focal application of glutamate following pairings of parallel and climbing fiber stimulation added support to a suggested postsynaptic locus of the PSD effect. 4. The application of aniracetam potentiated EPSP peak amplitude by 40%, but these values returned to baseline as a result of pairings. With the removal of aniracetam from the bath 20 min after pairings, normal levels of pairing-specific EPSP depression were observed, indicating that the effect did not result from direct desensitization of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid (AMPA) receptors. 5. Incubation of slices in the protein kinase inhibitor H-7 potentiated EPSP peak amplitudes slightly (9%), but peak amplitudes returned to baseline levels after pairings. The net reduction in EPSP peak amplitude of < 10% after pairings suggested that H-7 partially

  3. Interparental violence and children's long-term psychosocial adjustment: the mediating role of parenting practices.

    PubMed

    Gámez-Guadix, Manuel; Almendros, Carmen; Carrobles, José Antonio; Muñoz-Rivas, Marina

    2012-03-01

    The objectives of this study were: (a) to examine the direct and indirect relationships among witnessing interparental violence, parenting practices, and children's long-term psychosocial adjustment; (b) to analyze the possible gender differences in the relationships specified. The sample consisted of 1295 Spanish university students (M age = 21.21, SD = 4.04). We performed statistical analyses using structural equation modeling. The results showed that witnessing parental violence as a child is related to poor long-term psychosocial adjustment during the child's adult years. Furthermore, we found that parenting practices fully mediated the relation between witnessing interparental violence and the child's long-term adjustment. The multigroup analyses showed that most of the relations among the variables did not differ significantly by gender. However, the relation between harsh discipline and antisocial behavior was stronger for males, whereas the relation between harsh discipline and depressive symptoms was stronger for females. Finally, we discuss the implications of these findings for the clinicians and specialists who plan and develop intervention programs for populations at risk. PMID:22379705

  4. Postsynaptic long-term enhancement (LTE) by dopamine may be mediated by Ca2+ and calmodulin.

    PubMed

    Mochida, S; Libet, B

    1990-04-01

    Long-term enhancement (LTE), of postsynaptic slow depolarizing responses to a muscarinic agonist (MCh), follows a brief exposure of the rabbit superior cervical ganglion to another transmitter, dopamine (DA). Either reduction of external Ca2+ (to 1.0 mM or 0.2 mM) or presence of a specific calmodulin antagonist (calmidazolium at 5 microM) blocked DA induction of this LTE. However, unlike LTP in hippocampus, induction of LTE is not mediated by depolarization-dependent influx of Ca2+.

  5. Chronic Deep Cerebellar Stimulation Promotes Long-Term Potentiation, Microstructural Plasticity, and Reorganization of Perilesional Cortical Representation in a Rodent Model

    PubMed Central

    Cooperrider, Jessica; Furmaga, Havan; Plow, Ela; Park, Hyun-Joo; Chen, Zhihong; Kidd, Grahame; Baker, Kenneth B.; Gale, John T.

    2014-01-01

    Control over postinjury CNS plasticity is a major frontier of science that, if conquered, would open new avenues for treatment of neurological disorders. Here we investigate the functional, physiological, and structural changes in the cerebral cortex associated with chronic deep brain stimulation of the cerebellar output, a treatment approach that has been shown to improve postischemia motor recovery in a rodent model of cortical infarcts. Long–Evans rats were pretrained on the pasta-matrix retrieval task, followed by induction of focal cortical ischemia and implantation of a macroelectrode in the contralesional lateral cerebellar nucleus. Animals were assigned to one of three treatment groups pseudorandomly to balance severity of poststroke motor deficits: REGULAR stimulation, BURST stimulation, or SHAM. Treatment initiated 2 weeks post surgery and continued for 5 weeks. At the end, animals were randomly selected for perilesional intracortical microstimulation mapping and tissue sampling for Western blot analysis or contributed tissue for 3D electron microscopy. Evidence of enhanced cortical plasticity with therapeutically effective stimulation is shown, marked by greater perilesional reorganization in stimulation- treated animals versus SHAM. BURST stimulation was significantly effective for promoting distal forepaw cortical representation. Stimulation-treated animals showed a twofold increase in synaptic density compared with SHAM. In addition, treated animals demonstrated increased expression of synaptic markers of long-term potentiation and plasticity, including synaptophysin, NMDAR1, CaMKII, and PSD95. These findings provide a critical foundation of how deep cerebellar stimulation may guide plastic reparative reorganization after nonprogressive brain injury and indicate strong translational potential. PMID:24990924

  6. Long-term neurobehavioural impact of the postnatal environment in rats: manipulations, effects and mediating mechanisms.

    PubMed

    Pryce, Christopher R; Feldon, Joram

    2003-01-01

    The major characteristics of the postnatal environment of the rat pup are its mother and littermates. The pup, which is poorly developed at birth, matures rapidly in this environment, and regulates the behaviour and physiology of the dam and littermates, as well as vice versa. The study of the impact of the rat's postnatal environment on its long-term neurobehavioural development is of fundamental importance. In fact, it is one of the major examples--at the interface of the biological, social and medical sciences--of animal models for the study of the interaction between the environment and the genome in both the acute and chronic regulation of the phenotype. Specific experimental manipulations of the rat postnatal environment have been demonstrated to exert robust and marked effects on neurobiological, physiological and behavioural phenotypes in adulthood. In the present review we present some of the major findings, including some original data, and discuss what these existing data can tell us about the long-term neurobehavioural effects of the postnatal environment in rats, the external and internal mechanisms that mediate these effects, and the most appropriate directions for future basic and applied research in this area. PMID:12732223

  7. Long-Term Plasticity Mediated by mGluR1 at a Retinal Reciprocal Synapse

    PubMed Central

    Vigh, Jozsef; Li, Geng-Lin; Hull, Court; von Gersdorff, Henrique

    2013-01-01

    Summary The flow of information across the retina is controlled by reciprocal synapses between bipolar cell terminals and amacrine cells. However, the synaptic delays and properties of plasticity at these synapses are not known. Here we report that glutamate release from goldfish Mb-type bipolar cell terminals can trigger fast (delay of 2–3 ms) and transient GABAA IPSCs and a much slower and more sustained GABAC feedback. Synaptically released glutamate activated mGluR1 receptors on amacrine cells and, depending on the strength of presynaptic activity, potentiated subsequent feedback. This poststimulus enhancement of GABAergic feedback lasted for up to 10 min. This form of mGluR1-mediated long-term synaptic plasticity may provide retinal reciprocal synapses with adaptive capabilities. PMID:15882646

  8. Presynaptic long-term depression mediated by Gi/o-coupled receptors

    PubMed Central

    Atwood, Brady K.; Lovinger, David M.; Mathur, Brian N.

    2014-01-01

    Long-term depression (LTD) of the efficacy of synaptic transmission is now recognized as an important mechanism for regulation of information storage and control of actions, as well as synapse, neuron, and circuit development. Studies of LTD mechanisms have focused mainly on postsynaptic AMPA receptor trafficking. However, the focus has now expanded to include presynaptically expressed plasticity; the predominant form being initiated by presynaptically expressed Gi/o-coupled metabotropic receptor (Gi/o-GPCR) activation. Several forms of LTD involving activation of different presynaptic Gi/o-GPCRs as a “common pathway” are described. Here, we review the literature on presynaptic Gi/o-GPCR-mediated LTD, discuss known mechanisms, gaps in our knowledge, and evaluate if all Gi/o-GPCR are capable of inducing presynaptic LTD. PMID:25160683

  9. Reassessment of long-term depression in cerebellar Purkinje cells in mice carrying mutated GluA2 C terminus.

    PubMed

    Yamaguchi, Kazuhiko; Itohara, Shigeyoshi; Ito, Masao

    2016-09-01

    Long-term depression (LTD) of synaptic transmission from parallel fibers (PFs) to a Purkinje cell (PC) in the cerebellum has been considered to be a core mechanism of motor learning. Recently, however, discrepancies between LTD and motor learning have been reported in mice with a mutation that targeted the expression of PF-PC LTD by blocking AMPA-subtype glutamate receptor internalization regulated via the phosphorylation of AMPA receptors. In these mice, motor learning behavior was normal, but no PF-PC LTD was observed. We reexamined slices obtained from these GluA2 K882A and GluA2 Δ7 knockin mutants at 3-6 mo of age. The conventional protocols of stimulation did not induce LTD in these mutant mice, as previously reported, but surprisingly, LTD was induced using certain modified protocols. Such modifications involved increases in the number of PF stimulation (from one to two or five), replacement of climbing fiber stimulation with somatic depolarization (50 ms), filling a patch pipette with a Cs(+)-based solution, or extension of the duration of conjunction. We also found that intracellular infusion of a selective PKCα inhibitor (Gö6976) blocked LTD induction in the mutants, as in WT, suggesting that functional compensation occurred downstream of PKCα. The possibility that LTD in the mutants was caused by changes in membrane resistance, access resistance, or presynaptic property was excluded. The present results demonstrate that LTD is inducible by intensified conjunctive stimulations even in K882A and Δ7 mutants, indicating no contradiction against the LTD hypothesis of motor learning. PMID:27551099

  10. Reassessment of long-term depression in cerebellar Purkinje cells in mice carrying mutated GluA2 C terminus

    PubMed Central

    Yamaguchi, Kazuhiko; Itohara, Shigeyoshi; Ito, Masao

    2016-01-01

    Long-term depression (LTD) of synaptic transmission from parallel fibers (PFs) to a Purkinje cell (PC) in the cerebellum has been considered to be a core mechanism of motor learning. Recently, however, discrepancies between LTD and motor learning have been reported in mice with a mutation that targeted the expression of PF–PC LTD by blocking AMPA-subtype glutamate receptor internalization regulated via the phosphorylation of AMPA receptors. In these mice, motor learning behavior was normal, but no PF–PC LTD was observed. We reexamined slices obtained from these GluA2 K882A and GluA2 Δ7 knockin mutants at 3–6 mo of age. The conventional protocols of stimulation did not induce LTD in these mutant mice, as previously reported, but surprisingly, LTD was induced using certain modified protocols. Such modifications involved increases in the number of PF stimulation (from one to two or five), replacement of climbing fiber stimulation with somatic depolarization (50 ms), filling a patch pipette with a Cs+-based solution, or extension of the duration of conjunction. We also found that intracellular infusion of a selective PKCα inhibitor (Gö6976) blocked LTD induction in the mutants, as in WT, suggesting that functional compensation occurred downstream of PKCα. The possibility that LTD in the mutants was caused by changes in membrane resistance, access resistance, or presynaptic property was excluded. The present results demonstrate that LTD is inducible by intensified conjunctive stimulations even in K882A and Δ7 mutants, indicating no contradiction against the LTD hypothesis of motor learning. PMID:27551099

  11. Long-term effects of a universal family intervention: mediation through parent-adolescent conflict.

    PubMed

    Jensen, Michaeline R; Wong, Jessie J; Gonzales, Nancy A; Dumka, Larry E; Millsap, Roger; Coxe, Stefany

    2014-01-01

    This randomized trial of a family-focused preventive intervention for Mexican American middle schoolers examined internalizing, externalizing, and substance use outcomes in late adolescence, 5 years after completing the intervention. Parent-adolescent conflict was tested as a mediator of these effects. The role of parent and adolescent acculturation in these pathways was also examined. There were 494 seventh-grade adolescents and their primary female caregivers randomized to receive either a 9-week multicomponent intervention or a brief workshop control group. Assessments were conducted at pretest, 2-year follow-up (9th grade), and 5-year follow-up (when most participants were in the 12th grade). The Bridges program significantly reduced mother-adolescent conflict measured in the 9th grade, with conflict mediating program effects on internalizing and externalizing symptoms, adolescent substance use, and diagnosed internalizing disorder in late adolescence. Mother and child acculturation were both significantly predictive of late adolescence outcomes. Contrary to hypotheses, neither mother nor child acculturation emerged as a significant predictor of mother-adolescent conflict, and the interaction of mother and adolescent acculturation was similarly not related to mother-adolescent conflict. Intervention effects were largely consistent across different levels of acculturation. These findings provide support for the efficacy of family-focused intervention during early adolescence, both in reducing mental health problems and substance use in the long term and in impacting parent-adolescent conflict processes that appear to play an important role in the development of later adjustment problems. PMID:24730357

  12. Mediators of the Long-Term Impact of Child Sexual Abuse: Perceived Stigma, Betrayal, Powerlessness, and Self-Blame.

    ERIC Educational Resources Information Center

    Coffey, Patricia; And Others

    1996-01-01

    This study tested 192 women who had been sexually abused as children, to see if perceived stigma, betrayal, powerlessness, and self-blame mediated long-term effects of child sexual abuse. Levels of psychological distress experienced by adult survivors of abuse were found to be mediated by feelings of stigma and self-blame. (Author/PB)

  13. Intracellular correlates of acquisition and long-term memory of classical conditioning in Purkinje cell dendrites in slices of rabbit cerebellar lobule HVI.

    PubMed

    Schreurs, B G; Gusev, P A; Tomsic, D; Alkon, D L; Shi, T

    1998-07-15

    Intradendritic recordings in Purkinje cells from a defined area in parasaggital slices of cerebellar lobule HVI, obtained after rabbits were given either paired (classical conditioning) or explicitly unpaired (control) presentations of tone and periorbital electrical stimulation, were used to assess the nature and duration of conditioning-specific changes in Purkinje cell dendritic membrane excitability. We found a strong relationship between the level of conditioning and Purkinje cell dendritic membrane excitability after initial acquisition of the conditioned response. Moreover, conditioning-specific increases in Purkinje cell excitability were still present 1 month after classical conditioning. Although dendritically recorded membrane potential, input resistance, and amplitude of somatic and dendritic spikes were not different in cells from paired or control animals, the size of a potassium channel-mediated transient hyperpolarization was significantly smaller in cells from animals that received classical conditioning. In slices of lobule HVI obtained from naive rabbits, the conditioning-related increases in membrane excitability could be mimicked by application of potassium channel antagonist tetraethylammonium chloride, iberiotoxin, or 4-aminopyridine. However, only 4-aminopyridine was able to reduce the transient hyperpolarization. The pharmacological data suggest a role for potassium channels and, possibly, channels mediating an IA-like current, in learning-specific changes in membrane excitability. The conditioning-specific increase in Purkinje cell dendritic excitability produces an afterhyperpolarization, which is hypothesized to release the cerebellar deep nuclei from inhibition, allowing conditioned responses to be elicited via the red nucleus and accessory abducens motorneurons.

  14. Short and long-term changes in gene expression mediated by the activation of TLR9

    PubMed Central

    Klaschik, Sven; Tross, Debra; Shirota, Hidekazu; Klinman, Dennis M.

    2009-01-01

    CpG DNA binds to Toll-like receptor 9 to stimulate a strong innate immune response. The magnitude, duration and scope of CpG-induced changes in gene expression is incompletely understood despite extensive studies of TLR9 mediated signal transduction pathways. In particular, the prolonged effects of CpG DNA on gene activation have not been investigated despite evidence that a single dose of CpG DNA alters immune reactivity for several weeks. This study used gene expression analysis to monitor changes in mRNA levels for 14 days, and identified the genes, pathways and functional groups triggered in vivo following CpG DNA administration. Two discrete peaks of gene activation (at 3 hr and 5 days) were observed after CpG injection. Both the behavior and function of genes activated during the second peak differed from those triggered shortly after CpG administration. Initial gene up-regulation corresponded to a period when TLR9 ligation stimulated genes functionally associated with the generation of innate and adaptive immune responses (e.g. the NF-kB and B-cell receptor pathways). The second peak reflected processes associated with cell division (e.g., cell cycle and DNA replication & repair). The complex bimodal pattern of gene expression elicited by CpG DNA administration provides novel insights into the long term effects of TLR9 engagement on genes associated with immunity and cell proliferation. PMID:20005572

  15. Long-term potentiation decay and memory loss are mediated by AMPAR endocytosis.

    PubMed

    Dong, Zhifang; Han, Huili; Li, Hongjie; Bai, Yanrui; Wang, Wei; Tu, Man; Peng, Yan; Zhou, Limin; He, Wenting; Wu, Xiaobin; Tan, Tao; Liu, Mingjing; Wu, Xiaoyan; Zhou, Weihui; Jin, Wuyang; Zhang, Shu; Sacktor, Todd Charlton; Li, Tingyu; Song, Weihong; Wang, Yu Tian

    2015-01-01

    Long-term potentiation (LTP) of synaptic strength between hippocampal neurons is associated with learning and memory, and LTP dysfunction is thought to underlie memory loss. LTP can be temporally and mechanistically classified into decaying (early-phase) LTP and nondecaying (late-phase) LTP. While the nondecaying nature of LTP is thought to depend on protein synthesis and contribute to memory maintenance, little is known about the mechanisms and roles of decaying LTP. Here, we demonstrated that inhibiting endocytosis of postsynaptic α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptors (AMPARs) prevents LTP decay, thereby converting it into nondecaying LTP. Conversely, restoration of AMPAR endocytosis by inhibiting protein kinase Mζ (PKMζ) converted nondecaying LTP into decaying LTP. Similarly, inhibition of AMPAR endocytosis prolonged memory retention in normal animals and reduced memory loss in a murine model of Alzheimer's disease. These results strongly suggest that an active process that involves AMPAR endocytosis mediates the decay of LTP and that inhibition of this process can prolong the longevity of LTP as well as memory under both physiological and pathological conditions.

  16. Long-Term Effects of a Universal Family Intervention: Mediation Through Parent-Adolescent Conflict

    PubMed Central

    Jensen, M.; Wong, J.J.; Gonzales, N.A.; Dumka, L.E.; Millsap, R.; Coxe, S.

    2014-01-01

    Objective This randomized trial of a family-focused preventive intervention for Mexican American middle schoolers examined internalizing, externalizing, and substance use outcomes in late adolescence, five years after completing the intervention. Parent-adolescent conflict was tested as a mediator of these effects. The role of parent and adolescent acculturation in these pathways was also examined. Method 498 7th grade adolescents and their primary female caregivers were randomized to receive either a 9-week, multi-component intervention or a brief workshop control group. Assessments were conducted at pre-test, two year follow-up (9th grade), and five year follow-up (when most participants were in the 12th grade). Results The Bridges program significantly reduced mother-adolescent conflict measured in the 9th grade, with conflict mediating program effects on internalizing and externalizing symptoms, adolescent substance use, and diagnosed internalizing disorder in late adolescence. Mother and child acculturation were both significantly predictive of late adolescence outcomes. Contrary to hypotheses, neither mother nor child acculturation emerged as a significant predictor of mother-adolescent conflict, and the interaction of mother and adolescent acculturation was similarly not related to mother-adolescent conflict. Intervention effects were largely consistent across different levels of acculturation. Conclusions These findings provide support for the efficacy of family-focused intervention during early adolescence, both in reducing mental health problems and substance use in the long term, as well as in impacting parent-adolescent conflict processes that appear to play an important role in the development of later adjustment problems. PMID:24730357

  17. SCOP/PHLPP1β mediates circadian regulation of long-term recognition memory

    PubMed Central

    Shimizu, Kimiko; Kobayashi, Yodai; Nakatsuji, Erika; Yamazaki, Maya; Shimba, Shigeki; Sakimura, Kenji; Fukada, Yoshitaka

    2016-01-01

    Learning and memory depend on the time of day in various organisms, but it is not clear whether and how the circadian clock regulates memory performance. Here we show that consolidation of long-term recognition memory is a circadian-regulated process, which is blunted by disruption of the hippocampal clock. We focused on SCOP, a key molecule regulating hippocampus-dependent long-term memory for objects. The amounts of SCOP and its binding partner K-Ras in the hippocampal membrane rafts exhibit robust circadian changes, and SCOP knockdown in the hippocampal CA1 impairs long-term memory at night. Circadian changes in stimulus-dependent activation of ERK in the hippocampal neurons are dependent on the SCOP levels in the membrane rafts, while Scop knockout abrogates the activation rhythm. We conclude that long-term memory formation is regulated by the circadian clock through SCOP dynamics in the membrane rafts of the hippocampal CA1. PMID:27686624

  18. Long-Term Effects of Child Corporal Punishment on Depressive Symptoms in Young Adults: Potential Moderators and Mediators

    ERIC Educational Resources Information Center

    Turner, Heather A.; Muller, Paul A.

    2004-01-01

    Based on a sample of 649 students from 3 New England colleges, this study examined the long-term effects of childhood corporal punishment on symptoms of depression and considered factors that may moderate or mediate the association. Similar to national studies, approximately 40% of the sample reported experiencing some level of corporal punishment…

  19. Distinct dopamine neurons mediate reward signals for short- and long-term memories.

    PubMed

    Yamagata, Nobuhiro; Ichinose, Toshiharu; Aso, Yoshinori; Plaçais, Pierre-Yves; Friedrich, Anja B; Sima, Richard J; Preat, Thomas; Rubin, Gerald M; Tanimoto, Hiromu

    2015-01-13

    Drosophila melanogaster can acquire a stable appetitive olfactory memory when the presentation of a sugar reward and an odor are paired. However, the neuronal mechanisms by which a single training induces long-term memory are poorly understood. Here we show that two distinct subsets of dopamine neurons in the fly brain signal reward for short-term (STM) and long-term memories (LTM). One subset induces memory that decays within several hours, whereas the other induces memory that gradually develops after training. They convey reward signals to spatially segregated synaptic domains of the mushroom body (MB), a potential site for convergence. Furthermore, we identified a single type of dopamine neuron that conveys the reward signal to restricted subdomains of the mushroom body lobes and induces long-term memory. Constant appetitive memory retention after a single training session thus comprises two memory components triggered by distinct dopamine neurons.

  20. Distinct dopamine neurons mediate reward signals for short- and long-term memories

    PubMed Central

    Yamagata, Nobuhiro; Ichinose, Toshiharu; Aso, Yoshinori; Plaçais, Pierre-Yves; Friedrich, Anja B.; Sima, Richard J.; Preat, Thomas; Rubin, Gerald M.; Tanimoto, Hiromu

    2015-01-01

    Drosophila melanogaster can acquire a stable appetitive olfactory memory when the presentation of a sugar reward and an odor are paired. However, the neuronal mechanisms by which a single training induces long-term memory are poorly understood. Here we show that two distinct subsets of dopamine neurons in the fly brain signal reward for short-term (STM) and long-term memories (LTM). One subset induces memory that decays within several hours, whereas the other induces memory that gradually develops after training. They convey reward signals to spatially segregated synaptic domains of the mushroom body (MB), a potential site for convergence. Furthermore, we identified a single type of dopamine neuron that conveys the reward signal to restricted subdomains of the mushroom body lobes and induces long-term memory. Constant appetitive memory retention after a single training session thus comprises two memory components triggered by distinct dopamine neurons. PMID:25548178

  1. Distinct dopamine neurons mediate reward signals for short- and long-term memories.

    PubMed

    Yamagata, Nobuhiro; Ichinose, Toshiharu; Aso, Yoshinori; Plaçais, Pierre-Yves; Friedrich, Anja B; Sima, Richard J; Preat, Thomas; Rubin, Gerald M; Tanimoto, Hiromu

    2015-01-13

    Drosophila melanogaster can acquire a stable appetitive olfactory memory when the presentation of a sugar reward and an odor are paired. However, the neuronal mechanisms by which a single training induces long-term memory are poorly understood. Here we show that two distinct subsets of dopamine neurons in the fly brain signal reward for short-term (STM) and long-term memories (LTM). One subset induces memory that decays within several hours, whereas the other induces memory that gradually develops after training. They convey reward signals to spatially segregated synaptic domains of the mushroom body (MB), a potential site for convergence. Furthermore, we identified a single type of dopamine neuron that conveys the reward signal to restricted subdomains of the mushroom body lobes and induces long-term memory. Constant appetitive memory retention after a single training session thus comprises two memory components triggered by distinct dopamine neurons. PMID:25548178

  2. GABA-Mediated Presynaptic Inhibition Is Required for Precision of Long-Term Memory

    ERIC Educational Resources Information Center

    Cullen, Patrick K.; Dulka, Brooke N.; Ortiz, Samantha; Riccio, David C.; Jasnow, Aaron M.

    2014-01-01

    Though much attention has been given to the neural structures that underlie the long-term consolidation of contextual memories, little is known about the mechanisms responsible for the maintenance of memory precision. Here, we demonstrate a rapid time-dependent decline in memory precision in GABA [subscript B(1a)] receptor knockout mice. First, we…

  3. PKG-Mediated MAPK Signaling Is Necessary for Long-Term Operant Memory in "Aplysia"

    ERIC Educational Resources Information Center

    Michel, Maximilian; Green, Charity L.; Eskin, Arnold; Lyons, Lisa C.

    2011-01-01

    Signaling pathways necessary for memory formation, such as the mitogen-activated protein kinase (MAPK) pathway, appear highly conserved across species and paradigms. Learning that food is inedible (LFI) represents a robust form of associative, operant learning that induces short- (STM) and long-term memory (LTM) in "Aplysia." We investigated the…

  4. Lentiviral Vectors Mediate Long-Term and High Efficiency Transgene Expression in HEK 293T cells

    PubMed Central

    Mao, Yingying; Yan, Renhe; Li, Andrew; Zhang, Yanling; Li, Jinlong; Du, Hongyan; Chen, Baihong; Wei, Wenjin; Zhang, Yi; Sumners, Colin; Zheng, Haifa; Li, Hongwei

    2015-01-01

    . Surprisingly, neither the HS4 insulator nor the UCOE sequence improved the GFP expression level or stability. Clonal cell lines with HCV E1 gene were generated from LV-CMV-E1 vector-infected 293T cells. A representative recombinant cell line maintained stable E1expression for at least 9 weeks without significant difference in morphology compared with untreated 293T cells. Conclusion: The results suggest that all five vectors can stably transduce 293T cells, producing long term transgene expression with different efficiencies. However, neither the insulator nor the UCOE improved the GFP expression. The vectors containing the promoter CMV or CMV (β-globin intron) generated the highest gene expressions, manifesting as more favorable candidates for recombinant protein production in HEK293T cells. PMID:26005375

  5. Nitric oxide-dependent long-term depression but not endocannabinoid-mediated long-term potentiation is crucial for visual recognition memory

    PubMed Central

    Tamagnini, Francesco; Barker, Gareth; Warburton, E Clea; Burattini, Costanza; Aicardi, Giorgio; Bashir, Zafar I

    2013-01-01

    Synaptic plasticity in perirhinal cortex is essential for recognition memory. Nitric oxide and endocannabinoids (eCBs), which are produced in the postsynaptic cell and act on the presynaptic terminal, are implicated in mechanisms of long-term potentiation (LTP) and long-term depression (LTD) in other brain regions. In this study, we examine these two retrograde signalling cascades in perirhinal cortex synaptic plasticity and in visual recognition memory in the rat. We show that inhibition of NO-dependent signalling prevented both carbachol- and activity (5 Hz)-dependent LTD but not activity (100 Hz theta burst)-dependent LTP in the rat perirhinal cortex in vitro. In contrast, inhibition of the eCB-dependent signalling prevented LTP but not the two forms of LTD in vitro. Local administration into perirhinal cortex of the nitric oxide synthase inhibitor NPA (2 μm) disrupted acquisition of long-term visual recognition memory. In contrast, AM251 (10 μm), a cannabinoid receptor 1 antagonist, did not impair visual recognition memory. The results of this study demonstrate dissociation between putative retrograde signalling mechanisms in LTD and LTP in perirhinal cortex. Thus, LTP relies on cannabinoid but not NO signalling, whilst LTD relies on NO- but not eCB-dependent signalling. Critically, these results also establish, for the first time, that NO- but not eCB-dependent signalling is important in perirhinal cortex-dependent visual recognition memory. PMID:23671159

  6. Mediators of the long-term impact of child sexual abuse: perceived stigma, betrayal, powerlessness, and self-blame.

    PubMed

    Coffey, P; Leitenberg, H; Henning, K; Turner, T; Bennett, R T

    1996-05-01

    Using a community sample of 192 adult women who had been sexually abused during childhood, the present study tested the hypothesis that perceived stigma, betrayal, powerlessness, and self-blame mediate the long-term effects of child sexual abuse. A path analysis indicated that the level of psychological distress currently experienced by adult women who had been sexually abused in childhood was mediated by feelings of stigma and self-blame. This result provides partial support for Finkelhor and Browne's (1985) traumagenic dynamics model of child sexual abuse. The limitations of the study are discussed. PMID:8735380

  7. Out of place: mediating health and social care in Ontario's long-term care sector.

    PubMed

    Daly, Tamara

    2007-01-01

    The paper discusses two reforms in Ontario's long-term care. The first is the commercialization of home care as a result of the implementation of a "managed competition" delivery model. The second is the Ministry of Health and Long-Term Care's privileging of "health care" over "social care" through changes to which types of home care and home support services receive public funding. It addresses the effects of these reforms on the state–non-profit relationship, and the shifting balance between public funding of health and social care. At a program level, and with few exceptions, homemaking services have been cut from home care, and home support services are more medicalized. With these changes, growing numbers of people no longer eligible to receive publicly funded home care services look for other alternatives: they draw available resources from home support, they draw on family and friend networks, they hire privately and pay out of pocket, they leave home and enter an institution, or they do without.

  8. Divorce mediation and resolution of child custody disputes: long-term effects.

    PubMed

    Dillon, P A; Emery, R E

    1996-01-01

    Separated parents randomly assigned to either mediation or traditional adversarial methods for resolving child custody disputes were surveyed nine years postsettlement. Noncustodial parents assigned to mediation reported more frequent current contact with their children and greater involvement in current decisions about them. Parents in the mediation group also reported more frequent communication about their children during the period since dispute resolution.

  9. The Role of Lactate-Mediated Metabolic Coupling between Astrocytes and Neurons in Long-Term Memory Formation

    PubMed Central

    Steinman, Michael Q.; Gao, Virginia; Alberini, Cristina M.

    2016-01-01

    Long-term memory formation, the ability to retain information over time about an experience, is a complex function that affects multiple behaviors, and is an integral part of an individual’s identity. In the last 50 years many scientists have focused their work on understanding the biological mechanisms underlying memory formation and processing. Molecular studies over the last three decades have mostly investigated, or given attention to, neuronal mechanisms. However, the brain is composed of different cell types that, by concerted actions, cooperate to mediate brain functions. Here, we consider some new insights that emerged from recent studies implicating astrocytic glycogen and glucose metabolisms, and particularly their coupling to neuronal functions via lactate, as an essential mechanism for long-term memory formation. PMID:26973477

  10. Long-term effectiveness and mediators of a need-supportive physical activity coaching among Flemish sedentary employees.

    PubMed

    Van Hoecke, Ann-Sophie; Delecluse, Christophe; Opdenacker, Joke; Lipkens, Luc; Martien, Sofie; Boen, Filip

    2013-09-01

    This study examined the long-term and mediation effects of a need-supportive coaching programme on physical activity. Sedentary employees (n = 92) of the university of Leuven received 4 months of physical activity coaching, based on the self-determination theory, by coaches with a bachelor's degree in kinesiology who are specializing in health-related physical activity (n = 30). The programme consisted of a limited number of individual contact moments (i.e. an intake session, three follow-up contacts and an out-take session), either face-to-face, by phone or by e-mail. Self-reported physical activity, social support, self-efficacy and autonomous motivation were assessed in the coaching group (n = 92) and a control group (n = 34) at three moments: before the intervention (i.e. pre-test), after the intervention (i.e. post-test) and 1 year after pre-test measurements (i.e. follow-up test). Results revealed significant 3 (time) × 2 (groups) interaction effects on strenuous and total physical activity. Moreover, whereas the control group remained stable from pre- to post-test, the coaching group increased significantly in moderate, strenuous and total physical activity. Additionally, the coaching group increased significantly in mild, moderate, strenuous and total physical activity from pre- to follow-up tests, whereas the control group did not change. Bootstrapping analyses indicated that self-efficacy and autonomous motivation significantly mediated the intervention effect on physical activity from pre- to post-test, while social support significantly mediated the long-term effect. This study provides evidence for the long-term effectiveness of a need-supportive physical activity programme that might be efficient at the community level.

  11. Long-term fasting decreases mitochondrial avian UCP-mediated oxygen consumption in hypometabolic king penguins

    PubMed Central

    Rey, Benjamin; Halsey, Lewis G.; Dolmazon, Virginie; Rouanet, Jean-Louis; Roussel, Damien; Handrich, Yves; Butler, Patrick J.; Duchamp, Claude

    2008-01-01

    In endotherms, regulation of the degree of mitochondrial coupling affects cell metabolic efficiency. Thus it may be a key contributor to minimizing metabolic rate during long periods of fasting. The aim of the present study was to investigate whether variation in mitochondrial avian uncoupling proteins (avUCP), as putative regulators of mitochondrial oxidative phosphorylation, may contribute to the ability of king penguins (Aptenodytes patagonicus) to withstand fasting for several weeks. After 20 days of fasting, king penguins showed a reduced rate of whole animal oxygen consumption (V̇o2; −33%) at rest, together with a reduced abundance of avUCP and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1-α) mRNA in pectoralis muscle (−54%, −36%, respectively). These parameters were restored after the birds had been refed for 3 days. Furthermore, in recently fed, but not in fasted penguins, isolated muscle mitochondria showed a guanosine diphosphate-inhibited, fatty acid plus superoxide-activated respiration, indicating the presence of a functional UCP. It was calculated that variation in mitochondrial UCP-dependent respiration in vitro may contribute to nearly 20% of the difference in resting V̇o2 between fed or refed penguins and fasted penguins measured in vivo. These results suggest that the lowering of avUCP activity during periods of long-term energetic restriction may contribute to the reduction in metabolic rate and hence the ability of king penguins to face prolonged periods of fasting. PMID:18495832

  12. Long-term fasting decreases mitochondrial avian UCP-mediated oxygen consumption in hypometabolic king penguins.

    PubMed

    Rey, Benjamin; Halsey, Lewis G; Dolmazon, Virginie; Rouanet, Jean-Louis; Roussel, Damien; Handrich, Yves; Butler, Patrick J; Duchamp, Claude

    2008-07-01

    In endotherms, regulation of the degree of mitochondrial coupling affects cell metabolic efficiency. Thus it may be a key contributor to minimizing metabolic rate during long periods of fasting. The aim of the present study was to investigate whether variation in mitochondrial avian uncoupling proteins (avUCP), as putative regulators of mitochondrial oxidative phosphorylation, may contribute to the ability of king penguins (Aptenodytes patagonicus) to withstand fasting for several weeks. After 20 days of fasting, king penguins showed a reduced rate of whole animal oxygen consumption (Vo2; -33%) at rest, together with a reduced abundance of avUCP and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC1-alpha) mRNA in pectoralis muscle (-54%, -36%, respectively). These parameters were restored after the birds had been refed for 3 days. Furthermore, in recently fed, but not in fasted penguins, isolated muscle mitochondria showed a guanosine diphosphate-inhibited, fatty acid plus superoxide-activated respiration, indicating the presence of a functional UCP. It was calculated that variation in mitochondrial UCP-dependent respiration in vitro may contribute to nearly 20% of the difference in resting Vo2 between fed or refed penguins and fasted penguins measured in vivo. These results suggest that the lowering of avUCP activity during periods of long-term energetic restriction may contribute to the reduction in metabolic rate and hence the ability of king penguins to face prolonged periods of fasting. PMID:18495832

  13. Interneuronal Nitric Oxide Signaling Mediates Post-synaptic Long-Term Depression of Striatal Glutamatergic Synapses.

    PubMed

    Rafalovich, Igor V; Melendez, Alexandria E; Plotkin, Joshua L; Tanimura, Asami; Zhai, Shenyu; Surmeier, D James

    2015-11-17

    Experience-driven plasticity of glutamatergic synapses on striatal spiny projection neurons (SPNs) is thought to be essential to goal-directed behavior and habit formation. One major form of striatal plasticity, long-term depression (LTD), has long appeared to be expressed only pre-synaptically. Contrary to this view, nitric oxide (NO) generated by striatal interneurons was found to induce a post-synaptically expressed form of LTD at SPN glutamatergic synapses. This form of LTD was dependent on signaling through guanylyl cyclase and protein kinase G, both of which are abundantly expressed by SPNs. NO-LTD was unaffected by local synaptic activity or antagonism of endocannabinoid (eCb) and dopamine receptors, all of which modulate canonical, pre-synaptic LTD. Moreover, NO signaling disrupted induction of this canonical LTD by inhibiting dendritic Ca(2+) channels regulating eCb synthesis. These results establish an interneuron-dependent, heterosynaptic form of post-synaptic LTD that could act to promote stability of the striatal network during learning.

  14. Parenting and Family Stress as Mediators of the Long-Term Effects of Child Abuse.

    ERIC Educational Resources Information Center

    Wind, Tiffany Weissmann; Silvern, Louise

    1994-01-01

    Data on child physical/sexual abuse, family stress histories, perceived parental warmth, and current psychological functioning were gathered from 259 working women. Multiple regression analyses showed that parental warmth strongly influenced or mediated the relationship of intrafamilial child abuse to depression and self-esteem levels. However,…

  15. Early life stress and hippocampal neurogenesis in the neonate: sexual dimorphism, long term consequences and possible mediators

    PubMed Central

    Lajud, Naima; Torner, Luz

    2015-01-01

    Adverse early life experience decreases adult hippocampal neurogenesis and results in increased vulnerability to neuropsychiatric disorders. Despite that the effects of postnatal stress on neurogenesis have been widely studied in adult individuals, few efforts have been done to evaluate its immediate effects on the developing hippocampus. Moreover, it is not clear whether postnatal stress causes a differential impact in hippocampus development in male and female neonates that could be related to emotional deficits in adulthood. It has been proposed that the long term effects of early stress exposure rise from a persistent HPA axis activation during sensitive time windows; nevertheless the exact mechanisms and mediators remain unknown. Here, we summarize the immediate and late effects of early life stress on hippocampal neurogenesis in male and female rat pups, compare its later consequences in emotionality, and highlight some relevant mediator peptides that could be potentially involved in programming. PMID:25741234

  16. Early life stress and hippocampal neurogenesis in the neonate: sexual dimorphism, long term consequences and possible mediators.

    PubMed

    Lajud, Naima; Torner, Luz

    2015-01-01

    Adverse early life experience decreases adult hippocampal neurogenesis and results in increased vulnerability to neuropsychiatric disorders. Despite that the effects of postnatal stress on neurogenesis have been widely studied in adult individuals, few efforts have been done to evaluate its immediate effects on the developing hippocampus. Moreover, it is not clear whether postnatal stress causes a differential impact in hippocampus development in male and female neonates that could be related to emotional deficits in adulthood. It has been proposed that the long term effects of early stress exposure rise from a persistent HPA axis activation during sensitive time windows; nevertheless the exact mechanisms and mediators remain unknown. Here, we summarize the immediate and late effects of early life stress on hippocampal neurogenesis in male and female rat pups, compare its later consequences in emotionality, and highlight some relevant mediator peptides that could be potentially involved in programming.

  17. Cerebellar vermis H₂ receptors mediate fear memory consolidation in mice.

    PubMed

    Gianlorenço, A C L; Riboldi, A M; Silva-Marques, B; Mattioli, R

    2015-02-01

    Histaminergic fibers are present in the molecular and granular layers of the cerebellum and have a high density in the vermis and flocullus. Evidence supports that the cerebellar histaminergic system is involved in memory consolidation. Our recent study showed that histamine injections facilitate the retention of an inhibitory avoidance task, which was abolished by pretreatment with an H2 receptor antagonist. In the present study, we investigated the effects of intracerebellar post training injections of H1 and H2 receptor antagonists as well as the selective H2 receptor agonist on fear memory consolidation. The cerebellar vermi of male mice were implanted with guide cannulae, and after three days of recovery, the inhibitory avoidance test was performed. Immediately after a training session, animals received a microinjection of the following histaminergic drugs: experiment 1, saline or chlorpheniramine (0.016, 0.052 or 0.16 nmol); experiment 2, saline or ranitidine (0.57, 2.85 or 5.07 nmol); and experiment 3, saline or dimaprit (1, 2 or 4 nmol). Twenty-four hours later, a retention test was performed. The data were analyzed using one-way analysis of variance (ANOVA) and Duncan's tests. Animals microinjected with chlorpheniramine did not show any behavioral effects at the doses that we used. Intra-cerebellar injection of the H2 receptor antagonist ranitidine inhibited, while the selective H2 receptor agonist dimaprit facilitated, memory consolidation, suggesting that H2 receptors mediate memory consolidation in the inhibitory avoidance task in mice. PMID:25524412

  18. Cerebellar vermis H₂ receptors mediate fear memory consolidation in mice.

    PubMed

    Gianlorenço, A C L; Riboldi, A M; Silva-Marques, B; Mattioli, R

    2015-02-01

    Histaminergic fibers are present in the molecular and granular layers of the cerebellum and have a high density in the vermis and flocullus. Evidence supports that the cerebellar histaminergic system is involved in memory consolidation. Our recent study showed that histamine injections facilitate the retention of an inhibitory avoidance task, which was abolished by pretreatment with an H2 receptor antagonist. In the present study, we investigated the effects of intracerebellar post training injections of H1 and H2 receptor antagonists as well as the selective H2 receptor agonist on fear memory consolidation. The cerebellar vermi of male mice were implanted with guide cannulae, and after three days of recovery, the inhibitory avoidance test was performed. Immediately after a training session, animals received a microinjection of the following histaminergic drugs: experiment 1, saline or chlorpheniramine (0.016, 0.052 or 0.16 nmol); experiment 2, saline or ranitidine (0.57, 2.85 or 5.07 nmol); and experiment 3, saline or dimaprit (1, 2 or 4 nmol). Twenty-four hours later, a retention test was performed. The data were analyzed using one-way analysis of variance (ANOVA) and Duncan's tests. Animals microinjected with chlorpheniramine did not show any behavioral effects at the doses that we used. Intra-cerebellar injection of the H2 receptor antagonist ranitidine inhibited, while the selective H2 receptor agonist dimaprit facilitated, memory consolidation, suggesting that H2 receptors mediate memory consolidation in the inhibitory avoidance task in mice.

  19. School Engagement Mediates Long Term Prevention Effects for Mexican American Adolescents

    PubMed Central

    Gonzales, Nancy A.; Wong, Jessie J.; Toomey, Russell B.; Millsap, Roger; Dumka, Larry E.; Mauricio, Anne M.

    2014-01-01

    This five year follow-up of a randomized clinical trial evaluated the efficacy of a family-focused intervention delivered in middle school to increase school engagement following transition to high school (2 years posttest), and also evaluated mediated effects through school engagement on multiple problem outcomes in late adolescence (5 years posttest). The study sample included 516 Mexican American adolescents who participated in a randomized trial of the Bridges to High School Program (Bridges/ Puentes). Path models representing the direct and indirect effects of the program on four outcome variables were evaluated using school engagement measured in the 9th grade as a mediator. The program significantly increased school engagement, with school engagement mediating intervention effects on internalizing symptoms, adolescent substance use, and school dropout in late adolescence when most adolescents were in the 12th grade. Effects on substance use were stronger for youth at higher risk based on pretest report of substance use initiation. There were no direct or indirect intervention effects on externalizing symptoms. Findings support that school engagement is an important prevention target for Mexican American adolescents. PMID:24398825

  20. School engagement mediates long-term prevention effects for Mexican American adolescents.

    PubMed

    Gonzales, Nancy A; Wong, Jessie J; Toomey, Russell B; Millsap, Roger; Dumka, Larry E; Mauricio, Anne M

    2014-12-01

    This 5-year follow-up of a randomized clinical trial evaluated the efficacy of a family-focused intervention delivered in middle school to increase school engagement following transition to high school (2 years post-test), and also evaluated mediated effects through school engagement on multiple problem outcomes in late adolescence (5 years post-test). The study sample included 516 Mexican American adolescents who participated in a randomized trial of the Bridges to High School Program (Bridges/Puentes). Path models representing the direct and indirect effects of the program on four outcome variables were evaluated using school engagement measured in the 9th grade as a mediator. The program significantly increased school engagement, with school engagement mediating intervention effects on internalizing symptoms, adolescent substance use, and school dropout in late adolescence when most adolescents were in the 12th grade. Effects on substance use were stronger for youth at higher risk based on pretest report of substance use initiation. There were no direct or indirect intervention effects on externalizing symptoms. Findings support that school engagement is an important prevention target for Mexican American adolescents. PMID:24398825

  1. School engagement mediates long-term prevention effects for Mexican American adolescents.

    PubMed

    Gonzales, Nancy A; Wong, Jessie J; Toomey, Russell B; Millsap, Roger; Dumka, Larry E; Mauricio, Anne M

    2014-12-01

    This 5-year follow-up of a randomized clinical trial evaluated the efficacy of a family-focused intervention delivered in middle school to increase school engagement following transition to high school (2 years post-test), and also evaluated mediated effects through school engagement on multiple problem outcomes in late adolescence (5 years post-test). The study sample included 516 Mexican American adolescents who participated in a randomized trial of the Bridges to High School Program (Bridges/Puentes). Path models representing the direct and indirect effects of the program on four outcome variables were evaluated using school engagement measured in the 9th grade as a mediator. The program significantly increased school engagement, with school engagement mediating intervention effects on internalizing symptoms, adolescent substance use, and school dropout in late adolescence when most adolescents were in the 12th grade. Effects on substance use were stronger for youth at higher risk based on pretest report of substance use initiation. There were no direct or indirect intervention effects on externalizing symptoms. Findings support that school engagement is an important prevention target for Mexican American adolescents.

  2. Apical Organelle Secretion by Toxoplasma Controls Innate and Adaptive Immunity and Mediates Long-Term Protection.

    PubMed

    Sloves, Pierre-Julien; Mouveaux, Thomas; Ait-Yahia, Saliha; Vorng, Han; Everaere, Laetitia; Sangare, Lamba Omar; Tsicopoulos, Anne; Tomavo, Stanislas

    2015-11-01

    Apicomplexan parasites have unique apical rhoptry and microneme secretory organelles that are crucial for host infection, although their role in protection against Toxoplasma gondii infection is not thoroughly understood. Here, we report a novel function of the endolysosomal T. gondii sortilin-like receptor (TgSORTLR), which mediates trafficking to functional apical organelles and their subsequent secretion of virulence factors that are critical to the induction of sterile immunity against parasite reinfection. We further demonstrate that the T. gondii armadillo repeats-only protein (TgARO) mutant, which is deficient only in apical secretion of rhoptries, is also critical in mounting protective immunity. The lack of TgSORTLR and TgARO proteins completely inhibited T-helper 1-dependent adaptive immunity and compromised the function of natural killer T-cell-mediated innate immunity. Our findings reveal an essential role for apical secretion in promoting sterile protection against T. gondii and provide strong evidence for rhoptry-regulated discharge of antigens as a key effector for inducing protective immunity.

  3. Role for Endogenous BDNF in Endocannabinoid-Mediated Long-Term Depression at Neocortical Inhibitory Synapses1,2,3

    PubMed Central

    Zhao, Liangfang; Li-Wen Yeh, Mason

    2015-01-01

    Abstract The endogenous cannabinoid (endocannabinoid) system is an important regulator of synaptic function. Endocannabinoids acutely modulate inhibitory and excitatory transmission, and also mediate long-term depression at GABAergic and glutamatergic synapses. Typically, endocannabinoid synthesis and release is stimulated by depolarization-induced calcium influx and/or activation of phospholipase-C (PLC) signaling triggered by mGluR activation. Recently it has been shown that brain-derived neurotrophic factor (BDNF) can also induce endocannabinoid release. Although there is growing evidence for cross-talk between BDNF and endocannabinoid signaling, little is known about the functional relevance of these interactions. In the present studies, we examined BDNF−endocannabinoid interactions in regulating activity-dependent long-term depression at inhibitory synapses (iLTD). We found that theta burst stimulation (TBS) in layer 2/3 of mouse somatosensory cortical slices can induce a form of endocannabinoid-mediated iLTD that is independent of metabotropic glutamate receptor (mGluR) activation. This endocannabinoid-dependent iLTD, however, requires endogenous BDNF-trkB signaling, as it is blocked by a trk tyrosine kinase inhibitor and by a trkB receptor antagonist, and also requires activation of diacylglycerol lipase (DAG-lipase, DGL). In addition, endocannabinoid-mediated iLTD can be induced by combining a subthreshold concentration of exogenous BDNF with weak TBS stimulation that by itself is insufficient to induce iLTD. Taken together, our results suggest that TBS can induce the release of endogenous BDNF, which triggers DGL-dependent endocannabinoid mobilization and cannabinoid receptor-dependent iLTD at layer 2/3 cortical synapses. PMID:25938134

  4. Long-term Amelioration of Feline Mucopolysaccharidosis VI After AAV-mediated Liver Gene Transfer

    PubMed Central

    Cotugno, Gabriella; Annunziata, Patrizia; Tessitore, Alessandra; O'Malley, Thomas; Capalbo, Anita; Faella, Armida; Bartolomeo, Rosa; O'Donnell, Patricia; Wang, Ping; Russo, Fabio; Sleeper, Meg M; Knox, Van W; Fernandez, Steven; Levanduski, Leah; Hopwood, John; De Leonibus, Elvira; Haskins, Mark; Auricchio, Alberto

    2011-01-01

    Mucopolysaccharidosis VI (MPS VI) is caused by deficient arylsulfatase B (ARSB) activity resulting in lysosomal storage of glycosaminoglycans (GAGs). MPS VI is characterized by dysostosis multiplex, organomegaly, corneal clouding, and heart valve thickening. Gene transfer to a factory organ like liver may provide a lifetime source of secreted ARSB. We show that intravascular administration of adeno-associated viral vectors (AAV) 2/8-TBG-felineARSB in MPS VI cats resulted in ARSB expression up to 1 year, the last time point of the study. In newborn cats, normal circulating ARSB activity was achieved following delivery of high vector doses (6 × 1013 genome copies (gc)/kg) whereas delivery of AAV2/8 vector doses as low as 2 × 1012 gc/kg resulted in higher than normal serum ARSB levels in juvenile MPS VI cats. In MPS VI cats showing high serum ARSB levels, independent of the age at treatment, we observed: (i) clearance of GAG storage, (ii) improvement of long bone length, (iii) reduction of heart valve thickness, and (iv) improvement in spontaneous mobility. Thus, AAV2/ 8-mediated liver gene transfer represents a promising therapeutic strategy for MPS VI patients. PMID:21119624

  5. Chronic administration of sulbutiamine improves long term memory formation in mice: possible cholinergic mediation.

    PubMed

    Micheau, J; Durkin, T P; Destrade, C; Rolland, Y; Jaffard, R

    1985-08-01

    Thiamine deficiency in both man and animals is known to produce memory dysfunction and cognitive disorders which have been related to an impairment of cholinergic activity. The present experiment was aimed at testing whether, inversely, chronic administration of large doses of sulbutiamine would have a facilitative effect on memory and would induce changes in central cholinergic activity. Accordingly mice received 300 mg/kg of sulbutiamine daily for 10 days. They were then submitted to an appetitive operant level press conditioning test. When compared to control subjects, sulbutiamine treated mice learned the task at the same rate in a single session but showed greatly improved performance when tested 24 hr after partial acquisition of the same task. Parallel neurochemical investigations showed that the treatment induced a slight (+ 10%) but significant increase in hippocampal sodium-dependent high affinity choline uptake. The present findings and previous results suggest that sulbutiamine improves memory formation and that this behavioral effect could be mediated by an increase in hippocampal cholinergic activity. PMID:4059305

  6. Endocannabinoids Mediate Muscarinic Acetylcholine Receptor-Dependent Long-Term Depression in the Adult Medial Prefrontal Cortex

    PubMed Central

    Martin, Henry G. S.; Bernabeu, Axel; Lassalle, Olivier; Bouille, Clément; Beurrier, Corinne; Pelissier-Alicot, Anne-Laure; Manzoni, Olivier J.

    2015-01-01

    Cholinergic inputs into the prefrontal cortex (PFC) are associated with attention and cognition; however there is evidence that acetylcholine also has a role in PFC dependent learning and memory. Muscarinic acetylcholine receptors (mAChR) in the PFC can induce synaptic plasticity, but the underlying mechanisms remain either opaque or unresolved. We have characterized a form of mAChR mediated long-term depression (LTD) at glutamatergic synapses of layer 5 principal neurons in the adult medial PFC. This mAChR LTD is induced with the mAChR agonist carbachol and inhibited by selective M1 mAChR antagonists. In contrast to other cortical regions, we find that this M1 mAChR mediated LTD is coupled to endogenous cannabinoid (eCB) signaling. Inhibition of the principal eCB CB1 receptor blocked carbachol induced LTD in both rats and mice. Furthermore, when challenged with a sub-threshold carbachol application, LTD was induced in slices pretreated with the monoacylglycerol lipase (MAGL) inhibitor JZL184, suggesting that the eCB 2-arachidonylglyerol (2-AG) mediates M1 mAChR LTD. Yet, when endogenous acetylcholine was released from local cholinergic afferents in the PFC using optogenetics, it failed to trigger eCB-LTD. However coupling patterned optical and electrical stimulation to generate local synaptic signaling allowed the reliable induction of LTD. The light—electrical pairing induced LTD was M1 mAChR and CB1 receptor mediated. This shows for the first time that connecting excitatory synaptic activity with coincident endogenously released acetylcholine controls synaptic gain via eCB signaling. Together these results shed new light on the mechanisms of synaptic plasticity in the adult PFC and expand on the actions of endogenous cholinergic signaling. PMID:26648844

  7. Endocannabinoids Mediate Muscarinic Acetylcholine Receptor-Dependent Long-Term Depression in the Adult Medial Prefrontal Cortex.

    PubMed

    Martin, Henry G S; Bernabeu, Axel; Lassalle, Olivier; Bouille, Clément; Beurrier, Corinne; Pelissier-Alicot, Anne-Laure; Manzoni, Olivier J

    2015-01-01

    Cholinergic inputs into the prefrontal cortex (PFC) are associated with attention and cognition; however there is evidence that acetylcholine also has a role in PFC dependent learning and memory. Muscarinic acetylcholine receptors (mAChR) in the PFC can induce synaptic plasticity, but the underlying mechanisms remain either opaque or unresolved. We have characterized a form of mAChR mediated long-term depression (LTD) at glutamatergic synapses of layer 5 principal neurons in the adult medial PFC. This mAChR LTD is induced with the mAChR agonist carbachol and inhibited by selective M1 mAChR antagonists. In contrast to other cortical regions, we find that this M1 mAChR mediated LTD is coupled to endogenous cannabinoid (eCB) signaling. Inhibition of the principal eCB CB1 receptor blocked carbachol induced LTD in both rats and mice. Furthermore, when challenged with a sub-threshold carbachol application, LTD was induced in slices pretreated with the monoacylglycerol lipase (MAGL) inhibitor JZL184, suggesting that the eCB 2-arachidonylglyerol (2-AG) mediates M1 mAChR LTD. Yet, when endogenous acetylcholine was released from local cholinergic afferents in the PFC using optogenetics, it failed to trigger eCB-LTD. However coupling patterned optical and electrical stimulation to generate local synaptic signaling allowed the reliable induction of LTD. The light-electrical pairing induced LTD was M1 mAChR and CB1 receptor mediated. This shows for the first time that connecting excitatory synaptic activity with coincident endogenously released acetylcholine controls synaptic gain via eCB signaling. Together these results shed new light on the mechanisms of synaptic plasticity in the adult PFC and expand on the actions of endogenous cholinergic signaling.

  8. A new polymer-based laccase for decolorization of AO7: long-term storage and mediator reuse.

    PubMed

    Zhang, Xiaolin; Pan, Bingcai; Wu, Bing; Zhang, Weiming; Lv, Lu

    2014-07-01

    To address the bottlenecks of laccase-based catalysis, i.e., poor long-term stability and potential secondary pollution caused by synthetic mediator, we fabricated a new biocatalyst (N-PS-Lac) through adsorption of laccase onto polystyrene anion exchangers (N-PS) binding quaternary ammonium groups. After 2-year storage, the residual activity of N-PS-Lac remained as high as 101.7%, while that for native laccase was only 14.6%. Also, N-PS-Lac exhibited improved durability against pH variation and thermal treatment at 60°C. Gaussian curve fitting of FT-IR spectra indicated that laccase conformation of N-PS-Lac was rigidified, possibly because of the host geometric restriction and the host-laccase electrostatic attraction. A two-step method, i.e., adsorption of an azo dye AO7 by N-PS and then ectopic degradation by the immobilized laccase, was proposed to reuse the mediator HOBT for seven cyclic runs, where N-PS-Lac kept the constant decolorization efficiency. AO7 solution was detoxified completely after decolorization by the two-step method. PMID:24862000

  9. A new polymer-based laccase for decolorization of AO7: long-term storage and mediator reuse.

    PubMed

    Zhang, Xiaolin; Pan, Bingcai; Wu, Bing; Zhang, Weiming; Lv, Lu

    2014-07-01

    To address the bottlenecks of laccase-based catalysis, i.e., poor long-term stability and potential secondary pollution caused by synthetic mediator, we fabricated a new biocatalyst (N-PS-Lac) through adsorption of laccase onto polystyrene anion exchangers (N-PS) binding quaternary ammonium groups. After 2-year storage, the residual activity of N-PS-Lac remained as high as 101.7%, while that for native laccase was only 14.6%. Also, N-PS-Lac exhibited improved durability against pH variation and thermal treatment at 60°C. Gaussian curve fitting of FT-IR spectra indicated that laccase conformation of N-PS-Lac was rigidified, possibly because of the host geometric restriction and the host-laccase electrostatic attraction. A two-step method, i.e., adsorption of an azo dye AO7 by N-PS and then ectopic degradation by the immobilized laccase, was proposed to reuse the mediator HOBT for seven cyclic runs, where N-PS-Lac kept the constant decolorization efficiency. AO7 solution was detoxified completely after decolorization by the two-step method.

  10. Effects of reversible pharmacological shutdown of cerebellar flocculus on the memory of long-term horizontal vestibulo-ocular reflex adaptation in monkeys.

    PubMed

    Anzai, Mari; Kitazawa, Hiromasa; Nagao, Soichi

    2010-11-01

    The adaptation of the horizontal vestibulo-ocular reflex (HVOR) provides an experimental model for motor learning. Two studies, using cats and mice, respectively, have recently suggested pharmacologically that the memory of adaptation is located multiply in the cerebellum and brainstem. Here, we examined the effects of acute cerebellar flocculus shutdown on the adaptation in four monkeys. Two hours of 0.11Hz-10° turntable oscillation while viewing a stationary checked-patterned screen through the left-right reversing prism decreased the HVOR gains by 0.16, and 3 days of prism wearing combined with 2h of daily turntable oscillation decreased the HVOR gains by 0.27. Injections of lidocaine into bilateral flocculi did not affect the nonadapted HVOR gains, but depressed the visual suppression of the HVOR. They recovered the HVOR gains decreased by 2h of training, but very little affected the HVOR gains decreased by previous 2 days of training. Injections of control Ringer's solution did not affect the gains adapted by 2h or 3 days of training. These results are consistent with the previous studies, and suggest that the memory trace of adaptation of the HVOR initially resides in the flocculus but later resides, presumably, in the vestibular nuclei in the monkey.

  11. IGF-1-mediated osteoblastic niche expansion enhances long-term hematopoietic stem cell engraftment after murine bone marrow transplantation.

    PubMed

    Caselli, Anna; Olson, Timothy S; Otsuru, Satoru; Chen, Xiaohua; Hofmann, Ted J; Nah, Hyun-Duck; Grisendi, Giulia; Paolucci, Paolo; Dominici, Massimo; Horwitz, Edwin M

    2013-10-01

    The efficiency of hematopoietic stem cell (HSC) engraftment after bone marrow (BM) transplantation depends largely on the capacity of the marrow microenvironment to accept the transplanted cells. While radioablation of BM damages osteoblastic stem cell niches, little is known about their restoration and mechanisms governing their receptivity to engraft transplanted HSCs. We previously reported rapid restoration and profound expansion of the marrow endosteal microenvironment in response to marrow radioablation. Here, we show that this reorganization represents proliferation of mature endosteal osteoblasts which seem to arise from a small subset of high-proliferative, relatively radio-resistant endosteal cells. Multiple layers of osteoblasts form along the endosteal surface within 48 hours after total body irradiation, concomitant with a peak in marrow cytokine expression. This niche reorganization fosters homing of the transplanted hematopoietic cells to the host marrow space and engraftment of long-term-HSC. Inhibition of insulin-like growth factor (IGF)-1-receptor tyrosine kinase signaling abrogates endosteal osteoblast proliferation and donor HSC engraftment, suggesting that the cytokine IGF-1 is a crucial mediator of endosteal niche reorganization and consequently donor HSC engraftment. Further understanding of this novel mechanism of IGF-1-dependent osteoblastic niche expansion and HSC engraftment may yield clinical applications for improving engraftment efficiency after clinical HSC transplantation.

  12. Endocannabinoid-mediated long-term depression of afferent excitatory synapses in hippocampal pyramidal cells and GABAergic interneurons.

    PubMed

    Péterfi, Zoltán; Urbán, Gabriella M; Papp, Orsolya I; Németh, Beáta; Monyer, Hannah; Szabó, Gábor; Erdélyi, Ferenc; Mackie, Ken; Freund, Tamás F; Hájos, Norbert; Katona, István

    2012-10-10

    Although endocannabinoids have emerged as essential retrograde messengers in several forms of synaptic plasticity, it remains controversial whether they mediate long-term depression (LTD) of glutamatergic synapses onto excitatory and inhibitory neurons in the hippocampus. Here, we show that parvalbumin- and somatostatin/metabotropic glutamate receptor 1(a) (mGlu(1a))-positive GABAergic interneurons express diacylglycerol lipase-α (DGL-α), a synthesizing enzyme of the endocannabinoid 2-arachidonoylglycerol (2-AG), albeit at lower levels than principal cells. Moreover, this lipase accumulates postsynaptically around afferent excitatory synapses in all three cell types. To address the role of retrograde 2-AG signaling in LTD, we investigated two forms: (1) produced by postsynaptic spiking paired with subsequent presynaptic stimulation or (2) induced by group I mGlu activation by (S)-3,5-dihydroxyphenylglycine (DHPG). Neither form of LTD was evoked in the presence of the mGlu(5) antagonist MPEP [2-methyl-6-(phenylethynyl)-pyridine], the DGL inhibitor THL [N-formyl-l-leucine (1S)-1-[[(2S,3S)-3-hexyl-4-oxo-2-oxetanyl]methyl]dodecyl ester], or the intracellularly applied Ca(2+) chelator BAPTA in CA1 pyramidal cells, fast-spiking interneurons (representing parvalbumin-containing cells) and interneurons projecting to stratum lacunosum-moleculare (representing somatostatin/mGlu(1a)-expressing interneurons). Both forms of LTD were completely absent in CB(1) cannabinoid receptor knock-out mice, whereas pharmacological blockade of CB(1) led to inconsistent results. Notably, in accordance with their lower DGL-α level, a higher stimulation frequency or higher DHPG concentration was required for LTD induction in interneurons compared with pyramidal cells. These findings demonstrate that hippocampal principal cells and interneurons produce endocannabinoids to mediate LTD in a qualitatively similar, but quantitatively different manner. The shifted induction threshold implies that

  13. Coactivation of metabotropic glutamate receptors and of voltage-gated calcium channels induces long-term depression in cerebellar Purkinje cells in vitro.

    PubMed

    Daniel, H; Hemart, N; Jaillard, D; Crepel, F

    1992-01-01

    Using an in vitro slice preparation, we studied the effects, on parallel fiber (PF)-mediated EPSPs, of coactivation of metabotropic-glutamate receptors and of voltage-gated calcium (Ca) channels of Purkinje cells (PCs) by bath application of 50 microM trans-1-amino-cyclopentyl-1,3-dicarboxylate (trans-ACPD) and by direct depolarization of the cells, respectively. These effects were compared with changes in synaptic efficacy obtained when alpha-amino-3hydroxy-5-methylisoxalone-4-propionate (AMPA) receptors of PCs were also activated through stimulation of PFs during the pairing protocol, as well as when similar experiments were performed without trans-ACPD in the bath. In a control medium, pairing for 1 min of PF-mediated EPSPs evoked at 1 Hz with Ca spikes evoked by steady depolarization of PCs (n = 13) led to LTD of synaptic transmission in 9 cases whereas for the others EPSPs were not affected. No LTD occurred in 9 out of 10 other cells tested when PF stimulation was omitted during the 1 min period of Ca spike firing of PCs. Bath application of 50 microM trans-ACPD, in conjunction with the same pairing protocol as before (n = 8), led to a significantly larger LTD of PF-mediated EPSPs after washing out of this drug. Moreover, a clear-cut LTD of PF-mediated EPSPs was also observed in 5 of the 8 other cells, when PF stimulation was omitted during Ca spike firing in the presence of trans-ACPD.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Long-Term Care

    MedlinePlus

    ... this page please turn Javascript on. Long-Term Care What Is Long-Term Care? Long-term care involves a variety of services ... the Escape (Esc) button on your keyboard.) Most Care Provided at Home Long-term care is provided ...

  15. Neurexin-neuroligin transsynaptic interaction mediates learning-related synaptic remodeling and long-term facilitation in aplysia.

    PubMed

    Choi, Yun-Beom; Li, Hsiu-Ling; Kassabov, Stefan R; Jin, Iksung; Puthanveettil, Sathyanarayanan V; Karl, Kevin A; Lu, Yang; Kim, Joung-Hun; Bailey, Craig H; Kandel, Eric R

    2011-05-12

    Neurexin and neuroligin, which undergo heterophilic interactions with each other at the synapse, are mutated in some patients with autism spectrum disorder, a set of disorders characterized by deficits in social and emotional learning. We have explored the role of neurexin and neuroligin at sensory-to-motor neuron synapses of the gill-withdrawal reflex in Aplysia, which undergoes sensitization, a simple form of learned fear. We find that depleting neurexin in the presynaptic sensory neuron or neuroligin in the postsynaptic motor neuron abolishes both long-term facilitation and the associated presynaptic growth induced by repeated pulses of serotonin. Moreover, introduction into the motor neuron of the R451C mutation of neuroligin-3 linked to autism spectrum disorder blocks both intermediate-term and long-term facilitation. Our results suggest that activity-dependent regulation of the neurexin-neuroligin interaction may govern transsynaptic signaling required for the storage of long-term memory, including emotional memory that may be impaired in autism spectrum disorder.

  16. Nitromusk and Polycyclic Musk Compounds as Long-Term Inhibitors of Cellular Xenobiotic Defense Systems Mediated by Multidrug Transporters

    PubMed Central

    Luckenbach, Till; Epel, David

    2005-01-01

    Synthetic musk compounds, widely used as fragrances in consumer products, have been detected in human tissue and, surprisingly, in aquatic organisms such as fish and mollusks. Although their persistence and potential to bioaccumulate are of concern, the toxicity and environmental risks of these chemicals are generally regarded as low. Here, however, we show that nitromusks and polycyclic musks inhibit the activity of multidrug efflux transporters responsible for multixenobiotic resistance (MXR) in gills of the marine mussel Mytilus californianus. The IC10 (concentration that inhibits 10%) values for the different classes of musks were in the range of 0.09–0.39 μM, and IC50 values were 0.74–2.56 μM. The immediate consequence of inhibition of efflux transporters is that normally excluded xenobiotics will now be able to enter the cell. Remarkably, the inhibitory effects of a brief 2-hr exposure to musks were only partially reversed after a 24- to 48-hr recovery period in clean seawater. This unexpected consequence of synthetic musks—a long-term loss of efflux transport activity—will result in continued accumulation of normally excluded toxicants even after direct exposure to the musk has ended. These findings also point to the need to determine whether other environmental chemicals have similar long-term effects on these transporters. The results are relevant to human health because they raise the possibility that exposure to common xenobiotics and pharmaceuticals could cause similar long-term inhibition of these transporters and lead to increased exposure to normally excluded toxicants. PMID:15626642

  17. Short- and long-term beta-carotene supplementation do not influence T cell-mediated immunity in healthy elderly persons.

    PubMed

    Santos, M S; Leka, L S; Ribaya-Mercado, J D; Russell, R M; Meydani, M; Hennekens, C H; Gaziano, J M; Meydani, S N

    1997-10-01

    Supplementation of healthy elderly persons with beta-carotene has been considered a way to enhance immune responses. In study 1 the short-term effect of beta-carotene (90 mg/d for 3 wk) on immunity was assessed in a randomized, double-blind, placebo-controlled longitudinal comparison of healthy elderly women. In study 2 the long-term effect of beta-carotene (50 mg every other day for 10-12 y) on immunity was assessed in a randomized, double-blind, placebo-controlled longitudinal comparison of men enrolled in the Physicians' Health Study. Subjects from both studies taking active supplements had significantly greater plasma beta-carotene concentrations than did subjects taking placebo. The pre- to postintervention change in delayed-type hypersensitivity skin test responses between beta-carotene and placebo groups in the short-term study was not significantly different, nor was the response between treatment groups in the long-term study. There were no significant effects due to beta-carotene supplementation on in vitro lymphocyte proliferation, production of interleukin 2, or production of prostaglandin E2 as a result of short- or long-term beta-carotene supplementation. In addition, there were no differences in the profiles of lymphocyte subsets [total T cells (CD3+), T helper cells (CD4+), T cytotoxic-suppressor cells (CD8+), and B cells (CD19+)] due to short- or long-term beta-carotene supplementation, nor were there differences in percentages of CD16+ natural killer cells or activated lymphocytes (cells expressing interleukin 2 transferrin receptor) due to long-term beta-carotene supplementation. Consistent results from these two trials show that beta-carotene supplementation did not have an enhancing or suppressive effect on T cell-mediated immunity of healthy elderly.

  18. Out of Place: Mediating Health and Social Care in Ontario’s Long-Term Care Sector*

    PubMed Central

    Daly, Tamara

    2014-01-01

    The paper discusses two reforms in Ontario’s long-term care. The first is the commercialization of home care as a result of the implementation of a “managed competition” delivery model. The second is the Ministry of Health and Long-Term Care’s privileging of “health care” over “social care” through changes to which types of home care and home support services receive public funding. It addresses the effects of these reforms on the state–non-profit relationship, and the shifting balance between public funding of health and social care. At a program level, and with few exceptions, homemaking services have been cut from home care, and home support services are more medicalized. With these changes, growing numbers of people no longer eligible to receive publicly funded home care services look for other alternatives: they draw available resources from home support, they draw on family and friend networks, they hire privately and pay out of pocket, they leave home and enter an institution, or they do without. PMID:21598747

  19. Divergent short- and long-term effects of acute stress in object recognition memory are mediated by endogenous opioid system activation.

    PubMed

    Nava-Mesa, Mauricio O; Lamprea, Marisol R; Múnera, Alejandro

    2013-11-01

    Acute stress induces short-term object recognition memory impairment and elicits endogenous opioid system activation. The aim of this study was thus to evaluate whether opiate system activation mediates the acute stress-induced object recognition memory changes. Adult male Wistar rats were trained in an object recognition task designed to test both short- and long-term memory. Subjects were randomly assigned to receive an intraperitoneal injection of saline, 1 mg/kg naltrexone or 3 mg/kg naltrexone, four and a half hours before the sample trial. Five minutes after the injection, half the subjects were submitted to movement restraint during four hours while the other half remained in their home cages. Non-stressed subjects receiving saline (control) performed adequately during the short-term memory test, while stressed subjects receiving saline displayed impaired performance. Naltrexone prevented such deleterious effect, in spite of the fact that it had no intrinsic effect on short-term object recognition memory. Stressed subjects receiving saline and non-stressed subjects receiving naltrexone performed adequately during the long-term memory test; however, control subjects as well as stressed subjects receiving a high dose of naltrexone performed poorly. Control subjects' dissociated performance during both memory tests suggests that the short-term memory test induced a retroactive interference effect mediated through light opioid system activation; such effect was prevented either by low dose naltrexone administration or by strongly activating the opioid system through acute stress. Both short-term memory retrieval impairment and long-term memory improvement observed in stressed subjects may have been mediated through strong opioid system activation, since they were prevented by high dose naltrexone administration. Therefore, the activation of the opioid system plays a dual modulating role in object recognition memory.

  20. NPY-Induced Phase Shifts of PER2::LUC Rhythms are Mediated by Long-Term Suppression of Neuronal Excitability in a Phase-Specific Manner

    PubMed Central

    Besing, Rachel C.; Hablitz, Lauren M.; Paul, Jodi R.; Johnson, Russell L.; Prosser, Rebecca A.; Gamble, Karen L.

    2013-01-01

    Endogenous circadian rhythms are entrained to the 24-h light/dark cycle by both light and nonphotic stimuli. During the day, nonphotic stimuli, such as novel-wheel induced exercise, produce large phase advances. Neuropeptide Y (NPY) release from the thalamus onto suprachiasmatic nucleus (SCN) neurons at least partially mediates this nonphotic signal. We examined the hypothesis that NPY-induced phase advances are accompanied by suppression of PER2 and are mediated by long-term depression of neuronal excitability in a phase-specific manner. First, we found that NPY-induced phase advances in PER2::LUC SCN cultures are largest when NPY (2.35 µM) is given in the early part of the day (circadian time [CT] 0–6). In addition, PER2::LUC levels in NPY-treated (compared to vehicle-treated) samples were suppressed beginning 6–7 h after treatment. Similar NPY application to organotypic Per1::GFP SCN cultures resulted in long-term suppression of spike rate of GFP+ cells when slices were treated with NPY during the early or middle of the day (zeitgeber time [ZT] 2 or 6), but not during the late day (ZT 10). Furthermore, 1-h bath application of NPY to acute SCN brain slices decreased general neuronal activity measured through extracellular recordings. Finally, NPY-induced phase advances of PER2::LUC rhythms were blocked by latent depolarization with 34.5 mM [K+] 3 h after NPY application. These results suggest that NPY-induced phase advances may be mediated by long-term depression of neuronal excitability. This model is consistent with findings in other brain regions that NPY-induced persistent hyperpolarization underlies mechanisms of energy homeostasis, anxiety-related behavior, and thalamocortical synchronous firing. PMID:22324550

  1. CA1 Pyramidal Cell Theta-Burst Firing Triggers Endocannabinoid-Mediated Long-Term Depression at Both Somatic and Dendritic Inhibitory Synapses

    PubMed Central

    Younts, Thomas J.; Chevaleyre, Vivien

    2013-01-01

    Endocannabinoids (eCBs) are retrograde lipid messengers that, by targeting presynaptic type 1 cannabinoid receptors (CB1Rs), mediate short- and long-term synaptic depression of neurotransmitter release throughout the brain. Short-term depression is typically triggered by postsynaptic, depolarization-induced calcium rises, whereas long-term depression is induced by synaptic activation of Gq/11 protein-coupled receptors. Here we report that a physiologically relevant pattern of postsynaptic activity, in the form of theta-burst firing (TBF) of hippocampal CA1 pyramidal neurons, can trigger long-term depression of inhibitory transmission (iLTD) in rat hippocampal slices. Paired recordings between CA1 interneurons and pyramidal cells, followed by post hoc morphological reconstructions of the interneurons' axon, revealed that somatic and dendritic inhibitory synaptic inputs equally expressed TBF-induced iLTD. Simultaneous recordings from neighboring pyramidal cells demonstrated that eCB signaling triggered by TBF was highly restricted to only a single, active cell. Furthermore, pairing submaximal endogenous activation of metabotropic glutamate or muscarinic acetylcholine receptors with submaximal TBF unmasked associative iLTD. Although CB1Rs are also expressed at Schaffer-collateral excitatory terminals, long-term plasticity under various recording conditions was spared at these synapses. Consistent with this observation, TBF also shifted the balance of excitation and inhibition in favor of excitatory throughput, thereby altering information flow through the CA1 circuit. Given the near ubiquity of burst-firing activity patterns and CB1R expression in the brain, the properties described here may be a general means by which neurons fine tune the strength of their inputs in a cell-wide and cell-specific manner. PMID:23966696

  2. Photoperiod-mediated impairment of long-term potention and learning and memory in male white-footed mice.

    PubMed

    Walton, J C; Chen, Z; Weil, Z M; Pyter, L M; Travers, J B; Nelson, R J

    2011-02-23

    Adult mammalian brains are capable of some structural plasticity. Although the basic cellular mechanisms underlying learning and memory are being revealed, extrinsic factors contributing to this plasticity remain unspecified. White-footed mice (Peromyscus leucopus) are particularly well suited to investigate brain plasticity because they show marked seasonal changes in structure and function of the hippocampus induced by a distinct environmental signal, viz., photoperiod (i.e. the number of hours of light/day). Compared to animals maintained in 16 h of light/day, exposure to 8 h of light/day for 10 weeks induces several phenotypic changes in P. leucopus, including reduction in brain mass and hippocampal volume. To investigate the functional consequences of reduced hippocampal size, we examined the effects of photoperiod on spatial learning and memory in the Barnes maze, and on long-term potentiation (LTP) in the hippocampus, a leading candidate for a synaptic mechanism underlying spatial learning and memory in rodents. Exposure to short days for 10 weeks decreased LTP in the Schaffer collateral-CA1 pathway of the hippocampus and impaired spatial learning and memory ability in the Barnes maze. Taken together, these results demonstrate a functional change in the hippocampus in male white-footed mice induced by day length. PMID:21145376

  3. Biochemical responses and mitochondrial mediated activation of apoptosis on long-term effect of aspartame in rat brain.

    PubMed

    Ashok, Iyaswamy; Sheeladevi, Rathinasamy

    2014-01-01

    Aspartame, an artificial sweetener, is very widely used in many foods and beverages. But there are controversies about its metabolite which is marked for its toxicity. Hence it is believed to be unsafe for human use. Previous studies have reported on methanol exposure with involvements of free radicals on excitotoxicity of neuronal apoptosis. Hence, this present study is proposed to investigate whether or not chronic aspartame (FDA approved Daily Acceptable Intake (ADI),40 mg/kg bwt) administration could release methanol, and whether or not it can induce changes in brain oxidative stress status and gene and protein expression of anti-apoptotic Bcl-2 and pro-apoptotic Bax and caspase-3 in the rat brain region. To mimic the human methanol metabolism, Methotrexate (MTX)-treated Wistar strain male albino rats were used and after the oral administration of aspartame, the effects were studied along with controls and MTX-treated controls. Aspartame exposure resulted with a significant increase in the enzymatic activity in protein carbonyl, lipid peroxidation levels, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase and catalase activity in (aspartame MTX)-treated animals and with a significant decrease in reduced glutathione, glutathione reductase and protein thiol, pointing out the generation of free radicals. The gene and protein expression of pro apoptotic marker Bax showed a marked increase whereas the anti-apoptotic marker Bcl-2 decreased markedly indicating the aspartame is harmful at cellular level. It is clear that long term aspartame exposure could alter the brain antioxidant status, and can induce apoptotic changes in brain.

  4. Long-term impact of parental divorce on intimate relationship quality in adulthood and the mediating role of psychosocial resources.

    PubMed

    Mustonen, Ulla; Huurre, Taina; Kiviruusu, Olli; Haukkala, Ari; Aro, Hillevi

    2011-08-01

    The purpose of this 16-year prospective follow-up study was to investigate the association between parental divorce in childhood and intimate relationship quality in adulthood. The mediating role of psychosocial resources (parent-child relationships at 16 years, self-esteem and social support at 32 years) in this association was also studied. All 16 year olds of one Finnish city completed questionnaires at school and were followed up by postal questionnaires at 32 years of age (n = 1,471). Results showed that women and men from divorced families were more often divorced or separated at the age of 32 years than those from nondivorced families. However, parental divorce was associated with poorer intimate relationship quality only among women. Women from divorced families also had poorer relationships with their father and mother in adolescence, and they had lower self-esteem and satisfaction with social support in adulthood than women from intact families. No such associations were found among men. The impact of parental divorce on intimate relationship quality among women was partially mediated by mother-daughter relationship, self-esteem, and satisfaction with social support. The mediating role of mother-daughter relationship was not direct, however, but was mediated via self-esteem and satisfaction with social support. Our findings indicate that parental divorce affects daughters more than sons. In the context of parental divorce, the mother-daughter relationship in adolescence is important for the development of later psychosocial resources and, via them, for intimate relationship quality.

  5. Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non-obese humans.

    PubMed

    Meydani, Simin N; Das, Sai K; Pieper, Carl F; Lewis, Michael R; Klein, Sam; Dixit, Vishwa D; Gupta, Alok K; Villareal, Dennis T; Bhapkar, Manjushri; Huang, Megan; Fuss, Paul J; Roberts, Susan B; Holloszy, John O; Fontana, Luigi

    2016-07-01

    Calorie restriction (CR) inhibits inflammation and slows aging in many animal species, but in rodents housed in pathogen-free facilities, CR impairs immunity against certain pathogens. However, little is known about the effects of long-term moderate CR on immune function in humans. In this multi-center, randomized clinical trial to determine CR's effect on inflammation and cell-mediated immunity, 218 healthy non-obese adults (20-50 y), were assigned 25% CR (n=143) or an ad-libitum (AL) diet (n=75), and outcomes tested at baseline, 12, and 24 months of CR. CR induced a 10.4% weight loss over the 2-y period. Relative to AL group, CR reduced circulating inflammatory markers, including total WBC and lymphocyte counts, ICAM-1 and leptin. Serum CRP and TNF-α concentrations were about 40% and 50% lower in CR group, respectively. CR had no effect on the delayed-type hypersensitivity skin response or antibody response to vaccines, nor did it cause difference in clinically significant infections. In conclusion, long-term moderate CR without malnutrition induces a significant and persistent inhibition of inflammation without impairing key in vivo indicators of cell-mediated immunity. Given the established role of these pro-inflammatory molecules in the pathogenesis of multiple chronic diseases, these CR-induced adaptations suggest a shift toward a healthy phenotype. PMID:27410480

  6. Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non-obese humans.

    PubMed

    Meydani, Simin N; Das, Sai K; Pieper, Carl F; Lewis, Michael R; Klein, Sam; Dixit, Vishwa D; Gupta, Alok K; Villareal, Dennis T; Bhapkar, Manjushri; Huang, Megan; Fuss, Paul J; Roberts, Susan B; Holloszy, John O; Fontana, Luigi

    2016-07-01

    Calorie restriction (CR) inhibits inflammation and slows aging in many animal species, but in rodents housed in pathogen-free facilities, CR impairs immunity against certain pathogens. However, little is known about the effects of long-term moderate CR on immune function in humans. In this multi-center, randomized clinical trial to determine CR's effect on inflammation and cell-mediated immunity, 218 healthy non-obese adults (20-50 y), were assigned 25% CR (n=143) or an ad-libitum (AL) diet (n=75), and outcomes tested at baseline, 12, and 24 months of CR. CR induced a 10.4% weight loss over the 2-y period. Relative to AL group, CR reduced circulating inflammatory markers, including total WBC and lymphocyte counts, ICAM-1 and leptin. Serum CRP and TNF-α concentrations were about 40% and 50% lower in CR group, respectively. CR had no effect on the delayed-type hypersensitivity skin response or antibody response to vaccines, nor did it cause difference in clinically significant infections. In conclusion, long-term moderate CR without malnutrition induces a significant and persistent inhibition of inflammation without impairing key in vivo indicators of cell-mediated immunity. Given the established role of these pro-inflammatory molecules in the pathogenesis of multiple chronic diseases, these CR-induced adaptations suggest a shift toward a healthy phenotype.

  7. Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non-obese humans

    PubMed Central

    Meydani, Simin N.; Das, Sai K.; Pieper, Carl F.; Lewis, Michael R.; Klein, Sam; Dixit, Vishwa D.; Gupta, Alok K.; Villareal, Dennis T.; Bhapkar, Manjushri; Huang, Megan; Fuss, Paul J.; Roberts, Susan B.; Holloszy, John O.; Fontana, Luigi

    2016-01-01

    Calorie restriction (CR) inhibits inflammation and slows aging in many animal species, but in rodents housed in pathogen-free facilities, CR impairs immunity against certain pathogens. However, little is known about the effects of long-term moderate CR on immune function in humans. In this multi-center, randomized clinical trial to determine CR's effect on inflammation and cell-mediated immunity, 218 healthy non-obese adults (20-50 y), were assigned 25% CR (n=143) or an ad-libitum (AL) diet (n=75), and outcomes tested at baseline, 12, and 24 months of CR. CR induced a 10.4% weight loss over the 2-y period. Relative to AL group, CR reduced circulating inflammatory markers, including total WBC and lymphocyte counts, ICAM-1 and leptin. Serum CRP and TNF-α concentrations were about 40% and 50% lower in CR group, respectively. CR had no effect on the delayed-type hypersensitivity skin response or antibody response to vaccines, nor did it cause difference in clinically significant infections. In conclusion, long-term moderate CR without malnutrition induces a significant and persistent inhibition of inflammation without impairing key in vivo indicators of cell-mediated immunity. Given the established role of these pro-inflammatory molecules in the pathogenesis of multiple chronic diseases, these CR-induced adaptations suggest a shift toward a healthy phenotype. PMID:27410480

  8. Protein kinases, nitric oxide and long-term depression of synapses in the cerebellum.

    PubMed

    Crepel, F; Jaillard, D

    1990-10-01

    We have analysed the effects of polymyxin B, a potent inhibitor of calcium-dependent protein kinases, of L-N-monomethylarginine, an inhibitor of nitric oxide synthesis, and of methylene blue which prevents activation of soluble guanylate cyclase, on long-term depression of parallel fibre-mediated EPSPs of rat cerebellar Purkinje cells in slices maintained in-vitro. In control conditions, a long-term depression of parallel fibre-mediated EPSPs was consistently induced by their pairing with calcium spikes directly elicited in the postsynaptic cells. This long-term change in synaptic strength was not observed in the presence of polymyxin B, of L-N-monomethylarginine, or of methylene blue, suggesting that calcium-dependent protein kinases and nitric oxide are both involved.

  9. Long-term nitric oxide deficiency causes muscarinic supersensitivity and reduces β3-adrenoceptor-mediated relaxation, causing rat detrusor overactivity

    PubMed Central

    Mónica, F Z T; Bricola, A A O; Báu, F R; Freitas, L L Lopes; Teixeira, S A; Muscará, M N; Abdalla, F M F; Porto, C S; De Nucci, G; Zanesco, A; Antunes, E

    2008-01-01

    Background and purpose: Overactive bladder is a complex and widely prevalent condition, but little is known about its physiopathology. We have carried out morphological, biochemical and functional assays to investigate the effects of long-term nitric oxide (NO) deficiency on muscarinic receptor and β-adrenoceptor modulation leading to overactivity of rat detrusor muscle. Experimental approach: Male Wistar rats received Nω-nitro-L-arginine methyl ester (L-NAME) in drinking water for 7–30 days. Functional responses to muscarinic and β-adrenoceptor agonists were measured in detrusor smooth muscle (DSM) strips in Krebs–Henseleit solution. Measurements of [3H]inositol phosphate, NO synthase (NOS) activity, [3H]quinuclidinyl benzilate ([3H]QNB) binding and bladder morphology were also performed. Key results: Long-term L-NAME treatment significantly increased carbachol-induced DSM contractile responses after 15 and 30 days; relaxing responses to the β3-adrenoceptor agonist BRL 37-344 were significantly reduced at 30 days. Constitutive NOS activity in bladder was reduced by 86% after 7 days and maintained up to 30 days of L-NAME treatment. Carbachol increased sixfold the [3H]inositol phosphate in bladder tissue from rats treated with L-NAME. [3H]QNB was bound with an apparent KD twofold higher in bladder membranes after L-NAME treatment compared with that in control. No morphological alterations in DSM were found. Conclusions and implications: Long-term NO deficiency increased rat DSM contractile responses to a muscarinic agonist, accompanied by significantly enhanced KD values for muscarinic receptors and [3H]inositol phosphate accumulation in bladder. This supersensitivity for muscarinic agonists along with reductions of β3-adrenoceptor-mediated relaxations indicated that overactive DSM resulted from chronic NO deficiency. PMID:18297104

  10. Up-regulation of 5-HT2B receptor density and receptor-mediated glycogenolysis in mouse astrocytes by long-term fluoxetine administration.

    PubMed

    Kong, Ebenezer K C; Peng, Liang; Chen, Ye; Yu, Albert C H; Hertz, Leif

    2002-02-01

    The effects were studied of short-term (1 week) versus long-term (2-3 weeks) fluoxetine treatment of primary cultures of mouse astrocytes, differentiated by treatment with dibutyryl cyclic AMP. From previous experiments it is known that acute treatment with fluoxetine stimulates glycogenolysis and increases free cytosolic Ca2+ concentration ([Ca2+]i]) in these cultures, whereas short-term (one week) treatment with 10 microM down-regulates the effects on glycogen and [Ca2+]i, when fluoxetine administration is renewed (or when serotonin is administered). Moreover, antagonist studies have shown that these responses are evoked by activation of a 5-HT2, receptor that is different from the 5-HT2A receptor and therefore at that time tentatively were interpreted as being exerted on 5-HT2C receptors. In the present study the cultures were found by RT-PCR to express mRNA for 5-HT2A and 5-HT2B receptors, but not for the 5-HT2C receptor, identifying the 5-HT2 receptor activated by fluoxetine as the 5-HT2B receptor, the most recently cloned 5-Ht2 receptor and a 5-HT receptor known to be more abundant in human, than in rodent, brain. Both short-term and long-term treatment with fluoxetine increased the specific binding of [3H]mesulergine, a ligand for alL three 5-HT2 receptors. Long-term treatment with fluoxetine caused an agonist-induced up-regulation of the glycogenolytic response to renewed administration of fluoxetine, whereas short-term treatment abolished the fluoxetine-induced hydrolysis of glycogen. Thus, during a treatment period similar to that required for fluoxetine's clinical response to occur, 5-HT2B-mediated effects are initially down-regulated and subsequently up-regulated. PMID:11930908

  11. Differential Modulation of GABAA Receptors Underlies Postsynaptic Depolarization- and Purinoceptor-Mediated Enhancement of Cerebellar Inhibitory Transmission: A Non-Stationary Fluctuation Analysis Study

    PubMed Central

    Ono, Yumie; Saitow, Fumihito; Konishi, Shiro

    2016-01-01

    Cerebellar GABAergic inhibitory transmission between interneurons and Purkinje cells (PCs) undergoes a long-lasting enhancement following different stimulations, such as brief depolarization or activation of purinergic receptors of postsynaptic PCs. The underlying mechanisms, however, are not completely understood. Using a peak-scaled non-stationary fluctuation analysis, we therefore aimed at characterizing changes in the electrophysiological properties of GABAA receptors in PCs of rat cerebellar cortex during depolarization-induced “rebound potentiation (RP)” and purinoceptor-mediated long-term potentiation (PM-LTP), because both RP and PM-LTP likely depend on postsynaptic mechanisms. Stimulation-evoked inhibitory postsynaptic currents (eIPSCs) were recorded from PCs in neonatal rat cerebellar slices. Our analysis showed that postsynaptic membrane depolarization induced RP of eIPSCs in association with significant increase in the number of synaptic GABAA receptors without changing the channel conductance. By contrast, bath application of ATP induced PM-LTP of eIPSCs with a significant increase of the channel conductance of GABAA receptors without affecting the receptor number. Pretreatment with protein kinase A (PKA) inhibitors, H-89 and cAMPS-Rp, completely abolished the PM-LTP. The CaMKII inhibitor KN-62 reported to abolish RP did not alter PM-LTP. These results suggest that the signaling mechanism underlying PM-LTP could involve ATP-induced phosphorylation of synaptic GABAA receptors, thereby resulting in upregulation of the channel conductance by stimulating adenylyl cyclase-PKA signaling cascade, possibly via activation of P2Y11 purinoceptor. Thus, our findings reveal that postsynaptic GABAA receptors at the interneuron-PC inhibitory synapses are under the control of two distinct forms of long-term potentiation linked with different second messenger cascades. PMID:26930485

  12. Long-term effects of rapamycin treatment on insulin mediated phosphorylation of Akt/PKB and glycogen synthase activity

    SciTech Connect

    Varma, Shailly; Shrivastav, Anuraag; Changela, Sheena; Khandelwal, Ramji L.

    2008-04-01

    Protein kinase B (Akt/PKB) is a Ser/Thr kinase that is involved in the regulation of cell proliferation/survival through mammalian target of rapamycin (mTOR) and the regulation of glycogen metabolism through glycogen synthase kinase 3{beta} (GSK-3{beta}) and glycogen synthase (GS). Rapamycin is an inhibitor of mTOR. The objective of this study was to investigate the effects of rapamycin pretreatment on the insulin mediated phosphorylation of Akt/PKB phosphorylation and GS activity in parental HepG2 and HepG2 cells with overexpression of constitutively active Akt1/PKB-{alpha} (HepG2-CA-Akt/PKB). Rapamycin pretreatment resulted in a decrease (20-30%) in the insulin mediated phosphorylation of Akt1 (Ser 473) in parental HepG2 cells but showed an upregulation of phosphorylation in HepG2-CA-Akt/PKB cells. Rictor levels were decreased (20-50%) in parental HepG2 cells but were not significantly altered in the HepG2-CA-Akt/PKB cells. Furthermore, rictor knockdown decreased the phosphorylation of Akt (Ser 473) by 40-60% upon rapamycin pretreatment. GS activity followed similar trends as that of phosphorylated Akt and so with rictor levels in these cells pretreated with rapamycin; parental HepG2 cells showed a decrease in GS activity, whereas as HepG2-CA-Akt/PKB cells showed an increase in GS activity. The changes in the levels of phosphorylated Akt/PKB (Ser 473) correlated with GS and protein phoshatase-1 activity.

  13. IDO and regulatory T cell support are critical for cytotoxic T lymphocyte-associated Ag-4 Ig-mediated long-term solid organ allograft survival.

    PubMed

    Sucher, Robert; Fischler, Klaus; Oberhuber, Rupert; Kronberger, Irmgard; Margreiter, Christian; Ollinger, Robert; Schneeberger, Stefan; Fuchs, Dietmar; Werner, Ernst R; Watschinger, Katrin; Zelger, Bettina; Tellides, George; Pilat, Nina; Pratschke, Johann; Margreiter, Raimund; Wekerle, Thomas; Brandacher, Gerald

    2012-01-01

    Costimulatory blockade of CD28-B7 interaction with CTLA4Ig is a well-established strategy to induce transplantation tolerance. Although previous in vitro studies suggest that CTLA4Ig upregulates expression of the immunoregulatory enzyme IDO in dendritic cells, the relationship of CTLA4Ig and IDO in in vivo organ transplantation remains unclear. In this study, we studied whether concerted immunomodulation in vivo by CTLA4Ig depends on IDO. C57BL/6 recipients receiving a fully MHC-mismatched BALB/c heart graft treated with CTLA4Ig + donor-specific transfusion showed indefinite graft survival (>100 d) without signs of chronic rejection or donor specific Ab formation. Recipients with long-term surviving grafts had significantly higher systemic IDO activity as compared with rejectors, which markedly correlated with intragraft IDO and Foxp3 levels. IDO inhibition with 1-methyl-dl-tryptophan, either at transplant or at postoperative day 50, abrogated CTLA4Ig + DST-induced long-term graft survival. Importantly, IDO1 knockout recipients experienced acute rejection and graft survival comparable to controls. In addition, αCD25 mAb-mediated depletion of regulatory T cells (Tregs) resulted in decreased IDO activity and again prevented CTLA4Ig + DST induced indefinite graft survival. Our results suggest that CTLA4Ig-induced tolerance to murine cardiac allografts is critically dependent on synergistic cross-linked interplay of IDO and Tregs. These results have important implications for the clinical development of this costimulatory blocker.

  14. Similar cation channels mediate protection from cerebellar exitotoxicity by exercise and inheritance

    PubMed Central

    Ben-Ari, Shani; Ofek, Keren; Barbash, Shahar; Meiri, Hanoch; Kovalev, Eugenia; Greenberg, David Samuel; Soreq, Hermona; Shoham, Shai

    2012-01-01

    Abstract Exercise and inherited factors both affect recovery from stroke and head injury, but the underlying mechanisms and interconnections between them are yet unknown. Here, we report that similar cation channels mediate the protective effect of exercise and specific genetic background in a kainate injection model of cerebellar stroke. Microinjection to the cerebellum of the glutamatergic agonist, kainate, creates glutamatergic excito-toxicity characteristic of focal stroke, head injury or alcoholism. Inherited protection and prior exercise were both accompanied by higher cerebellar expression levels of the Kir6.1 ATP-dependent potassium channel in adjacent Bergmann glia, and voltage-gated KVbeta2 and cyclic nucleotide-gated cation HCN1 channels in basket cells. Sedentary FVB/N and exercised C57BL/6 mice both expressed higher levels of these cation channels compared to sedentary C57BL/6 mice, and were both found to be less sensitive to glutamate toxicity. Moreover, blocking ATP-dependent potassium channels with Glibenclamide enhanced kainate-induced cell death in cerebellar slices from the resilient sedentary FVB/N mice. Furthermore, exercise increased the number of acetylcholinesterase-positive fibres in the molecular layer, reduced cerebellar cytokine levels and suppressed serum acetylcholinesterase activity, suggesting anti-inflammatory protection by enhanced cholinergic signalling. Our findings demonstrate for the first time that routine exercise and specific genetic backgrounds confer protection from cerebellar glutamatergic damages by similar molecular mechanisms, including elevated expression of cation channels. In addition, our findings highlight the involvement of the cholinergic anti-inflammatory pathway in insult-inducible cerebellar processes. These mechanisms are likely to play similar roles in other brain regions and injuries as well, opening new venues for targeted research efforts. PMID:21507200

  15. Neutrophil elastase mediates acute pathogenesis and is a determinant of long-term behavioral recovery after traumatic injury to the immature brain.

    PubMed

    Semple, Bridgette D; Trivedi, Alpa; Gimlin, Kayleen; Noble-Haeusslein, Linda J

    2015-02-01

    While neutrophil elastase (NE), released by activated neutrophils, is a key mediator of secondary pathogenesis in adult models of brain ischemia and spinal cord injury, no studies to date have examined this protease in the context of the injured immature brain, where there is notable vulnerability resulting from inadequate antioxidant reserves and prolonged exposure to infiltrating neutrophils. We thus reasoned that NE may be a key determinant of secondary pathogenesis, and as such, adversely influence long-term neurological recovery. To address this hypothesis, wild-type (WT) and NE knockout (KO) mice were subjected to a controlled cortical impact at post-natal day 21, approximating a toddler-aged child. To determine if NE is required for neutrophil infiltration into the injured brain, and whether this protease contributes to vasogenic edema, we quantified neutrophil numbers and measured water content in the brains of each of these genotypes. While leukocyte trafficking was indistinguishable between genotypes, vasogenic edema was markedly attenuated in the NE KO. To determine if early pathogenesis is dependent on NE, indices of cell death (TUNEL and activated caspase-3) were quantified across genotypes. NE KO mice showed a reduction in these markers of cell death in the injured hippocampus, which corresponded to greater preservation of neuronal integrity as well as reduced expression of heme oxygenase-1, a marker of oxidative stress. WT mice, treated with a competitive inhibitor of NE at 2, 6 and 12h post-injury, likewise showed a reduction in cell death and oxidative stress compared to vehicle-treated controls. We next examined the long-term behavioral and structural consequences of NE deficiency. NE KO mice showed an improvement in long-term spatial memory retention and amelioration of injury-induced hyperactivity. However, volumetric and stereological analyses found comparable tissue loss in the injured cortex and hippocampus independent of genotype. Further

  16. Endothelin-1 Mediates Brain Microvascular Dysfunction Leading to Long-Term Cognitive Impairment in a Model of Experimental Cerebral Malaria

    PubMed Central

    Freeman, Brandi D.; Martins, Yuri C.; Akide-Ndunge, Oscar B.; Bruno, Fernando P.; Wang, Hua; Tanowitz, Herbert B.; Spray, David C.; Desruisseaux, Mahalia S.

    2016-01-01

    Plasmodium falciparum infection causes a wide spectrum of diseases, including cerebral malaria, a potentially life-threatening encephalopathy. Vasculopathy is thought to contribute to cerebral malaria pathogenesis. The vasoactive compound endothelin-1, a key participant in many inflammatory processes, likely mediates vascular and cognitive dysfunctions in cerebral malaria. We previously demonstrated that C57BL6 mice infected with P. berghei ANKA, our fatal experimental cerebral malaria model, sustained memory loss. Herein, we demonstrate that an endothelin type A receptor (ETA) antagonist prevented experimental cerebral malaria-induced neurocognitive impairments and improved survival. ETA antagonism prevented blood-brain barrier disruption and cerebral vasoconstriction during experimental cerebral malaria, and reduced brain endothelial activation, diminishing brain microvascular congestion. Furthermore, exogenous endothelin-1 administration to P. berghei NK65-infected mice, a model generally regarded as a non-cerebral malaria negative control for P. berghei ANKA infection, led to experimental cerebral malaria-like memory deficits. Our data indicate that endothelin-1 is critical in the development of cerebrovascular and cognitive impairments with experimental cerebral malaria. This vasoactive peptide may thus serve as a potential target for adjunctive therapy in the management of cerebral malaria. PMID:27031954

  17. Assessing the value of post-processed state-of-the-art long-term weather forecast ensembles for agricultural water management mediated by farmers' behaviours

    NASA Astrophysics Data System (ADS)

    Li, Yu; Giuliani, Matteo; Castelletti, Andrea

    2016-04-01

    Recent advances in modelling of coupled ocean-atmosphere dynamics significantly improved skills of long-term climate forecast from global circulation models (GCMs). These more accurate weather predictions are supposed to be a valuable support to farmers in optimizing farming operations (e.g. crop choice, cropping and watering time) and for more effectively coping with the adverse impacts of climate variability. Yet, assessing how actually valuable this information can be to a farmer is not straightforward and farmers' response must be taken into consideration. Indeed, in the context of agricultural systems potentially useful forecast information should alter stakeholders' expectation, modify their decisions, and ultimately produce an impact on their performance. Nevertheless, long-term forecast are mostly evaluated in terms of accuracy (i.e., forecast quality) by comparing hindcast and observed values and only few studies investigated the operational value of forecast looking at the gain of utility within the decision-making context, e.g. by considering the derivative of forecast information, such as simulated crop yields or simulated soil moisture, which are essential to farmers' decision-making process. In this study, we contribute a step further in the assessment of the operational value of long-term weather forecasts products by embedding these latter into farmers' behavioral models. This allows a more critical assessment of the forecast value mediated by the end-users' perspective, including farmers' risk attitudes and behavioral patterns. Specifically, we evaluate the operational value of thirteen state-of-the-art long-range forecast products against climatology forecast and empirical prediction (i.e. past year climate and historical average) within an integrated agronomic modeling framework embedding an implicit model of the farmers' decision-making process. Raw ensemble datasets are bias-corrected and downscaled using a stochastic weather generator, in

  18. The p53 inhibitor MDM2 facilitates Sonic Hedgehog-mediated tumorigenesis and influences cerebellar foliation.

    PubMed

    Malek, Reem; Matta, Jennifer; Taylor, Natalie; Perry, Mary Ellen; Mendrysa, Susan M

    2011-01-01

    Disruption of cerebellar granular neuronal precursor (GNP) maturation can result in defects in motor coordination and learning, or in medulloblastoma, the most common childhood brain tumor. The Sonic Hedgehog (Shh) pathway is important for GNP proliferation; however, the factors regulating the extent and timing of GNP proliferation, as well as GNP differentiation and migration are poorly understood. The p53 tumor suppressor has been shown to negatively regulate the activity of the Shh effector, Gli1, in neural stem cells; however, the contribution of p53 to the regulation of Shh signaling in GNPs during cerebellar development has not been determined. Here, we exploited a hypomorphic allele of Mdm2 (Mdm2(puro)), which encodes a critical negative regulator of p53, to alter the level of wild-type MDM2 and p53 in vivo. We report that mice with reduced levels of MDM2 and increased levels of p53 have small cerebella with shortened folia, reminiscent of deficient Shh signaling. Indeed, Shh signaling in Mdm2-deficient GNPs is attenuated, concomitant with decreased expression of the Shh transducers, Gli1 and Gli2. We also find that Shh stimulation of GNPs promotes MDM2 accumulation and enhances phosphorylation at serine 166, a modification known to increase MDM2-p53 binding. Significantly, loss of MDM2 in Ptch1(+/-) mice, a model for Shh-mediated human medulloblastoma, impedes cerebellar tumorigenesis. Together, these results place MDM2 at a major nexus between the p53 and Shh signaling pathways in GNPs, with key roles in cerebellar development, GNP survival, cerebellar foliation, and MB tumorigenesis. PMID:21437245

  19. Long-term aerosol-mediated changes in cloud radiative forcing of deep clouds at the top and bottom of the atmosphere over the Southern Great Plains

    NASA Astrophysics Data System (ADS)

    Yan, Hongru; Li, Zhanqing; Huang, Jianping; Cribb, Maureen; Liu, Jianjun

    2014-02-01

    Aerosols can alter the macro- and micro-physical properties of deep convective clouds (DCC) and their radiative forcing (CRF). This study presents what is arguably the first long-term estimate of the aerosol-mediated changes in CRF (AMCRF) for deep cloud systems derived from decade-long continuous ground-based and satellite observations, model simulations and reanalysis data. Measurements were made at the US Department of Energy's Atmospheric Radiation Measurement Program's Southern Great Plains (SGP) site. Satellite retrievals are from the Geostationary Operational Environmental Satellite (GOES). Increases in aerosol loading were accompanied by the thickening of DCC cores and the expansion and thinning of anvils, due presumably to the aerosol invigoration effect (AIV) and the aerosol microphysical effect (AME). Meteorological variables dictating these cloud processes were investigated. Consistent with previous findings, the AIV is most significant when the atmosphere is moist and unstable with weak wind shear. Such aerosol-mediated systematic changes in DCC core thickness and anvil size alter CRF at the top of atmosphere (TOA) and at the surface. Using extensive observations, ~300 DCC systems were identified over a 10 yr period at the SGP site (2000-2011) and analyzed. Daily mean AMCRF at the TOA and at the surface are 29.3 W m-2 and 22.2 W m-2, respectively. This net warming effect due to changes in DCC microphysics offsets the cooling resulting from the first aerosol indirect effect.

  20. Long-term aerosol-mediated changes in cloud radiative forcing of deep clouds at the top and bottom of the atmosphere over the Southern Great Plains

    NASA Astrophysics Data System (ADS)

    Yan, Hongru; Li, Zhanqing; Huang, Jianping; Cribb, Maureen; Liu, Jianjun

    2014-07-01

    Aerosols can alter the macro- and micro-physical properties of deep convective clouds (DCCs) and their radiative forcing (CRF). This study presents what is arguably the first long-term estimate of the aerosol-mediated changes in CRF (AMCRF) for deep cloud systems derived from decade-long continuous ground-based and satellite observations, model simulations, and reanalysis data. Measurements were made at the US Department of Energy's Atmospheric Radiation Measurement Program's Southern Great Plains (SGP) site. Satellite retrievals are from the Geostationary Operational Environmental Satellite. Increases in aerosol loading were accompanied by the thickening of DCC cores and the expansion and thinning of anvils, due presumably to the aerosol invigoration effect (AIV) and the aerosol microphysical effect. Meteorological variables dictating these cloud processes were investigated. Consistent with previous findings, the AIV is most significant when the atmosphere is moist and unstable with weak wind shear. Such aerosol-mediated systematic changes in DCC core thickness and anvil size alter CRF at the top of atmosphere (TOA) and at the surface. Using extensive observations, ~300 DCC systems were identified over a 10 years period at the SGP site (2000-2011) and analyzed. Daily mean AMCRF at the TOA and at the surface are 29.3 W m-2 and 22.2 W m-2, respectively. This net warming effect due to changes in DCC microphysics offsets the cooling resulting from the first aerosol indirect effect.

  1. A BTLA-mediated bait and switch strategy permits Listeria expansion in CD8α(+) DCs to promote long-term T cell responses.

    PubMed

    Yang, Xuanming; Zhang, Xunmin; Sun, Yonglian; Tu, Tony; Fu, May Lynne; Miller, Mendy; Fu, Yang-Xin

    2014-07-01

    Listeria monocytogenes infected CD8α(+) DCs in the spleen are essential for CD8(+) T cell generation. CD8α(+) DCs are also necessary for Listeria expansion and dissemination within the host. The mechanisms that regulate CD8α(+) DCs to allow Listeria expansion are unclear. We find that activating the B and T lymphocyte attenuator (BTLA), a coinhibitory receptor for T cells, suppresses, while blocking BTLA enhances, both the primary and memory CD8 T cell responses against Listeria. Btla(-/-) mice have lower effector and memory CD8(+) T cells while paradoxically also being more resistant to Listeria. Although bacterial entry into Btla(-/-) CD8α(+) DCs is unaffected, Listeria fails to expand within these cells. BTLA signaling limits Fas/FasL-mediated suppression of Listeria expansion within CD8α(+) DCs to more effectively alert adaptive immune cells. This study uncovers a BTLA-mediated strategy used by the host that permits Listeria proliferation to enable increasing T cell responses for long-term protection.

  2. Working memory mediates the relationship between intellectual enrichment and long-term memory in multiple sclerosis: an exploratory analysis of cognitive reserve.

    PubMed

    Sandry, Joshua; Sumowski, James F

    2014-09-01

    Some individuals with multiple sclerosis (MS) show decrements in long-term memory (LTM) while other individuals do not. The theory of cognitive reserve suggests that individuals with greater pre-morbid intellectual enrichment are protected from disease-related cognitive decline. How intellectual enrichment affords this benefit remains poorly understood. The present study tested an exploratory meditational hypothesis whereby working memory (WM) capacity may mediate the relationship between intellectual enrichment and verbal LTM decline in MS. Intellectual enrichment, verbal LTM, and WM capacity were estimated with the Wechsler Test of Adult Reading and Peabody Picture Vocabulary Test, delayed recall of the Hopkins Verbal Learning Test-Revised and Logical Memory of the Wechsler Memory Scale, and Digit Span Total, respectively. Intellectual enrichment predicted LTM (B=.54; p=.003) and predicted WM capacity (B=.91; p<.001). WM capacity predicted LTM, (B=.44; p<.001) and fully mediated the relationship between intellectual enrichment (B=.24; p=.27) and LTM (B=.33, p=.03), Sobel test, Z=3.31, p<.001. These findings implicate WM capacity as an underlying mechanism of cognitive reserve and are an initial first step in understanding the relationship between intellectual enrichment, WM, and LTM in MS. PMID:25017699

  3. Myosin II ATPase activity mediates the long-term potentiation-induced exodus of stable F-actin bound by drebrin A from dendritic spines.

    PubMed

    Mizui, Toshiyuki; Sekino, Yuko; Yamazaki, Hiroyuki; Ishizuka, Yuta; Takahashi, Hideto; Kojima, Nobuhiko; Kojima, Masami; Shirao, Tomoaki

    2014-01-01

    The neuronal actin-binding protein drebrin A forms a stable structure with F-actin in dendritic spines. NMDA receptor activation causes an exodus of F-actin bound by drebrin A (DA-actin) from dendritic spines, suggesting a pivotal role for DA-actin exodus in synaptic plasticity. We quantitatively assessed the extent of DA-actin localization to spines using the spine-dendrite ratio of drebrin A in cultured hippocampal neurons, and found that (1) chemical long-term potentiation (LTP) stimulation induces rapid DA-actin exodus and subsequent DA-actin re-entry in dendritic spines, (2) Ca(2+) influx through NMDA receptors regulates the exodus and the basal accumulation of DA-actin, and (3) the DA-actin exodus is blocked by myosin II ATPase inhibitor, but is not blocked by myosin light chain kinase (MLCK) or Rho-associated kinase (ROCK) inhibitors. These results indicate that myosin II mediates the interaction between NMDA receptor activation and DA-actin exodus in LTP induction. Furthermore, myosin II seems to be activated by a rapid actin-linked mechanism rather than slow MLC phosphorylation. Thus the myosin-II mediated DA-actin exodus might be an initial event in LTP induction, triggering actin polymerization and spine enlargement.

  4. Myosin II ATPase Activity Mediates the Long-Term Potentiation-Induced Exodus of Stable F-Actin Bound by Drebrin A from Dendritic Spines

    PubMed Central

    Mizui, Toshiyuki; Sekino, Yuko; Yamazaki, Hiroyuki; Ishizuka, Yuta; Takahashi, Hideto; Kojima, Nobuhiko; Kojima, Masami; Shirao, Tomoaki

    2014-01-01

    The neuronal actin-binding protein drebrin A forms a stable structure with F-actin in dendritic spines. NMDA receptor activation causes an exodus of F-actin bound by drebrin A (DA-actin) from dendritic spines, suggesting a pivotal role for DA-actin exodus in synaptic plasticity. We quantitatively assessed the extent of DA-actin localization to spines using the spine-dendrite ratio of drebrin A in cultured hippocampal neurons, and found that (1) chemical long-term potentiation (LTP) stimulation induces rapid DA-actin exodus and subsequent DA-actin re-entry in dendritic spines, (2) Ca2+ influx through NMDA receptors regulates the exodus and the basal accumulation of DA-actin, and (3) the DA-actin exodus is blocked by myosin II ATPase inhibitor, but is not blocked by myosin light chain kinase (MLCK) or Rho-associated kinase (ROCK) inhibitors. These results indicate that myosin II mediates the interaction between NMDA receptor activation and DA-actin exodus in LTP induction. Furthermore, myosin II seems to be activated by a rapid actin-linked mechanism rather than slow MLC phosphorylation. Thus the myosin-II mediated DA-actin exodus might be an initial event in LTP induction, triggering actin polymerization and spine enlargement. PMID:24465547

  5. Immunological Ignorance Allows Long-Term Gene Expression After Perinatal Recombinant Adeno-Associated Virus-Mediated Gene Transfer to Murine Airways

    PubMed Central

    Carlon, Marianne S.; Vidović, Dragana; Dooley, James; da Cunha, Marina Mori; Maris, Michael; Lampi, Youlia; Toelen, Jaan; Van den Haute, Chris; Baekelandt, Veerle; Deprest, Jan; Verbeken, Erik; Liston, Adrian; Gijsbers, Rik

    2014-01-01

    Abstract Gene therapy of the lung has the potential to treat life-threatening diseases such as cystic fibrosis and α1-antitrypsin or surfactant deficiencies. A major hurdle for successful gene therapy is the development of an immune response against the transgene and/or viral vector. We hypothesized that by targeting the airways in the perinatal period, induction of an immune response against the vector particle could be prevented because of immaturity of the immune system, in turn allowing repeated gene transfer later in adult life to ensure long-term gene expression. Therefore, we readministered recombinant adeno-associated viral vector serotype 5 (rAAV2/5) to mouse airways 3 and 6 months after initial perinatal gene transfer. Our findings demonstrate that perinatal rAAV2/5-mediated gene transfer to the airways avoids a strong immune response. This immunological ignorance allows the readministration of an autologous vector later in adult life, resulting in efficient and stable gene transfer up to 7 months, without evidence of a decrease in transgene expression. Together, these data provide a basis to further explore perinatal gene therapy for pulmonary conditions with adequate gene expression up to 7 months. PMID:24548076

  6. Long-term changes in food availability mediate the effects of temperature on growth, development and survival in striped marsh frog larvae: implications for captive breeding programmes

    PubMed Central

    Courtney Jones, Stephanie K.; Munn, Adam J.; Penman, Trent D.; Byrne, Phillip G.

    2015-01-01

    Food availability and temperature are known to trigger phenotypic change, but the interactive effects between these factors are only beginning to be considered. The aim of this study was to examine the independent and interactive effects of long-term stochastic food availability and water temperature on larval survivorship, growth and development of the striped marsh frog, Limnodynastes peronii. Larval L. peronii were reared in conditions of either constant or stochastic food availability and in water at three different temperatures (18, 22 and 26°C), and effects on survival, growth and development were quantified. Over the experimental period, larval growth rate was highest and survivorship lowest at the warmest temperature. However, changes in food availability mediated the effects of temperature, with slower larval growth and higher survivorship in stochastic food availability treatments. Tadpoles in the stochastic food availability treatments did not reach metamorphosis during the experimental period, suggesting that developmental stasis may have been induced by food restriction. Overall, these results demonstrate that changes in food availability alter the effects of water temperature on survival, growth and development. From an applied perspective, understanding how environmental factors interact to cause phenotypic change may assist with amphibian conservation by improving the number of tadpoles generated in captive breeding programmes. PMID:27293714

  7. Long-term maintenance of Na+ channels at nodes of Ranvier depends on glial contact mediated by gliomedin and NrCAM.

    PubMed

    Amor, Veronique; Feinberg, Konstantin; Eshed-Eisenbach, Yael; Vainshtein, Anya; Frechter, Shahar; Grumet, Martin; Rosenbluth, Jack; Peles, Elior

    2014-04-01

    Clustering of Na(+) channels at the nodes of Ranvier is coordinated by myelinating glia. In the peripheral nervous system, axoglial contact at the nodes is mediated by the binding of gliomedin and glial NrCAM to axonal neurofascin 186 (NF186). This interaction is crucial for the initial clustering of Na(+) channels at heminodes. As a result, it is not clear whether continued axon-glial contact at nodes of Ranvier is required to maintain these channels at the nodal axolemma. Here, we report that, in contrast to mice that lack either gliomedin or NrCAM, absence of both molecules (and hence the glial clustering signal) resulted in a gradual loss of Na(+) channels and other axonal components from the nodes, the formation of binary nodes, and dysregulation of nodal gap length. Therefore, these mice exhibit neurological abnormalities and slower nerve conduction. Disintegration of the nodes occurred in an orderly manner, starting with the disappearance of neurofascin 186, followed by the loss of Na(+) channels and ankyrin G, and then βIV spectrin, a sequence that reflects the assembly of nodes during development. Finally, the absence of gliomedin and NrCAM led to the invasion of the outermost layer of the Schwann cell membrane beyond the nodal area and the formation of paranodal-like junctions at the nodal gap. Our results reveal that axon-glial contact mediated by gliomedin, NrCAM, and NF186 not only plays a role in Na(+) channel clustering during development, but also contributes to the long-term maintenance of Na(+) channels at nodes of Ranvier.

  8. Long-Term Effects of an Internet-Mediated Pedometer-Based Walking Program for Chronic Obstructive Pulmonary Disease: Randomized Controlled Trial

    PubMed Central

    Moy, Marilyn L; Martinez, Carlos H; Kadri, Reema; Roman, Pia; Holleman, Robert G; Kim, Hyungjin Myra; Nguyen, Huong Q; Cohen, Miriam D; Goodrich, David E; Giardino, Nicholas D

    2016-01-01

    Background Regular physical activity (PA) is recommended for persons with chronic obstructive pulmonary disease (COPD). Interventions that promote PA and sustain long-term adherence to PA are needed. Objective We examined the effects of an Internet-mediated, pedometer-based walking intervention, called Taking Healthy Steps, at 12 months. Methods Veterans with COPD (N=239) were randomized in a 2:1 ratio to the intervention or wait-list control. During the first 4 months, participants in the intervention group were instructed to wear the pedometer every day, upload daily step counts at least once a week, and were provided access to a website with four key components: individualized goal setting, iterative feedback, educational and motivational content, and an online community forum. The subsequent 8-month maintenance phase was the same except that participants no longer received new educational content. Participants randomized to the wait-list control group were instructed to wear the pedometer, but they did not receive step-count goals or instructions to increase PA. The primary outcome was health-related quality of life (HRQL) assessed by the St George’s Respiratory Questionnaire Total Score (SGRQ-TS); the secondary outcome was daily step count. Linear mixed-effect models assessed the effect of intervention over time. One participant was excluded from the analysis because he was an outlier. Within the intervention group, we assessed pedometer adherence and website engagement by examining percent of days with valid step-count data, number of log-ins to the website each month, use of the online community forum, and responses to a structured survey. Results Participants were 93.7% male (223/238) with a mean age of 67 (SD 9) years. At 12 months, there were no significant between-group differences in SGRQ-TS or daily step count. Between-group difference in daily step count was maximal and statistically significant at month 4 (P<.001), but approached zero in months 8

  9. Rescue of Cyclic AMP Mediated Long Term Potentiation Impairment in the Hippocampus of Mecp2 Knockout (Mecp2-/y) Mice by Rolipram

    PubMed Central

    Balakrishnan, Saju; Niebert, Marcus; Richter, Diethelm W.

    2016-01-01

    Rett syndrome (RTT) patients experience learning difficulties and memory loss. Analogous deficits of hippocampal plasticity are reported in mouse models of RTT. To elucidate the underlying pathophysiology, we studied long term potentiation (LTP) at the CA3 to CA1 synapses in the hippocampus in acute brain slices from WT and Mecp2-/y mice, by either activating cAMP dependent pathway or using high frequency stimulation, by means of patch clamp. We have observed that, the NMDA channel current characteristics remain unchanged in the Mecp2-/y mice. The adenylyl cyclase (AC) agonist forskolin evoked a long lasting potentiation of evoked EPSCs in WT CA1 neurons, but only minimally enhanced the EPSCs in the Mecp2-/y mice. This weaker potentiation in Mecp2-/y mice was ameliorated by application of phosphodiesterase 4 inhibitor rolipram. The hyperpolarization activated cyclic nucleotide gated channel current (Ih) was potentiated to similar extent by forskolin in both phenotypes. Multiple tetanus induced cAMP-dependent plasticity was also impaired in the Mecp2-/y mice, and was also partially rescued by rolipram. Western blot analysis of CA region of Mecp2-/y mice hippocampus revealed more than twofold up-regulation of protein kinase A (PKA) regulatory subunits, while the expression of the catalytic subunit remained unchanged. We hypothesize that the overexpressed PKA regulatory subunits buffer cAMP and restrict the PKA mediated phosphorylation of target proteins necessary for LTP. Blocking the degradation of cAMP, thereby saturating the regulatory subunits alleviated this defect. PMID:26869885

  10. Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non obese humans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Calorie restriction (CR) inhibits inflammation and slows aging in many animal species, but in rodents housed in pathogen-free facilities, CR impairs immunity against certain pathogens. However, little is known about the effects of long-term moderate CR on immune function in humans. In this multi-cen...

  11. LKB1 Regulates Cerebellar Development by Controlling Sonic Hedgehog-mediated Granule Cell Precursor Proliferation and Granule Cell Migration

    PubMed Central

    Men, Yuqin; Zhang, Aizhen; Li, Haixiang; Jin, Yecheng; Sun, Xiaoyang; Li, Huashun; Gao, Jiangang

    2015-01-01

    The Liver Kinase B1 (LKB1) gene plays crucial roles in cell differentiation, proliferation and the establishment of cell polarity. We created LKB1 conditional knockout mice (LKB1Atoh1 CKO) to investigate the function of LKB1 in cerebellar development. The LKB1Atoh1 CKO mice displayed motor dysfunction. In the LKB1Atoh1 CKO cerebellum, the overall structure had a larger volume and morelobules. LKB1 inactivationled to an increased proliferation of granule cell precursors (GCPs), aberrant granule cell migration and overproduction of unipolar brush cells. To investigate the mechanism underlying the abnormal foliation, we examined sonic hedgehog signalling (Shh) by testing its transcriptional mediators, the Gli proteins, which regulate the GCPs proliferation and cerebellar foliation during cerebellar development. The expression levels of Gli genes were significantly increased in the mutant cerebellum. In vitro assays showed that the proliferation of cultured GCPs from mutant cerebellum significantly increased, whereas the proliferation of mutant GCPs significantly decreased in the presence of a Shh inhibitor GDC-0049. Thus, LKB1 deficiency in the LKB1Atoh1 CKO mice enhanced Shh signalling, leading to the excessive GCP proliferation and the formation of extra lobules. We proposed that LKB1 regulates cerebellar development by controlling GCPs proliferation through Shh signalling during cerebellar development. PMID:26549569

  12. Disturbed mitotic progression and genome segregation are involved in cell transformation mediated by nano-TiO2 long-term exposure

    SciTech Connect

    Huang Shing; Chueh Pinju; Lin Yunwei; Shih Tungsheng; Chuang Showmei

    2009-12-01

    Titanium dioxide (TiO2) nano-particles (< 100 nm in diameter) have been of interest in a wide range of applications, such as in cosmetics and pharmaceuticals because of their low toxicity. However, recent studies have shown that TiO2 nano-particles (nano-TiO2) induce cytotoxicity and genotoxicity in various lines of cultured cells as well as tumorigenesis in animal models. The biological roles of nano-TiO2 are shown to be controversial and no comprehensive study paradigm has been developed to investigate their molecular mechanisms. In this study, we showed that short-term exposure to nano-TiO2 enhanced cell proliferation, survival, ERK signaling activation and ROS production in cultured fibroblast cells. Moreover, long-term exposure to nano-TiO2 not only increased cell survival and growth on soft agar but also the numbers of multinucleated cells and micronucleus (MN) as suggested in confocal microscopy analysis. Cell cycle phase analysis showed G2/M delay and slower cell division in long-term exposed cells. Most importantly, long-term TiO2 exposure remarkably affected mitotic progression at anaphase and telophase leading to aberrant multipolar spindles and chromatin alignment/segregation. Moreover, PLK1 was demonstrated as the target for nano-TiO2 in the regulation of mitotic progression and exit. Notably, a higher fraction of sub-G1 phase population appeared in TiO2-exposed cells after releasing from G2/M synchronization. Our results demonstrate that long-term exposure to nano-TiO2 disturbs cell cycle progression and duplicated genome segregation, leading to chromosomal instability and cell transformation.

  13. Calcium-Permeable AMPA Receptors Mediate the Induction of the Protein Kinase A-Dependent Component of Long-Term Potentiation in the Hippocampus

    PubMed Central

    Park, Pojeong; Sanderson, Thomas M.; Amici, Mascia; Choi, Sun-Lim; Bortolotto, Zuner A.; Zhuo, Min

    2016-01-01

    Two forms of NMDA receptor (NMDAR)-dependent long-term potentiation (LTP) at hippocampal CA1 synapses can be distinguished based on their sensitivity to inhibitors of protein kinase A (PKA). The PKA-dependent form requires multiple episodes of high-frequency stimulation (HFS) or theta burst stimuli (TBS) with a spacing between episodes in the order of minutes. To investigate the mechanism by which spaced episodes induce the PKA-dependent form of LTP, we have compared, in interleaved experiments, spaced (s) and compressed (c) TBS protocols in the rat CA1 synapses. We find that LTP induced by sTBS, but not that induced by cTBS, involves the insertion of calcium-permeable (CP) AMPARs, as assessed using pharmacological and electrophysiological criteria. Furthermore, a single TBS when paired with rolipram [4-(3-(cyclopentyloxy)-4-methoxyphenyl)pyrrolidin-2-one], to activate PKA, generates an LTP that also involves the insertion of CP-AMPARs. These data demonstrate that the involvement of CP-AMPARs in LTP is critically determined by the timing of the induction trigger and is associated specifically with the PKA-dependent form of LTP. SIGNIFICANCE STATEMENT Long-term potentiation is a family of synaptic mechanisms that are believed to be important for learning and memory. Two of the most extensively studied forms are triggered by the synaptic activation of NMDA receptors and expressed by changes in AMPA receptor function. They can be distinguished on the basis of their requirement for activation of a protein kinase, PKA. We show that the PKA-dependent form also involves the transient insertion of calcium-permeable AMPA receptors. These results have implications for relating synaptic plasticity to learning and memory and suggest a specific linkage between PKA activation and the rapid synaptic insertion of calcium-permeable AMPA receptors during long-term potentiation. PMID:26758849

  14. Long-term environmental stewardship.

    SciTech Connect

    Nagy, Michael David

    2010-08-01

    The purpose of this Supplemental Information Source Document is to effectively describe Long-Term Environmental Stewardship (LTES) at Sandia National Laboratories/New Mexico (SNL/NM). More specifically, this document describes the LTES and Long-Term Stewardship (LTS) Programs, distinguishes between the LTES and LTS Programs, and summarizes the current status of the Environmental Restoration (ER) Project.

  15. Presynaptic long-term plasticity

    PubMed Central

    Yang, Ying; Calakos, Nicole

    2013-01-01

    Long-term synaptic plasticity is a major cellular substrate for learning, memory, and behavioral adaptation. Although early examples of long-term synaptic plasticity described a mechanism by which postsynaptic signal transduction was potentiated, it is now apparent that there is a vast array of mechanisms for long-term synaptic plasticity that involve modifications to either or both the presynaptic terminal and postsynaptic site. In this article, we discuss current and evolving approaches to identify presynaptic mechanisms as well as discuss their limitations. We next provide examples of the diverse circuits in which presynaptic forms of long-term synaptic plasticity have been described and discuss the potential contribution this form of plasticity might add to circuit function. Finally, we examine the present evidence for the molecular pathways and cellular events underlying presynaptic long-term synaptic plasticity. PMID:24146648

  16. Cerebellar learning mechanisms

    PubMed Central

    Freeman, John H.

    2014-01-01

    The mechanisms underlying cerebellar learning are reviewed with an emphasis on old arguments and new perspectives on eyeblink conditioning. Eyeblink conditioning has been used for decades a model system for elucidating cerebellar learning mechanisms. The standard model of the mechanisms underlying eyeblink conditioning is that there two synaptic plasticity processes within the cerebellum that are necessary for acquisition of the conditioned response: 1) long-term depression (LTD) at parallel fiber-Purkinje cell synapses and 2) long-term potentiation (LTP) at mossy fiber-interpositus nucleus synapses. Additional Purkinje cell plasticity mechanisms may also contribute to eyeblink conditioning including LTP, excitability, and entrainment of deep nucleus activity. Recent analyses of the sensory input pathways necessary for eyeblink conditioning indicate that the cerebellum regulates its inputs to facilitate learning and maintain plasticity. Cerebellar learning during eyeblink conditioning is therefore a dynamic interactive process which maximizes responding to significant stimuli and suppresses responding to irrelevant or redundant stimuli. PMID:25289586

  17. Long term complications of diabetes

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000327.htm Long term complications of diabetes To use the sharing ... sores and infections. If it goes on too long, your toes, foot, or leg may need to ...

  18. Abdominal Pain, Long-Term

    MedlinePlus

    MENU Return to Web version Abdominal Pain, Long-term See complete list of charts. Ongoing or recurrent abdominal pain, also called chronic pain, may be difficult to diagnose, causing frustration for ...

  19. Long-term biomass research

    SciTech Connect

    Not Available

    1981-03-01

    Some of DOE's long term R and D programs for biomass are summarized in this article. These include research efforts in the fields of anaerobic digestion, energy farming, short rotation cultivation and aquatic farming. (DMC)

  20. Inhibition of the Motor Protein Eg5/Kinesin-5 in Amyloid β-Mediated Impairment of Hippocampal Long-Term Potentiation and Dendritic Spine Loss.

    PubMed

    Freund, Ronald K; Gibson, Emily S; Potter, Huntington; Dell'Acqua, Mark L

    2016-05-01

    Alzheimer's disease (AD) is characterized by neurofibrillary tangles, amyloid plaques, and neurodegeneration. However, this pathology is preceded by increased soluble amyloid beta (Aβ) 1-42 oligomers that interfere with the glutamatergic synaptic plasticity required for learning and memory, includingN-methyl-d-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP). In particular, soluble Aβ(1-42) acutely inhibits LTP and chronically causes synapse loss. Many mechanisms have been proposed for Aβ-induced synaptic dysfunction, but we recently found that Aβ(1-42) inhibits the microtubule motor protein Eg5/kinesin-5. Here we compared the impacts of Aβ(1-42) and monastrol, a small-molecule Eg5 inhibitor, on LTP in hippocampal slices and synapse loss in neuronal cultures. Acute (20-minute) treatment with monastrol, like Aβ, completely inhibited LTP at doses >100 nM. In addition, 1 nM Aβ(1-42) or 50 nM monastrol inhibited LTP #x223c;50%, and when applied together caused complete LTP inhibition. At concentrations that impaired LTP, neither Aβ(1-42) nor monastrol inhibited NMDAR synaptic responses until #x223c;60 minutes, when only #x223c;25% inhibition was seen for monastrol, indicating that NMDAR inhibition was not responsible for LTP inhibition by either agent when applied for only 20 minutes. Finally, 48 hours of treatment with either 0.5-1.0μM Aβ(1-42) or 1-5μM monastrol reduced the dendritic spine/synapse density in hippocampal cultures up to a maximum of #x223c;40%, and when applied together at maximal concentrations, no additional spine loss resulted. Thus, monastrol can mimic and in some cases occlude the impact of Aβon LTP and synapse loss, suggesting that Aβinduces acute and chronic synaptic dysfunction in part through inhibiting Eg5.

  1. Cannabis use and involuntary admission may mediate long-term adherence in first-episode psychosis patients: a prospective longitudinal study

    PubMed Central

    2013-01-01

    Background This study aimed to examine factors associated with treatment adherence in first-episode psychosis (FEP) patients followed up over 8 years, especially involuntary first admission and stopping cannabis use. Methods This prospective, longitudinal study of FEP patients collected data on symptoms, adherence, functioning, and substance use. Adherence to treatment was the main outcome variable and was categorized as ‘good’ or ‘bad’. Cannabis use during follow-up was stratified as continued use, stopped use, and never used. Bivariate and logistic regression models identified factors significantly associated with adherence and changes in adherence over the 8-year follow-up period. Results Of the 98 FEP patients analyzed at baseline, 57.1% had involuntary first admission, 74.4% bad adherence, and 52% cannabis use. Good adherence at baseline was associated with Global Assessment of Functioning score (p = 0.019), Hamilton Depression Rating Scale score (p = 0.017) and voluntary admission (p < 0.001). Adherence patterns over 8 years included: 43.4% patients always bad, 26.1% always good, 25% improved from bad to good. Among the improved adherence group, 95.7% had involuntary first admission and 38.9% stopped cannabis use. In the subgroup of patients with bad adherence at baseline, involuntary first admission and quitting cannabis use during follow up were associated with improved adherence. Conclusions The long-term association between treatment adherence and type of first admission and cannabis use in FEP patients suggest targets for intervention to improve clinical outcomes. PMID:24289797

  2. Long-term observation of permeability in sedimentary rocks under high-temperature and stress conditions and its interpretation mediated by microstructural investigations

    NASA Astrophysics Data System (ADS)

    Yasuhara, Hideaki; Kinoshita, Naoki; Ohfuji, Hiroaki; Takahashi, Manabu; Ito, Kazumasa; Kishida, Kiyoshi

    2015-07-01

    In this study, a series of long-term, intermittent permeability experiments utilizing Berea sandstone and Horonobe mudstone samples, with and without a single artificial fracture, is conducted for more than 1000 days to examine the evolution of rock permeability under relatively high-temperature and confining pressure conditions. Effluent element concentrations are also measured throughout the experiments. Before and after flow-through experiments, rock samples are prepared for X-ray diffraction, X-ray fluorescence, and scanning electron microscopy coupled with energy dispersive X-ray spectroscopy to examine the mineralogical changes between pre and postexperimental samples, and also for microfocus X-ray CT to evaluate the alteration of the microstructure. Although there are exceptions, the observed, qualitative evolution of permeability is found to be generally consistent in both the intact and the fractured rock samples—the permeability in the intact rock samples increases with time after experiencing no significant changes in permeability for the first several hundred days, while that in the fractured rock samples decreases with time. An evaluation of the Damkohler number and of the net dissolution, using the measured element concentrations, reveals that the increase in permeability can most likely be attributed to the relative dominance of the mineral dissolution in the pore spaces, while the decrease can most likely be attributed to the mineral dissolution/crushing at the propping asperities within the fracture. Taking supplemental observations by microfocus X-ray CT and using the intact sandstone samples, a slight increase in relatively large pore spaces is seen. This supports the increase in permeability observed in the flow-through experiments.

  3. Neurotoxicity of developmental hypothyroxinemia and hypothyroidism in rats: Impairments of long-term potentiation are mediated by phosphatidylinositol 3-kinase signaling pathway

    SciTech Connect

    Wang, Yi; Wei, Wei; Wang, Yuan; Dong, Jing; Song, Binbin; Min, Hui; Teng, Weiping; Chen, Jie

    2013-09-01

    Neurotoxicity of iodine deficiency-induced hypothyroidism during developmental period results in serious impairments of brain function, such as learning and memory. These impairments are largely irreversible, and the underlying mechanisms remain unclear. In addition to hypothyroidism, iodine deficiency may cause hypothyroxinemia, a relatively subtle form of thyroid hormone deficiency. Neurotoxicity of developmental hypothyroxinemia also potentially impairs learning and memory. However, more direct evidence of the associations between developmental hypothyroxinemia and impairments of learning and memory should be provided, and the underlying mechanisms remain to be elucidated. Thus, in the present study, we investigated the effects of developmental hypothyroxinemia and hypothyroidism on long-term potentiation (LTP), a widely accepted cellular model of learning and memory, in the hippocampal CA1 region. The activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway – a pathway closely associated with synaptic plasticity and learning and memory – was also investigated. Wistar rats were treated with iodine deficient diet or methimazole (MMZ) to induce developmental hypothyroxinemia or hypothyroidism. The results showed that developmental hypothyroxinemia caused by mild iodine deficiency and developmental hypothyroidism caused by severe iodine deficiency or MMZ significantly reduced the field-excitatory postsynaptic potential (f-EPSP) slope and the population spike (PS) amplitude. Decreased activation of the PI3K signaling pathway was also observed in rats subjected to developmental hypothyroxinemia or hypothyroidism. Our results may support the hypothesis that neurotoxicity of both developmental hypothyroxinemia and hypothyroidism causes damages to learning and memory. Our results also suggest that decreased activation of the PI3K signaling pathway may contribute to impairments of LTP caused by neurotoxicity of both developmental hypothyroxinemia and

  4. Ras-GRF2 mediates long-term potentiation, survival, and response to an enriched environment of newborn neurons in the hippocampus.

    PubMed

    Darcy, Michael J; Trouche, Stéphanie; Jin, Shan-Xue; Feig, Larry A

    2014-11-01

    Hippocampal adult neurogenesis contributes to key functions of the dentate gyrus (DG), including contextual discrimination. This is due, at least in part, to the unique form of plasticity that new neurons display at a specific stage of their development when compared with the surrounding principal neurons. In addition, the contribution that newborn neurons make to dentate function can be enhanced by an increase in their numbers induced by a stimulating environment. However, signaling mechanisms that regulate these properties of newborn neurons are poorly understood. Here, we show that Ras-GRF2 (GRF2), a calcium-regulated exchange factor that can activate Ras and Rac GTPases, contributes to both of these properties of newborn neurons. Using Ras-GRF2 knockout mice and wild-type mice stereotactically injected with retrovirus containing shRNA against the exchange factor, we demonstrate that GRF2 promotes the survival of newborn neurons of the DG at approximately 1-2 weeks after their birth. GRF2 also controls the distinct form of long-term potentiation that is characteristic of new neurons of the hippocampus through its effector Erk MAP kinase. Moreover, the enhancement of neuron survival that occurs after mice are exposed to an enriched environment also involves GRF2 function. Consistent with these observations, GRF2 knockout mice display defective contextual discrimination. Overall, these findings indicate that GRF2 regulates both the basal level and environmentally induced increase of newborn neuron survival, as well as in the induction of a distinct form of synaptic plasticity of newborn neurons that contributes to distinct features of hippocampus-derived learning and memory.

  5. Neurotoxicity of developmental hypothyroxinemia and hypothyroidism in rats: Impairments of long-term potentiation are mediated by phosphatidylinositol 3-kinase signaling pathway.

    PubMed

    Wang, Yi; Wei, Wei; Wang, Yuan; Dong, Jing; Song, Binbin; Min, Hui; Teng, Weiping; Chen, Jie

    2013-09-01

    Neurotoxicity of iodine deficiency-induced hypothyroidism during developmental period results in serious impairments of brain function, such as learning and memory. These impairments are largely irreversible, and the underlying mechanisms remain unclear. In addition to hypothyroidism, iodine deficiency may cause hypothyroxinemia, a relatively subtle form of thyroid hormone deficiency. Neurotoxicity of developmental hypothyroxinemia also potentially impairs learning and memory. However, more direct evidence of the associations between developmental hypothyroxinemia and impairments of learning and memory should be provided, and the underlying mechanisms remain to be elucidated. Thus, in the present study, we investigated the effects of developmental hypothyroxinemia and hypothyroidism on long-term potentiation (LTP), a widely accepted cellular model of learning and memory, in the hippocampal CA1 region. The activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway - a pathway closely associated with synaptic plasticity and learning and memory - was also investigated. Wistar rats were treated with iodine deficient diet or methimazole (MMZ) to induce developmental hypothyroxinemia or hypothyroidism. The results showed that developmental hypothyroxinemia caused by mild iodine deficiency and developmental hypothyroidism caused by severe iodine deficiency or MMZ significantly reduced the field-excitatory postsynaptic potential (f-EPSP) slope and the population spike (PS) amplitude. Decreased activation of the PI3K signaling pathway was also observed in rats subjected to developmental hypothyroxinemia or hypothyroidism. Our results may support the hypothesis that neurotoxicity of both developmental hypothyroxinemia and hypothyroidism causes damages to learning and memory. Our results also suggest that decreased activation of the PI3K signaling pathway may contribute to impairments of LTP caused by neurotoxicity of both developmental hypothyroxinemia and

  6. Adaptations of the vestibular system to short and long-term exposures to altered gravity

    NASA Astrophysics Data System (ADS)

    Bruce, L. L.

    2003-10-01

    Long-term space flight creates unique environmental conditions to which the vestibular system must adapt for optimal survival of a given organism. The development and maintenance of vestibular connections are controlled by environmental gravitational stimulation as well as genetically controlled molecular interactions. This paper describes the effects of hypergravity on axonal growth and dendritic morphology, respectively. Two aspects of this vestibular adaptation are examined: (1) How does long-term exposure to hypergravity affect the development of vestibular axons? (2) How does short-term exposure to extremely rapid changes in gravity, such as those that occur during shuttle launch and landing, affect dendrites of the vestibulocerebellar system? To study the effects of longterm exposures to altered gravity, embryonic rats that developed in hypergravity were compared to microgravity-exposed and control rats. Examination of the vestibular projections from epithelia devoted to linear and angular acceleration revealed that the terminal fields segregate differently in rat embryos that gestated in each of the gravitational environments.To study the effects of short-term exposures to altered gravity, mice were exposed briefly to strong vestibular stimuli and the vestibulocerebellum was examined for any resulting morphological changes. My data show that these stimuli cause intense vestibular excitation of cerebellar Purkinje cells, which induce up-regulation of clathrin-mediated endocytosis and other morphological changes that are comparable to those seen in long-term depression. This system provides a basis for studying how the vestibular environment can modify cerebellar function, allowing animals to adapt to new environments.

  7. Acquisition of contextual discrimination involves the appearance of a RAS-GRF1/p38 mitogen-activated protein (MAP) kinase-mediated signaling pathway that promotes long term potentiation (LTP).

    PubMed

    Jin, Shan-Xue; Arai, Junko; Tian, Xuejun; Kumar-Singh, Rajendra; Feig, Larry A

    2013-07-26

    RAS-GRF1 is a guanine nucleotide exchange factor with the ability to activate RAS and RAC GTPases in response to elevated calcium levels. We previously showed that beginning at 1 month of age, RAS-GRF1 mediates NMDA-type glutamate receptor (NMDAR)-induction of long term depression in the CA1 region of the hippocampus of mice. Here we show that beginning at 2 months of age, when mice first acquire the ability to discriminate between closely related contexts, RAS-GRF1 begins to contribute to the induction of long term potentiation (LTP) in the CA1 hippocampus by mediating the action of calcium-permeable, AMPA-type glutamate receptors (CP-AMPARs). Surprisingly, LTP induction by CP-AMPARs through RAS-GRF1 occurs via activation of p38 MAP kinase rather than ERK MAP kinase, which has more frequently been linked to LTP. Moreover, contextual discrimination is blocked by knockdown of Ras-Grf1 expression specifically in the CA1 hippocampus, infusion of a p38 MAP kinase inhibitor into the CA1 hippocampus, or the injection of an inhibitor of CP-AMPARs. These findings implicate the CA1 hippocampus in the developmentally dependent capacity to distinguish closely related contexts through the appearance of a novel LTP-supporting signaling pathway.

  8. Adaptations of the vestibular system to short and long-term exposures to altered gravity

    NASA Astrophysics Data System (ADS)

    Bruce, L.

    Long-term space flight creates unique environmental conditions to which the vestibular system must adapt for optimal survival. We are studying two aspects of this vestibular adaptation: (1) How does long-term exposure to microgravity and hypergravity affect the development of vestibular afferents? (2) How does short- term exposure to extremely rapid changes in gravity, such as those that occur during launch and landing, affect the vestibular system. During space flight the gravistatic receptors in the otolith organs are effectively unloaded. In hypergravity conditions they are overloaded. However, the angular acceleration receptors of the semicircular canals receive relatively normal stimulation in both micro- and hypergravity.Rat embryos exposed to microgravity from gestation day 10 (prior to vestibular function) until gestation day 20 (vestibular system is somewhat functional) showed that afferents from the posterior vertical canal projecting to the medial vestibular nucleus developed similarly in microgravity, hypergravity, and in controls . However, afferents from the saccule showed delayed development in microgravity as compared to development in hypergravity and in controls. Cerebellar plasticity is crucial for modification of sensory-motor control and learning. Thus we explored the possibility that strong vestibular stimuli would modify cerebellar motor control (i.e., eye movement, postural control, gut motility) by altering the morphology of cerebellar Purkinje cells. To study the effects of short-term exposures to strong vestibular stimuli we focused on structural changes in the vestibulo-cerebellum that are caused by strong vestibular stimuli. Adult mice were exposed to various combinations of constant and/or rapidly changing angular and linear accelerations for 8.5 min (the time length of shuttle launch). Our data shows that these stimuli cause intense excitation of cerebellar Purkinje cells, inducing up-regulation of clathrin-mediated endocytosis

  9. Long-term parenteral nutrition

    PubMed Central

    Ladefoged, Karin; Jarnum, Stig

    1978-01-01

    Nineteen patients (11 women and eight men) aged 20-68 received long-term parenteral nutrition, mostly at home, for six to 63 months (mean 19 months). Indications for LTPN were extensive, active Crohn's disease in three patients, intestinocutaneous fistulas in three, and short-bowel syndrome in the remaining 13 patients. Subclavian or intra-atrial (Broviac) catheters were most commonly used, for which the average life was four and seven months respectively. Complications of long-term parenteral nutrition included pneumothorax in four out of 48 subclavian vein punctures. Catheter-induced thrombosis of central veins was shown by phlebography 17 times in nine patients, and eight episodes of total occlusion occurred. Two of these patients had pulmonary infarction. Nineteen episodes of catheter sepsis occurred in 11 patients, but only one was fatal. Complications related to intestinal disease included intra-abdominal abscesses and intestinal fistulas, and disturbances of liver function. Five patients died, though in only two was death related to long-term parenteral nutrition. One of these patients died from catheter sepsis, the other had subdural haematoma possibly caused by anticoagulant treatment. Eight of the 14 surviving patients still needed parenteral nutrition. All received a disability pension, but six had an acceptable quality of life with almost normal social activities. Despite problems such as difficulties in maintaining standardised infusion programmes, it was concluded that long-term parenteral nutrition at home is practicable and consistent with an acceptable quality of life. ImagesFIG 2 PMID:98199

  10. Differential effects of short- and long-term bupivacaine treatment on α1-adrenoceptor-mediated contraction of isolated rat aorta rings and the reversal effect of lipid emulsion

    PubMed Central

    Guo, Hao; Zhang, He-fei; Xu, Wen-qi; Du, Qian; Zhao, Jing; Ren, Lei-ming

    2015-01-01

    Aim: Arterial function is significantly influenced by bupivacaine at both clinically relevant concentrations and toxic concentrations, but the underlying mechanisms are not fully understood. In the present study we investigated the role of α1-adrenoceptors in bupivacaine effects on isolated rat aortas. Methods: Isolated aortic rings were prepared from rats and suspended in an organ bath. Phenylephrine (Phe)-induced vasoconstriction and acetylcholine (ACh)-induced vasodilation were recorded through an isometric force transducer connected to a data acquisition system. Results: Administration of bupivacaine (30–300 μmol/L) produced mild vasoconstriction, and this response declined with repeated administrations. Treatment of the aortic rings with bupivacaine (3–30 μmol/L) for 20 min enhanced Phe-induced vasoconstriction, while treatment for 40 min suppressed Phe-induced vasoconstriction. Both the short- and long-term bupivacaine treatment suppressed ACh-induced vasodilation. Incubation of the aortic rings with 0.2%–0.6% lipid emulsion (LE) for 100 min significantly increased the pD2 and Emax values of Phe-induced vasoconstriction, and incubation with 0.4% LE for 100 min reversed the inhibition of bupivacaine on vasoconstriction induced by Phe (30 μmol/L). In contrast, incubation with LE suppressed ACh-induced vasodilation, even at a lower concentration and with a 5-min incubation. Conclusion: Bupivacaine exerts dual effects on α1-adrenoceptor-mediated vasoconstriction of isolated rat aortic rings: short-term treatment enhances the response, while long-term treatment inhibits it; the inhibition may be reversed via long-term incubation with LE. PMID:26073324

  11. Magnetic Beads Enhance Adhesion of NIH 3T3 Fibroblasts: A Proof-of-Principle In Vitro Study for Implant-Mediated Long-Term Drug Delivery to the Inner Ear

    PubMed Central

    Aliuos, Pooyan; Schulze, Jennifer; Schomaker, Markus; Reuter, Günter; Stolle, Stefan R. O.; Werner, Darja; Ripken, Tammo; Lenarz, Thomas; Warnecke, Athanasia

    2016-01-01

    Introduction Long-term drug delivery to the inner ear may be achieved by functionalizing cochlear implant (CI) electrodes with cells providing neuroprotective factors. However, effective strategies in order to coat implant surfaces with cells need to be developed. Our vision is to make benefit of electromagnetic field attracting forces generated by CI electrodes to bind BDNF-secreting cells that are labelled with magnetic beads (MB) onto the electrode surfaces. Thus, the effect of MB-labelling on cell viability and BDNF production were investigated. Materials and Methods Murine NIH 3T3 fibroblasts—genetically modified to produce BDNF—were labelled with MB. Results Atomic force and bright field microscopy illustrated the internalization of MB by fibroblasts after 24 h of cultivation. Labelling cells with MB did not expose cytotoxic effects on fibroblasts and allowed adhesion on magnetic surfaces with sufficient BDNF release. Discussion Our data demonstrate a novel approach for mediating enhanced long-term adhesion of BDNF-secreting fibroblasts on model electrode surfaces for cell-based drug delivery applications in vitro and in vivo. This therapeutic strategy, once transferred to cells suitable for clinical application, may allow the biological modifications of CI surfaces with cells releasing neurotrophic or other factors of interest. PMID:26918945

  12. Long-term data archiving

    SciTech Connect

    Moore, David Steven

    2009-01-01

    Long term data archiving has much value for chemists, not only to retain access to research and product development records, but also to enable new developments and new discoveries. There are some recent regulatory requirements (e.g., FDA 21 CFR Part 11), but good science and good business both benefit regardless. A particular example of the benefits of and need for long term data archiving is the management of data from spectroscopic laboratory instruments. The sheer amount of spectroscopic data is increasing at a scary rate, and the pressures to archive come from the expense to create the data (or recreate it if it is lost) as well as its high information content. The goal of long-term data archiving is to save and organize instrument data files as well as any needed meta data (such as sample ID, LIMS information, operator, date, time, instrument conditions, sample type, excitation details, environmental parameters, etc.). This editorial explores the issues involved in long-term data archiving using the example of Raman spectral databases. There are at present several such databases, including common data format libraries and proprietary libraries. However, such databases and libraries should ultimately satisfy stringent criteria for long term data archiving, including readability for long times into the future, robustness to changes in computer hardware and operating systems, and use of public domain data formats. The latter criterion implies the data format should be platform independent and the tools to create the data format should be easily and publicly obtainable or developable. Several examples of attempts at spectral libraries exist, such as the ASTM ANDI format, and the JCAMP-DX format. On the other hand, proprietary library spectra can be exchanged and manipulated using proprietary tools. As the above examples have deficiencies according to the three long term data archiving criteria, Extensible Markup Language (XML; a product of the World Wide Web

  13. Reactivation and reconsolidation of long-term memory in the crab Chasmagnathus: protein synthesis requirement and mediation by NMDA-type glutamatergic receptors.

    PubMed

    Pedreira, María Eugenia; Pérez-Cuesta, Luis María; Maldonado, Héctor

    2002-09-15

    Experiments with invertebrates support the view that intracellular events subserving the consolidation phase of memory are preserved across evolution. Here, we investigate whether such evolutionary persistence extends to reconsolidation mechanisms, which have recently received special attention in vertebrate studies. For this purpose, the memory model of the crab Chasmagnathus is used. A visual danger stimulus (VDS) elicits crab escaping, which declines after a few stimulus presentations. The long-lasting retention of this decrement, called context-signal memory (CSM), is mediated by an association between contextual cues of the training site and the VDS. The present results show amnesia for CSM in crabs re-exposed at 24 hr (day 2) for 5 min to the learning context, 24 hr after training, and injected with one of two amnesic agents, then tested 24 hr later. Agents and timing were either 15 microg of cycloheximide given between 1 hr before and 4 hr after re-exposure or 1 microg/gm (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine given between 1 hr before and 2 hr after re-exposure. The amnesic effects are specific to behavior that occurs a long time after reactivation but not a short time after. No CSM deficit is produced by such agents when crabs are exposed to a context different from that of training. Findings are consistent with those reported for vertebrates, with both showing that reactivation induces a recapitulation of the postacquisition cascade of intracellular events. The agreement between results from such phylogenetically disparate animals suggests that evolution may have adopted a given molecular cascade as the preferred means of encoding experiences in the nervous system.

  14. Cell Division Mode Change Mediates the Regulation of Cerebellar Granule Neurogenesis Controlled by the Sonic Hedgehog Signaling

    PubMed Central

    Yang, Rong; Wang, Minglei; Wang, Jia; Huang, Xingxu; Yang, Ru; Gao, Wei-Qiang

    2015-01-01

    Summary Symmetric and asymmetric divisions are important for self-renewal and differentiation of stem cells during neurogenesis. Although cerebellar granule neurogenesis is controlled by sonic hedgehog (SHH) signaling, whether and how this process is mediated by regulation of cell division modes have not been determined. Here, using time-lapse imaging and cell culture from neuronal progenitor-specific and differentiated neuron-specific reporter mouse lines (Math1-GFP and Dcx-DsRed) and Patched+/− mice in which SHH signaling is activated, we find evidence for the existence of symmetric and asymmetric divisions that are closely associated with progenitor proliferation and differentiation. While activation of the SHH pathway enhances symmetric progenitor cell divisions, blockade of the SHH pathway reverses the cell division mode change in Math1-GFP;Dcx-DsRed;Patched+/− mice by promoting asymmetric divisions or terminal neuronal symmetric divisions. Thus, cell division mode change mediates the regulation of cerebellar granule neurogenesis controlled by SHH signaling. PMID:26527387

  15. A left cerebellar pathway mediates language in prematurely-born young adults.

    PubMed

    Constable, R Todd; Vohr, Betty R; Scheinost, Dustin; Benjamin, Jennifer R; Fulbright, Robert K; Lacadie, Cheryl; Schneider, Karen C; Katz, Karol H; Zhang, Heping; Papademetris, Xenophon; Ment, Laura R

    2013-01-01

    Preterm (PT) subjects are at risk for developmental delay, and task-based studies suggest that developmental disorders may be due to alterations in neural connectivity. Since emerging data imply the importance of right cerebellar function for language acquisition in typical development, we hypothesized that PT subjects would have alternate areas of cerebellar connectivity, and that these areas would be responsible for differences in cognitive outcomes between PT subjects and term controls at age 20 years. Nineteen PT and 19 term control young adults were prospectively studied using resting-state functional MRI (fMRI) to create voxel-based contrast maps reflecting the functional connectivity of each tissue element in the grey matter through analysis of the intrinsic connectivity contrast degree (ICC-d). Left cerebellar ICC-d differences between subjects identified a region of interest that was used for subsequent seed-based connectivity analyses. Subjects underwent standardized language testing, and correlations with cognitive outcomes were assessed. There were no differences in gender, hand preference, maternal education, age at study, or Peabody Picture Vocabulary Test (PPVT) scores. Functional connectivity (FcMRI) demonstrated increased tissue connectivity in the biventer, simple and quadrangular lobules of the L cerebellum (p<0.05) in PTs compared to term controls; seed-based analyses from these regions demonstrated alterations in connectivity from L cerebellum to both R and L inferior frontal gyri (IFG) in PTs compared to term controls. For PTs but not term controls, there were significant positive correlations between these connections and PPVT scores (R IFG: r=0.555, p=0.01; L IFG: r=0.454, p=0.05), as well as Verbal Comprehension Index (VCI) scores (R IFG: r=0.472, p=0.04). These data suggest the presence of a left cerebellar language circuit in PT subjects at young adulthood. These findings may represent either a delay in maturation or the engagement of

  16. Long Term Surface Salinity Measurements

    NASA Technical Reports Server (NTRS)

    Schmitt, Raymond W.; Brown, Neil L.

    2005-01-01

    Our long-term goal is to establish a reliable system for monitoring surface salinity around the global ocean. Salinity is a strong indicator of the freshwater cycle and has a great influence on upper ocean stratification. Global salinity measurements have potential to improve climate forecasts if an observation system can be developed. This project is developing a new internal field conductivity cell that can be protected from biological fouling for two years. Combined with a temperature sensor, this foul-proof cell can be deployed widely on surface drifters. A reliable in-situ network of surface salinity sensors will be an important adjunct to the salinity sensing satellite AQUARIUS to be deployed by NASA in 2009. A new internal-field conductivity cell has been developed by N Brown, along with new electronics. This sensor system has been combined with a temperature sensor to make a conductivity - temperature (UT) sensor suitable for deployment on drifters. The basic sensor concepts have been proven on a high resolution CTD. A simpler (lower cost) circuit has been built for this application. A protection mechanism for the conductivity cell that includes antifouling protection has also been designed and built. Mr. A.Walsh of our commercial partner E-Paint has designed and delivered time-release formulations of antifoulants for our application. Mr. G. Williams of partner Clearwater Instrumentation advised on power and communication issues and supplied surface drifters for testing.

  17. Long-term equilibrium tides

    NASA Astrophysics Data System (ADS)

    Shaffer, John A.; Cerveny, Randall S.

    1998-08-01

    Extreme equilibrium tides, or ``hypertides,'' are computed in a new equilibrium tidal model combining algorithms of a version of the Chapront ELP-2000/82 Lunar Theory with the BER78 Milankovitch astronomical expansions. For the recent past, a high correspondence exists between computed semidiurnal tide levels and a record of coastal flooding demonstrating that astronomical alignment is a potential influence on such flooding. For the Holocene and near future, maximum tides demonstrate cyclic variations with peaks at near 5000 B.P. and 4000 A.P. On the late Quaternary timescale, variations in maximum equilibrium tide level display oscillations with periods of approximately 10,000, 100,000 and 400,000 years, because of precessional shifts in tidal maxima between vernal and autumnal equinoxes. While flooding occurs under the combined effects of tides and storms via ``storm surges,'' the most extensive flooding will occur with the coincidence of storms and the rarer hypertides and is thus primarily influenced by hypertides. Therefore we suggest that astronomical alignment's relationship to coastal flooding is probabilistic rather than deterministic. Data derived from this model are applicable to (1) archaeological and paleoclimatic coastal reconstructions, (2) long-term planning, for example, radioactive waste site selection, (3) sealevel change and paleoestuarine studies or (4) ocean-meteorological interactions.

  18. Widespread blunting of hypothalamic and amygdala-septal activity and behavior in rats with long-term hyperglycemia.

    PubMed

    Moreno-Cortés, M L; Gutiérrez-García, A G; Guillén-Ruiz, G; Romo-González, T; Contreras, C M

    2016-09-01

    Anxiety and depression in diabetic patients contributes to a poor prognosis, but possible causal relationships have been controversial. Anxiety, fear, and anhedonia are mediated by interactions between different deep structures of the temporal lobe (e.g., amygdala complex and hippocampus) and other forebrain-related structures (e.g., lateral septal nucleus). Connections between these structures and the hypothalamic orexinergic system are necessary for the maintenance of energy and wakefulness. However, few studies have explored the impact of long-term hyperglycemia in these structures on anxiety. We induced long-term hyperglycemia (glucose levels of ∼500mg/dl) in Wistar rats by injecting them with alloxan and simultaneously protecting them from hyperglycemia by injecting them daily with a low dose of insulin (i.e., just enough insulin to avoid death), thus maintaining hyperglycemia and ketonuria for as long as 6 weeks. Compared with controls, long-term hyperglycemic rats exhibited a significant reduction of Fos expression in the lateral septal nucleus and basolateral amygdala, but no differences were found in cerebellar regions. Orexin-A cells appeared to be inactive in the lateral hypothalamus. No differences were found in sucrose consumption or behavior in the elevated plus maze compared with the control group, but a decrease in general locomotion was observed. These data indicate a generalized blunting of the metabolic brain response, accompanied by a decrease in locomotion but no changes in hedonic- or anxiety-like behavior.

  19. Long-Term Planning in Higher Education.

    ERIC Educational Resources Information Center

    United Nations Educational, Scientific and Cultural Organization, Bangkok (Thailand). Principal Regional Office for Asia and the Pacific.

    This report presents the concepts and issues discussed at a Regional Symposium on Long-term Planning in Higher Education held in Dhaka, Bangladesh, September 21-30, 1986. Chapter 1 explores some fundamental issues about the rationale for the objectives of long-term planning. It defines long-term planning in higher education, considers its…

  20. Alteration of AMPA Receptor-Mediated Synaptic Transmission by Alexa Fluor 488 and 594 in Cerebellar Stellate Cells.

    PubMed

    Maroteaux, Matthieu; Liu, Siqiong June

    2016-01-01

    The fluorescent dyes, Alexa Fluor 488 and 594 are commonly used to visualize dendritic structures and the localization of synapses, both of which are critical for the spatial and temporal integration of synaptic inputs. However, the effect of the dyes on synaptic transmission is not known. Here we investigated whether Alexa Fluor dyes alter the properties of synaptic currents mediated by two subtypes of AMPA receptors (AMPARs) at cerebellar stellate cell synapses. In naive mice, GluA2-lacking AMPAR-mediated synaptic currents displayed an inwardly rectifying current-voltage (I-V) relationship due to blockade by cytoplasmic spermine at depolarized potentials. We found that the inclusion of 100 µm Alexa Fluor dye, but not 10 µm, in the pipette solution led to a gradual increase in the amplitude of EPSCs at +40 mV and a change in the I-V relationship from inwardly rectifying to more linear. In mice exposed to an acute stress, AMPARs switched to GluA2-containing receptors, and 100 µm Alexa Fluor 594 did not alter the I-V relationship of synaptic currents. Therefore, a high concentration of Alexa Fluor dye changed the I-V relationship of EPSCs at GluA2-lacking AMPAR synapses. PMID:27280156

  1. Alteration of AMPA Receptor-Mediated Synaptic Transmission by Alexa Fluor 488 and 594 in Cerebellar Stellate Cells123

    PubMed Central

    2016-01-01

    Abstract The fluorescent dyes, Alexa Fluor 488 and 594 are commonly used to visualize dendritic structures and the localization of synapses, both of which are critical for the spatial and temporal integration of synaptic inputs. However, the effect of the dyes on synaptic transmission is not known. Here we investigated whether Alexa Fluor dyes alter the properties of synaptic currents mediated by two subtypes of AMPA receptors (AMPARs) at cerebellar stellate cell synapses. In naive mice, GluA2-lacking AMPAR-mediated synaptic currents displayed an inwardly rectifying current–voltage (I–V) relationship due to blockade by cytoplasmic spermine at depolarized potentials. We found that the inclusion of 100 µm Alexa Fluor dye, but not 10 µm, in the pipette solution led to a gradual increase in the amplitude of EPSCs at +40 mV and a change in the I–V relationship from inwardly rectifying to more linear. In mice exposed to an acute stress, AMPARs switched to GluA2-containing receptors, and 100 µm Alexa Fluor 594 did not alter the I–V relationship of synaptic currents. Therefore, a high concentration of Alexa Fluor dye changed the I–V relationship of EPSCs at GluA2-lacking AMPAR synapses. PMID:27280156

  2. Alteration of AMPA Receptor-Mediated Synaptic Transmission by Alexa Fluor 488 and 594 in Cerebellar Stellate Cells.

    PubMed

    Maroteaux, Matthieu; Liu, Siqiong June

    2016-01-01

    The fluorescent dyes, Alexa Fluor 488 and 594 are commonly used to visualize dendritic structures and the localization of synapses, both of which are critical for the spatial and temporal integration of synaptic inputs. However, the effect of the dyes on synaptic transmission is not known. Here we investigated whether Alexa Fluor dyes alter the properties of synaptic currents mediated by two subtypes of AMPA receptors (AMPARs) at cerebellar stellate cell synapses. In naive mice, GluA2-lacking AMPAR-mediated synaptic currents displayed an inwardly rectifying current-voltage (I-V) relationship due to blockade by cytoplasmic spermine at depolarized potentials. We found that the inclusion of 100 µm Alexa Fluor dye, but not 10 µm, in the pipette solution led to a gradual increase in the amplitude of EPSCs at +40 mV and a change in the I-V relationship from inwardly rectifying to more linear. In mice exposed to an acute stress, AMPARs switched to GluA2-containing receptors, and 100 µm Alexa Fluor 594 did not alter the I-V relationship of synaptic currents. Therefore, a high concentration of Alexa Fluor dye changed the I-V relationship of EPSCs at GluA2-lacking AMPAR synapses.

  3. Long-term Aβ exposure augments mCa2+-independent mROS-mediated depletion of cardiolipin for the shift of a lethal transient mitochondrial permeability transition to its permanent mode in NARP cybrids: a protective targeting of melatonin.

    PubMed

    Hsiao, Chia-Wei; Peng, Tsung-I; Peng, Alexander C; Reiter, Russel J; Tanaka, Masashi; Lai, Yiu-Kay; Jou, Mei-Jie

    2013-01-01

    Mitochondrial dysfunction is a hallmark of amyloid β-peptide (Aβ)-induced neurodegeneration of Alzheimer's disease (AD). This study investigated whether mtDNA T8993G mutation-induced complex V inhibition, clinically associated with neurological muscle weakness, ataxia, and retinitis pigmentosa (NARP), is a potential risk factor for AD and the pathological link for long-term exposure of Aβ-induced mitochondrial toxicity and apoptosis in NARP cybrids. Using noninvasive fluorescence probe-coupled laser scanning imaging microscopy and NARP cybrids harboring 98% mutant genes along with its parental 143B osteosarcoma cells, we demonstrated that Aβ-augmented mitochondrial Ca(2+) (mCa(2+))-independent mitochondrial reactive oxygen species (mROS) formation for a cardiolipin (CL, a major mitochondrial protective phospholipid)-dependent lethal modulation of the mitochondrial permeability transition (MPT). Aβ augmented not only the amount but also the propagation rate of mROS-induced mROS formation to significantly depolarize mitochondrial membrane potential (∆Ψ(m)) and reduce mCa(2+) stress. Aβ-augmented mROS oxidized and depleted CL, thereby enhances mitochondrial fission and movement retardation, which promoted the NARP-augmented lethal transient-MPT (t-MPT) to switch to its irreversible mode of permanent-MPT (p-MPT). Interestingly, melatonin, a multiple mitochondrial protector, markedly reduced Aβ-augmented mROS formation and therefore significantly reduced mROS-mediated depolarization of ∆Ψ(m), fission of mitochondria and retardation of mitochondrial movement to stabilize CL and hence the MPT. In the presence of melatonin, Aβ-promoted p-MPT was reversed to a protective t-MPT, which preserved ∆Ψ(m) and lowered elevated mCa(2+) to sublethal levels for an enhanced mCa(2+)-dependent O(2) consumption. Thus, melatonin may potentially rescue AD patients associated with NARP symptoms. PMID:24446866

  4. Hippocampal Focal Knockout of CBP Affects Specific Histone Modifications, Long-Term Potentiation, and Long-Term Memory

    PubMed Central

    Barrett, Ruth M; Malvaez, Melissa; Kramar, Eniko; Matheos, Dina P; Arrizon, Abraham; Cabrera, Sara M; Lynch, Gary; Greene, Robert W; Wood, Marcelo A

    2011-01-01

    To identify the role of the histone acetyltransferase (HAT) CREB-binding protein (CBP) in neurons of the CA1 region of the hippocampus during memory formation, we examine the effects of a focal homozygous knockout of CBP on histone modifications, gene expression, synaptic plasticity, and long-term memory. We show that CBP is critical for the in vivo acetylation of lysines on histones H2B, H3, and H4. CBP's homolog p300 was unable to compensate for the loss of CBP. Neurons lacking CBP maintained phosphorylation of the transcription factor CREB, yet failed to activate CREB:CBP-mediated gene expression. Loss of CBP in dorsal CA1 of the hippocampus resulted in selective impairments to long-term potentiation and long-term memory for contextual fear and object recognition. Together, these results suggest a necessary role for specific chromatin modifications, selectively mediated by CBP in the consolidation of memories. PMID:21508930

  5. Concept Formation Skills in Long-Term Cochlear Implant Users

    ERIC Educational Resources Information Center

    Castellanos, Irina; Kronenberger, William G.; Beer, Jessica; Colson, Bethany G.; Henning, Shirley C.; Ditmars, Allison; Pisoni, David B.

    2015-01-01

    This study investigated if a period of auditory sensory deprivation followed by degraded auditory input and related language delays affects visual concept formation skills in long-term prelingually deaf cochlear implant (CI) users. We also examined if concept formation skills are mediated or moderated by other neurocognitive domains (i.e.,…

  6. Long-term solar-terrestrial observations

    NASA Technical Reports Server (NTRS)

    1988-01-01

    The results of an 18-month study of the requirements for long-term monitoring and archiving of solar-terrestrial data is presented. The value of long-term solar-terrestrial observations is discussed together with parameters, associated measurements, and observational problem areas in each of the solar-terrestrial links (the sun, the interplanetary medium, the magnetosphere, and the thermosphere-ionosphere). Some recommendations are offered for coordinated planning for long-term solar-terrestrial observations.

  7. The mysterious microcircuitry of the cerebellar nuclei

    PubMed Central

    Uusisaari, Marylka; De Schutter, Erik

    2011-01-01

    Abstract The microcircuitry of cerebellar cortex and, in particular, the physiology of its main element, the Purkinje neuron, has been extensively investigated and described. However, activity in Purkinje neurons, either as single cells or populations, does not directly mediate the cerebellar effects on the motor effector systems. Rather, the result of the entire cerebellar cortical computation is passed to the relatively small cerebellar nuclei that act as the final, integrative processing unit in the cerebellar circuitry. The nuclei ultimately control the temporal and spatial features of the cerebellar output. Given this key role, it is striking that the internal organization and the connectivity with afferent and efferent pathways in the cerebellar nuclei are rather poorly known. In the present review, we discuss some of the many critical shortcomings in the understanding of cerebellar nuclei microcircuitry: the extent of convergence and divergence of the cerebellar cortical pathway to the various cerebellar nuclei neurons and subareas, the possible (lack of) conservation of the finely-divided topographical organization in the cerebellar cortex at the level of the nuclei, as well as the absence of knowledge of the synaptic circuitry within the cerebellar nuclei. All these issues are important for predicting the pattern-extraction and encoding capabilities of the cerebellar nuclei and, until resolved, theories and models of cerebellar motor control and learning may err considerably. PMID:21521761

  8. Bestrophin1 Channels are Insensitive to Ethanol and Do not Mediate Tonic GABAergic Currents in Cerebellar Granule Cells

    PubMed Central

    Diaz, Marvin R.; Wadleigh, Aya; Hughes, Benjamin A.; Woodward, John J.; Valenzuela, C. Fernando

    2012-01-01

    The granule cell layer of the cerebellum functions in spatio-temporal encoding of information. Granule cells (GCs) are tonically inhibited by spillover of GABA released from Golgi cells and this tonic inhibition is facilitated by acute ethanol. Recently, it was demonstrated that a specialized Ca2+-activated anion-channel, bestrophin1 (Best1), found on glial cells, can release GABA that contributes up to 50–75% of the tonic GABAergic current. However, it is unknown if ethanol has any actions on Best1 function. Using whole-cell electrophysiology, we found that recombinant Best1 channels expressed in HEK-293 cells were insensitive to 40 and 80 mM ethanol. We attempted to measure the Best1-mediated component of the tonic current in slices using 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB). We confirmed that this agent blocks recombinant Best1 channels. Unexpectedly, we found that NPPB significantly potentiated the tonic current and the area and decay of GABAA-mediated spontaneous inhibitory post-synaptic currents (IPSCs) in GCs in rodent slices under two different recording conditions. To better isolate the Best1-dependent tonic current component, we blocked the Golgi cell component of the tonic current with tetrodotoxin and found that NPPB similarly and significantly potentiated the tonic current amplitude and decay time of miniature IPSCs. Two other Cl−-channel blockers were also tested: 4′-diisothiocyanatostilbene-2,2′-disulfonic acid disodium salt hydrate (DIDS) showed no effect on GABAergic transmission, while niflumic acid (NFA) significantly suppressed the tonic current noise, as well as the mIPSC frequency, amplitude, and area. These data suggest that acute ethanol exposure does not modulate Best1 channels and these findings serve to challenge recent data indicating that these channels participate in the generation of tonic GABAergic currents in cerebellar GCs. PMID:22275879

  9. Financing long-term care in Canada.

    PubMed

    Jacobs, P; Mills, C; Hollander, M

    1997-06-01

    Financial policies relating to long-term care in Canada are changing rapidly in response to demands for health care reform. This chapter focuses on the financial structure of institutional care, primarily nursing homes, in the western provinces of Alberta and British Columbia. Community-based long-term care is discussed briefly.

  10. Virtual Models of Long-Term Care

    ERIC Educational Resources Information Center

    Phenice, Lillian A.; Griffore, Robert J.

    2012-01-01

    Nursing homes, assisted living facilities and home-care organizations, use web sites to describe their services to potential consumers. This virtual ethnographic study developed models representing how potential consumers may understand this information using data from web sites of 69 long-term-care providers. The content of long-term-care web…

  11. Long-term preservation of Anammox bacteria

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Deposit of useful microorganisms in culture collections requires long-term preservation and successful reactivation techniques. The goal of this study was to develop a simple preservation protocol for the long-term storage and reactivation of the anammox biomass. To achieve this, anammox biomass w...

  12. Paying for long-term care.

    PubMed Central

    Estes, C L; Bodenheimer, T

    1994-01-01

    Everyone agrees that insurance for long-term care is inadequate in the United States. Disagreement exists, however, on whether such insurance should be provided through the private or public sector. Private insurance generally uses the experience-rating principle that persons with higher risk of illness are charged higher premiums. For private insurance for long-term care, this principle creates a dilemma. Most policies will be purchased by the elderly; yet, because the elderly have a high risk of needing long-term care, only about 20% of them can afford the cost of premiums. A public-private partnership by which the government partially subsidizes private long-term-care insurance is unlikely to resolve this dilemma. Only a social insurance program for long-term care can provide universal, affordable, and equitable coverage. PMID:8128712

  13. Purkinje cell stripes and long-term depression at the parallel fiber-Purkinje cell synapse

    PubMed Central

    Hawkes, Richard

    2014-01-01

    The cerebellar cortex comprises a stereotyped array of transverse zones and parasagittal stripes, built around multiple Purkinje cell subtypes, which is highly conserved across birds and mammals. This architecture is revealed in the restricted expression patterns of numerous molecules, in the terminal fields of the afferent projections, in the distribution of interneurons, and in the functional organization. This review provides an overview of cerebellar architecture with an emphasis on attempts to relate molecular architecture to the expression of long-term depression (LTD) at the parallel fiber-Purkinje cell (pf-PC) synapse. PMID:24734006

  14. Treatable causes of cerebellar ataxia.

    PubMed

    Ramirez-Zamora, Adolfo; Zeigler, Warren; Desai, Neeja; Biller, José

    2015-04-15

    The cerebellar ataxia syndromes are a heterogeneous group of disorders clinically characterized by the presence of cerebellar dysfunction. Initial assessment of patients with progressive cerebellar ataxia is complex because of an extensive list of potential diagnoses. A detailed history and comprehensive examination are required for an accurate diagnosis and hierarchical diagnostic investigations. Although no cure exists for most of these conditions, a small group of metabolic, hereditary, inflammatory, and immune-mediated etiologies of cerebellar ataxia are amenable to disease-modifying, targeted therapies. Over the past years, disease-specific treatments have emerged. Thus, clinicians must become familiar with these disorders because maximal therapeutic benefit is only possible when done early. In this article, we review disorders in which cerebellar ataxia is a prominent clinical feature requiring targeted treatments along with specific management recommendations.

  15. Excitotoxicity through NMDA receptors mediates cerebellar granule neuron apoptosis induced by prion protein 90-231 fragment.

    PubMed

    Thellung, Stefano; Gatta, Elena; Pellistri, Francesca; Corsaro, Alessandro; Villa, Valentina; Vassalli, Massimo; Robello, Mauro; Florio, Tullio

    2013-05-01

    Prion diseases recognize, as a unique molecular trait, the misfolding of CNS-enriched prion protein (PrP(C)) into an aberrant isoform (PrP(Sc)). In this work, we characterize the in vitro toxicity of amino-terminally truncated recombinant PrP fragment (amino acids 90-231, PrP90-231), on rat cerebellar granule neurons (CGN), focusing on glutamatergic receptor activation and Ca(2+) homeostasis impairment. This recombinant fragment assumes a toxic conformation (PrP90-231(TOX)) after controlled thermal denaturation (1 h at 53 °C) acquiring structural characteristics identified in PrP(Sc) (enrichment in β-structures, increased hydrophobicity, partial resistance to proteinase K, and aggregation in amyloid fibrils). By annexin-V binding assay, and evaluation of the percentage of fragmented and condensed nuclei, we show that treatment with PrP90-231(TOX), used in pre-fibrillar aggregation state, induces CGN apoptosis. This effect was associated with a delayed, but sustained elevation of [Ca(2+)]i. Both CGN apoptosis and [Ca(2+)]i increase were not observed using PrP90-231 in PrP(C)-like conformation. PrP90-231(TOX) effects were significantly reduced in the presence of ionotropic glutamate receptor antagonists. In particular, CGN apoptosis and [Ca(2+)]i increase were largely reduced, although not fully abolished, by pre-treatment with the NMDA antagonists APV and memantine, while the AMPA antagonist CNQX produced a lower, although still significant, effect. In conclusion, we report that CGN apoptosis induced by PrP90-231(TOX) correlates with a sustained elevation of [Ca(2+)]i mediated by the activation of NMDA and AMPA receptors.

  16. Cerebellar Hypoplasia

    MedlinePlus

    ... disorders that begin in early childhood, such as ataxia telangiectasia. In an infant or young child, symptoms of a disorder that features cerebellar hypoplasia might include floppy muscle tone, developmental or ...

  17. Cerebellar Degeneration

    MedlinePlus

    ... Degeneration? Cerebellar degeneration is a process in which neurons in the cerebellum - the area of the brain ... proteins that are necessary for the survival of neurons. Associated diseases: Diseases that are specific to the ...

  18. Long Term Effects of Food Poisoning

    MedlinePlus

    ... develop chronic arthritis. Brain and nerve damage A Listeria infection can lead to meningitis, an inflammation of ... brain. If a newborn infant is infected with Listeria , long-term consequences may include mental retardation, seizures, ...

  19. Asthma Medicines: Long-Term Control

    MedlinePlus

    ... Español Text Size Email Print Share Asthma Medicines: Long-term Control Page Content Article Body Corticosteroids Synthetic ... and sprinkle forms are available for young children. Long-Acting Beta2-Agonists Medications in the beta 2 - ...

  20. Long Term Outcomes after Pediatric Liver Transplantation

    PubMed Central

    2013-01-01

    Long term outcomes after liver transplantation are major determinants of quality of life and of the value of this heroic treatment. As short term outcomes are excellent, our community is turning to take a harder look at long term outcomes. The purpose of this paper is to review these outcomes, and highlight proposed treatments, as well as pressing topics needing to be studied. A systemic review of the English literature was carried in PubMed, covering all papers addressing long term outcomes in pediatric liver transplant from 2000-2013. Late outcomes after pediatric liver transplant affect the liver graft in the form of chronic liver dysfunction. The causes include rejection particularly humoral rejection, but also de novo autoimmune hepatitis, and recurrent disease. The metabolic syndrome is a major factor in long term cardiovascular complication risk. Secondary infections, kidney dysfunction and malignancy remain a reality of those patients. There is growing evidence of late cognitive and executive function delays affecting daily life productivity as well as likely adherence. Finally, despite a good health status, quality of life measures are comparable to those of children with chronic diseases. Long term outcomes are the new frontier in pediatric liver transplantation. Much is needed to improve graft survival, but also to avoid systemic morbidities from long term immunosuppression. Quality of life is a new inclusive measure that will require interventions and innovative approaches respectful not only on the patients but also of their social circle. PMID:24511516

  1. Developmental Cerebellar Cognitive Affective Syndrome in Ex-preterm Survivors Following Cerebellar Injury

    PubMed Central

    Brossard-Racine, Marie; du Plessis, Adre J.; Limperopoulos, Catherine

    2015-01-01

    Cerebellar injury is increasingly recognized as an important complication of very preterm birth. However, the neurodevelopmental consequences of early life cerebellar injury in prematurely born infants have not been well elucidated. We performed a literature search of studies published between 1997 and 2014 describing neurodevelopmental outcomes of preterm infants following direct cerebellar injury or indirect cerebellar injury/underdevelopment. Available data suggests that both direct and indirect mechanisms of cerebellar injury appear to stunt cerebellar growth and adversely affect neurodevelopment. This review also provides important insights into the highly integrated cerebral-cerebellar structural and functional correlates. Finally, this review highlights that early life impairment of cerebellar growth extends far beyond motor impairments and plays a critical, previously underrecognized role in the long-term cognitive, behavioral, and social deficits associated with brain injury among premature infants. These data point to a developmental form of the cerebellar cognitive affective syndrome previously described in adults. Longitudinal prospective studies using serial advanced magnetic resonance imaging techniques are needed to better delineate the full extent of the role of prematurity-related cerebellar injury and topography in the genesis of cognitive, social-behavioral dysfunction. PMID:25241880

  2. Anti-Yo antibody-mediated paraneoplastic cerebellar degeneration in a female patient with pleural malignant mesothelioma.

    PubMed

    Tanriverdi, Ozgur; Meydan, Nezih; Barutca, Sabri; Ozsan, Nazan; Gurel, Duygu; Veral, Ali

    2013-05-01

    Paraneoplastic cerebellar degeneration is a rare non-metastatic complication of malignancies. It presents with acute or subacute onset of ataxia, dysarthria and intention tremor. Paraneoplastic cerebellar degeneration is most commonly associated with malignancies of the ovary, breast and lung. The anti-Yo (anti-Purkinje cells) antibodies that specifically damage the Purkinje cells of the cerebellum are found in the serum and cerebrospinal fluid. Anti-Yo-related paraneoplastic cerebellar degeneration is most commonly found in women with gynecological and breast cancers, but it is reported in other malignancies. Patients with paraneoplastic syndromes most often present with neurologic symptoms before an underlying cancer is detected. We report a case of anti-Yo-related paraneoplastic cerebellar degeneration associated with pleural malignant mesothelioma in a 51-year-old female patient. She presented to our department with a 2-week history after the last chemotherapy of progressive dizziness related to head movement, nausea, vomiting, ataxia and unsteady gait. A western blot assay was negative for anti-Hu, anti-Ri, anti-Ma2, anti-CV2 and anti-amphiphysin paraneoplastic antibody markers but positive for anti-Yo. In conclusion, we report a case of paraneoplastic cerebellar degeneration in a patient with pleural malignant mesothelioma because of the rarity of this neurologic presentation after the diagnosis of malignant mesothelioma and of the association with anti-Yo antibodies.

  3. Long-term home care research.

    PubMed

    Green, J H

    1989-11-01

    The population of seniors is growing and health service reimbursement is shrinking. Long-term home health care services were developed with an assumption that the services would decrease costs. This assumption has not been validated. What has been recognized is that long-term home health care targets a new and growing population of frail seniors who need services but are probably not at risk for institutionalization. The impact of long-term home care services on the health status and quality of life of seniors and caregivers has been limited by outcome measurement problems. There are indications that the services improved life satisfaction and reduced services needs, but further evaluations need to replicate the outcomes. In effect, long-term outcomes have not been sufficiently explored. Further research also needs to assist us in identifying outcomes for certain services with precise target populations. Public policy questions are ahead. Should a program that can increase costs, has demonstrated some but not dramatic impacts on quality of life and health status, and has the possibility of expansion, be funded? The question is obviously debatable. From a nursing perspective of health promotion and prevention, the answer is "yes." Funding should be continued in conjunction with increased research on the program impacts. In Kane's (1988) analysis of the Channeling experiments, she summarized the situation effectively: Knowing these facts, we are now in a position to reformulate public policies to design a system of long-term care that satisfies the preferences of consumers and protects them from catastrophic long-term expenses, while promoting the triple virtues of acceptable, quality, equitable access, and defensible costs. . . Nothing in the Channeling results should prevent us from going ahead and trying to develop both community based and institutionally based long-term services in which this country can take pride.

  4. Purkinje Cell-Specific Knockout of the Protein Phosphatase PP2B Impairs Potentiation and Cerebellar Motor Learning

    PubMed Central

    Schonewille, M.; Belmeguenai, A.; Koekkoek, S.K.; Houtman, S.H.; Boele, H.J.; van Beugen, B.J.; Gao, Z.; Badura, A.; Ohtsuki, G.; Amerika, W.E.; Hosy, E.; Hoebeek, F.E.; Elgersma, Y.; Hansel, C.; De Zeeuw, C.I.

    2010-01-01

    SUMMARY Cerebellar motor learning is required to obtain procedural skills. Studies have provided supportive evidence for a potential role of kinase-mediated long-term depression (LTD) at the parallel fiber to Purkinje cell synapse in cerebellar learning. Recently, phosphatases have been implicated in the induction of potentiation of Purkinje cell activities in vitro, but it remains to be shown whether and how phosphatase-mediated potentiation contributes to motor learning. Here, we investigated its possible role by creating and testing a Purkinje cell-specific knockout of calcium/calmodulin-activated protein-phosphatase-2B (L7-PP2B). The selective deletion of PP2B indeed abolished postsynaptic long-term potentiation in Purkinje cells and their ability to increase their excitability, whereas LTD was unaffected. The mutants showed impaired “gain-decrease” and “gain-increase” adaptation of their vestibulo-ocular reflex (VOR) as well as impaired acquisition of classical delay conditioning of their eyeblink response. Thus, our data indicate that PP2B may indeed mediate potentiation in Purkinje cells and contribute prominently to cerebellar motor learning. PMID:20797538

  5. Representational Specificity of Within-Category Phonetic Variation in the Long-Term Mental Lexicon

    ERIC Educational Resources Information Center

    Ju, Min; Luce, Paul A.

    2006-01-01

    This study examines the potential encoding in long-term memory of subphonemic, within-category variation in voice onset time (VOT) and the degree to which this encoding of subtle variation is mediated by lexical competition. In 4 long-term repetition-priming experiments, magnitude of priming was examined as a function of variation in VOT in words…

  6. Long-term outcomes of autoimmune pancreatitis.

    PubMed

    Ikeura, Tsukasa; Miyoshi, Hideaki; Shimatani, Masaaki; Uchida, Kazushige; Takaoka, Makoto; Okazaki, Kazuichi

    2016-09-14

    Autoimmune pancreatitis (AIP) has been considered a favorable-prognosis disease; however, currently, there is limited information on natural course of AIP during long-term follow-up. Recently published studies regarding the long-term outcomes of AIP has demonstrated the developments of pancreatic stone formation, exocrine insufficiency, and endocrine insufficiency are observed in 5%-41%, 34%-82%, and 38%-57% of patients having the disease. Furthermore, the incidence rate of developing pancreatic cancer ranges from 0% to 4.8% during the long-term follow-up. The event of death from AIP-related complications other than accompanying cancer is likely to be rare. During follow-up of AIP patients, careful surveillance for not only relapse of the disease but also development of complications at regular intervals is needed. PMID:27678359

  7. Long-term outcomes of autoimmune pancreatitis

    PubMed Central

    Ikeura, Tsukasa; Miyoshi, Hideaki; Shimatani, Masaaki; Uchida, Kazushige; Takaoka, Makoto; Okazaki, Kazuichi

    2016-01-01

    Autoimmune pancreatitis (AIP) has been considered a favorable-prognosis disease; however, currently, there is limited information on natural course of AIP during long-term follow-up. Recently published studies regarding the long-term outcomes of AIP has demonstrated the developments of pancreatic stone formation, exocrine insufficiency, and endocrine insufficiency are observed in 5%-41%, 34%-82%, and 38%-57% of patients having the disease. Furthermore, the incidence rate of developing pancreatic cancer ranges from 0% to 4.8% during the long-term follow-up. The event of death from AIP-related complications other than accompanying cancer is likely to be rare. During follow-up of AIP patients, careful surveillance for not only relapse of the disease but also development of complications at regular intervals is needed. PMID:27678359

  8. Long-term outcomes of autoimmune pancreatitis

    PubMed Central

    Ikeura, Tsukasa; Miyoshi, Hideaki; Shimatani, Masaaki; Uchida, Kazushige; Takaoka, Makoto; Okazaki, Kazuichi

    2016-01-01

    Autoimmune pancreatitis (AIP) has been considered a favorable-prognosis disease; however, currently, there is limited information on natural course of AIP during long-term follow-up. Recently published studies regarding the long-term outcomes of AIP has demonstrated the developments of pancreatic stone formation, exocrine insufficiency, and endocrine insufficiency are observed in 5%-41%, 34%-82%, and 38%-57% of patients having the disease. Furthermore, the incidence rate of developing pancreatic cancer ranges from 0% to 4.8% during the long-term follow-up. The event of death from AIP-related complications other than accompanying cancer is likely to be rare. During follow-up of AIP patients, careful surveillance for not only relapse of the disease but also development of complications at regular intervals is needed.

  9. Long-Term Use of Benzodiazepines

    PubMed Central

    Potts, Nicholas L.S.; Krishnan, K. Ranga R.

    1992-01-01

    Problems associated with physical dependence and abuse of benzodiazepines by a small percentage of patients have reduced their popularity from the most commonly prescribed psychoactive drug in the 1970s to being prescribed for mainly short periods. Patients who benefit from long-term benzodiazepine use are nearly ignored by the medical community as a whole. This article details what patient population can improve from long-term benzodiazepine therapy, the risks and benefits of treatment, and how to select appropriate candidates. PMID:21229127

  10. Long-term outcomes after severe shock.

    PubMed

    Pratt, Cristina M; Hirshberg, Eliotte L; Jones, Jason P; Kuttler, Kathryn G; Lanspa, Michael J; Wilson, Emily L; Hopkins, Ramona O; Brown, Samuel M

    2015-02-01

    Severe shock is a life-threatening condition with very high short-term mortality. Whether the long-term outcomes among survivors of severe shock are similar to long-term outcomes of other critical illness survivors is unknown. We therefore sought to assess long-term survival and functional outcomes among 90-day survivors of severe shock and determine whether clinical predictors were associated with outcomes. Seventy-six patients who were alive 90 days after severe shock (received ≥1 μg/kg per minute of norepinephrine equivalent) were eligible for the study. We measured 3-year survival and long-term functional outcomes using the Medical Outcomes Study 36-Item Short-Form Health Survey, the EuroQOL 5-D-3L, the Hospital Anxiety and Depression Scale, the Impact of Event Scale-Revised, and an employment instrument. We also assessed the relationship between in-hospital predictors and long-term outcomes. The mean long-term survival was 5.1 years; 82% (62 of 76) of patients survived, of whom 49 were eligible for follow-up. Patients who died were older than patients who survived. Thirty-six patients completed a telephone interview a mean of 5 years after hospital admission. The patients' Physical Functioning scores were below U.S. population norms (P < 0.001), whereas mental health scores were similar to population norms. Nineteen percent of the patients had symptoms of depression, 39% had symptoms of anxiety, and 8% had symptoms of posttraumatic stress disorder. Thirty-six percent were disabled, and 17% were working full-time. Early survivors of severe shock had a high 3-year survival rate. Patients' long-term physical and psychological outcomes were similar to those reported for cohorts of less severely ill intensive care unit survivors. Anxiety and depression were relatively common, but only a few patients had symptoms of posttraumatic stress disorder. This study supports the observation that acute illness severity does not determine long-term outcomes. Even extremely

  11. Scenarios for long-term analysis

    SciTech Connect

    Wolbers, Stephen; /Fermilab

    2009-01-01

    Data Preservation and Long-Term Analysis of High Energy Physics (HEP) Experiments data is described and summarized in this talk. The summary covers information presented at the First Workshop on Data Preservation and Long-Term Analysis. Experiments representing e{sup +}e{sup -} collisions (LEP, B Factories and CLEO), ep collisions (H1 and ZEUS), p{bar p} collisions (CDF and D0) and others presented interesting information related to utilizing the large datasets collected over many years at these HEP facilities. Many questions and issues remain to be explored.

  12. [Cerebellar stroke].

    PubMed

    Paradowski, Michał; Zimny, Anna; Paradowski, Bogusław

    2015-01-01

    Cerebellar stroke belongs to a group of rare diseases of vascular origin. Cerebellum, supplied by three pairs of arteries (AICA, PICA, SCA) with many anastomoses between them is less susceptible for a stroke, especially ischemic one. Diagnosis of the stroke in this region is harder due to lower sensibility of commonly used CT of the head in case of stroke suspicion. The authors highlight clinical symptoms distinguishing between vascular territories or topographical locations of the stroke, diagnostic procedures, classical and surgical treatment, the most common misdiagnoses are also mentioned. The authors suggest a diagnostic and therapeutic algorithm development, including rtPA treatment criteria for ischemic cerebellar stroke. PMID:26181157

  13. Suppression of thyroid hormone receptor-mediated transcription and disruption of thyroid hormone-induced cerebellar morphogenesis by the polybrominated biphenyl mixture, BP-6.

    PubMed

    Ibhazehiebo, Kingsley; Iwasaki, Toshiharu; Okano-Uchida, Takayuki; Shimokawa, Noriaki; Ishizaki, Yasuki; Koibuchi, Noriyuki

    2011-08-01

    Polybrominated biphenyls (PBBs) are polyhalogenated, bioaccumulative flame retardant chemicals, which have been used in a variety of consumer and household products. They were accidentally introduced into the food chain in Michigan in 1973 and have remained a source of health concern. Studies have shown that exposure to PBB may cause adverse neurotoxic effects. We therefore examined the effects of BP-6, a PBB mixture, on thyroid hormone (TH) receptor (TR)-mediated transcription, on TH-induced Purkinje cell dendritogenesis, and on TH-induced cerebellar granule cell neurite extension. Our study shows that BP-6 suppressed TR-mediated transcription in CV-1 cells. Mammalian two-hybrid studies revealed that BP-6 did not inhibit coactivator binding to TR nor did it recruit corepressors to TR. Further examination using the liquid chemiluminescent DNA pull down assay revealed partial dissociation of TR from TH response element (TRE). In primary rat cerebellar culture, BP-6 significantly suppressed TH-induced dendrite arborization of Purkinje cells, and in reaggregate rat granule cell culture, impaired TH-induced neurite extension of granule cells. Taken together, our results indicate that BP-6 may disrupt TH homeostasis and consequently impair normal neuronal development. PMID:21396401

  14. Characteristics of Long-Term First Marriages.

    ERIC Educational Resources Information Center

    Fenell, David L.

    1993-01-01

    Investigated characteristics of long-term first marriages (over 20 years). Findings from 147 couples revealed: lifetime commitment to marriage, loyalty to spouse, strong moral values, respect for spouse as best friend, commitment to sexual fidelity, desire to be good parent, faith in God, desire to please and support spouse, good companion to…

  15. Long Term Transfer Effect of Metaphoric Allusion.

    ERIC Educational Resources Information Center

    Hayes, David A.; Mateja, John A.

    A study was conducted to investigate the long term transfer effect of metaphoric allusion used to clarify unfamiliar subject matter. Forty-nine high school students were given unfamiliar prose materials variously augmented by metaphoric allusion. The subjects' immediate performance on a transfer task was compared to their performance on an…

  16. Long-Term Stability of Social Participation

    ERIC Educational Resources Information Center

    Hyyppa, Markku T.; Maki, Juhani; Alanen, Erkki; Impivaara, Olli; Aromaa, Arpo

    2008-01-01

    The long-term stability of social participation was investigated in a representative urban population of 415 men and 579 women who had taken part in the nationwide Mini-Finland Health Survey in the years 1978-1980 and were re-examined 20 years later. Stability was assessed by means of the following tracking coefficients: kappa, proportion of…

  17. Evaluating Long-Term Disability Insurance Plans.

    ERIC Educational Resources Information Center

    Powell, Jan

    1992-01-01

    This report analyzes the factors involved in reviewing benefits and services of employer-sponsored group long-term disability plans for higher education institutions. Opening sections describe the evolution of disability insurance and its shape today. Further sections looks at the complex nature of "value" within a plan, relationship between plan…

  18. The long term characteristics of greenschist

    NASA Astrophysics Data System (ADS)

    Jang, Bo-An

    2016-04-01

    The greenschist in the Jinping II Hydropower Station in southwest China exhibits continuous creep behaviour because of the geological conditions in the region. This phenomenon illustrates the time-dependent deformation and progressive damage that occurs after excavation. In this study, the responses of greenschist to stress over time were determined in a series of laboratory tests on samples collected from the access tunnel walls at the construction site. The results showed that the greenschist presented time-dependent behaviour under long-term loading. The samples generally experienced two stages: transient creep and steady creep, but no accelerating creep. The periods of transient creep and steady creep increased with increasing stress levels. The long-term strength of the greenschist was identified based on the variation of creep strain and creep rate. The ratio of long-term strength to conventional strength was around 80% and did not vary much with confining pressures. A quantitative method for predicting the failure period of greenschist, based on analysis of the stress-strain curve, is presented and implemented. At a confining pressure of 40 MPa, greenschist was predicted to fail in 5000 days under a stress of 290 MPa and to fail in 85 days under the stress of 320 MPa, indicating that the long-term strength identified by the creep rate and creep strain is a reliable estimate.

  19. LONG TERM HYDROLOGICAL IMPACT ASSESSMENT (LTHIA)

    EPA Science Inventory

    LTHIA is a universal Urban Sprawl analysis tool that is available to all at no charge through the Internet. It estimates impacts on runoff, recharge and nonpoint source pollution resulting from past or proposed land use changes. It gives long-term average annual runoff for a lan...

  20. Long-Term Memory and Learning

    ERIC Educational Resources Information Center

    Crossland, John

    2011-01-01

    The English National Curriculum Programmes of Study emphasise the importance of knowledge, understanding and skills, and teachers are well versed in structuring learning in those terms. Research outcomes into how long-term memory is stored and retrieved provide support for structuring learning in this way. Four further messages are added to the…

  1. Who Recommends Long-Term Care Matters

    ERIC Educational Resources Information Center

    Kane, Robert L.; Bershadsky, Boris; Bershadsky, Julie

    2006-01-01

    Purpose: Making good consumer decisions requires having good information. This study compared long-term-care recommendations among various types of health professionals. Design and Methods: We gave randomly varied scenarios to a convenience national sample of 211 professionals from varying disciplines and work locations. For each scenario, we…

  2. Long-term lysimeter data on evapotranspiration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Long term crop evapotranspiration (ET) data measured using large weighing lysimeters have only been gathered in a few places in the world, yet are of great importance for ground truthing of many models of plant water use, mesoscale climate, remote sensing estimation of ET, climate change and climate...

  3. Professionalism in Long-Term Care Settings

    ERIC Educational Resources Information Center

    Lubinski, Rosemary

    2006-01-01

    Speech-language pathologists who serve elders in a variety of long-term care settings have a variety of professional skills and responsibilities. Fundamental to quality service is knowledge of aging and communication changes and disorders associated with this process, institutional alternatives, and the changing nature of today's elders in…

  4. Plutonium packaging and long-term storage

    NASA Astrophysics Data System (ADS)

    Lloyd, Jane A.; Wedman, Douglas E.

    2000-07-01

    It has been demonstrated that the Advanced Recovery and Integrated Extraction System (ARIES) packaging line at Los Alamos National Laboratory can successfully package plutonium to meet DOE requirements for safe long-term storage. The ARIES system has just completed the disassembly and conversion of its first cores ("pits") for nuclear weapons.

  5. Long-Term Sequelae of Stroke

    PubMed Central

    Teasell, Robert W.

    1992-01-01

    Scant attention has been paid to the long-term consequences and complications resulting from a stroke. Many stroke survivors go on to develop a variety of medical, musculoskeletal, and psychosocial complications, years after the acute stroke. The family physician is regularly called upon to deal with these problems, but is often hampered by a lack of resources. PMID:21221264

  6. Crossed Cerebellar Diaschisis

    PubMed Central

    Han, Shuguang; Wang, Xiaopeng; Xu, Kai; Hu, Chunfeng

    2016-01-01

    Abstract Crossed cerebellar diaschisis (CCD) describes a depression of oxidative metabolism glucose and blood flow in the cerebellum secondary to a supratentorial lesion in the contralateral cerebral hemisphere. PET/MR has the potential to become a powerful tool for demonstrating and imaging intracranial lesions .We herein report 3 cases of CCD imaging using a tri-modality PET/CT–MR set-up for investigating the value of adding MRI rather than CT to PET in clinical routine. We describe 3 patients with CCD and neurological symptoms in conjunction with abnormal cerebral fluorodeoxyglucose (FDG) positron emission tomography/computed tomography-magnetic resonance imaging (PET/CT–MR) manifestations including arterial spin-labeling (ASL) and T2-weighted images. In all, 18FDG-PET/CT detected positive FDG uptake in supratentorial lesions, and hypometabolism with atrophy in the contralateral cerebellum. More than that, hybrid PET/MRI provided a more accurate anatomic localization and ASL indicated disruption of the cortico-ponto-cerebellar pathway. Using pathology or long-term clinical follow-up to confirm the PET and ASL findings, the supratentorial lesions of the 3 patients were respectively diagnosed with cerebral infarction, recurrent glioma, and metastasis. The reports emphasize the significance of multimodality radiological examinations. Multimodality imaging contributes to proper diagnosis, management, and follow-up of supratentorial lesions with CCD. PMID:26765477

  7. Relationship between short- and long-term memory and short- and long-term extinction.

    PubMed

    Cammarota, Martín; Bevilaqua, Lia R M; Rossato, Janine I; Ramirez, Maria; Medina, Jorge H; Izquierdo, Iván

    2005-07-01

    Both the acquisition and the extinction of memories leave short- and long-term mnemonic traces. Here, we show that in male Wistar rats, the short-term memory for a step-down inhibitory avoidance task (IA) is resistant to extinction, and that its expression does not influence retrieval or extinction of long-term memory. It has been known for some time that short- and long-term inhibitory avoidance memory involve separate and parallel processes. Here we show that, instead, short-term extinction of IA long-term memory is the first step towards its long-term extinction, and that this link requires functional NMDA receptors and protein synthesis in the CA1 region of the dorsal hippocampus at the time of the first CS-no US presentation.

  8. Postsynaptic density-95 mimics and occludes hippocampal long-term potentiation and enhances long-term depression.

    PubMed

    Stein, Valentin; House, David R C; Bredt, David S; Nicoll, Roger A

    2003-07-01

    Previous studies have shown that overexpression of the protein PSD-95 (postsynaptic density-95) selectively enhances AMPA receptor-mediated synaptic responses in hippocampal pyramidal cells. To determine whether this effect is related to synaptic plasticity at these synapses, we examined whether PSD-95 expression mimics long-term potentiation (LTP), and also whether it influences LTP and long-term depression (LTD) in hippocampal slice cultures. Using simultaneous recording from transfected or infected cells and control pyramidal cells, we found that PSD-95, similar to LTP, increases the amplitude and frequency of miniature EPSCs. It also converts silent synapses to functional synapses, as does LTP. In addition, LTP is completely occluded in cells expressing PSD-95, whereas LTD is greatly enhanced. These results suggest that common mechanisms are involved in controlling synaptic AMPA receptors by PSD-95 and synaptic plasticity. PMID:12843250

  9. Alcohol Withdrawal and Cerebellar Mitochondria.

    PubMed

    Jung, Marianna E

    2015-08-01

    Cerebellar disorders trigger the symptoms of movement problems, imbalance, incoordination, and frequent fall. Cerebellar disorders are shown in various CNS illnesses including a drinking disorder called alcoholism. Alcoholism is manifested as an inability to control drinking in spite of adverse consequences. Human and animal studies have shown that cerebellar symptoms persist even after complete abstinence from drinking. In particular, the abrupt termination (ethanol withdrawal) of long-term excessive ethanol consumption has shown to provoke a variety of neuronal and mitochondrial damage to the cerebellum. Upon ethanol withdrawal, excitatory neurotransmitter molecules such as glutamate are overly released in brain areas including cerebellum. This is particularly relevant to the cerebellar neuronal network as glutamate signals are projected to Purkinje neurons through granular cells that are the most populated neuronal type in CNS. This excitatory neuronal signal may be elevated by ethanol withdrawal stress, which promotes an increase in intracellular Ca(2+) level and a decrease in a Ca(2+)-binding protein, both of which result in the excessive entry of Ca(2+) to the mitochondria. Subsequently, mitochondria undergo a prolonged opening of mitochondrial permeability transition pore and the overproduction of harmful free radicals, impeding adenosine triphosphate (ATP)-generating function. This in turn provokes the leakage of mitochondrial molecule cytochrome c to the cytosol, which triggers a cascade of adverse cytosol reactions. Upstream to this pathway, cerebellum under the condition of ethanol withdrawal has shown aberrant gene modifications through altered DNA methylation, histone acetylation, or microRNA expression. Interplay between these events and molecules may result in functional damage to cerebellar mitochondria and consequent neuronal degeneration, thereby contributing to motoric deficit. Mitochondria-targeting research may help develop a powerful new

  10. Alcohol Withdrawal and Cerebellar Mitochondria.

    PubMed

    Jung, Marianna E

    2015-08-01

    Cerebellar disorders trigger the symptoms of movement problems, imbalance, incoordination, and frequent fall. Cerebellar disorders are shown in various CNS illnesses including a drinking disorder called alcoholism. Alcoholism is manifested as an inability to control drinking in spite of adverse consequences. Human and animal studies have shown that cerebellar symptoms persist even after complete abstinence from drinking. In particular, the abrupt termination (ethanol withdrawal) of long-term excessive ethanol consumption has shown to provoke a variety of neuronal and mitochondrial damage to the cerebellum. Upon ethanol withdrawal, excitatory neurotransmitter molecules such as glutamate are overly released in brain areas including cerebellum. This is particularly relevant to the cerebellar neuronal network as glutamate signals are projected to Purkinje neurons through granular cells that are the most populated neuronal type in CNS. This excitatory neuronal signal may be elevated by ethanol withdrawal stress, which promotes an increase in intracellular Ca(2+) level and a decrease in a Ca(2+)-binding protein, both of which result in the excessive entry of Ca(2+) to the mitochondria. Subsequently, mitochondria undergo a prolonged opening of mitochondrial permeability transition pore and the overproduction of harmful free radicals, impeding adenosine triphosphate (ATP)-generating function. This in turn provokes the leakage of mitochondrial molecule cytochrome c to the cytosol, which triggers a cascade of adverse cytosol reactions. Upstream to this pathway, cerebellum under the condition of ethanol withdrawal has shown aberrant gene modifications through altered DNA methylation, histone acetylation, or microRNA expression. Interplay between these events and molecules may result in functional damage to cerebellar mitochondria and consequent neuronal degeneration, thereby contributing to motoric deficit. Mitochondria-targeting research may help develop a powerful new

  11. Long-term changes in Saturn's troposphere

    SciTech Connect

    Trafton, L.

    1985-09-01

    Attention is given to the results of a long term monitoring study of Saturn's H/sub 2/ quadrupole and CH/sub 4/ band absorptions outside the equatorial zone, over an interval of half a Saturn year that covers most of the perihelion half of Saturn's elliptical orbit (which is approximately bounded by the equinoxes). Marked long term changes are noted in the CH/sub 4/ absorption, accompanied by weakly opposite changes in the H/sub 2/ absorption. Seasonal changes are inferred on the basis of temporal variations in absorption. Spatial measurements have also been made in the 6450 A NH/sub 3/ band since the 1980 equinox. 42 references.

  12. Long-term reinforced fixed provisional restorations.

    PubMed

    Galindo, D; Soltys, J L; Graser, G N

    1998-06-01

    Extensive prosthodontic treatment often requires fabrication of long-term provisional restorations. Numerous materials and techniques have been described for prolonged insertion of interim restorations. This article describes a procedure for fabrication of long-term reinforced heat-processed provisional restorations based on a diagnostic wax-up. Reinforced heat-processed provisional restorations reduced flexure, which minimizes progressive loss of cement and diminished the possibility of recurrent decay. Occlusal stability and vertical dimension were maintained because of greater wear resistance. Occlusion, tooth contours, and pontic design developed in the provisional restoration were duplicated in the definitive restoration. The use of a matrix from a diagnostic wax-up facilitated fabrication of the prosthesis, and made the procedure less time-consuming and more predictable.

  13. [Taiwan long-term care insurance and the evolution of long-term care in Japan].

    PubMed

    Huang, Hui-Wen; Liu, Shu-Hui; Pai, Yu-Chu

    2010-08-01

    The proportion of elderly (65 years of age and older) in Taiwan has exceeded 10% since 2008. With more elderly, the number of patients suffering from dementia and disabilities has also been rapidly increasing. Japan also has been facing increasing demand for long-term care due to an aging society. Prior to 2000, social welfare programs in Japan, working to cope with changing needs, typically provided insufficient services, and geriatric patients were hospitalized unnecessarily, wasting medical resources and causing undue patient hardship. In response, Japan launched its long-term care insurance program in April 2000. Under the program, city, town and village-based organizations should take responsibility for providing care to the elderly in their place of residence. The program significantly improved previous financial shortfalls and long-term care supply and demand has been met by existing social welfare organization resources. In Taiwan, the provision of long-term care by county / city authorities has proven inconsistent, with performance deemed poor after its first decade of long-term care operations. Service was found to be affected by differences in available resources and insufficient long-term care administration. The cultures of Taiwan and Japan are similar. The authors visited the Japan Long-Term Care Insurance Institute in August 2009. Main issues involved in the implementation and evolution of the Japan long-term Care Insurance are reported on in this paper. We hope such may be useful information to those working to develop long-term care programs in Taiwan. PMID:20661859

  14. Cutaneous oxalosis after long-term hemodialysis.

    PubMed

    Abuelo, J G; Schwartz, S T; Reginato, A J

    1992-07-01

    A 27-year-old woman undergoing long-term hemodialysis developed cutaneous calcifications on her fingers. A skin biopsy specimen showed that the deposits were calcium oxalate. To our knowledge, only one previous article has reported pathologic and crystallographic studies on calcifications of the skin resulting from dialysis oxalosis. We speculate that vitamin C supplements, liberal tea consumption, an increased serum ionized calcium concentration, and the long duration of hemodialysis contributed to the production of these deposits.

  15. Long-term course of opioid addiction.

    PubMed

    Hser, Yih-Ing; Evans, Elizabeth; Grella, Christine; Ling, Walter; Anglin, Douglas

    2015-01-01

    Opioid addiction is associated with excess mortality, morbidities, and other adverse conditions. Guided by a life-course framework, we review the literature on the long-term course of opioid addiction in terms of use trajectories, transitions, and turning points, as well as other factors that facilitate recovery from addiction. Most long-term follow-up studies are based on heroin addicts recruited from treatment settings (mostly methadone maintenance treatment), many of whom are referred by the criminal justice system. Cumulative evidence indicates that opioid addiction is a chronic disorder with frequent relapses. Longer treatment retention is associated with a greater likelihood of abstinence, whereas incarceration is negatively related to subsequent abstinence. Over the long term, the mortality rate of opioid addicts (overdose being the most common cause) is about 6 to 20 times greater than that of the general population; among those who remain alive, the prevalence of stable abstinence from opioid use is low (less than 30% after 10-30 years of observation), and many continue to use alcohol and other drugs after ceasing to use opioids. Histories of sexual or physical abuse and comorbid mental disorders are associated with the persistence of opioid use, whereas family and social support, as well as employment, facilitates recovery. Maintaining opioid abstinence for at least five years substantially increases the likelihood of future stable abstinence. Recent advances in pharmacological treatment options (buprenorphine and naltrexone) include depot formulations offering longer duration of medication; their impact on the long-term course of opioid addiction remains to be assessed.

  16. Consequences of long-term hyperparathyroidism.

    PubMed

    Graal, M B; Wolffenbuttel, B H

    1998-07-01

    We describe a young woman with long-term untreated hyperparathyroidism with a superimposed vitamin D deficiency and an extremely decreased bone mineral density that was complicated by a vertebral fracture. Despite pretreatment with intravenous pamidronate and short-term vitamin D supplementation, severe and long-standing hypocalcaemia ('hungry bone syndrome') developed after parathyroidectomy. We discuss the consequences of hyperparathyroidism, especially the effects on bone, the complications of parathyroidectomy and the possibilities of preoperative treatment with bisphosphonates.

  17. Long-term consequences of anorexia nervosa.

    PubMed

    Meczekalski, Blazej; Podfigurna-Stopa, Agnieszka; Katulski, Krzysztof

    2013-07-01

    Anorexia nervosa (AN) is a psychiatric disorder that occurs mainly in female adolescents and young women. The obsessive fear of weight gain, critically limited food intake and neuroendocrine aberrations characteristic of AN have both short- and long-term consequences for the reproductive, cardiovascular, gastrointestinal and skeletal systems. Neuroendocrine changes include impairment of gonadotropin releasing-hormone (GnRH) pulsatile secretion and changes in neuropeptide activity at the hypothalamic level, which cause profound hypoestrogenism. AN is related to a decrease in bone mass density, which can lead to osteopenia and osteoporosis and a significant increase in fracture risk in later life. Rates of birth complications and low birth weight may be higher in women with previous AN. The condition is associated with fertility problems, unplanned pregnancies and generally negative attitudes to pregnancy. During pregnancy, women with the condition have higher rates of hyperemesis gravidarum, anaemia and obstetric complications, as well as impaired weight gain and compromised intrauterine foetal growth. It is reported that 80% of AN patients are affected by a cardiac complications such as sinus bradycardia, a prolonged QT interval on electrocardiography, arrythmias, myocardial mass modification and hypotension. A decrease in bone mineral density (BMD) is one of the most important medical consequences of AN. Reduced BMD may subsequently lead to a three- to seven-fold increased risk of spontaneous fractures. Untreated AN is associated with a significant increase in the risk of death. Better detection and sophisticated therapy should prevent the long-term consequences of this disorder. The aims of treatment are not only recovery but also prophylaxis and relief of the long-term effects of this disorder. Further investigations of the long-term disease risk are needed. PMID:23706279

  18. Electrodes for long-term esophageal electrocardiography.

    PubMed

    Niederhauser, Thomas; Haeberlin, Andreas; Marisa, Thanks; Jungo, Michael; Goette, Josef; Jacomet, Marcel; Abacherli, Roger; Vogel, Rolf

    2013-09-01

    The emerging application of long-term and high-quality ECG recording requires alternative electrodes to improve the signal quality and recording capability of surface skin electrodes. The esophageal ECG has the potential to overcome these limitations but necessitates novel recorder and lead designs. The electrode material is of particular interest, since the material has to ensure conflicting requirements like excellent biopotential recording properties and inertness. To this end, novel electrode materials like PEDOT and silver-PDMS as well as established electrode materials such as stainless steel, platinum, gold, iridium oxide, titanium nitride, and glassy carbon were investigated by long-term electrochemical impedance spectroscopy and model-based signal analysis using the derived in vitro interfacial properties in conjunction with a dedicated ECG amplifier. The results of this novel approach show that titanium nitride and iridium oxide featuring microstructured surfaces did not degrade when exposed to artificial acidic saliva. These materials provide low electrode potential drifts and insignificant signal distortion superior to surface skin electrodes making them compatible with accepted standards for ambulatory ECG. They are superior to the noble and polarizable metals such as platinum, silver, and gold that induced more signal distortions and are superior to esophageal stainless steel electrodes that corrode in artificial saliva. The study provides rigorous criteria for the selection of electrode materials for prolonged ECG recording by combining long-term in vitro electrode material properties with ECG signal quality assessment.

  19. [Long-term survival after severe trauma].

    PubMed

    Mutschler, W; Mutschler, M; Graw, M; Lefering, R

    2016-07-01

    Long-term survival after severe trauma is rarely addressed in German trauma journals although knowledge of life expectancy and identification of factors contributing to increased mortality are important for lifetime care management, development of service models, and targeting health promotion and prevention interventions. As reliable data in Germany are lacking, we compiled data mainly from the USA and Australia to describe life expectancy, risk factors, and predictors of outcome in patients experiencing traumatic spinal cord injury, traumatic brain injury, and polytrauma. Two years after trauma, life expectancy in all three categories was significantly lower than that of the general population. It depends strongly on severity of disability, age, and gender and is quantifiable. Whereas improvements in medical care have led to a marked decline in short-term mortality, surprisingly long-term survival in severe trauma has not changed over the past 30 years. Therefore, there is need to intensify long-term trauma patient care and to find new strategies to limit primary damage. PMID:27342106

  20. Titanium for long-term tritium storage

    SciTech Connect

    Heung, L.K.

    1994-12-01

    Due to the reduction of nuclear weapon stockpile, there will be an excess of tritium returned from the field. The excess tritium needs to be stored for future use, which might be several years away. A safe and cost effective means for long term storage of tritium is needed. Storing tritium in a solid metal tritide is preferred to storing tritium as a gas, because a metal tritide can store tritium in a compact form and the stored tritium will not be released until heat is applied to increase its temperature to several hundred degrees centigrade. Storing tritium as a tritide is safer and more cost effective than as a gas. Several candidate metal hydride materials have been evaluated for long term tritium storage. They include uranium, La-Ni-Al alloys, zirconium and titanium. The criteria used include material cost, radioactivity, stability to air, storage capacity, storage pressure, loading and unloading conditions, and helium retention. Titanium has the best combination of properties and is recommended for long term tritium storage.

  1. Long-term EEG in children.

    PubMed

    Montavont, A; Kaminska, A; Soufflet, C; Taussig, D

    2015-03-01

    Long-term video-EEG corresponds to a recording ranging from 1 to 24 h or even longer. It is indicated in the following situations: diagnosis of epileptic syndromes or unclassified epilepsy, pre-surgical evaluation for drug-resistant epilepsy, follow-up of epilepsy or in cases of paroxysmal symptoms whose etiology remains uncertain. There are some specificities related to paediatric care: a dedicated pediatric unit; continuous monitoring covering at least a full 24-hour period, especially in the context of pre-surgical evaluation; the requirement of presence by the parents, technician or nurse; and stronger attachment of electrodes (cup electrodes), the number of which is adapted to the age of the child. The chosen duration of the monitoring also depends on the frequency of seizures or paroxysmal events. The polygraphy must be adapted to the type and topography of movements. It is essential to have at least an electrocardiography (ECG) channel, respiratory sensor and electromyography (EMG) on both deltoids. There is no age limit for performing long-term video-EEG even in newborns and infants; nevertheless because of scalp fragility, strict surveillance of the baby's skin condition is required. In the specific context of pre-surgical evaluation, long-term video-EEG must record all types of seizures observed in the child. This monitoring is essential in order to develop hypotheses regarding the seizure onset zone, based on electroclinical correlations, which should be adapted to the child's age and the psychomotor development.

  2. Infective endocarditis: determinants of long term outcome

    PubMed Central

    Netzer, R O M; Altwegg, S C; Zollinger, E; Täuber, M; Carrel, T; Seiler, C

    2002-01-01

    Objective: To evaluate predictors of long term prognosis in infective endocarditis. Design: Retrospective cohort study. Setting: Tertiary care centre. Patients: 212 consecutive patients with infective endocarditis between 1980 and 1995 Main outcome measures: Overall and cardiac mortality; event-free survival; and the following events: recurrence, need for late valve surgery, bleeding and embolic complications, cerebral dysfunction, congestive heart failure. Results: During a mean follow up period of 89 months (range 1–244 months), 56% of patients died. In 180 hospital survivors, overall and cardiac mortality amounted to 45% and 24%, respectively. By multivariate analysis, early surgical treatment, infection by streptococci, age < 55 years, absence of congestive heart failure, and > 6 symptoms or signs of endocarditis during active infection were predictive of improved overall long term survival. Independent determinants of event-free survival were infection by streptococci and age < 55 years. Event-free survival was 17% at the end of follow up both in medically–surgically treated patients and in medically treated patients. Conclusions: Long term survival following infective endocarditis is 50% after 10 years and is predicted by early surgical treatment, age < 55 years, lack of congestive heart failure, and the initial presence of more symptoms of endocarditis. PMID:12067947

  3. Acute cerebellar ataxia

    MedlinePlus

    Cerebellar ataxia; Ataxia - acute cerebellar; Cerebellitis; Post-varicella acute cerebellar ataxia; PVACA ... virus. Viral infections that may cause this include chickenpox , Coxsackie disease, Epstein-Barr, and echovirus . Other causes ...

  4. The Long-Term Impact of High School Civics Curricula on Political Knowledge, Democratic Attitudes and Civic Behaviors: A Multi-Level Model of Direct and Mediated Effects through Communication. CIRCLE Working Paper #65

    ERIC Educational Resources Information Center

    Hutchens, Myiah J.; Eveland, William P., Jr.

    2009-01-01

    This report examines the effects of exposure to various elements of a civics curriculum on civic participation, two forms of political knowledge, internal political efficacy, political cynicism, news elaboration, discussion elaboration and various forms of interpersonal and mediated political communication behaviors. The data are based on a…

  5. Response to abdominal hysterectomy with bilateral salpingo-oophorectomy in postmenopausal woman with anti-yo antibody mediated paraneoplastic cerebellar degeneration.

    PubMed

    Bhargava, Amita; Bhushan, Bharat; Kasundra, Gaurav M; Shubhakaran, Khichar; Pujar, Guruprasad S; Banakar, Basavaraj

    2014-07-01

    Paraneoplastic cerebellar degeneration (PCD) is a rare neurological disorder characterized by a widespread loss of Purkinje cells associated with a progressive pancerebellar dysfunction. PCD often precedes the cancer diagnosis by months to years. Here, we report a case of 44-year old postmenopausal woman who presented with PCD symptoms and high levels of anti-Yo antibodies titer since 8 months. We failed to conclude any neoplastic focus after thorough laboratory and imaging study. She minimally responded to methylprednisolone and immunoglobulin therapies. Despite therapy she was severely disabled. Planned abdominal hysterectomy with bilateral salpingo-oophorectomy (AHBSO) was done, histology revealed grade IIA borderline serous papillary carcinoma of ovary. Her neurological deficit responded dramatically to AHBSO. It is first case report who emphasize the response of AHBSO with presentation of anti-Yo antibody-mediated PCD and hidden nidus in post menopausal women.

  6. PI3K signalling in GnRH actions on dispersed goldfish pituitary cells: relationship with PKC-mediated LH and GH release and regulation of long-term effects on secretion and total cellular hormone availability.

    PubMed

    Pemberton, Joshua G; Orr, Michael E; Stafford, James L; Chang, John P

    2014-09-01

    Goldfish pituitary cells are exposed to two GnRHs, salmon (s)GnRH and chicken (c)GnRH-II. Phosphoinositide 3-kinase (PI3K) and protein kinase C (PKC) both participate in acute sGnRH- and cGnRH-II-stimulated LH and GH release. Using goldfish pituitary cells, we examined the relationship between PI3K and PKC in acute LH and GH secretion, and PI3K involvement in chronic hormone release and total LH and GH availability. The PI3K inhibitor LY294002 did not affect PKC agonists-induced LH or GH release, and PKC agonists did not alter PI3K p85 phosphorylation, suggesting PKC activation is not upstream of PI3K in acute hormone release. In 2, 6, 12 and 24h treatments, LY294002 did not affect LH release but stimulated total LH availability at 6h. sGnRH stimulatory actions on LH release and total availability at 12 and 24h, and cGnRH-II effects on these parameters at 6h were inhibited by LY294002. LY294002 enhanced basal GH release at 2 and 6h, but reduced total GH at 12 and 24h. Increased GH release was seen following 6, 12 and 24h of sGnRH, and 2, 6 and 24h of cGnRH-II treatment but total GH availability was only elevated by 24h cGnRH-II treatment. Whereas LY294002 inhibited GH release responses to sGnRH at 12h and cGnRH-II at 6h, it attenuated cGnRH-II-elicited, but not sGnRH-induced, effects on total GH. These results indicate that PI3K differentially modulates long-term basal and GnRH-stimulated hormone release, and total hormone availability, in a time-, cell-type-, and GnRH isoform-selective manner.

  7. Evidence that limbic neural plasticity in the right hemisphere mediates partial kindling induced lasting increases in anxiety-like behavior: effects of low frequency stimulation (quenching?) on long term potentiation of amygdala efferents and behavior following kindling.

    PubMed

    Adamec, R E

    1999-08-21

    Behavioral and physiological effects of partial kindling of the right ventral hippocampus by perforant path (PP) stimulation were investigated in the cat. Partial kindling produced lasting changes in affect (increased defensive response to rats) and predatory attack (decreased pawing and biting attack). Partial kindling also induced long term potentiation (LTP) of amygdala efferent transmission to ventromedial hypothalamus (VMH) and periaqueductal gray (PAG) in left and right hemispheres. LTP of field population spikes evoked in area CA3 by PP stimulation was also observed. LTP was detected using evoked potential methods. These findings parallel previous studies of left PP-CA3 partial kindling. Analysis of covariance removing effects of LTP from behavioral changes suggests that initiation of increased defensiveness at 2 days after completion of partial kindling depended on LTP of left and right amygdalo-VMH and right amygdalo-PAG transmission. From 6 days after kindling onward, increased defensiveness depended on LTP of right amygdalo-PAG transmission. Depotentiation of amygdala efferent LTP by bilateral low frequency amygdala stimulation (LFS) (900 pulses at 1 Hz, once daily for 7 days) selectively reduced LTP in right amygdala efferents. At the same time, defensive, but not predatory attack behavior, was returned to levels seen prior to partial kindling. Both depotentiation and reduction of defensiveness were transient. Defensiveness increased to post-kindling levels by 76 days after LFS. At the same time, LTP was restored in the right amygdalo-PAG pathway. In contrast LTP in the right amygdalo-VMH pathway remained depotentiated. Effects of LFS were not due to damage, as thresholds to evoke amygdala efferent response were unchanged. These findings suggest that lasting change in affect following partial hippocampal kindling depends on LTP of right amygdala efferent transmission to PAG. The findings parallel studies of non-convulsant pharmacological induction of

  8. Long-term EARLINET dust observations

    NASA Astrophysics Data System (ADS)

    Mona, Lucia; Amiridis, Vassilis; Amodeo, Aldo; Binietoglou, Ioannis; D'Amico, Giuseppe; Schwarz, Anja; Papagiannopoulos, Nikolaos; Papayannis, Alexandros; Sicard, Michael; Comeron, Adolfo; Pappalardo, Gelsomina

    2015-04-01

    Systematic observations of Saharan dust events over Europe are performed from May 2000 by EARLINET, the European Aerosol Research LIdar NETwork. EARLINET is a coordinated network of stations that make use of advanced lidar methods for the vertical profiling of aerosols. The backbone of EARLINET network is a common schedule for performing the measurements and the quality assurance of instruments/data. Particular attention is paid to monitoring the Saharan dust intrusions over the European continent. The geographical distribution of the EARLINET stations is particularly appealing for the dust observation, with stations located all around the Mediterranean and in the center of the Mediterranean (Italian stations) where dust intrusions are frequent, and with several stations in the central Europe where dust penetrates occasionally. All aerosol backscatter and extinction profiles related to observations collected during these alerts are grouped in the devoted "Saharan dust" category of the EARLINET database. This category consists of about 4700 files (as of December 2013). Case studies involving several stations around Europe selected from this long-term database have been provided the opportunity to investigate dust modification processes during transport over the continent. More important, the long term EARLINET dust monitoring allows the investigation of the horizontal and vertical extent of dust outbreaks over Europe and the climatological analysis of dust optical intensive and extensive properties at continental scale. This long-term database is also a unique tool for a systematic comparison with dust model outputs and satellite-derived dust products. Because of the relevance for both dust modeling and satellite retrievals improvement, results about desert dust layers extensive properties as a function of season and source regions are investigated and will be presented at the conference. First comparisons with models outputs and CALIPSO dust products will be

  9. Human Behaviour in Long-Term Missions

    NASA Technical Reports Server (NTRS)

    1997-01-01

    In this session, Session WP1, the discussion focuses on the following topics: Psychological Support for International Space Station Mission; Psycho-social Training for Man in Space; Study of the Physiological Adaptation of the Crew During A 135-Day Space Simulation; Interpersonal Relationships in Space Simulation, The Long-Term Bed Rest in Head-Down Tilt Position; Psychological Adaptation in Groups of Varying Sizes and Environments; Deviance Among Expeditioners, Defining the Off-Nominal Act in Space and Polar Field Analogs; Getting Effective Sleep in the Space-Station Environment; Human Sleep and Circadian Rhythms are Altered During Spaceflight; and Methodological Approach to Study of Cosmonauts Errors and Its Instrumental Support.

  10. Long Term Analysis for the BAM device

    NASA Astrophysics Data System (ADS)

    Bonino, D.; Gardiol, D.

    2011-02-01

    Algorithms aimed at the evaluation of critical quantities are based on models with many parameters, which values are estimated from data. The knowledge, with high accuracy, of these values and the control of their temporal evolution are important features. In this work, we focus on the latter subject, and we show a proposed pipeline for the BAM (Basic Angle Monitoring) Long Term Analysis, aimed at the study of the calibration parameters of the BAM device and of the Basic Angle variation, searching for unwanted trends, cyclic features, or other potential unexpected behaviours.

  11. Long-term outcomes in multiple gestations.

    PubMed

    Rand, Larry; Eddleman, Keith A; Stone, Joanne

    2005-06-01

    Children born from a multiple gestation are at increased risk for cerebral palsy, learning disability, and language and neurobehavioral deficits. With the increased incidence of multiple pregnancies and use of assisted reproductive technology (ART), these issues are more commonly affecting parents. Long-term outcomes are a critical part of preconceptual and early pregnancy counseling for parents faced with a multiple gestation or considering ART, and the provider should be well versed on issues surrounding zygosity, gestational age, higher-order multiples, and the effects of options such as multifetal pregnancy reduction. PMID:15922795

  12. Long-Term Wind Power Variability

    SciTech Connect

    Wan, Y. H.

    2012-01-01

    The National Renewable Energy Laboratory started collecting wind power data from large commercial wind power plants (WPPs) in southwest Minnesota with dedicated dataloggers and communication links in the spring of 2000. Over the years, additional WPPs in other areas were added to and removed from the data collection effort. The longest data stream of actual wind plant output is more than 10 years. The resulting data have been used to analyze wind power fluctuations, frequency distribution of changes, the effects of spatial diversity, and wind power ancillary services. This report uses the multi-year wind power data to examine long-term wind power variability.

  13. Long-term effects of sibling incest.

    PubMed

    Daie, N; Witztum, E; Eleff, M

    1989-11-01

    Although sexual abuse of children is recognized as a serious problem, sibling incest has received relatively little attention. A distinction has been made between power-oriented sibling incest and nurturance-oriented incest. The authors review the relevant literature and present four clinical examples. The cases illustrate the broad range of sibling incest and demonstrate its effects, including the long-term consequences for the perpetrator. Lasting difficulties in establishing and maintaining close relationships, especially sexual ones, are prominent features of each case. Without denying the occurrences of benign sex-play between siblings, the authors emphasize exploitation and abuse as pathogenic aspects of sibling incest.

  14. Performance considerations in long-term spaceflight

    NASA Technical Reports Server (NTRS)

    Akins, F. R.

    1979-01-01

    Maintenance of skilled performance during extended space flight is of critical importance to both the health and safety of crew members and to the overall success of mission goals. An examination of long term effects and performance requirements is therefore a factor of immense importance to the planning of future missions. Factors that were investigated include: definition of performance categories to be investigated; methods for assessing and predicting performance levels; in-flight factors which can affect performance; and factors pertinent to the maintenance of skilled performance.

  15. Long-term space flights - personal impressions

    NASA Astrophysics Data System (ADS)

    Polyakov, V. V.

    During a final 4-month stage of a 1-year space flight of cosmonauts Titov and Manarov, a physician, Valery Polyakov was included on a crew for the purpose of evaluating their health, correcting physical status to prepare for the spacecraft reentry and landing operations. The complex program of scientific investigations and experiments performed by the physician included an evaluation of adaptation reactions of the human body at different stages of space mission using clinicophysiological and biochemical methods; testing of alternative regimes of exercise and new countermeasures to prevent an unfavourable effect of long-term weightlessness.

  16. 17 CFR 256.224 - Other long-term debt.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Other long-term debt. 256.224... COMPANY ACT OF 1935 6. Long-Term Debt § 256.224 Other long-term debt. This account shall include all long-term debt to nonassociates and not subject to current settlement. Note: Subaccounts shall be...

  17. 17 CFR 256.224 - Other long-term debt.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Other long-term debt. 256.224... COMPANY ACT OF 1935 6. Long-Term Debt § 256.224 Other long-term debt. This account shall include all long-term debt to nonassociates and not subject to current settlement. Note: Subaccounts shall be...

  18. 47 CFR 54.303 - Long term support.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Long term support. 54.303 Section 54.303... SERVICE Universal Service Support for High Cost Areas § 54.303 Long term support. (a) Beginning January 1... shall receive Long Term Support. Beginning July 1, 2004, no carrier shall receive Long Term Support....

  19. 47 CFR 54.303 - Long term support.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 3 2011-10-01 2011-10-01 false Long term support. 54.303 Section 54.303... SERVICE Universal Service Support for High Cost Areas § 54.303 Long term support. (a) Beginning January 1... shall receive Long Term Support. Beginning July 1, 2004, no carrier shall receive Long Term Support....

  20. Toward a comprehensive long term nicotine policy

    PubMed Central

    Gray, N; Henningfield, J; Benowitz, N; Connolly, G; Dresler, C; Fagerstrom, K; Jarvis, M; Boyle, P

    2005-01-01

    Global tobacco deaths are high and rising. Tobacco use is primarily driven by nicotine addiction. Overall tobacco control policy is relatively well agreed upon but a long term nicotine policy has been less well considered and requires further debate. Reaching consensus is important because a nicotine policy is integral to the target of reducing tobacco caused disease, and the contentious issues need to be resolved before the necessary political changes can be sought. A long term and comprehensive nicotine policy is proposed here. It envisages both reducing the attractiveness and addictiveness of existing tobacco based nicotine delivery systems as well as providing alternative sources of acceptable clean nicotine as competition for tobacco. Clean nicotine is defined as nicotine free enough of tobacco toxicants to pass regulatory approval. A three phase policy is proposed. The initial phase requires regulatory capture of cigarette and smoke constituents liberalising the market for clean nicotine; regulating all nicotine sources from the same agency; and research into nicotine absorption and the role of tobacco additives in this process. The second phase anticipates clean nicotine overtaking tobacco as the primary source of the drug (facilitated by use of regulatory and taxation measures); simplification of tobacco products by limitation of additives which make tobacco attractive and easier to smoke (but tobacco would still be able to provide a satisfying dose of nicotine). The third phase includes a progressive reduction in the nicotine content of cigarettes, with clean nicotine freely available to take the place of tobacco as society's main nicotine source. PMID:15923465

  1. Long term changes in the polar vortices

    NASA Astrophysics Data System (ADS)

    Braathen, Geir O.

    2015-04-01

    As the amount of halogens in the stratosphere is slowly declining and the ozone layer slowly recovers it is of interest to see how the meteorological conditions in the vortex develop over the long term since such changes might alter the foreseen ozone recovery. In conjunction with the publication of the WMO Antarctic and Arctic Ozone Bulletins, WMO has acquired the ERA Interim global reanalysis data set for several meteorological parameters. This data set goes from 1979 - present. These long time series of data can be used for several useful studies of the long term development of the polar vortices. Several "environmental indicators" for vortex change have been calculated, and a climatology, as well as trends, for these parameters will be presented. These indicators can act as yardsticks and will be useful for understanding past and future changes in the polar vortices and how these changes affect polar ozone depletion. Examples of indicators are: vortex mean temperature, vortex minimum temperature, vortex mean PV, vortex "importance" (PV*area), vortex break-up time, mean and maximum wind speed. Data for both the north and south polar vortices have been analysed at several isentropic levels from 350 to 850 K. A possible link between changes in PV and sudden stratospheric warmings will be investigated, and the results presented.

  2. Long-Term Care Policy: Singapore's Experience.

    PubMed

    Chin, Chee Wei Winston; Phua, Kai-Hong

    2016-01-01

    Singapore, like many developed countries, is facing the challenge of a rapidly aging population and the increasing need to provide long-term care (LTC) services for elderly in the community. The Singapore government's philosophy on care for the elderly is that the family should be the first line of support, and it has relied on voluntary welfare organizations (VWOs) or charities for the bulk of LTC service provision. For LTC financing, it has emphasized the principles of co-payment and targeting of state support to the low-income population through means-tested government subsidies. It has also instituted ElderShield, a national severe disability insurance scheme. This paper discusses some of the challenges facing LTC policy in Singapore, particularly the presence of perverse financial incentives for hospitalization, the pitfalls of over-reliance on VWOs, and the challenges facing informal family caregivers. It discusses the role of private LTC insurance in LTC financing, bearing in mind demand- and supply-side failures that have plagued the private LTC insurance market. It suggests the need for more standardized needs assessment and portable LTC benefits, with reference to the Japanese Long-Term Care Insurance program, and also discusses the need to provide more support to informal family caregivers. PMID:26808468

  3. Long-term anticoagulation. Indications and management.

    PubMed Central

    Stults, B M; Dere, W H; Caine, T H

    1989-01-01

    Each year half a million persons in the United States receive long-term anticoagulant therapy to prevent venous and arterial thromboembolism. Unfortunately, the relative benefits and risks of anticoagulant therapy have not been adequately quantified for many thromboembolic disorders, and the decisions as to whether, for how long, and how intensely to administer anticoagulation are often complex and controversial. Several expert panels have published recommendations for anticoagulant therapy for different thromboembolic disorders; the primary area of disagreement among these panels concerns the optimal intensity of anticoagulation. Recent research and analytic reviews have helped to clarify both the risk factors for and the appropriate diagnostic evaluation of anticoagulant-induced hemorrhage. Clinicians must be aware of the nonhemorrhagic complications of anticoagulant therapy, particularly during pregnancy. The administration of anticoagulants is difficult both in relation to dosing and long-term monitoring. Knowledge of the pharmacology of the anticoagulants, an organized approach to ongoing monitoring, and thorough patient education may facilitate the safe and effective use of these drugs. PMID:2686173

  4. Long-term outcome in personality disorders.

    PubMed

    Stone, M H

    1993-03-01

    Personality disorders meeting DSM or ICD criteria represent the severe end of the broad spectrum of personality configurations involving maladaptive traits. The literature regarding long-term outcome of personality disorders is sparse. Most attention is devoted to formerly institutionalised patients with borderline, antisocial, or schizotypal disorders. Borderline patients at 10-25-year follow-up have a wide range of outcomes, from clinical recovery (50-60%) to suicide (3-9%). Certain factors (e.g. artistic talent) conduce to higher recovery rates, others (e.g. parental cruelty) to lower rates. Schizoid and schizotypal patients tend to remain isolated, and to lead marginal lives. The long-term outcome in antisocial persons is bleak if psychopathic traits are prominent. Personality traits and their corresponding disorders are egosyntonic, harden into habit, and are both slow to change and hard to modify. There is no one treatment of choice. Psychoanalysis and related methods work best within the anxious/inhibited group; cognitive/behavioural techniques are well suited to the disorders requiring limit setting and the amelioration of maladaptive habits. PMID:8453424

  5. Long term perfusion system supporting adipogenesis.

    PubMed

    Abbott, Rosalyn D; Raja, Waseem K; Wang, Rebecca Y; Stinson, Jordan A; Glettig, Dean L; Burke, Kelly A; Kaplan, David L

    2015-08-01

    Adipose tissue engineered models are needed to enhance our understanding of disease mechanisms and for soft tissue regenerative strategies. Perfusion systems generate more physiologically relevant and sustainable adipose tissue models, however adipocytes have unique properties that make culturing them in a perfusion environment challenging. In this paper we describe the methods involved in the development of two perfusion culture systems (2D and 3D) to test their applicability for long term in vitro adipogenic cultures. It was hypothesized that a silk protein biomaterial scaffold would provide a 3D framework, in combination with perfusion flow, to generate a more physiologically relevant sustainable adipose tissue engineered model than 2D cell culture. Consistent with other studies evaluating 2D and 3D culture systems for adipogenesis we found that both systems successfully model adipogenesis, however 3D culture systems were more robust, providing the mechanical structure required to contain the large, fragile adipocytes that were lost in 2D perfused culture systems. 3D perfusion also stimulated greater lipogenesis and lipolysis and resulted in decreased secretion of LDH compared to 2D perfusion. Regardless of culture configuration (2D or 3D) greater glycerol was secreted with the increased nutritional supply provided by perfusion of fresh media. These results are promising for adipose tissue engineering applications including long term cultures for studying disease mechanisms and regenerative approaches, where both acute (days to weeks) and chronic (weeks to months) cultivation are critical for useful insight. PMID:25843606

  6. Long Term Changes in the Polar Vortices

    NASA Astrophysics Data System (ADS)

    Braathen, Geir O.

    2016-04-01

    As the amount of halogens in the stratosphere is slowly declining and the ozone layer slowly recovers it is of interest to see how the meteorological conditions in the vortex develop over the long term since such changes might alter the foreseen ozone recovery. In conjunction with the publication of the WMO Antarctic and Arctic Ozone Bulletins, WMO has acquired the ERA Interim global reanalysis data set for several meteorological parameters. This data set goes from 1979 - present. These long time series of data can be used for several useful studies of the long term development of the polar vortices. Several "environmental indicators" for vortex change have been calculated, and a climatology, as well as trends, for these parameters will be presented. These indicators can act as yardsticks and will be useful for understanding past and future changes in the polar vortices and how these changes affect polar ozone depletion. Examples of indicators are: vortex mean temperature, vortex minimum temperature, vortex mean PV, vortex "importance" (PV*area), vortex break-up time, mean and maximum wind speed. Data for both the north and south polar vortices have been analysed at several isentropic levels from 350 to 850 K. A possible link between changes in PV and sudden stratospheric warmings will be investigated, and the results presented. The unusual meteorological conditions of the 2015 south polar vortex and the 2010/11 and 2015/16 north polar vortices will be compared to other recent years.

  7. Long term perfusion system supporting adipogenesis

    PubMed Central

    Abbott, Rosalyn D.; Raja, Waseem K.; Wang, Rebecca Y.; Stinson, Jordan A.; Glettig, Dean L.; Burke, Kelly A.; Kaplan, David L.

    2015-01-01

    Adipose tissue engineered models are needed to enhance our understanding of disease mechanisms and for soft tissue regenerative strategies. Perfusion systems generate more physiologically relevant and sustainable adipose tissue models, however adipocytes have unique properties that make culturing them in a perfusion environment challenging. In this paper we describe the methods involved in the development of two perfusion culture systems (2D and 3D) to test their applicability for long term in vitro adipogenic cultures. It was hypothesized that a silk protein biomaterial scaffold would provide a 3D framework, in combination with perfusion flow, to generate a more physiologically relevant sustainable adipose tissue engineered model than 2D cell culture. Consistent with other studies evaluating 2D and 3D culture systems for adipogenesis we found that both systems successfully model adipogensis, however 3D culture systems were more robust, providing the mechanical structure required to contain the large, fragile adipocytes that were lost in 2D perfused culture systems. 3D perfusion also stimulated greater lipogenesis and lipolysis and resulted in decreased secretion of LDH compared to 2D perfusion. Regardless of culture configuration (2D or 3D) greater glycerol was secreted with the increased nutritional supply provided by perfusion of fresh media. These results are promising for adipose tissue engineering applications including long term cultures for studying disease mechanisms and regenerative approaches, where both acute (days to weeks) and chronic (weeks to months) cultivation are critical for useful insight. PMID:25843606

  8. Long-term mechanical ventilation and nutrition.

    PubMed

    Ambrosino, Nicolino; Clini, Enrico

    2004-05-01

    Mechanical ventilation (MV) in chronic situations is commonly used, either delivered invasively or by means of non-invasive interfaces, to control hypoventilation in patients with chest wall, neuromuscular or obstructive lung diseases (either in adulthood or childhood). The global prevalence of ventilator-assisted individuals (VAI) in Europe ranges from 2 to 30 per 100000 population according to different countries. Nutrition is a common problem to face with in patients with chronic respiratory diseases: nonetheless, it is a key component in the long-term management of underweight COPD patients whose muscular disfunction may rapidly turn to peripheral muscle waste. Since long-term mechanical ventilation (LTMV) is usually prescribed in end-stage respiratory diseases with poor nutritional status, nutrition and dietary intake related problems need to be carefully assessed and corrected in these patients. This paper aims to review the most recent innovations in the field of nutritional status and food intake-related problems of VAI (both in adulthood and in childhood).

  9. Toward a comprehensive long term nicotine policy.

    PubMed

    Gray, N; Henningfield, J E; Benowitz, N L; Connolly, G N; Dresler, C; Fagerstrom, K; Jarvis, M J; Boyle, P

    2005-06-01

    Global tobacco deaths are high and rising. Tobacco use is primarily driven by nicotine addiction. Overall tobacco control policy is relatively well agreed upon but a long term nicotine policy has been less well considered and requires further debate. Reaching consensus is important because a nicotine policy is integral to the target of reducing tobacco caused disease, and the contentious issues need to be resolved before the necessary political changes can be sought. A long term and comprehensive nicotine policy is proposed here. It envisages both reducing the attractiveness and addictiveness of existing tobacco based nicotine delivery systems as well as providing alternative sources of acceptable clean nicotine as competition for tobacco. Clean nicotine is defined as nicotine free enough of tobacco toxicants to pass regulatory approval. A three phase policy is proposed. The initial phase requires regulatory capture of cigarette and smoke constituents liberalising the market for clean nicotine; regulating all nicotine sources from the same agency; and research into nicotine absorption and the role of tobacco additives in this process. The second phase anticipates clean nicotine overtaking tobacco as the primary source of the drug (facilitated by use of regulatory and taxation measures); simplification of tobacco products by limitation of additives which make tobacco attractive and easier to smoke (but tobacco would still be able to provide a satisfying dose of nicotine). The third phase includes a progressive reduction in the nicotine content of cigarettes, with clean nicotine freely available to take the place of tobacco as society's main nicotine source. PMID:15923465

  10. Long-term Trend of Sunspot Numbers

    NASA Astrophysics Data System (ADS)

    Gao, P. X.

    2016-10-01

    Using the Hilbert–Huang Transform method, we investigate the long-term trend of yearly mean total sunspot numbers in the time interval of 1700–2015, which come from the World Data Center—the sunspot Index and long-term solar observations. The main findings of this study are summarized below. (1) From the adaptive trend, which is extracted from the yearly mean total sunspot numbers, we can find that the value gradually increases during the time period 1700–1975, then decreases gradually from 1975 to 2015. (2) The Centennial Gleissberg Cycle is extracted from the yearly mean total sunspot numbers and confirms that a new grand minimum is in progress; the Dalton Minimum, the Gleissberg Minimum, and low level of solar activity during solar cycle 24 (the part of the new grand minimum) all can be understood as minima of the Centennial Gleissberg Cycle. (3) Based on the adaptive (overall) trend, and the 100-year and longer timescale trend of yearly mean total sunspot numbers, we can infer that the level of solar activity during the new grand minimum may be close to that during the Gleissberg Minimum, slightly higher than that during the Dalton Minimum, and significantly higher than that during the Maunder Minimum. Our results do not support the suggestion that a new grand minimum, somewhat resembling the Maunder Minimum, is in progress.

  11. Long term perfusion system supporting adipogenesis.

    PubMed

    Abbott, Rosalyn D; Raja, Waseem K; Wang, Rebecca Y; Stinson, Jordan A; Glettig, Dean L; Burke, Kelly A; Kaplan, David L

    2015-08-01

    Adipose tissue engineered models are needed to enhance our understanding of disease mechanisms and for soft tissue regenerative strategies. Perfusion systems generate more physiologically relevant and sustainable adipose tissue models, however adipocytes have unique properties that make culturing them in a perfusion environment challenging. In this paper we describe the methods involved in the development of two perfusion culture systems (2D and 3D) to test their applicability for long term in vitro adipogenic cultures. It was hypothesized that a silk protein biomaterial scaffold would provide a 3D framework, in combination with perfusion flow, to generate a more physiologically relevant sustainable adipose tissue engineered model than 2D cell culture. Consistent with other studies evaluating 2D and 3D culture systems for adipogenesis we found that both systems successfully model adipogenesis, however 3D culture systems were more robust, providing the mechanical structure required to contain the large, fragile adipocytes that were lost in 2D perfused culture systems. 3D perfusion also stimulated greater lipogenesis and lipolysis and resulted in decreased secretion of LDH compared to 2D perfusion. Regardless of culture configuration (2D or 3D) greater glycerol was secreted with the increased nutritional supply provided by perfusion of fresh media. These results are promising for adipose tissue engineering applications including long term cultures for studying disease mechanisms and regenerative approaches, where both acute (days to weeks) and chronic (weeks to months) cultivation are critical for useful insight.

  12. Long-term habituation of the C-start escape response in zebrafish larvae.

    PubMed

    Roberts, Adam C; Pearce, Kaycey C; Choe, Ronny C; Alzagatiti, Joseph B; Yeung, Anthony K; Bill, Brent R; Glanzman, David L

    2016-10-01

    The cellular and molecular basis of long-term memory in vertebrates remains poorly understood. Knowledge regarding long-term memory has been impeded by the enormous complexity of the vertebrate brain, particularly the mammalian brain, as well as by the relative complexity of the behavioral alterations examined in most studies of long-term memory in vertebrates. Here, we demonstrate a long-term form of nonassociative learning-specifically, long-term habituation (LTH)-of a simple reflexive escape response, the C-start, in zebrafish larvae. The C-start is triggered by the activation of one of a pair of giant neurons in the zebrafish's hindbrain, the Mauthner cells. We show that LTH of the C-start requires the activity of NMDA receptors and involves macromolecular synthesis. We further show that the long-term habituated reflex can by rapidly dishabituated by a brief tactile stimulus. Our results set the stage for rigorous, mechanistic investigations of the long-term memory for habituation of a reflexive behavioral response, one that is mediated by a relatively simple, neurobiologically tractable, neural circuit. Moreover, the demonstration of NMDAR and transcriptionally dependent LTH in a translucent vertebrate organism should facilitate the use of optical recording, and optogenetic manipulation, of neuronal activity to elucidate the cellular basis of a long-term vertebrate memory. PMID:27555232

  13. Long-term habituation of the C-start escape response in zebrafish larvae.

    PubMed

    Roberts, Adam C; Pearce, Kaycey C; Choe, Ronny C; Alzagatiti, Joseph B; Yeung, Anthony K; Bill, Brent R; Glanzman, David L

    2016-10-01

    The cellular and molecular basis of long-term memory in vertebrates remains poorly understood. Knowledge regarding long-term memory has been impeded by the enormous complexity of the vertebrate brain, particularly the mammalian brain, as well as by the relative complexity of the behavioral alterations examined in most studies of long-term memory in vertebrates. Here, we demonstrate a long-term form of nonassociative learning-specifically, long-term habituation (LTH)-of a simple reflexive escape response, the C-start, in zebrafish larvae. The C-start is triggered by the activation of one of a pair of giant neurons in the zebrafish's hindbrain, the Mauthner cells. We show that LTH of the C-start requires the activity of NMDA receptors and involves macromolecular synthesis. We further show that the long-term habituated reflex can by rapidly dishabituated by a brief tactile stimulus. Our results set the stage for rigorous, mechanistic investigations of the long-term memory for habituation of a reflexive behavioral response, one that is mediated by a relatively simple, neurobiologically tractable, neural circuit. Moreover, the demonstration of NMDAR and transcriptionally dependent LTH in a translucent vertebrate organism should facilitate the use of optical recording, and optogenetic manipulation, of neuronal activity to elucidate the cellular basis of a long-term vertebrate memory.

  14. Strength and timing of motor responses mediated by rebound firing in the cerebellar nuclei after Purkinje cell activation.

    PubMed

    Witter, Laurens; Canto, Cathrin B; Hoogland, Tycho M; de Gruijl, Jornt R; De Zeeuw, Chris I

    2013-01-01

    The cerebellum refines the accuracy and timing of motor performance. How it encodes information to perform these functions is a major topic of interest. We performed whole cell and extracellular recordings of Purkinje cells (PCs) and cerebellar nuclei neurons (CNs) in vivo, while activating PCs with light in transgenic mice. We show for the first time that graded activation of PCs translates into proportional CN inhibition and induces rebound activity in CNs, which is followed by graded motor contractions timed to the cessation of the stimulus. Moreover, activation of PC ensembles led to disinhibition of climbing fiber activity, which coincided with rebound activity in CNs. Our data indicate that cessation of concerted activity in ensembles of PCs can regulate both timing and strength of movements via control of rebound activity in CNs.

  15. Long-term performance of filtration layer

    NASA Astrophysics Data System (ADS)

    Radfar, A.; Rockaway, T. D.

    2013-12-01

    Permeable pavements are commonly employed to capture and divert stormwater before it enters the stormwater or sewer conveyance systems. During a storm event, runoff water passes through the permeable pavement surface, enters a storage gallery and finally exfiltrates into the surrounding soil. Thus, the ability of the system to store an appropriate volume of runoff water is an important consideration for stormwater control design. Traditionally, crushed stone or other porous material has been used to provide the necessary interstitial void space to store the runoff water. Unfortunately, over time the available void space within the storage gallery is reduced due to settlement, biological growth and sediment accumulation. This gradual reduction in void space reduces the long-term effectiveness of these stormwater controls by limiting its ability to store and pass runoff water. This study examined the long-term performance of the storage gallery layer with respect to its ability to both store and pass runoff water. As the porosity within the storage gallery decreased, it was anticipated that volumetric water content within the gallery would increase and that time necessary to drain the gallery would increase as well. The effects of the gallery porosity were assessed over a one-year study using both laboratory experimentation and monitoring data from naturally occurring rain events. Changes in gallery porosity were first assessed by correlating monitoring piezometer data with surface infiltration testing; building a relation between know volume of poured water being used for the test and the associated pressure head at the base of the gallery. As a known volume of water enters the system, volume change in the gallery directly correlate to increases in pressure head. Second, the time required for water to permeate through pavers and gallery layer to trigger the TDRs in the filtration layer and the time to drain it from the crushed stone were calculated and compared by

  16. Managing soils for long-term productivity

    PubMed Central

    Syers, J. K.

    1997-01-01

    Meeting the goal of long-term agricultural productivity requires that soil degradation be halted and reversed. Soil fertility decline is a key factor in soil degradation and is probably the major cause of declining crop yields. There is evidence that the contribution of declining soil fertility to soil degradation has been underestimated.
    Sensitivity to soil degradation is implicit in the assessment of the sustainability of land management practices, with wide recognition of the fact that soils vary in their ability to resist change and recover subsequent to stress. The concept of resilience in relation to sustainability requires further elaboration and evaluation.
    In the context of soil degradation, a decline in soil fertility is primarily interpreted as the depletion of organic matter and plant nutrients. Despite a higher turnover rate of organic matter in the tropics there is no intrinsic difference between the organic matter content of soils from tropical and temperate regions. The level of organic matter in a soil is closely related to the above and below ground inputs. In the absence of adequate organic material inputs and where cultivation is continuous, soil organic matter declines progressively. Maintaining the quantity and quality of soil organic matter should be a guiding principle in developing management practices.
    Soil microbial biomass serves as an important reservoir of nitrogen (N), phosphorus (P) and sulphur (S), and regulates the cycling of organic matter and nutrients. Because of its high turnover rate, microbial biomass reacts quickly to changes in management and is a sensitive indicator for monitoring and predicting changes in soil organic matter. Modelling techniques have been reasonably successful in predicting changes in soil organic matter with different organic material inputs, but there is little information from the tropics.
    Nutrient depletion through harvested crop components and residue removal, and by leaching and soil

  17. Trigeminal high-frequency stimulation produces short- and long-term modification of reflex blink gain

    PubMed Central

    Ryan, Michael; Kaminer, Jaime; Enmore, Patricia

    2013-01-01

    Reflex blinks provide a model system for investigating motor learning in normal and pathological states. We investigated whether high-frequency stimulation (HFS) of the supraorbital branch of the trigeminal nerve before the R2 blink component (HFS-B) decreases reflex blink gain in alert rats. As with humans (Mao JB, Evinger C. J Neurosci 21: RC151, 2001), HFS-B significantly reduced blink size in the first hour after treatment for rats. Repeated days of HFS-B treatment produced long-term depression of blink circuits. Blink gain decreased exponentially across days, indicating a long-term depression of blink circuits. Additionally, the HFS-B protocol became more effective at depressing blink amplitude across days of treatment. This depression was not habituation, because neither long- nor short-term blink changes occurred when HFS was presented after the R2. To investigate whether gain modifications produced by HFS-B involved cerebellar networks, we trained rats in a delay eyelid conditioning paradigm using HFS-B as the unconditioned stimulus and a tone as the conditioned stimulus. As HFS-B depresses blink circuits and delay conditioning enhances blink circuit activity, occlusion should occur if they share neural networks. Rats acquiring robust eyelid conditioning did not exhibit decreases in blink gain, whereas rats developing low levels of eyelid conditioning exhibited weak, short-term reductions in blink gain. These results suggested that delay eyelid conditioning and long-term HFS-B utilize some of the same cerebellar circuits. The ability of repeated HFS-B treatment to depress trigeminal blink circuit activity long term implied that it may be a useful protocol to reduce hyperexcitable blink circuits that underlie diseases like benign essential blepharospasm. PMID:24285868

  18. Emotional behavior in long-term marriage.

    PubMed

    Carstensen, L L; Gottman, J M; Levenson, R W

    1995-03-01

    In exploring the emotional climate of long-term marriages, this study used an observational coding system to identify specific emotional behaviors expressed by middle-aged and older spouses during discussions of a marital problem. One hundred and fifty-six couples differing in age and marital satisfaction were studied. Emotional behaviors expressed by couples differed as a function of age, gender, and marital satisfaction. In older couples, the resolution of conflict was less emotionally negative and more affectionate than in middle-aged marriages. Differences between husbands and wives and between happy and unhappy marriages were also found. Wives were more affectively negative than husbands, whereas husbands were more defensive than wives, and unhappy marriages involved greater exchange of negative affect than happy marriages.

  19. Long-term monitoring for closed sites

    SciTech Connect

    Golchert, N.W.; Sedlet, J.; Veluri, V.R.

    1985-01-01

    A procedure is presented for planning and implementing a long-term environmental monitoring program for closed low-level radioactive waste disposal sites. The initial task in this procedure is to collect the available information on the legal/regulatory requirements, site and area characteristics, source term, pathway analysis, and prior monitoring results. This information is coupled with parameters such as half-life and retardation factors to develop a monitoring program. As examples, programs are presented for a site that has had little or no waste migration, and for sites where waste has been moved by suface water, by ground water, and by air. Sampling techniques and practices are discussed relative to how a current program would be structured and projections are made on techniques and practices expected to be available in the future. 8 refs., 2 figs.

  20. Long term evolution of comet Halleys orbit.

    NASA Astrophysics Data System (ADS)

    Dvorak, R.; Kribbel, J.

    1987-03-01

    The aim of the paper is to study the long term evolution of comet Halleys orbit taking into account small errors in the initial conditions. Recent papers deal with mapping methods to model cometary dynamics; (e.g. Petrosky and Broucke, 1987 and Chirikov and Vecheslavov, 1986). They will be discussed critically and compared with our own results. We then tested the model using numerical integration methods. For the moment we limited our calculation to 2.105 years, but a 106 year integration is still in progress. We show the expected dynamical evolution of Hallyes orbit taking into account also smaller and larger errors of the initial conditions (nongravitational effects are only roughly estimated). Finally we discuss alsothe controversal opinions concerning the role of the planets (especially the earth).

  1. Long-term control of root growth

    DOEpatents

    Burton, Frederick G.; Cataldo, Dominic A.; Cline, John F.; Skiens, W. Eugene

    1992-05-26

    A method and system for long-term control of root growth without killing the plants bearing those roots involves incorporating a 2,6-dinitroaniline in a polymer and disposing the polymer in an area in which root control is desired. This results in controlled release of the substituted aniline herbicide over a period of many years. Herbicides of this class have the property of preventing root elongation without translocating into other parts of the plant. The herbicide may be encapsulated in the polymer or mixed with it. The polymer-herbicide mixture may be formed into pellets, sheets, pipe gaskets, pipes for carrying water, or various other forms. The invention may be applied to other protection of buried hazardous wastes, protection of underground pipes, prevention of root intrusion beneath slabs, the dwarfing of trees or shrubs and other applications. The preferred herbicide is 4-difluoromethyl-N,N-dipropyl-2,6-dinitro-aniline, commonly known as trifluralin.

  2. Energy medicine for long-term disabilities.

    PubMed

    Trieschmann, R B

    1999-01-01

    Energy medicine techniques derive from traditional Chinese medicine and are based upon the concept that health and healing are dependent upon a balance of vital energy, a still mind, and controlled emotions. Physical dysfunctions result from disordered patterns of energy of long standing and reversal of the physical problem requires a return to balanced and ordered energy. Qi Gong (Chi Kung) is a system which teaches an individual to live in a state of energy balance. Shen Qi is a sophisticated form of Qi Gong which relies on no external physical interventions but rather relies on mind control to prevent illness, heal existing physical and emotional problems, and promote health and happiness. This paper will describe the use of these techniques with people who have long-term physical disabilities.

  3. [Enteral nutrition through long-term jejunostomy].

    PubMed

    Fernández, T; Neira, P; Enríquez, C

    2008-01-01

    We present the case of a female patient suffering a peritonitis episode after subtotal gastrectomy due to gastric neoplasm in relation to lesser curvature necrosis extending to the anterior esophageal wall. This an uncommon andsevere complication that made mandatory further aggressive surgery: transection of the abdominal esophagus, transection of the gastric stump, and cervical esophagostomy with creation of a jejunostomy with a needle catheter for feeding. This digestive tube access technique is generally used during major abdominal post-surgery until oral intake is reestablished. Our patient has been 187 days with this therapy since reconstruction of the GI tract was ruled out due to tumoral infiltration of the colon and tumor recurrence at the gastrohepatic omentum. To date, there has been no complication from permanence and/or long-term use of this technique.

  4. Radiation risk during long-term spaceflight

    NASA Astrophysics Data System (ADS)

    Petrov, V. M.

    Cosmonauts` exposure to cosmic rays during long-term spaceflight can cause unfavorable effects in health and risk for the crew members` lives. All unfavorable effects induced by exposure should be taken into consideration for the risk estimation. They should include both the acute deterministic effects and delayed effects called stochastic. On the ground the limitation of unfavorable consequences of acute exposure is achieved by means of establishing dose limits. But in space applications this approach can't be acceptable. Establishing a fixed dose limit is adequate to introducing indefinite reserve coefficient and therefore ineffective usage of spacecraft resource. The method of radiation risk calculation caused by acute and delayed effects of cosmonauts' exposure is discussed and substantiated in the report. Peculiarities of the impact of permanent radiation sources (galactic cosmic rays and trapped radiation) and the variable one (solar cosmic rays) are taken into consideration.

  5. Long-term control of root growth

    SciTech Connect

    Burton, F.G.; Cataldo, D.A.; Cline, J.F.; Skiens, W.E.

    1992-05-26

    A method and system for long-term control of root growth without killing the plants bearing those roots involves incorporating a 2,6-dinitroaniline in a polymer and disposing the polymer in an area in which root control is desired. This results in controlled release of the substituted aniline herbicide over a period of many years. Herbicides of this class have the property of preventing root elongation without translocating into other parts of the plant. The herbicide may be encapsulated in the polymer or mixed with it. The polymer-herbicide mixture may be formed into pellets, sheets, pipe gaskets, pipes for carrying water, or various other forms. The invention may be applied to other protection of buried hazardous wastes, protection of underground pipes, prevention of root intrusion beneath slabs, the dwarfing of trees or shrubs and other applications. The preferred herbicide is 4-difluoromethyl-N,N-dipropyl-2,6-dinitro-aniline, commonly known as trifluralin. 7 figs.

  6. Reducing long-term reservoir performance uncertainty

    SciTech Connect

    Lippmann, M.J.

    1988-04-01

    Reservoir performance is one of the key issues that have to be addressed before going ahead with the development of a geothermal field. In order to select the type and size of the power plant and design other surface installations, it is necessary to know the characteristics of the production wells and of the produced fluids, and to predict the changes over a 10--30 year period. This is not a straightforward task, as in most cases the calculations have to be made on the basis of data collected before significant fluid volumes have been extracted from the reservoir. The paper describes the methodology used in predicting the long-term performance of hydrothermal systems, as well as DOE/GTD-sponsored research aimed at reducing the uncertainties associated with these predictions. 27 refs., 1 fig.

  7. Radiation risk during long-term spaceflight.

    PubMed

    Petrov, V M

    2002-01-01

    Cosmonauts' exposure to cosmic rays during long-term spaceflight can cause unfavorable effects in health and risk for the crew members' lives. All unfavorable effects induced by exposure should be taken into consideration for the risk estimation. They should include both the acute deterministic effects and delayed effects called stochastic. On the ground the limitation of unfavorable consequences of acute exposure is achieved by means of establishing dose limits. But in space applications this approach can't be acceptable. Establishing a fixed dose limit is adequate to introducing indefinite reserve coefficient and therefore ineffective usage of spacecraft resource. The method of radiation risk calculation caused by acute and delayed effects of cosmonauts' exposure is discussed and substantiated in the report. Peculiarities of the impact of permanent radiation sources (galactic cosmic rays and trapped radiation) and the variable one (solar cosmic rays) are taken into consideration. PMID:12539775

  8. Safety of long-term PPI therapy.

    PubMed

    Reimer, Christina

    2013-06-01

    Proton pump inhibitors have become the mainstay of medical treatment of acid-related disorders. Long-term use is becoming increasingly common, in some cases without a proper indication. A large number of mainly observational studies on a very wide range of possible associations have been published in the past decade and are critically reviewed in this article and the existing evidence is evaluated and translated into possible clinical consequences. Based on the existing evidence the benefits of PPI treatment seem to outweigh potential risks in the large majority of patients especially if PPI use is based on a relevant indication. The concern for complications should primarily be directed at elderly, malnourished with significant co-morbidity. In this population an increased risk for enteric infections, fractures and nutritional deficiencies might have clinical consequences and should lead to a careful evaluation of the indication for PPI treatment. PMID:23998981

  9. Long term performance of radon mitigation systems

    SciTech Connect

    Prill, R.; Fisk, W.J.

    2002-03-01

    Researchers installed radon mitigation systems in 12 houses in Spokane, Washington and Coeur d'Alene, Idaho during the heating season 1985--1986 and continued to monitor indoor radon quarterly and annually for ten years. The mitigation systems included active sub-slab ventilation, basement over-pressurization, and crawlspace isolation and ventilation. The occupants reported various operational problems with these early mitigation systems. The long-term radon measurements were essential to track the effectiveness of the mitigation systems over time. All 12 homes were visited during the second year of the study, while a second set 5 homes was visited during the fifth year to determine the cause(s) of increased radon in the homes. During these visits, the mitigation systems were inspected and measurements of system performance were made. Maintenance and modifications were performed to improve system performance in these homes.

  10. Advanced long term cryogenic storage systems

    NASA Technical Reports Server (NTRS)

    Brown, Norman S.

    1987-01-01

    Long term, cryogenic fluid storage facilities will be required to support future space programs such as the space-based Orbital Transfer Vehicle (OTV), Telescopes, and Laser Systems. An orbital liquid oxygen/liquid hydrogen storage system with an initial capacity of approximately 200,000 lb will be required. The storage facility tank design must have the capability of fluid acquisition in microgravity and limit cryogen boiloff due to environmental heating. Cryogenic boiloff management features, minimizing Earth-to-orbit transportation costs, will include advanced thick multilayer insulation/integrated vapor cooled shield concepts, low conductance support structures, and refrigeration/reliquefaction systems. Contracted study efforts are under way to develop storage system designs, technology plans, test article hardware designs, and develop plans for ground/flight testing.

  11. Brodie's abscess. A long-term review.

    PubMed

    Stephens, M M; MacAuley, P

    1988-09-01

    In 20 patients with 21 Brodie's abscesses, a long-term review revealed that 13 occurred in the second decade of life. All had local symptoms for six weeks or more. The tibia was involved in 11 cases and seven of these were in the proximal metaphysis. The erythrocyte sedimentation rate (ESR) was elevated in only six cases. When the ESR was more than 40 mm per hour, recurrence was more likely. Staphylococcus aureus was cultured from 11 abscesses. Curettage and antibiotics for six weeks were adequate for treatment in most cases. However, lesions larger than 3 cm in diameter should be grafted, and patients with an elevated ESR require more aggressive decompression and prolonged antibiotic therapy. Lesions within the neck of the femur pose particular anatomic problems and should not be approached laterally. All cases were followed to full bone maturity. No significant leg length inequality was clinically or roentgenologically apparent. If an abscess was juxtaphyseal, deformity of the epiphysis could develop.

  12. Managing Records for the Long Term - 12363

    SciTech Connect

    Montgomery, John V.; Gueretta, Jeanie

    2012-07-01

    The U.S. Department of Energy (DOE) is responsible for managing vast amounts of information documenting historical and current operations. This information is critical to the operations of the DOE Office of Legacy Management. Managing legacy records and information is challenging in terms of accessibility and changing technology. The Office of Legacy Management is meeting these challenges by making records and information management an organizational priority. The Office of Legacy Management mission is to manage DOE post-closure responsibilities at former Cold War weapons sites to ensure the future protection of human health and the environment. These responsibilities include environmental stewardship and long-term preservation and management of operational and environmental cleanup records associated with each site. A primary organizational goal for the Office of Legacy Management is to 'Preserve, Protect, and Share Records and Information'. Managing records for long-term preservation is an important responsibility. Adequate and dedicated resources and management support are required to perform this responsibility successfully. Records tell the story of an organization and may be required to defend an organization in court, provide historical information, identify lessons learned, or provide valuable information for researchers. Loss of records or the inability to retrieve records because of poor records management processes can have serious consequences and even lead to an organisation's downfall. Organizations must invest time and resources to establish a good records management program because of its significance to the organization as a whole. The Office of Legacy Management will continue to research and apply innovative ways of doing business to ensure that the organization stays at the forefront of effective records and information management. DOE is committed to preserving records that document our nation's Cold War legacy, and the Office of Legacy

  13. Long-term dynamics of Typha populations

    USGS Publications Warehouse

    Grace, J.B.; Wetzel, R.G.

    1998-01-01

    The zonation of Typha populations in an experimental pond in Michigan was re-examined 15 years after the original sampling to gain insight into the long-term dynamics. Current distributions of Typha populations were also examined in additional experimental ponds at the site that have been maintained for 23 years. The zonation between T. latifolia and T. angustifolia in the previously studied pond 15 years after the initial sampling revealed that the density and distribution of shoots had not changed significantly. Thus, it appears that previously reported results (based on 7- year old populations) have remained consistent over time. Additional insight into the interaction between these two taxa was sought by comparing mixed and monoculture stands in five experimental ponds that have remained undisturbed for their 23-year history. The maximum depth of T. latifolia, the shallow- water species, was not significantly reduced when growing in the presence of the more flood tolerant T. angustifolia. In contrast, the minimum depth of T. angustifolia was reduced from 0 to 37 cm when in the presence of T. latifolia. When total populations were compared between monoculture and mixed stands, the average density of T. angustifolia shoots was 59.4 percent lower in mixed stands while the density of T. latifolia was 32 percent lower, with T. angustifolia most affected at shallow depths (reduced by 92 percent) and T. latifolia most affected at the deepest depths (reduced by 60 percent). These long-term observations indicate that competitive displacement between Typha taxa has remained stable over time.

  14. Long-term effects of dynamic aortomyoplasty.

    PubMed

    Chachques, J C; Haab, F; Cron, C; Fischer, E C; Grandjean, P; Bruneval, P; Acar, C; Jebara, V A; Fontaliran, F; Carpentier, A F

    1994-07-01

    Aortomyoplasty consists of wrapping the latissimus dorsi muscle (LDM) around the ascending aorta and electrostimulating it during diastole. The ascending aorta will act as an ectopic neo-ventricle compressed during diastole, thus reproducing the effects of long-term diastolic counterpulsation. In 5 goats, the right LDM was transferred to the thoracic cavity after removal of the second rib. The ascending aorta was enlarged by a pericardial patch and wrapped with the LDM. Postoperative electrostimulation was delivered in a counterpulsating manner. Hemodynamic studies were performed at 12 and 24 months postoperatively. Percent increase in the subendocardial viability index (diastolic pressure-time index/systolic tension-time index) was calculated using unassisted and assisted cardiac cycles with the stimulator off versus the stimulator on at a 1:1 ratio in the basal state and after acute heart failure was induced by the administration of high doses of propranolol hydrochloride. Diastolic counterpulsation of the ascending aorta resulted in significant improvement in the subendocardial viability index long term, both in basal state conditions and after induced cardiac failure. During heart failure, aortomyoplasty increased the cardiac output and decreased systemic vascular resistance. Histopathologic studies up to 24 months showed preservation of the histologic structure of the aortic wall and no evidence of thromboembolism. Tight adhesions developed between the aortic wall (including the pericardial patch) and the LDM. The diameters of the enlarged aortas showed no significant differences compared with diameters immediately postoperatively. In conclusion, aortomyoplasty produces chronic diastolic augmentation with preservation of aortic structure. After induction of heart failure, aortomyoplasty offers efficient circulatory support.

  15. Financing Long Term Care. Selected Topics in Long Term Care. Volume 3.

    ERIC Educational Resources Information Center

    Greenberg, Jay; Doth, David

    This document, one in a series developed to provide technical assistance to 22 Long-Term Care Gerontology Centers, is designed to be a financial resource guide. Current major funding sources are detailed, followed by an examination of the issues and problems associated with current financing systems. Programmatic issues associated with Medicare…

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

    PubMed Central

    Bliss, Timothy V.P.; Cooke, Sam F

    2011-01-01

    Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke. PMID:21779718

  17. Neuritin activates insulin receptor pathway to up-regulate Kv4.2-mediated transient outward K+ current in rat cerebellar granule neurons.

    PubMed

    Yao, Jin-Jing; Gao, Xiao-Fei; Chow, Chi-Wing; Zhan, Xiao-Qin; Hu, Chang-Long; Mei, Yan-Ai

    2012-11-30

    Neuritin is a new neurotrophic factor discovered in a screen to identify genes involved in activity-dependent synaptic plasticity. Neuritin also plays multiple roles in the process of neural development and synaptic plasticity. The receptors for binding neuritin and its downstream signaling effectors, however, remain unclear. Here, we report that neuritin specifically increases the densities of transient outward K(+) currents (I(A)) in rat cerebellar granule neurons (CGNs) in a time- and concentration-dependent manner. Neuritin-induced amplification of I(A) is mediated by increased mRNA and protein expression of Kv4.2, the main α-subunit of I(A). Exposure of CGNs to neuritin markedly induces phosphorylation of ERK (pERK), Akt (pAkt), and mammalian target of rapamycin (pmTOR). Neuritin-induced I(A) and increased expression of Kv4.2 are attenuated by ERK, Akt, or mTOR inhibitors. Unexpectedly, pharmacological blockade of insulin receptor, but not the insulin-like growth factor 1 receptor, abrogates the effect of neuritin on I(A) amplification and Kv4.2 induction. Indeed, neuritin activates downstream signaling effectors of the insulin receptor in CGNs and HeLa. Our data reveal, for the first time, an unanticipated role of the insulin receptor in previously unrecognized neuritin-mediated signaling. PMID:23066017

  18. Kainate receptor-mediated apoptosis in primary cultures of cerebellar granule cells is attenuated by mitogen-activated protein and cyclin-dependent kinase inhibitors

    PubMed Central

    Giardina, Sarah F; Beart, Philip M

    2002-01-01

    Previous studies have suggested that neuronal apoptosis is the result of an abortive attempt to re-enter the cell cycle, and more recently the cyclin-dependent (CDKs) and the mitogen-activated protein (MAP) kinases, two superfamilies of kinases that influence and control cell cycle progression, have been implicated in neuronal apoptosis. Here, to examine whether CDK/MAPK related pathways are involved in excitotoxicity, we studied the actions of various kinase inhibitors on apoptosis induced by the ionotropic glutamate (Glu) receptor agonist, kainate (KA), in primary cultures of murine cerebellar granule cells (CGCs). KA-mediated neurotoxicity was concentration-dependent, as determined by a cell viability assay monitoring the reduction of 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and largely apoptotic in nature, as shown by morphological examination and labelling of DNA fragmentation in situ using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP digoxigenin nick-end labelling (TUNEL). KA-mediated neurotoxicity and apoptosis was completely attenuated by the mixed CDK and MAP kinase inhibitor, olomoucine, in a concentration-dependent manner (50 – 600 μM), and partially by roscovitine (1 – 100 μM), a more selective CDK inihibitor. The p38 MAP kinase inhibitor, SB203580 (1 – 100 μM), partially attenuated KA receptor-mediated apoptosis, as did the MAP kinase kinase inhibitors PD98509 (1 – 100 μM) and U0126 (1 – 100 μM). These findings provide new evidence for a complex network of interacting pathways involving CDK/MAPK that control apoptosis downstream of KA receptor activation in excitotoxic neuronal cell death. PMID:11934814

  19. Long-term histopathology of allografts in sensitized kidney recipients.

    PubMed

    Miura, Masayoshi; Harada, Hiroshi; Fukasawa, Yuichiro; Hotta, Kiyohiko; Itoh, Yosuke; Tamaki, Tohru

    2012-07-01

    Successful desensitization therapy has brought satisfying short-term outcomes in the recipients with anti-donor antibody. We analyzed the long-term pathology of the allografts in the sensitized kidney recipients. Eleven stable recipients after desensitization against positive flow cytometry T-cell crossmatch (FTXM) were included. They were divided into two groups, based on the protocol biopsies findings at three to eight yr (group 1: subclinical glomerulitis and/or peritubular capillaritis, n = 5 and group 2: no rejection, n = 6). Estimated glomerular filtration rate (eGFR), presence of donor-specific antibody (DSA), mean channel shift (MCS) of FTXM, urine protein levels, acute antibody-mediated rejection (AAMR) episodes, and protocol biopsy findings were compared. Chronic transplant glomerulopathy was found in final biopsy of all group 1 cases. DSA was positive in 60% but C4d was positive in 20% case of the group 1. The history of AAMR was only found in the group 1. There was no difference in eGFR decline or proteinuria. The MCS of FTXM was higher in the group 1. The recipients with AAMR history, high MCS in FTXM, and subclinical microvascular inflammation in the early protocol biopsies have risk for developing chronic rejection in long term.

  20. Dendro-somatic distribution of calcium-mediated electrogenesis in Purkinje cells from rat cerebellar slice cultures

    PubMed Central

    Pouille, F; Cavelier, P; Desplantez, T; Beekenkamp, H; Craig, P J; Beattie, R E; Volsen, S G; Bossu, J L

    2000-01-01

    The role of Ca2+ entry in determining the electrical properties of cerebellar Purkinje cell (PC) dendrites and somata was investigated in cerebellar slice cultures. Immunohistofluorescence demonstrated the presence of at least three distinct types of Ca2+ channel proteins in PCs: the α1A subunit (P/Q type Ca2+ channel), the α1G subunit (T type) and the α1E subunit (R type). In PC dendrites, the response started in 66 % of cases with a slow depolarization (50 ± 15 ms) triggering one or two fast (∼1 ms) action potentials (APs). The slow depolarization was identified as a low-threshold non-P/Q Ca2+ AP initiated, most probably, in the dendrites. In 16 % of cases, this response propagated to the soma to elicit an initial burst of fast APs. Somatic recordings revealed three modes of discharge. In mode 1, PCs display a single or a short burst of fast APs. In contrast, PCs fire repetitively in mode 2 and 3, with a sustained discharge of APs in mode 2, and bursts of APs in mode 3. Removal of external Ca2+ or bath applications of a membrane-permeable Ca2+ chelator abolished repetitive firing. Tetraethylammonium (TEA) prolonged dendritic and somatic fast APs by a depolarizing plateau sensitive to Cd2+ and to ω-conotoxin MVII C or ω-agatoxin TK. Therefore, the role of Ca2+ channels in determining somatic PC firing has been investigated. Cd2+ or P/Q type Ca2+ channel-specific toxins reduced the duration of the discharge and occasionallyinduced the appearance of oscillations in the membrane potential associated with bursts of APs. In summary, we demonstrate that Ca2+ entry through low-voltage gated Ca2+ channels, not yet identified, underlies a dendritic AP rarelyeliciting a somatic burst of APs whereas Ca2+ entry through P/Q type Ca2+ channels allowed a repetitive firing mainly by inducing a Ca2+-dependent hyperpolarization. PMID:10970428

  1. A case of follicular lymphoma associated with paraneoplastic cerebellar degeneration.

    PubMed

    Shimazu, Yayoi; Minakawa, Eiko N; Nishikori, Momoko; Ihara, Masafumi; Hashi, Yuichiro; Matsuyama, Hirofumi; Hishizawa, Masakatsu; Yoshida, Sonoyo; Kitano, Toshiyuki; Kondo, Tadakazu; Ishikawa, Takayuki; Takahashi, Ryosuke; Takaori-Kondo, Akifumi

    2012-01-01

    Paraneoplastic neurological disorders (PND) are neurological effects of malignancy that are recognized as immune-mediated disorders caused by aberrant expression of a tumor antigen that is normally expressed in the nervous system. We report a case of cerebellar ataxia which turned out to be paraneoplastic cerebellar degeneration, a subtype of PND that develops cerebellar symptoms, that was caused by follicular lymphoma. After chemotherapy, the patient attained sufficient improvement of cerebellar symptoms along with complete remission of lymphoma. Paraneoplastic cerebellar degeneration should be recognized as a rare complication of lymphoma as it is important to start proper treatment before the neurological symptoms become irreversible.

  2. LONG-TERM MONITORING SENSOR NETWORK

    SciTech Connect

    Stephen P. Farrington; John W. Haas; Neal Van Wyck

    2003-10-16

    Long-term monitoring (LTM) associated with subsurface contamination sites is a key element of Long Term Stewardship and Legacy Management across the Department of Energy (DOE) complex. However, both within the DOE and elsewhere, LTM is an expensive endeavor, often exceeding the costs of the remediation phase of a clean-up project. The primary contributors to LTM costs are associated with labor. Sample collection, storage, preparation, analysis, and reporting can add a significant financial burden to project expense when extended over many years. Development of unattended, in situ monitoring networks capable of providing quantitative data satisfactory to regulatory concerns has the potential to significantly reduce LTM costs. But survival and dependable operation in a difficult environment is a common obstacle to widespread use across the DOE complex or elsewhere. Deploying almost any sensor in the subsurface for extended periods of time will expose it to chemical and microbial degradation. Over the time-scales required for in situ LTM, even the most advanced sensor systems may be rendered useless. Frequent replacement or servicing (cleaning) of sensors is expensive and labor intensive, offsetting most, if not all, of the cost savings realized with unattended, in situ sensors. To enable facile, remote monitoring of contaminants and other subsurface parameters over prolonged periods, Applied Research Associates, Inc has been working to develop an advanced LTM sensor network consisting of three key elements: (1) an anti-fouling sensor chamber that can accommodate a variety of chemical and physical measurement devices based on electrochemical, optical and other techniques; (2) two rapid, cost effective, and gentle means of emplacing sensor packages either at precise locations directly in the subsurface or in pre-existing monitoring wells; and (3) a web browser-based data acquisition and control system (WebDACS) utilizing field-networked microprocessor-controlled smart

  3. Robotics for Long-Term Monitoring

    SciTech Connect

    Shahin, Sarkis; Duran, Celso

    2002-07-01

    While long-term monitoring and stewardship means many things to many people, DOE has defined it as The physical controls, institutions, information, and other mechanisms needed to ensure protection of people and the environment at sites where DOE has completed or plans to complete cleanup (e.g., landfill closures, remedial actions, and facility stabilization). Across the United States, there are thousands of contaminated sites with multiple contaminants released from multiple sources where contaminants have transported and commingled. The U.S. government and U.S. industry are responsible for most of the contamination and are landowners of many of these contaminated properties. These sites must be surveyed periodically for various criteria including structural deterioration, water intrusion, integrity of storage containers, atmospheric conditions, and hazardous substance release. The surveys, however, are intrusive, time-consuming, and expensive and expose survey personnel to radioactive contamination. In long-term monitoring, there's a need for an automated system that will gather and report data from sensors without costly human labor. In most cases, a SCADA (Supervisory Control and Data Acquisition) unit is used to collect and report data from a remote location. A SCADA unit consists of an embedded computer with data acquisition capabilities. The unit can be configured with various sensors placed in different areas of the site to be monitored. A system of this type is static, i.e., the sensors, once placed, cannot be moved to other locations within the site. For those applications where the number of sampling locations would require too many sensors, or where exact location of future problems is unknown, a mobile sensing platform is an ideal solution. In many facilities that undergo regular inspections, the number of video cameras and air monitors required to eliminate the need for human inspections is very large and far too costly. HCET's remote harsh

  4. Treatment for childhood cancer -- long-term risks

    MedlinePlus

    ... ency/patientinstructions/000849.htm Treatment for childhood cancer - long-term risks To use the sharing features on ... has. Being aware of your child's risk of long-term health problems can help you follow-up ...

  5. Long-term strategies for the treatment of Refsum's disease using therapeutic apheresis.

    PubMed

    Zolotov, D; Wagner, S; Kalb, K; Bunia, J; Heibges, A; Klingel, R

    2012-01-01

    Refsum's disease is a rare autosomal recessive disorder of fatty acid metabolism. Poorly metabolized phytanic acid accumulates in fatty tissues, including myelin sheaths and internal organs, leading to retinitis pigmentosa, peripheral polyneuropathy, cerebellar ataxia, and renal, cardiac or liver impairment. Dietary restriction of phytanic acid in some cases is not sufficient to prevent acute attacks and stabilize the progressive course. Phytanic acid bound to large low density lipoproteins (LDL) and very low density lipoproteins (VLDL) molecules offers the possibility of extracorporeal elimination by lipid apheresis. We report on the long-term lipid apheresis treatment of four patients with severe Refsum's disease. Retinitis pigmentosa, peripheral polyneuropathy, cerebellar ataxia, anosmia, and sensorineural hearing loss were major symptoms exhibiting a progressive course. Lipid apheresis was performed for 5-13 years without severe complications. Maximum levels of phytanic acid before commencing chronic lipid apheresis were >300 mg/l. During steady state with lipid apheresis, mean phytanic acid before treatments was 87 mg/l and was reduced to 36 mg/l. Mean reduction rate was 59% per treatment. In all patients, abnormal motor nerve conduction velocity with signs of chronic denervation improved, morphological and functional stabilization of eye involvement was observed. Lipid apheresis prevented the extension of the disease to previously unaffected organs in three patients. Extracorporeal elimination of lipoprotein-phytanic acid complexes by lipid apheresis represents a pathophysiologically guided therapeutic approach, resulting in long-term improvement or stabilization of overall rehabilitation in patients with progressive Refsum's disease.

  6. Intermediate- and long-term earthquake prediction.

    PubMed

    Sykes, L R

    1996-04-30

    Progress in long- and intermediate-term earthquake prediction is reviewed emphasizing results from California. Earthquake prediction as a scientific discipline is still in its infancy. Probabilistic estimates that segments of several faults in California will be the sites of large shocks in the next 30 years are now generally accepted and widely used. Several examples are presented of changes in rates of moderate-size earthquakes and seismic moment release on time scales of a few to 30 years that occurred prior to large shocks. A distinction is made between large earthquakes that rupture the entire downdip width of the outer brittle part of the earth's crust and small shocks that do not. Large events occur quasi-periodically in time along a fault segment and happen much more often than predicted from the rates of small shocks along that segment. I am moderately optimistic about improving predictions of large events for time scales of a few to 30 years although little work of that type is currently underway in the United States. Precursory effects, like the changes in stress they reflect, should be examined from a tensorial rather than a scalar perspective. A broad pattern of increased numbers of moderate-size shocks in southern California since 1986 resembles the pattern in the 25 years before the great 1906 earthquake. Since it may be a long-term precursor to a great event on the southern San Andreas fault, that area deserves detailed intensified study.

  7. Transuranic waste: long-term planning

    SciTech Connect

    Young, K.C.

    1985-07-01

    Societal concerns for the safe handling and disposal of toxic waste are behind many of the regulations and the control measures in effect today. Transuranic waste, a specific category of toxic (radioactive) waste, serves as a good example of how regulations and controls impact changes in waste processing - and vice versa. As problems would arise with waste processing, changes would be instituted. These changes improved techniques for handling and disposal of transuranic waste, reduced the risk of breached containment, and were usually linked with regulatory changes. Today, however, we face a greater public awareness of and concern for toxic waste control; thus, we must anticipate potential problems and work on resolving them before they can become real problems. System safety analyses are valuable aids in long-term planning for operations involving transuranic as well as other toxic materials. Examples of specific system safety analytical methods demonstrate how problems can be anticipated and resolution initiated in a timely manner having minimal impacts upon allocation of resource and operational goals. 7 refs., 1 fig.

  8. Long-term data storage in diamond

    PubMed Central

    Dhomkar, Siddharth; Henshaw, Jacob; Jayakumar, Harishankar; Meriles, Carlos A.

    2016-01-01

    The negatively charged nitrogen vacancy (NV−) center in diamond is the focus of widespread attention for applications ranging from quantum information processing to nanoscale metrology. Although most work so far has focused on the NV− optical and spin properties, control of the charge state promises complementary opportunities. One intriguing possibility is the long-term storage of information, a notion we hereby introduce using NV-rich, type 1b diamond. As a proof of principle, we use multicolor optical microscopy to read, write, and reset arbitrary data sets with two-dimensional (2D) binary bit density comparable to present digital-video-disk (DVD) technology. Leveraging on the singular dynamics of NV− ionization, we encode information on different planes of the diamond crystal with no cross-talk, hence extending the storage capacity to three dimensions. Furthermore, we correlate the center’s charge state and the nuclear spin polarization of the nitrogen host and show that the latter is robust to a cycle of NV− ionization and recharge. In combination with super-resolution microscopy techniques, these observations provide a route toward subdiffraction NV charge control, a regime where the storage capacity could exceed present technologies.

  9. Long-term adequacy of metal resources

    USGS Publications Warehouse

    Singer, D.A.

    1977-01-01

    Although the earth's crust contains vast quantities of metals, extraction technologies and associated costs are inextricably bound to three fundamental geological factors - the amount of metal available in the earth's crust in each range of grades, the mineralogical form and chemical state of the metal, and the spatial distribution of the metal. The energy required to recover a given amount of metal increases substantially as grade declines. Most metal is produced from sulphide or oxide minerals, whereas most metal in the crust may be locked in the structures of the more refractory silicates. Recovery from silicate minerals could require orders of magnitude more energy than that used at present as also could exploitation of small, widely scattered or thin, deeply buried deposits. Although specific information on the fundamental factors is not available, each factor must in turn tend to further restrict exploitation. Independence of average grade and tonnage for many deposit types further reduces the availability of rock as a source of metal. In the long term, effects of these factors will be large increases in price for many metals. ?? 1977.

  10. Intermediate- and long-term earthquake prediction.

    PubMed Central

    Sykes, L R

    1996-01-01

    Progress in long- and intermediate-term earthquake prediction is reviewed emphasizing results from California. Earthquake prediction as a scientific discipline is still in its infancy. Probabilistic estimates that segments of several faults in California will be the sites of large shocks in the next 30 years are now generally accepted and widely used. Several examples are presented of changes in rates of moderate-size earthquakes and seismic moment release on time scales of a few to 30 years that occurred prior to large shocks. A distinction is made between large earthquakes that rupture the entire downdip width of the outer brittle part of the earth's crust and small shocks that do not. Large events occur quasi-periodically in time along a fault segment and happen much more often than predicted from the rates of small shocks along that segment. I am moderately optimistic about improving predictions of large events for time scales of a few to 30 years although little work of that type is currently underway in the United States. Precursory effects, like the changes in stress they reflect, should be examined from a tensorial rather than a scalar perspective. A broad pattern of increased numbers of moderate-size shocks in southern California since 1986 resembles the pattern in the 25 years before the great 1906 earthquake. Since it may be a long-term precursor to a great event on the southern San Andreas fault, that area deserves detailed intensified study. Images Fig. 1 PMID:11607658

  11. Long-term corrosion testing pan.

    SciTech Connect

    Wall, Frederick Douglas; Brown, Neil R.

    2008-08-01

    This document describes the testing and facility requirements to support the Yucca Mountain Project long-term corrosion testing needs. The purpose of this document is to describe a corrosion testing program that will (a) reduce model uncertainty and variability, (b) reduce the reliance upon overly conservative assumptions, and (c) improve model defensibility. Test matrices were developed for 17 topical areas (tasks): each matrix corresponds to a specific test activity that is a subset of the total work performed in a task. A future document will identify which of these activities are considered to be performance confirmation activities. Detailed matrices are provided for FY08, FY09 and FY10 and rough order estimates are provided for FY11-17. Criteria for the selection of appropriate test facilities were developed through a meeting of Lead Lab and DOE personnel on October 16-17, 2007. These criteria were applied to the testing activities and recommendations were made for the facility types appropriate to carry out each activity. The facility requirements for each activity were assessed and activities were identified that can not be performed with currently available facilities. Based on this assessment, a total of approximately 10,000 square feet of facility space is recommended to meet all future testing needs, given that all testing is consolidated to a single location. This report is a revision to SAND2007-7027 to address DOE comments and add a series of tests to address NWTRB recommendations.

  12. Long-term corrosion testing plan.

    SciTech Connect

    Wall, Frederick Douglas; Brown, Neil R.

    2009-02-01

    This document describes the testing and facility requirements to support the Yucca Mountain Project long-term corrosion testing program. The purpose of this document is to describe a corrosion testing program that will (a) reduce model uncertainty and variability, (b) reduce the reliance upon overly conservative assumptions, and (c) improve model defensibility. Test matrices were developed for 17 topical areas (tasks): each matrix corresponds to a specific test activity that is a subset of the total work performed in a task. A future document will identify which of these activities are considered to be performance confirmation activities. Detailed matrices are provided for FY08, FY09 and FY10 and rough order estimates are provided for FY11-17. Criteria for the selection of appropriate test facilities were developed through a meeting of Lead Lab and DOE personnel on October 16-17, 2007. These criteria were applied to the testing activities and recommendations were made for the facility types appropriate to carry out each activity. The facility requirements for each activity were assessed and activities were identified that can not be performed with currently available facilities. Based on this assessment, a total of approximately 10,000 square feet of facility space is recommended to accommodate all future testing, given that all testing is consolidated to a single location. This report is a revision to SAND2008-4922 to address DOE comments.

  13. Long-term changes in Saturn's troposphere

    NASA Astrophysics Data System (ADS)

    Trafton, L.

    1985-09-01

    The author reports the results of monitoring Saturn's H2 quadrupole and CH4 band absorptions outside of the equatorial zone over one-half of Saturn's year. This interval covers most of the perihelion half of Saturn's elliptical orbit, which happens to be approximately bounded by the equinoxes. Marked long-term changes occur in the CH4 absorption accompanied by weakly opposite changes in the H2 absorption. Around the 1980 equinox, the H2 and CH4 absorptions in the northern hemisphere appear to be discontinuous with those in the southern hemisphere. This discontinuity and the temporal variation of the absorptions are evidence for seasonal changes. The absorption variations can be attributed to a variable haze in Saturn's troposphere, responding to changes in temperature and insolation through the processes of sublimation and freezing. The author models the vertical haze distribution of Saturn's south temperate latitudes during 1971 - 1977 in terms of a distribution having a particle scale height equal to a fraction of the atmospheric scale height. He also reports spatial measurements of the absorption in the 6450 Å NH3 band made annually since the 1980 equinox.

  14. Long-term plutonium storage: Design concepts

    SciTech Connect

    Wilkey, D.D.; Wood, W.T.; Guenther, C.D.

    1994-08-01

    An important part of the Department of Energy (DOE) Weapons Complex Reconfiguration (WCR) Program is the development of facilities for long-term storage of plutonium. The WCR design goals are to provide storage for metals, oxides, pits, and fuel-grade plutonium, including material being held as part of the Strategic Reserve and excess material. Major activities associated with plutonium storage are sorting the plutonium inventory, material handling and storage support, shipping and receiving, and surveillance of material in storage for both safety evaluations and safeguards and security. A variety of methods for plutonium storage have been used, both within the DOE weapons complex and by external organizations. This paper discusses the advantages and disadvantages of proposed storage concepts based upon functional criteria. The concepts discussed include floor wells, vertical and horizontal sleeves, warehouse storage on vertical racks, and modular storage units. Issues/factors considered in determining a preferred design include operational efficiency, maintenance and repair, environmental impact, radiation and criticality safety, safeguards and security, heat removal, waste minimization, international inspection requirements, and construction and operational costs.

  15. Long-term predictions using natural analogues

    SciTech Connect

    Ewing, R.C.

    1995-09-01

    One of the unique and scientifically most challenging aspects of nuclear waste isolation is the extrapolation of short-term laboratory data (hours to years) to the long time periods (10{sup 3}-10{sup 5} years) required by regulatory agencies for performance assessment. The direct validation of these extrapolations is not possible, but methods must be developed to demonstrate compliance with government regulations and to satisfy the lay public that there is a demonstrable and reasonable basis for accepting the long-term extrapolations. Natural systems (e.g., {open_quotes}natural analogues{close_quotes}) provide perhaps the only means of partial {open_quotes}validation,{close_quotes} as well as data that may be used directly in the models that are used in the extrapolation. Natural systems provide data on very large spatial (nm to km) and temporal (10{sup 3}-10{sup 8} years) scales and in highly complex terranes in which unknown synergisms may affect radionuclide migration. This paper reviews the application (and most importantly, the limitations) of data from natural analogue systems to the {open_quotes}validation{close_quotes} of performance assessments.

  16. The long-term variability of Vega

    NASA Astrophysics Data System (ADS)

    Butkovskaya, V.; Plachinda, S.; Valyavin, G.; Baklanova, D.; Lee, B.-C.

    2011-12-01

    Over the time of 60 years Vega (α Lyrae = HD 172167, A0V) has been generally accepted as a standard star in the near-infrared, optical, and ultraviolet regions. But is the spectrophotometric standard Vega really non-variable star? Researchers give very different answers to this question. We aim to search a periodicity in our results of spectropolarimetric study of Vega, namely periodic variations in equivalent width of the spectral lines and longitudinal magnetic field measurements. High-accuracy spectropolarimetric observations of Vega have been performed during 26 nights from 1997 to 2010 using the Coudé spectrograph of the 2.6-m Shain reflector at the Crimean Astrophysical Observatory (CrAO, Ukraine) and during 4 nights in 2007 and 2008 using the echelle spectrograph BOES at the Bohyunsan Optical Astronomy Observatory (BOAO, South Korea). The long-term (year-to-year) variability of Vega was confirmed. It was concluded that this variability does not have magnetic nature. The paper is dedicated to the memory of V.P. Merezhin.

  17. Long-term potentiation: peeling the onion.

    PubMed

    Nicoll, Roger A; Roche, Katherine W

    2013-11-01

    Since the discovery of long-term potentiation (LTP), thousands of papers have been published on this phenomenon. With this massive amount of information, it is often difficult, especially for someone not directly involved in the field, not to be overwhelmed. The goal of this review is to peel away as many layers as possible, and probe the core properties of LTP. We would argue that the many dozens of proteins that have been implicated in the phenomenon are not essential, but rather modulate, often in indirect ways, the threshold and/or magnitude of LTP. What is required is NMDA receptor activation followed by CaMKII activation. The consequence of CaMKII activation is the rapid recruitment of AMPA receptors to the synapse. This recruitment is independent of AMPA receptor subunit type, but absolutely requires an adequate pool of surface receptors. An important unresolved issue is how exactly CaMKII activation leads to modifications in the PSD to allow rapid enrichment. This article is part of the Special Issue entitled 'Glutamate Receptor-Dependent Synaptic Plasticity'. PMID:23439383

  18. Long-term observations of siamang behaviour.

    PubMed

    Chivers, D J; Raemaekers, J J; Aldrich-Blake, F P

    1975-01-01

    Long-term observations are presented on the behaviour of the siamang ape, Symphalangus syndactylus, in the lowland forest of central Malaya. The data were collected during two dry and three fruiting seasons between 1969 and 1973 inclusive on two groups with adjacent ranges; comparisons are made within and between sample periods, and between groups. The influence of weather on daily activities is considered. Food intake is analysed in terms of number of food trees, number of visits to these trees, and the cumulative time spent feeding on various food categories. Ranging behaviour is investigated in terms of distance travelled, area covered, and distribution of time and of food trees about the range. The occurrence of calling is described and compared with that of the white-handed gibbon in the same area. A discussion ensues on each of these aspects of behaviour in turn. Emphasis is laid on the similarity of behaviour of the two groups at any one time, and on the degree of their response to the fluctuations of environment variables. Finally, the application to siamang of ranging concepts currently used in animal behaviour is considered briefly.

  19. Long-Term Consequences of Neonatal Injury

    PubMed Central

    Beggs, Simon

    2015-01-01

    The maturation of the central nervous system’s (CNS’s) sensory connectivity is driven by modality-specific sensory input in early life. For the somatosensory system, this input is the physical, tactile interaction with the environment. Nociceptive circuitry is functioning at the time of birth; however, there is still considerable organization and refinement of this circuitry that occurs postnatally, before full discrimination of tactile and noxious input is possible. This fine-tuning involves separation of tactile and nociceptive afferent input to the spinal cord’s dorsal horn and the maturation of local and descending inhibitory circuitry. Disruption of that input in early postnatal life (for example, by tissue injury or other noxious stimulus), can have a profound influence on subsequent development, and consequently the mature functioning of pain systems. In this review, the impact of neonatal surgical incision on nociceptive circuitry is discussed in terms of the underlying developmental neurobiology. The changes are complex, occurring at multiple anatomical sites within the CNS, and including both neuronal and glial cell populations. The altered sensory input from neonatal injury selectively modulates neuronal excitability within the spinal cord, disrupts inhibitory control, and primes the immune system, all of which contribute to the adverse long-term consequences of early pain exposure. PMID:26174217

  20. Long-term outcome in aqueductal stenosis.

    PubMed

    Villani, R; Tomei, G; Gaini, S M; Grimoldi, N; Spagnoli, D; Bello, L

    1995-03-01

    In this study, 78 patients with aqueductal stenosis were submitted to detailed neurodevelopmental assessment with a follow-up of 5-25 years. Sixty-eight percent of patients were categorized as normal; they either attended normal school courses or had regular jobs. Among these, 34% had some motor abnormalities (ataxia, mild hemiparesis, visual disturbances). Twenty-four percent (19 cases) were moderately disabled (trainable retardation) and 8% (6 cases) were severely handicapped. Epilepsy was observed in 13% of the cases. Incidence of recurrent and generalized seizures paralleled neurodevelopmental outcome (5% in normal, 16% in moderately disabled and 50% in severely disabled patients). Endocrine dysfunctions were evident in 28% of the cases and were characterized by precocious or delayed puberty, amenorrhea and somatic underdevelopment. No patient with ventricular enlargement and a cortical mantle width below 20 mm showed a good outcome. Large ventricles were compatible with normal mental development when compensated with a corresponding cranial vault enlargement. In patients with normal mental status and motor abnormalities, long-term CT scan findings revealed the presence of focal brain abnormalities (poroencephaly, brain atrophy, calcifications, extracerebral collections). PMID:7773981

  1. Long-term oxygen therapy: battling breathlessness.

    PubMed

    Wick, Jeannette Y

    2012-12-01

    Approximately 1 million of the 1.4 million Americans (71%) receiving long-term oxygen therapy (LTOT) are Medicare beneficiaries, confirming that LTOT is most often prescribed for individuals 65 years of age or older. Although several conditions create a need for supplemental oxygen, the majority of patients have chronic obstructive pulmonary disease (COPD). People with healthy lungs can extract the oxygen from air, while those with damaged lungs need higher oxygen concentrations. They can supplement their oxygen using one of three options: high-pressure oxygen tanks, liquid oxygen, or oxygen concentrators. The multicenter Nocturnal Oxygen Therapy Trial and the smaller Medical Research Council study identified LTOT as an intervention that improved survival in patients with COPD or chronic respiratory failure, approximately doubling survival at 19 months in patients who were adherent to oxygen. Despite its advantages, LTOT is plagued with problems: compliance with clinical guidelines, patient adherence, and cost. Fires associated with smoking in the vicinity of supplemental oxygen are the leading cause of residential fire deaths in the United States.

  2. Long term prediction of flood occurrence

    NASA Astrophysics Data System (ADS)

    Aguilar, Cristina; Montanari, Alberto; José Polo, María

    2016-05-01

    How long a river remembers its past is still an open question. Perturbations occurring in large catchments may impact the flow regime for several weeks and months, therefore providing a physical explanation for the occasional tendency of floods to occur in clusters. The research question explored in this paper may be stated as follows: can higher than usual river discharges in the low flow season be associated to a higher probability of floods in the subsequent high flow season? The physical explanation for such association may be related to the presence of higher soil moisture storage at the beginning of the high flow season, which may induce lower infiltration rates and therefore higher river runoff. Another possible explanation is persistence of climate, due to presence of long-term properties in atmospheric circulation. We focus on the Po River at Pontelagoscuro, whose catchment area amounts to 71 000 km2. We look at the stochastic connection between average river flows in the pre-flood season and the peak flows in the flood season by using a bivariate probability distribution. We found that the shape of the flood frequency distribution is significantly impacted by the river flow regime in the low flow season. The proposed technique, which can be classified as a data assimilation approach, may allow one to reduce the uncertainty associated to the estimation of the flood probability.

  3. Neurological long term consequences of deep diving.

    PubMed

    Todnem, K; Nyland, H; Skeidsvoll, H; Svihus, R; Rinck, P; Kambestad, B K; Riise, T; Aarli, J A

    1991-04-01

    Forty commercial saturation divers, mean age 34.9 (range 24-49) years, were examined one to seven years after their last deep dive (190-500 metres of seawater). Four had by then lost their divers' licence because of neurological problems. Twenty seven (68%) had been selected by neurological examination and electroencephalography before the deep dives. The control group consisted of 100 men, mean age 34.0 (range 22-48) years. The divers reported significantly more symptoms from the nervous system. Concentration difficulties and paraesthesia in feet and hands were common. They had more abnormal neurological findings by neurological examination compatible with dysfunction in the lumbar spinal cord or roots. They also had a larger proportion of abnormal electroencephalograms than the controls. The neurological symptoms and findings were highly significantly correlated with exposure to deep diving (depth included), but even more significantly correlated to air and saturation diving and prevalence of decompression sickness. Visual evoked potentials, brainstem auditory evoked potentials, and magnetic resonance imaging of the brain did not show more abnormal findings in the divers. Four (10%) divers had had episodes of cerebral dysfunction during or after the dives; two had had seizures, one had had transitory cerebral ischaemia and one had had transitory global amnesia. It is concluded that deep diving may have a long term effect on the nervous system of the divers.

  4. Long-term treatment outcome in acromegaly.

    PubMed

    Holdaway, I M; Rajasoorya, C R; Gamble, G D; Stewart, A W

    2003-08-01

    A number of groups have developed guidelines to indicate whether an individual with acromegaly has been cured by treatment. However, studies to date do not provide a robust definition of biochemical remission of the disorder based on correlation with long-term outcome. Available data suggest that those with a random serum growth hormone (GH) level of <2.5 microg/l, or a glucose-suppressed GH level of <1 microg/l following treatment have mortality figures indistinguishable from the general population. However, the confidence limits for these mortality estimates are quite wide. It remains possible that growth hormone levels lower than 1 microg/l for random samples, or even lower when using ultrasensitive GH assays, may indicate superior outcome, but this remains to be confirmed. There are limited data relating serum insulin-like growth factor-I (IGF-I) levels to outcome, although normalisation of serum IGF-I clearly improves outcome compared with continued elevation of measurements after treatment. Current evidence suggests that a post-treatment random serum GH <2.5 microg/l and a normal serum IGF-I value defines biochemical cure. Available data suggest that achieving similar growth hormone levels after treatment also reduces the prevalence of chronic complications of the disorder, which is subsequently reflected in improved mortality. PMID:12914751

  5. Long Term Storage of Lyophilized Liposomal Formulations

    PubMed Central

    Payton, N.M.; Wempe, M.F.; Xu, Y.; Anchordoquy, T.J.

    2014-01-01

    Because aqueous liposomal formulations containing multiply unsaturated lipids are susceptible to chemical degradation, these formulations are often lyophilized. Despite their limited chemical stability, interest in the use of multiply unsaturated lipids to promote intracellular delivery has increased considerably in recent years. The goal of the current study was to examine the long term storage stability of lyophilized formulations containing lipids with increasing levels of unsaturation, and various strategies which can be employed to improve stability. Aqueous lipid-trehalose formulations containing 1,2-dilinolenoyl-sn-glycero-3-phosphocholine (DLPC), 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLinPC) or 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) were lyophilized and stored at temperatures ranging from 4°C to 60°C. We observed that the lipid degradation rate increased as the storage temperature and unsaturation level were increased. Even the cleanest sugars which are available commercially contain iron contaminants, and it was observed that the chelation of these iron contaminants significantly improved the stability of DLPC during storage. However, the glass transition temperature of the sugar which was included in the formulation, the reduction of the oxygen in the aqueous sample prior to lyophilization, the inclusion of helper lipids (i.e., cholesterol), and the rate of freezing did not significantly improve stability. PMID:25308534

  6. Long-term behavior of ceramic materials

    SciTech Connect

    Anson, D.; Ramesh, K.S.

    1992-02-19

    This topical report has been prepared in response to the need to address the question of long term durability of high-strength structural ceramic materials. In a new project to demonstrate the use of such materials as replacements for metals in the hot gas path of industrial gas turbines, the longest projected test bed run will be 1000 hours. Creep in ceramic materials seldom exceeds one percent strain before failure, but the strain takes place almost entirely in the intergranular regions, which can be severely weakened by accumulated damage as creep occurs. In this report, we discuss the nature of creep in silicon nitride and silicon carbide ceramic materials, the method of evaluating creep, and the interpretation of data obtained under various creep test conditions. A review of creep data illustrates the importance of intergranular phases and of the history of the material. Also, in most cases, the histories applying to laboratory investigations are different from those that will apply to engineering situations in which measurable creep will be generally unacceptable. Fatigue in ceramic materials usually is assessed in static fatigue tests, which are dependent on the same types of grain boundary damage as those occurring in creep, but over shorter time periods. Corrosion of silicon-based ceramics by oxygen and water vapor results in the formation of protective SiO{sub 2} under gas turbine operating conditions.

  7. 22 CFR 228.12 - Long-term leases.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Long-term leases. 228.12 Section 228.12 Foreign... Transactions for USAID Financing § 228.12 Long-term leases. Any commodity obtained under a long-term lease..., a long-term lease is defined as a single lease of more than 180 days, or repetitive or...

  8. 22 CFR 228.12 - Long-term leases.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Long-term leases. 228.12 Section 228.12 Foreign... Transactions for USAID Financing § 228.12 Long-term leases. Any commodity obtained under a long-term lease..., a long-term lease is defined as a single lease of more than 180 days, or repetitive or...

  9. Notch is required for long-term memory in Drosophila

    PubMed Central

    Presente, Asaf; Boyles, Randy S.; Serway, Christine N.; de Belle, J. Steven; Andres, Andrew J.

    2004-01-01

    A role for Notch in the elaboration of existing neural processes is emerging that is distinct from the increasingly well understood function of this gene in binary cell-fate decisions. Several research groups, by using a variety of organisms, have shown that Notch is important in the development of neural ultrastructure. Simultaneously, Presenilin (Psn) was identified both as a key mediator of Notch signaling and as a site of genetic lesions that cause early-onset Alzheimer's disease. Here we demonstrate that Notch loss of function produces memory deficits in Drosophila melanogaster. The effects are specific to long-term memory, which is thought to depend on ultrastructural remodeling. We propose that Notch plays an important role in the neural plasticity underlying consolidated memory. PMID:14752200

  10. Notch is required for long-term memory in Drosophila.

    PubMed

    Presente, Asaf; Boyles, Randy S; Serway, Christine N; de Belle, J Steven; Andres, Andrew J

    2004-02-10

    A role for Notch in the elaboration of existing neural processes is emerging that is distinct from the increasingly well understood function of this gene in binary cell-fate decisions. Several research groups, by using a variety of organisms, have shown that Notch is important in the development of neural ultrastructure. Simultaneously, Presenilin (Psn) was identified both as a key mediator of Notch signaling and as a site of genetic lesions that cause early-onset Alzheimer's disease. Here we demonstrate that Notch loss of function produces memory deficits in Drosophila melanogaster. The effects are specific to long-term memory, which is thought to depend on ultrastructural remodeling. We propose that Notch plays an important role in the neural plasticity underlying consolidated memory.

  11. Dopamine controls persistence of long-term memory storage.

    PubMed

    Rossato, Janine I; Bevilaqua, Lia R M; Izquierdo, Iván; Medina, Jorge H; Cammarota, Martín

    2009-08-21

    The paradigmatic feature of long-term memory (LTM) is its persistence. However, little is known about the mechanisms that make some LTMs last longer than others. In rats, a long-lasting fear LTM vanished rapidly when the D1 dopamine receptor antagonist SCH23390 was injected into the dorsal hippocampus 12 hours, but not immediately or 9 hours, after the fearful experience. Conversely, intrahippocampal application of the D1 agonist SK38393 at the same critical post-training time converted a rapidly decaying fear LTM into a persistent one. This effect was mediated by brain-derived neurotrophic factor and regulated by the ventral tegmental area (VTA). Thus, the persistence of LTM depends on activation of VTA/hippocampus dopaminergic connections and can be specifically modulated by manipulating this system at definite post-learning time points.

  12. Legislation on Long-Term Care Insurance. Report No. 11.

    ERIC Educational Resources Information Center

    Wisconsin State Legislative Council, Madison.

    This report presents Wisconsin state legislation on long-term care insurance. Part I summarizes key provisions of six 1987 assembly bills concerned with long-term care insurance. Part II describes activities of the Wisconsin State Legislative Council's Special Committee on Long-Term Health Care Insurance. Part III provides background information…

  13. 22 CFR 228.18 - Long-term leases.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Long-term leases. 228.18 Section 228.18 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT RULES FOR PROCUREMENT OF COMMODITIES AND SERVICES FINANCED BY... USAID Financing § 228.18 Long-term leases. Any commodity obtained under a long-term lease agreement...

  14. 22 CFR 228.18 - Long-term leases.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Long-term leases. 228.18 Section 228.18 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT RULES FOR PROCUREMENT OF COMMODITIES AND SERVICES FINANCED BY... USAID Financing § 228.18 Long-term leases. Any commodity obtained under a long-term lease agreement...

  15. 22 CFR 228.18 - Long-term leases.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Long-term leases. 228.18 Section 228.18 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT RULES FOR PROCUREMENT OF COMMODITIES AND SERVICES FINANCED BY... USAID Financing § 228.18 Long-term leases. Any commodity obtained under a long-term lease agreement...

  16. Protein kinase M ζ and the maintenance of long-term memory.

    PubMed

    Zhang, Yang; Zong, Wei; Zhang, Lei; Ma, Yuanye; Wang, Jianhong

    2016-10-01

    Although various molecules have been found to mediate the processes of memory acquisition and consolidation, the molecular mechanism to maintain memory still remains elusive. In recent years, a molecular pathway focusing on protein kinase Mζ (PKMζ) has become of interest to researchers because of its potential role in long-term memory maintenance. PKMζ is an isoform of protein kinase C (PKC) and has a related structure that influences its function in maintaining memory. Considerable evidence has been gathered on PKMζ activity, including loss of function studies using PKMζ inhibitors, such as PKMζ inhibitory peptide (ZIP), suggesting PKMζ plays an important role in long-term memory maintenance. This review provides an overview of the role of PKMζ in long-term memory and outlines the molecular structure of PKMζ, the molecular mechanism of PKMζ in long-term memory maintenance and future directions of PKMζ research.

  17. GDF15 regulates Kv2.1-mediated outward K+ current through the Akt/mTOR signalling pathway in rat cerebellar granule cells

    PubMed Central

    Wang, Chang-Ying; Huang, An-Qi; Zhou, Meng-Hua; Mei, Yan-Ai

    2014-01-01

    GDF15 (growth/differentiation factor 15), a novel member of the TGFβ (transforming growth factor β) superfamily, plays critical roles in the central and peripheral nervous systems, but the signal transduction pathways and receptor subtypes involved are not well understood. In the present paper, we report that GDF15 specifically increases the IK (delayed-rectifier outward K+ current) in rat CGNs (cerebellar granule neurons) in time- and concentration-dependent manners. The GDF15-induced amplification of the IK is mediated by the increased expression and reduced lysosome-dependent degradation of the Kv2.1 protein, the main α-subunit of the IK channel. Exposure of CGNs to GDF15 markedly induced the phosphorylation of ERK (extracellular-signal-regulated kinase), Akt and mTOR (mammalian target of rapamycin), but the GDF15-induced IK densities and increased expression of Kv2.1 were attenuated only by Akt and mTOR, and not ERK, inhibitors. Pharmacological inhibition of the Src-mediated phosphorylation of TGFβR2 (TGFβ receptor 2), not TGFβR1, abrogated the effect of GDF15 on IK amplification and Kv2.1 induction. Immunoprecipitation assays showed that GDF15 increased the tyrosine phosphorylation of TGFβRII in the CGN lysate. The results of the present study reveal a novel regulation of Kv2.1 by GDF15 mediated through the TGFβRII-activated Akt/mTOR pathway, which is a previously uncharacterized Smad-independent mechanism of GDF15 signalling. PMID:24597762

  18. Chronic suppression of inositol 1,4,5-triphosphate receptor-mediated calcium signaling in cerebellar purkinje cells alleviates pathological phenotype in spinocerebellar ataxia 2 mice.

    PubMed

    Kasumu, Adebimpe W; Liang, Xia; Egorova, Polina; Vorontsova, Daria; Bezprozvanny, Ilya

    2012-09-12

    Spinocerebellar ataxia 2 (SCA2) is a neurodegenerative disorder characterized by progressive ataxia. SCA2 results from a poly(Q) (polyglutamine) expansion in the cytosolic protein ataxin-2 (Atx2). Cerebellar Purkinje cells (PCs) are primarily affected in SCA2, but the cause of PC dysfunction and death in SCA2 is poorly understood. In previous studies, we reported that mutant but not wild-type Atx2 specifically binds the inositol 1,4,5-trisphosphate receptor (InsP(3)R) and increases its sensitivity to activation by InsP3. We further proposed that the resulting supranormal calcium (Ca2+) release from the PC endoplasmic reticulum plays a key role in the development of SCA2 pathology. To test this hypothesis, we achieved a chronic suppression of InsP(3)R-mediated Ca2+ signaling by adenoassociated virus-mediated expression of the inositol 1,4,5-phosphatase (Inpp5a) enzyme (5PP) in PCs of a SCA2 transgenic mouse model. We determined that recombinant 5PP overexpression alleviated age-dependent dysfunction in the firing pattern of SCA2 PCs. We further discovered that chronic 5PP overexpression also rescued age-dependent motor incoordination and PC death in SCA2 mice. Our findings further support the important role of supranormal Ca2+ signaling in SCA2 pathogenesis and suggest that partial inhibition of InsP3-mediated Ca2+ signaling could provide therapeutic benefit for the patients afflicted with SCA2 and possibly other SCAs.

  19. Scientific Understanding from Long Term Observations: Insights from the Long Term Ecological Research (LTER) Program

    NASA Astrophysics Data System (ADS)

    Gosz, J.

    2001-12-01

    The network dedicated to Long Term Ecological Research (LTER) in the United States has grown to 24 sites since it was formed in 1980. Long-term research and monitoring are performed on parameters thatare basic to all ecosystems and are required to understand patterns, processes, and relationship to change. Collectively, the sites in the LTER Network provide opportunities to contrast marine, coastal, and continental regions, the full range of climatic gradients existing in North America, and aquatic and terrestrial habitats in a range of ecosystem types. The combination of common core areas and long-term research and monitoring in many habitats have allowed unprecedented abilities to understand and compare complex temporal and spatial dynamics associated with issues like climate change, effects of pollution, biodiversity and landuse. For example, McMurdo Dry Valley in the Antarctic has demonstrated an increase in glacier mass since 1993 which coincides with a period of cooler than normal summers and more than average snowfall. In contrast, the Bonanza Creek and Toolik Lake sites in Alaska have recorded a warming period unprecedented in the past 200 years. Nitrogen deposition effects have been identified through long-term watershed studies on biogeochemical cycles, especially at Coweeta Hydrological Lab, Harvard Forest, and the Hubbard Brook Experimental Forest. In aquatic systems, such as the Northern Temperate Lakes site, long-term data revealed time lags in effects of invaders and disturbance on lake communities. Biological recovery from an effect such as lake acidification was shown to lag behind chemical recovery. The long-term changes documented over 2 decades have been instrumental in influencing management practices in many of the LTER areas. In Puerto Rico, the Luquillo LTER demonstrated that dams obstruct migrations of fish and freshwater shrimp and water abstraction at low flows can completely obliterate downstream migration of juveniles and damage

  20. The neuronal response at extended timescales: long-term correlations without long-term memory

    PubMed Central

    Soudry, Daniel; Meir, Ron

    2014-01-01

    Long term temporal correlations frequently appear at many levels of neural activity. We show that when such correlations appear in isolated neurons, they indicate the existence of slow underlying processes and lead to explicit conditions on the dynamics of these processes. Moreover, although these slow processes can potentially store information for long times, we demonstrate that this does not imply that the neuron possesses a long memory of its input, even if these processes are bidirectionally coupled with neuronal response. We derive these results for a broad class of biophysical neuron models, and then fit a specific model to recent experiments. The model reproduces the experimental results, exhibiting long term (days-long) correlations due to the interaction between slow variables and internal fluctuations. However, its memory of the input decays on a timescale of minutes. We suggest experiments to test these predictions directly. PMID:24744724

  1. Long-term infrared photometry of Seyferts

    NASA Astrophysics Data System (ADS)

    Glass, I. S.

    2004-05-01

    Long-term (up to 10 000 d) monitoring has been undertaken for 41 Seyferts in the near-infrared (1.25-3.45 μm). All but two showed variability, with amplitudes at K in the range <0.1 to >1.1 mag. The time-scale for detectable change is from about one week to a few years. Where contemporary observations of variability in X-rays, ultraviolet (UV) or visible light exist, it is found that the near-infrared varies in a similar way, though in some cases the shorter-wavelength infrared (IR) bands are diluted by underlying galaxy radiation. A simple cross-correlation study indicates that there is evidence for delays of up to several hundred d between the variations seen at the shortest wavelengths (U or J) and the longest (L) in many galaxies. In particular, the data for Fairall 9 now extend to twice the interval covered in earlier publications and the delay between its UV and IR outputs is seen to persist. An analysis of the fluxes shows that, for any given galaxy, the colours of the variable component of its nucleus are usually independent of the level of activity. The state of activity of the galaxy can be parameterized. Taken over the whole sample, the colours of the variable components fall within moderately narrow ranges. In particular, the H-K colour is appropriate to a blackbody of temperature 1600 K. The H-K excess for a heavily reddened nucleus can be determined and used to find EB-V, which can be compared to the values found from the visible region broad line ratios. Using flux-flux diagrams, the flux within the aperture from the underlying galaxies can often be determined without the need for model surface brightness profiles. In many galaxies it is apparent that there must be an additional constant contribution from warm dust.

  2. LONG TERM IN SITU DISPOSAL ENGINEERING STUDY

    SciTech Connect

    ADAMS; CARLSON; BROCKMAN

    2003-07-23

    Patent application pulled per Ken Norris (FH General Counsel). The objective of this study is to devise methods, produce conceptual designs, examine and select alternatives, and estimate costs for the demonstration of long-term (300-year) in situ disposal of an existing waste disposal site. The demonstration site selected is the 216-A-24 Crib near the 200 East Area. The site contains a fission product inventory and has experienced plant, animal, and inadvertent than intrusion. Of the potential intrusive events and transport pathways at the site, potential human intrusion has been given primary consideration in barrier design. Intrusion by wind, plants, and animals has been given secondary consideration. Groundwater modeling for a number of barrier configurations has been carried out to help select a barrier that will minimize water infiltration and waste/water contact time. The estimated effective lifetime and cost of 20 barrier schemes, using a variety of materials, have been evaluated. The schemes studied include single component surface barriers, multicomponent barriers, and massively injected grout barriers. Five barriers with high estimated effective lifetimes and relatively low costs have been selected for detailed evaluation. They are basalt riprap barriers, massive soil barriers, salt basin barriers, multi-component fine/coarse barriers, and cemented basalt barriers. A variety of materials and configurations for marking the site have also been considered. A decision analysis was completed to select a barrier scheme for demonstration. The analysis indicated that the basalt riprap alternative would be the preferred choice for a full-scale demonstration. The recommended approach is to demonstrate the basalt riprap barrier at the 216-A-24 Crib as soon as possible. Methods and costs of assessing effectiveness of the demonstration are also described. Preliminary design modifications and costs for applying the five selected barrier schemes to other site types are

  3. Hormonal changes during long-term isolation.

    PubMed

    Custaud, M A; Belin de Chantemele, E; Larina, I M; Nichiporuk, I A; Grigoriev, A; Duvareille, M; Gharib, C; Gauquelin-Koch, G

    2004-05-01

    Confinement and inactivity induce considerable psychological and physiological modifications through social and sensory deprivation. The aim of the SFINCSS-99 experiment was to determine the cardiovascular and hormonal pattern of blood volume regulation during long-term isolation and confinement. Simulation experiments were performed in pressurized chambers similar in size to the volumes of modern space vehicles. Group I consisted of four Russian male volunteers, who spent 240 days in a 100-m(3 )chamber. Group II included four males (one German and three Russians) who spent 110 days in isolation (200-m(3) module). The blood samples, taken before, during and after the isolation period, were used to determine haematocrit (Ht), growth hormone (GH), active renin, aldosterone, and osmolality levels. From the urine samples, electrolytes, osmolality, nitrites, nitrates, cortisol, antidiuretic hormone (ADH), aldosterone, normetanephrine and metanephrine levels were determined. The increase in plasma volume (PV) that is associated with a tendency for a decrease in plasma active renin is likely to be due to decreased sympathetic activity, and concords with the changes in urinary catecholamine levels during confinement. Urinary catecholamine levels were significantly higher during the recovery period than during confinement. This suggests that the sympathoadrenal system was activated, and concords with the increase in heart rate. Vascular resistance is determined by not only the vasoconstrictor but also vasodilator systems. The ratio of nitrite/nitrate in urine, as an indicator of nitric oxide release, did not reveal any significant changes. Analysis of data suggests that the duration of the isolation was a main factor involved in the regulation of hormones.

  4. Long term cultivation of larger benthic Foraminifera

    NASA Astrophysics Data System (ADS)

    Wöger, Julia; Eder, Wolfgang; Kinoshita, Shunichi; Antonino, Briguglio; Carles, Ferrandes-Cañadell; Hohenegger, Johann

    2015-04-01

    Benthic Foraminifera are used in a variety of applications employing numerous different methods, i.e. ecological monitoring, studying the effects of ocean acidification, reconstructing palaeo-bathymetry or investigating palaeo-salinity and palaeo-temperature to name only a few. To refine our understanding of ecological influences on larger benthic foraminiferal biology and to review inferences from field observations, culture experiments have become an indispensable tool. While culture experiments on smaller benthic foraminifera have become increasingly frequent in the past century, reports of the cultivation of symbiont bearing larger Foraminifera are rare. Generally, cultivation experiments can be divided into two groups: Culturing of populations and cultivation of single specimens allowing individual investigation. The latter differ form the former by several restrictions resulting from the need to limit individual motility without abridging microenvironmental conditions in the Foraminiferans artificial habitat, necessary to enable the individual to development as unfettered as possible. In this study we present first experiences and preliminary results of the long-term cultivation of larger benthic Foraminifera conducted at the 'Tropical Biosphere Research Station Sesoko Island, University of the Ryukyus', Japan, trying to reproduce natural conditions as closely as possible. Individuals of three species of larger benthic Foraminifera (Heterostegina depressa, Palaeonummulites venosus and Operculina complanata) have been cultured since April 2014. At the time of the general assembly the cultivation experiments will have been going on for more than one year, with the aim to investigate growth rates, longevities and reproduction strategies for comparison with results statistically inferred from application of the of the 'natural laboratory' method. The most important factor influencing foraminiferal health and development was found to be light intensity and light

  5. A new long-term care manifesto.

    PubMed

    Kane, Robert L

    2015-04-01

    This article argues for a fresh look at how we provide long-term care (LTC) for older persons. Essentially, LTC offers a compensatory service that responds to frailty. Policy debate around LTC centers on costs, but we are paying for something we really don't want. Building societal enthusiasm (or even support) for LTC will require re-inventing and re-branding. LTC has three basic components: personal care, housing, and health care (primarily chronic disease management). They can be delivered in a variety of settings. It is rare to find all three done well simultaneously. Personal care (PC) needs to be both competent and compassionate. Housing must provide at least minimal amenities and foster autonomy; when travel time for PC raises costs dramatically, some form of clustered housing may be needed. Health care must be proactive, aimed at preventing exacerbations of chronic disease and resultant hospitalizations. Enhancing preferences means allowing taking informed risks. Payment incentives should reward both quality of care and quality of life, but positive outcomes must be defined as slowing decline. Paying for services but not for housing under Medicaid would automatically level the playing field between nursing homes (NH) and community-based services. Regulations should achieve greater parity between NH and community care and include both positive and negative feedback. Providing post-acute care should be separate from LTC. Using the tripartite LTC framework, we can create innovative flexible approaches to providing needed services for frail older persons in formats that are both desirable and affordable. Such care will be more socially desirable and hence worth paying for.

  6. Narp regulates long-term aversive effects of morphine withdrawal

    PubMed Central

    Reti, Irving M.; Crombag, Hans S.; Takamiya, Kogo; Sutton, Jeffrey M.; Guo, Ning; Dinenna, Megan L.; Huganir, Richard L.; Holland, Peter C.; Baraban, Jay M.

    2008-01-01

    Although long-lasting effects of drug withdrawal are thought to play a key role in motivating continued drug use, the mechanisms mediating this type of drug-induced plasticity are unclear. As Narp is an immediate early gene product that is secreted at synaptic sites and binds to AMPA receptors, it has been implicated in mediating enduring forms of synaptic plasticity. In previous studies, we found that Narp is selectively induced by morphine withdrawal in the extended amygdala, a group of limbic nuclei that mediate aversive behavioral responses. Accordingly, in this study, we evaluated whether long-term aversive effects of morphine withdrawal are altered in Narp KO mice. We found that acute physical signs of morphine withdrawal are unaffected by Narp deletion. However, Narp KO mice acquire and sustain more aversive responses to the environment conditioned with morphine withdrawal than WT controls. Paradoxically, Narp KO mice undergo accelerated extinction of this heightened aversive response. Taken together, these studies suggest that Narp modulates both acquisition and extinction of aversive responses to morphine withdrawal and, therefore, may regulate plasticity processes underlying drug addiction. PMID:18729628

  7. Long term property prediction of polyethylene nanocomposites

    NASA Astrophysics Data System (ADS)

    Shaito, Ali Al-Abed

    properties of the nanocomposites was analyzed by examining tensile and creep-recovery behavior of the films at temperatures in the range of 25 to -100°C. Within the measured temperature range, the materials showed a nonlinear temperature dependent response. The time-temperature superposition principle was successfully used to predict the long term behavior of LLDPE nanocomposites.

  8. Long-Term Space Astrophysics Program

    NASA Technical Reports Server (NTRS)

    Nowark, Michael A.

    2001-01-01

    This is the final report for our Long-Term Space Astrophysics Program (NRA 94-OSS-12) grant NAG 5-3225. The proposal is entitled 'Spectral and Temporal Properties of Black Hole Candidates', and began funding in May 1995, and ran through 31 Aug 2000. The project summary from the original proposal was as follows: 'We will study the spectral and temporal properties of black hole candidates (BHC) by using data from archival sources (e.g., EXOSAT, Ginga, ROSAT) and proposed follow-up observations with modern instruments (e.g., ASCA, XTE). Our spectral studies will focus on identifying the basic characteristics and luminosities of the emission components in the various 'states' of BHC. We hope to understand and quantify the global energetics of these states. Our temporal studies will focus on expanding and classifying our knowledge of BHC variability properties in each state. We will explore the nature of quasi-periodic oscillations in BHC. We will combine our spectral and temporal studies by analyzing time lags and variability coherence between energy channels. In addition, we will investigate ways of correlating observed variability behavior with specific emission components.' We have accomplished many of these goals laid out within the original proposal. As originally proposed, we have utilized both archival and proprietary satellite data. In terms of archival data, we have utilized data from the Advanced Satellite for Cosmology and Astrophysics (ASCA), ROSAT, and the Rossi X-ray Timing Explorer (RXTE). We also obtained proprietary data from ASCA, RXTE, and the Extreme Ultraviolet Explorer (EUVE). In terms of sources, we have examined a wide variety of both galactic black hole candidates and extra-galactic black holes. For the galactic black holes we have observed and analyzed both the low/hard state and the high/soft state. We have performed both spectral and timing analyses on all of these objects. In addition, we have also examined a number of neutron stars or

  9. Long term prognosis of reactive salmonella arthritis

    PubMed Central

    Leirisalo-Repo, M; Helenius, P; Hannu, T; Lehtinen, A; Kreula, J; Taavitsainen, M; Koskimies, S

    1997-01-01

    OBJECTIVES—Reactive joint complications triggered by salmonella gastroenteritis are increasingly reported, but the outcome and long term prognosis of the patients is incompletely known. This study looked at the prognosis of salmonella arthritis in patients hospitalised in 1970-1986.
METHODS—Hospital records from two hospitals in southern Finland were screened for patients with the discharge diagnosis of salmonellosis or reactive, postinfectious arthritis or Reiter's disease. For the patients with confirmed diagnosis of reactive salmonella arthritis, data about the acute disease were collected from the hospital records. A follow up study was performed.
RESULTS—There were 63 patients (28 women, 35 men, mean age 36.5 years) with salmonella arthritis. Urethritis occurred in 27%, eye inflammation in 13%, and low back pain in 44% of the patients. HLA-B27 was present in 88%. More men than women were HLA-B27 positive. HLA-B27 positive patients had higher erythrocyte sedimentation rate (mean 80.9 v 46.5 mm 1st h, p = 0.0180). Also, extra-articular features and radiological sacroiliitis were seen only in HLA-B27 positive patients. A follow up study was performed on 50 patients mean 11.0 (range 5-22 years) later. Twenty patients had recovered completely. Ten patients had mild joint symptoms, 11 patients had had a new acute transient arthritis, and five acute iritis. Eight patients had developed chronic spondyloarthropathy. Radiological sacroiliitis was seen in six of 44 patients, more frequently in male than in female patients (32% v 0%; p = 0.0289). Recurrent or chronic arthritis, iritis or radiological sacroiliitis developed only in HLA-B27 positive patients.
CONCLUSION—Joint symptoms are common after reactive salmonella arthritis. HLA-B27 contributes to the severity of acute disease and to the late prognosis.

 PMID:9370874

  10. Purkinje cell dysfunction and alteration of long-term synaptic plasticity in fetal alcohol syndrome.

    PubMed

    Servais, Laurent; Hourez, Raphaël; Bearzatto, Bertrand; Gall, David; Schiffmann, Serge N; Cheron, Guy

    2007-06-01

    In cerebellum and other brain regions, neuronal cell death because of ethanol consumption by the mother is thought to be the leading cause of neurological deficits in the offspring. However, little is known about how surviving cells function. We studied cerebellar Purkinje cells in vivo and in vitro to determine whether function of these cells was altered after prenatal ethanol exposure. We observed that Purkinje cells that were prenatally exposed to ethanol presented decreased voltage-gated calcium currents because of a decreased expression of the gamma-isoform of protein kinase C. Long-term depression at the parallel fiber-Purkinje cell synapse in the cerebellum was converted into long-term potentiation. This likely explains the dramatic increase in Purkinje cell firing and the rapid oscillations of local field potential observed in alert fetal alcohol syndrome mice. Our data strongly suggest that reversal of long-term synaptic plasticity and increased firing rates of Purkinje cells in vivo are major contributors to the ataxia and motor learning deficits observed in fetal alcohol syndrome. Our results show that calcium-related neuronal dysfunction is central to the pathogenesis of the neurological manifestations of fetal alcohol syndrome and suggest new methods for treatment of this disorder.

  11. Long-term Nicotine Replacement Therapy

    PubMed Central

    Schnoll, Robert A.; Goelz, Patricia M.; Veluz-Wilkins, Anna; Blazekovic, Sonja; Powers, Lindsay; Leone, Frank T.; Gariti, Peter; Wileyto, E. Paul; Hitsman, Brian

    2015-01-01

    and extended treatment arms (20.3% vs 23.8%; OR, 1.17 [95% CI, 0.69-1.98]; P = .57). Similarly, we found no difference in week 52 abstinence rates between participants in the extended and standard treatment arms (26.0% vs 21.7%; OR, 1.33 [95% CI, 0.72-2.45]; P = .36). Treatment duration was not associated with any adverse effects or adherence to the counseling regimen, but participants in the maintenance treatment arm reported lower adherence to the nicotine patch regimen compared with those in the standard and extended treatment arms (mean [SD], 3.94 [2.5], 4.61 [2.0], and 4.7 [2.4] patches/wk, respectively; F2,522 = 6.03; P = .003). CONCLUSIONS AND RELEVANCE The findings support the safety of long-term use of nicotine patch treatment, although they do not support efficacy beyond 24 weeks of treatment in a broad group of smokers. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01047527 PMID:25705872

  12. Stochastic Induction of Long-Term Potentiation and Long-Term Depression.

    PubMed

    Antunes, G; Roque, A C; Simoes-de-Souza, F M

    2016-01-01

    Long-term depression (LTD) and long-term potentiation (LTP) of granule-Purkinje cell synapses are persistent synaptic alterations induced by high and low rises of the intracellular calcium ion concentration ([Ca(2+)]), respectively. The occurrence of LTD involves the activation of a positive feedback loop formed by protein kinase C, phospholipase A2, and the extracellular signal-regulated protein kinase pathway, and its expression comprises the reduction of the population of synaptic AMPA receptors. Recently, a stochastic computational model of these signalling processes demonstrated that, in single synapses, LTD is probabilistic and bistable. Here, we expanded this model to simulate LTP, which requires protein phosphatases and the increase in the population of synaptic AMPA receptors. Our results indicated that, in single synapses, while LTD is bistable, LTP is gradual. Ca(2+) induced both processes stochastically. The magnitudes of the Ca(2+) signals and the states of the signalling network regulated the likelihood of LTP and LTD and defined dynamic macroscopic Ca(2+) thresholds for the synaptic modifications in populations of synapses according to an inverse Bienenstock, Cooper and Munro (BCM) rule or a sigmoidal function. In conclusion, our model presents a unifying mechanism that explains the macroscopic properties of LTP and LTD from their dynamics in single synapses. PMID:27485552

  13. Stochastic Induction of Long-Term Potentiation and Long-Term Depression

    PubMed Central

    Antunes, G.; Roque, A. C.; Simoes-de-Souza, F. M.

    2016-01-01

    Long-term depression (LTD) and long-term potentiation (LTP) of granule-Purkinje cell synapses are persistent synaptic alterations induced by high and low rises of the intracellular calcium ion concentration ([Ca2+]), respectively. The occurrence of LTD involves the activation of a positive feedback loop formed by protein kinase C, phospholipase A2, and the extracellular signal-regulated protein kinase pathway, and its expression comprises the reduction of the population of synaptic AMPA receptors. Recently, a stochastic computational model of these signalling processes demonstrated that, in single synapses, LTD is probabilistic and bistable. Here, we expanded this model to simulate LTP, which requires protein phosphatases and the increase in the population of synaptic AMPA receptors. Our results indicated that, in single synapses, while LTD is bistable, LTP is gradual. Ca2+ induced both processes stochastically. The magnitudes of the Ca2+ signals and the states of the signalling network regulated the likelihood of LTP and LTD and defined dynamic macroscopic Ca2+ thresholds for the synaptic modifications in populations of synapses according to an inverse Bienenstock, Cooper and Munro (BCM) rule or a sigmoidal function. In conclusion, our model presents a unifying mechanism that explains the macroscopic properties of LTP and LTD from their dynamics in single synapses. PMID:27485552

  14. Reforming long-term care financing through insurance

    PubMed Central

    Meiners, Mark R.

    1988-01-01

    Until recently, insurance for long-term care was not viewed as feasible. This perception has changed dramatically in the past few years. Several models of long-term care insurance have begun to be tested. Although the application of insurance principles to long-term care is still new, the emergence of private market interest in developing long-term care insurance has been a catalyst to renewed public-policy support for reforming the way we pay for long-term care. States, in particular, have become interested in developing public-private partnerships to support the emergence of long-term care insurance that could help relieve the mounting pressure on Medicaid budgets. PMID:10312962

  15. Long-Term Monitoring of Global Climate Forcings and Feedbacks

    NASA Technical Reports Server (NTRS)

    Hansen, J. (Editor); Rossow, W. (Editor); Fung, I. (Editor)

    1993-01-01

    A workshop on Long-Term Monitoring of Global Climate Forcings and Feedbacks was held February 3-4, 1992, at NASA's Goddard Institute for Space Studies to discuss the measurements required to interpret long-term global temperature changes, to critique the proposed contributions of a series of small satellites (Climsat), and to identify needed complementary monitoring. The workshop concluded that long-term (several decades) of continuous monitoring of the major climate forcings and feedbacks is essential for understanding long-term climate change.

  16. Information exchange between short term and long term operations

    NASA Astrophysics Data System (ADS)

    Weijs, Steven

    2016-04-01

    This research focuses on the interactions between optimal short term and long term operations of managed water systems. Stochastic Dynamic Programming is used as a framework to find and analyze optimal operations. When considering optimal operations under uncertainty, the short term operations are influenced by the long term optimal policy through the value function of the end-state at the short term horizon. Conversely, the optimal long-term operations are influenced by the value of future decisions, which is partly determined by the short term operations. This leads to a two-way information flow between short and long term operations. The implications of this information flow are discussed.

  17. Long-Term Monitoring of Global Climate Forcings and Feedbacks

    SciTech Connect

    Hansen, J.; Rossow, W.; Fung, I.

    1993-09-01

    A workshop on Long-Term Monitoring of Global Climate Forcings and Feedbacks was held February 3-4, 1992, at NASA's Goddard Institute for Space Studies to discuss the measurements required to interpret long-term global temperature changes, to critique the proposed contributions of a series of small satellites (Climsat), and to identify needed complementary monitoring. The workshop concluded that long-term (several decades) of continuous monitoring of the major climate forcings and feedbacks is essential for understanding long-term climate change. Separate abstracts have been prepared for articles from this report.

  18. Striatal-cerebellar networks mediate consolidation in a motor sequence learning task: An fMRI study using dynamic causal modelling.

    PubMed

    Tzvi, Elinor; Stoldt, Anne; Witt, Karsten; Krämer, Ulrike M

    2015-11-15

    The fast and slow learning stages of motor sequence learning are suggested to be realized through plasticity in a distributed cortico-striato-cerebellar network. To better understand the causal interactions within this network in the different phases of motor sequence learning, we investigated the effective connectivity within this network during encoding (Day 1) and after consolidation (Day 2) of a serial reaction time task. Using Dynamic Causal Modelling of fMRI data, we found general changes in network connections reflected in altered input nodes and endogenous connections when comparing the early and fast learning session to the late and slow learning session. Whereas encoding of a motor memory early on modulated several connections in a distributed network, slow learning resulted in a pruned network. More specifically, we found a negative modulation of connections from left M1 to right cerebellum, right premotor cortex to left cerebellum, as well as backward connections from putamen to cerebellum bilaterally in the encoding session. While connections during pre-sleep were significantly modulated by learning per se (i.e., specifically modulated by performance on sequence conditions), the connections observed after sleep were rather modulated by general performance (i.e., modulated by performance on both sequence and random conditions). A forward connection from left cerebellum to right putamen was found to be consistent across participants for the sequence condition only during slow learning. Together these findings suggest that whereas encoding in the fast learning phase requires plasticity in several connections implementing both motor and perceptual learning components, slow learning is mediated through connectivity from left cerebellum to right putamen.

  19. Factors Affecting Long-Term Abstinence from Substances Use

    ERIC Educational Resources Information Center

    Elsheikh, Salah Elgaily

    2008-01-01

    Objective: The purpose of this study is to explore the attitudes of abstainers from drug use that relate to the factors leading to long-term abstinence. Materials and Methods: Cross-sectional study was carried out in Al-Amal Hospital to examine, which attitudes of abstainers related to long-term abstinence. A random survey was conducted on 62…

  20. Long Term Agroecosystem Research in the southern plains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Southern Plains (SP) site of the Long Term Agroecosystem Research (LTAR) network is headquartered at USDA-ARS’s Grazinglands Research Laboratory (GRL) in El Reno, Oklahoma. The GRL was established in 1948. A long-term watershed and climate research program was established in the Little Washita ...

  1. Helping People Make Better Long-Term-Care Decisions

    ERIC Educational Resources Information Center

    Kane, Robert L.; Boston, Krista; Chilvers, Mary

    2007-01-01

    Purpose: The purpose of this article is to describe an innovative online system to support long-term-care decision making. Design and Methods: The Long-Term Care Choices tool is a web-based system that uses expert opinion and structures decision making. Results: The system has been well accepted, and most users find it easy to use. Implications:…

  2. Day Care as a Long-Term Care Service Study.

    ERIC Educational Resources Information Center

    Zaki, Gamel; Zaki, Sylvia

    Day care is a growing service in the field of long-term care, increasing the options available to the impaired elderly. To study the development of adult day care centers in southeastern New England, and to identify the relationship of day care centers to the long term care network of services, the 11 day care centers in the catchment area of the…

  3. 78 FR 36449 - State Long-Term Care Ombudsman Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-18

    ... from the Long- Term Care Ombudsman program with less variation in the quality, efficiency, and... State Long-Term Care Ombudsman programs (Ombudsman programs) serve as advocates for residents of nursing homes, board and care homes, assisted living facilities and similar adult care facilities. They work...

  4. 7 CFR 1773.44 - Long-term debt.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 12 2011-01-01 2011-01-01 false Long-term debt. 1773.44 Section 1773.44 Agriculture...-term debt. The CPA's workpapers must document that he/she: (a) Confirmed RUS, FFB, and RTB debt to the...); (b) Confirmed other long-term debt directly with the lender; (c) Examined notes executed or...

  5. 7 CFR 1773.44 - Long-term debt.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 12 2010-01-01 2010-01-01 false Long-term debt. 1773.44 Section 1773.44 Agriculture...-term debt. The CPA's workpapers must document that he/she: (a) Confirmed RUS, FFB, and RTB debt to the...); (b) Confirmed other long-term debt directly with the lender; (c) Examined notes executed or...

  6. 3 CFR - Long-Term Gulf Coast Restoration Support Plan

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 3 The President 1 2011-01-01 2011-01-01 false Long-Term Gulf Coast Restoration Support Plan... Restoration Support Plan Memorandum for the Heads of Executive Departments and Agencies The oil spill in the... a plan of Federal support for the long-term economic and environmental restoration of the Gulf...

  7. 41 CFR 51-6.3 - Long-term procurements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 41 Public Contracts and Property Management 1 2012-07-01 2009-07-01 true Long-term procurements. 51-6.3 Section 51-6.3 Public Contracts and Property Management Other Provisions Relating to Public... § 51-6.3 Long-term procurements. (a) Contracting activities are encouraged to investigate...

  8. 41 CFR 51-6.3 - Long-term procurements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 41 Public Contracts and Property Management 1 2013-07-01 2013-07-01 false Long-term procurements. 51-6.3 Section 51-6.3 Public Contracts and Property Management Other Provisions Relating to Public... § 51-6.3 Long-term procurements. (a) Contracting activities are encouraged to investigate...

  9. 7 CFR 1773.44 - Long-term debt.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 12 2012-01-01 2012-01-01 false Long-term debt. 1773.44 Section 1773.44 Agriculture... (CONTINUED) POLICY ON AUDITS OF RUS BORROWERS RUS Required Audit Procedures and Documentation § 1773.44 Long... 691, Confirmation Schedule—Long-term Obligation to RUS as of; or RTB Form 12, Confirmation...

  10. 7 CFR 1773.44 - Long-term debt.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 12 2014-01-01 2013-01-01 true Long-term debt. 1773.44 Section 1773.44 Agriculture... (CONTINUED) POLICY ON AUDITS OF RUS BORROWERS RUS Required Audit Procedures and Documentation § 1773.44 Long... 691, Confirmation Schedule—Long-term Obligation to RUS as of; or RTB Form 12, Confirmation...

  11. 7 CFR 1773.44 - Long-term debt.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 12 2013-01-01 2013-01-01 false Long-term debt. 1773.44 Section 1773.44 Agriculture... (CONTINUED) POLICY ON AUDITS OF RUS BORROWERS RUS Required Audit Procedures and Documentation § 1773.44 Long... 691, Confirmation Schedule—Long-term Obligation to RUS as of; or RTB Form 12, Confirmation...

  12. 41 CFR 51-6.3 - Long-term procurements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 41 Public Contracts and Property Management 1 2011-07-01 2009-07-01 true Long-term procurements. 51-6.3 Section 51-6.3 Public Contracts and Property Management Other Provisions Relating to Public... § 51-6.3 Long-term procurements. (a) Contracting activities are encouraged to investigate...

  13. 41 CFR 51-6.3 - Long-term procurements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 41 Public Contracts and Property Management 1 2014-07-01 2014-07-01 false Long-term procurements. 51-6.3 Section 51-6.3 Public Contracts and Property Management Other Provisions Relating to Public... § 51-6.3 Long-term procurements. (a) Contracting activities are encouraged to investigate...

  14. Standards for Psychological Services in Long-Term Care Facilities.

    ERIC Educational Resources Information Center

    Morrow-Howell, Nancy; Lichtenberg, Peter A.; Smith, Michael; Frazer, Deborah; Molinari, Victor; Rosowsky, Erlene; Crose, Royda; Stillwell, Nick; Kramer, Nanette; Hartman-Stein, Paula; Qualls, Sara; Salamon, Michael; Duffy, Michael; Parr, Joyce; Gallagher-Thompson, Dolores

    1998-01-01

    Describes the development of standards for psychological practice in long-term care facilities. The standards, which were developed by Psychologists in Long-Term Care, address provider characteristics, methods of referral, assessment practices, treatment, and ethical issues. Offers suggestions for use of the standards. (MKA)

  15. Developmental Dyslexia and Explicit Long-Term Memory

    ERIC Educational Resources Information Center

    Menghini, Deny; Carlesimo, Giovanni Augusto; Marotta, Luigi; Finzi, Alessandra; Vicari, Stefano

    2010-01-01

    The reduced verbal long-term memory capacities often reported in dyslexics are generally interpreted as a consequence of their deficit in phonological coding. The present study was aimed at evaluating whether the learning deficit exhibited by dyslexics was restricted only to the verbal component of the long-term memory abilities or also involved…

  16. Elder Rights and the Long-Term Care Ombudsman Program.

    ERIC Educational Resources Information Center

    Netting, F. Ellen; And Others

    1995-01-01

    Examines important issues facing the Long-Term Care Ombudsman Program. Provides a historical overview of the policy and programmatic and research issues that surround the Older Americans Act. Explains ombudsmen's activities in their local communities and explores social workers' roles under the auspices of long-term care ombudsman programs. (RJM)

  17. Contribution of Cerebellar Sensorimotor Adaptation to Hippocampal Spatial Memory

    PubMed Central

    Passot, Jean-Baptiste; Sheynikhovich, Denis; Duvelle, Éléonore; Arleo, Angelo

    2012-01-01

    Complementing its primary role in motor control, cerebellar learning has also a bottom-up influence on cognitive functions, where high-level representations build up from elementary sensorimotor memories. In this paper we examine the cerebellar contribution to both procedural and declarative components of spatial cognition. To do so, we model a functional interplay between the cerebellum and the hippocampal formation during goal-oriented navigation. We reinterpret and complete existing genetic behavioural observations by means of quantitative accounts that cross-link synaptic plasticity mechanisms, single cell and population coding properties, and behavioural responses. In contrast to earlier hypotheses positing only a purely procedural impact of cerebellar adaptation deficits, our results suggest a cerebellar involvement in high-level aspects of behaviour. In particular, we propose that cerebellar learning mechanisms may influence hippocampal place fields, by contributing to the path integration process. Our simulations predict differences in place-cell discharge properties between normal mice and L7-PKCI mutant mice lacking long-term depression at cerebellar parallel fibre-Purkinje cell synapses. On the behavioural level, these results suggest that, by influencing the accuracy of hippocampal spatial codes, cerebellar deficits may impact the exploration-exploitation balance during spatial navigation. PMID:22485133

  18. The relationship between interannual and long-term cloud feedbacks

    SciTech Connect

    Zhou, Chen; Zelinka, Mark D.; Dessler, Andrew E.; Klein, Stephen A.

    2015-12-11

    The analyses of Coupled Model Intercomparison Project phase 5 simulations suggest that climate models with more positive cloud feedback in response to interannual climate fluctuations also have more positive cloud feedback in response to long-term global warming. Ensemble mean vertical profiles of cloud change in response to interannual and long-term surface warming are similar, and the ensemble mean cloud feedback is positive on both timescales. However, the average long-term cloud feedback is smaller than the interannual cloud feedback, likely due to differences in surface warming pattern on the two timescales. Low cloud cover (LCC) change in response to interannual and long-term global surface warming is found to be well correlated across models and explains over half of the covariance between interannual and long-term cloud feedback. In conclusion, the intermodel correlation of LCC across timescales likely results from model-specific sensitivities of LCC to sea surface warming.

  19. Long-Term Dynamics of Autonomous Fractional Differential Equations

    NASA Astrophysics Data System (ADS)

    Liu, Tao; Xu, Wei; Xu, Yong; Han, Qun

    This paper aims to investigate long-term dynamic behaviors of autonomous fractional differential equations with effective numerical method. The long-term dynamic behaviors predict where systems are heading after long-term evolution. We make some modification and transplant cell mapping methods to autonomous fractional differential equations. The mapping time duration of cell mapping is enlarged to deal with the long memory effect. Three illustrative examples, i.e. fractional Lotka-Volterra equation, fractional van der Pol oscillator and fractional Duffing equation, are studied with our revised generalized cell mapping method. We obtain long-term dynamics, such as attractors, basins of attraction, and saddles. Compared with some existing stability and numerical results, the validity of our method is verified. Furthermore, we find that the fractional order has its effect on the long-term dynamics of autonomous fractional differential equations.

  20. [Long-term care insurance in taiwan: theory and challenges].

    PubMed

    Lee, Jwo-Leun; Lung, Chi-Hsuan; Liu, Li-Fan

    2010-08-01

    Long-term care insurance, now being intensively discussed as part of the formal governmental agenda, is widely expected to be inaugurated by 2011. As all entitled citizens will be enrolled compulsorily in accordance with social insurance rules, tight scrutiny in the planning process is strongly advised. Equity of financial mechanisms and the efficiency of the delivery system for long-term care should also be carefully considered and maximized. This study explores major empirical suggestions for Taiwan's long-term care insurance scheme from a primarily theoretical point of view. The three relevant issues deliberated in this paper include risk sharing and financial equity in long-term care insurance and long-term care system delivery efficiency. Content focuses on concepts that may be easily misunderstood or misinterpreted by medical professionals.

  1. Environmental Management Long-Term Stewardship Transition Guidance

    SciTech Connect

    Kristofferson, Keith

    2001-11-01

    Long-term stewardship consists of those actions necessary to maintain and demonstrate continued protection of human health and the environment after the completion of facility cleanup. Long-term stewardship is administered and overseen by the U.S. Department of Energy Environmental Management Office of Science and Technology. This report describes the background of long-term stewardship and gives general guidance about considerations when ownership and/or responsibility of a site should be transferred to a long-term stewardship program. This guidance document will assist the U.S. Department of Energy in: (a) ensuring that the long-term stewardship program leads transition planning with respect to facility and site areas, and (b) describing the classes and types of criteria and data required to initiate transition for areas and sites where the facility mission has ended and cleanup is complete.

  2. The relationship between interannual and long-term cloud feedbacks

    NASA Astrophysics Data System (ADS)

    Zhou, Chen; Zelinka, Mark D.; Dessler, Andrew E.; Klein, Stephen A.

    2015-12-01

    Analyses of Coupled Model Intercomparison Project phase 5 simulations suggest that climate models with more positive cloud feedback in response to interannual climate fluctuations also have more positive cloud feedback in response to long-term global warming. Ensemble mean vertical profiles of cloud change in response to interannual and long-term surface warming are similar, and the ensemble mean cloud feedback is positive on both timescales. However, the average long-term cloud feedback is smaller than the interannual cloud feedback, likely due to differences in surface warming pattern on the two timescales. Low cloud cover (LCC) change in response to interannual and long-term global surface warming is found to be well correlated across models and explains over half of the covariance between interannual and long-term cloud feedback. The intermodel correlation of LCC across timescales likely results from model-specific sensitivities of LCC to sea surface warming.

  3. A Cohort Study on Long-Term Adverse Effects of Parental Drinking: Background and Study Design

    PubMed Central

    Lund, Ingunn Olea; Bukten, Anne; Storvoll, Elisabet E; Moan, Inger Synnøve; Skurtveit, Svetlana; Handal, Marte; Nordfjærn, Trond; Brunborg, Geir Scott; Rossow, Ingeborg

    2015-01-01

    Although many studies have addressed adverse outcomes in children of parents with alcohol abuse/dependence, less is known about the possible long-term effects of more normative patterns of parental alcohol consumption, including drinking at lower risk levels and heavy episodic or binge drinking. The extent of harm from parental drinking may therefore be underestimated. With this research proposal, we describe a project that aims to assess possible long-term adverse effects of parental drinking by combining survey and nationwide registry data. Advantages of a longitudinal general population cohort design include that it allows for detailed information on parental drinking through survey data and identification of possible negative long-term health and social outcomes from exposure to parental drinking 1–19 years after exposure through continuously updated nationwide registers. The rich information available from combining survey and registry data allows us to take into account important confounders, mediators, and moderators. PMID:26688663

  4. Concept Formation Skills in Long-Term Cochlear Implant Users

    PubMed Central

    Castellanos, Irina; Kronenberger, William G.; Beer, Jessica; Colson, Bethany G.; Henning, Shirley C.; Ditmars, Allison; Pisoni, David B.

    2015-01-01

    This study investigated if a period of auditory sensory deprivation followed by degraded auditory input and related language delays affects visual concept formation skills in long-term prelingually deaf cochlear implant (CI) users. We also examined if concept formation skills are mediated or moderated by other neurocognitive domains (i.e., language, working memory, and executive control). Relative to normally hearing (NH) peers, CI users displayed significantly poorer performance in several specific areas of concept formation, especially when multiple comparisons and relational concepts were components of the task. Differences in concept formation between CI users and NH peers were fully explained by differences in language and inhibition–concentration skills. Language skills were also found to be more strongly related to concept formation in CI users than in NH peers. The present findings suggest that complex relational concepts may be adversely affected by a period of early prelingual deafness followed by access to underspecified and degraded sound patterns and spoken language transmitted by a CI. Investigating a unique clinical population such as early-implanted prelingually deaf children with CIs can provide new insights into foundational brain–behavior relations and developmental processes. PMID:25583706

  5. Concept formation skills in long-term cochlear implant users.

    PubMed

    Castellanos, Irina; Kronenberger, William G; Beer, Jessica; Colson, Bethany G; Henning, Shirley C; Ditmars, Allison; Pisoni, David B

    2015-01-01

    This study investigated if a period of auditory sensory deprivation followed by degraded auditory input and related language delays affects visual concept formation skills in long-term prelingually deaf cochlear implant (CI) users. We also examined if concept formation skills are mediated or moderated by other neurocognitive domains (i.e., language, working memory, and executive control). Relative to normally hearing (NH) peers, CI users displayed significantly poorer performance in several specific areas of concept formation, especially when multiple comparisons and relational concepts were components of the task. Differences in concept formation between CI users and NH peers were fully explained by differences in language and inhibition-concentration skills. Language skills were also found to be more strongly related to concept formation in CI users than in NH peers. The present findings suggest that complex relational concepts may be adversely affected by a period of early prelingual deafness followed by access to underspecified and degraded sound patterns and spoken language transmitted by a CI. Investigating a unique clinical population such as early-implanted prelingually deaf children with CIs can provide new insights into foundational brain-behavior relations and developmental processes.

  6. Laminin degradation by plasmin regulates long-term potentiation.

    PubMed

    Nakagami, Y; Abe, K; Nishiyama, N; Matsuki, N

    2000-03-01

    Plasmin is converted from its zymogen plasminogen by tissue type or urokinase type plasminogen activator (PA) and degrades many components of the extracellular matrix (ECM). To explore the possibility that the PA-plasmin system regulates synaptic plasticity, we investigated the effect of plasmin on degradation of ECM and synaptic plasticity by using organotypic hippocampal cultures. High-frequency stimulation produced long-term potentiation (LTP) in control slices, whereas the potentiation was induced but not maintained in slices pretreated with 100 nM plasmin for 6 hr. The baseline synaptic responses were not affected by pretreatment with plasmin. The impairment of LTP maintenance was not observed in slices pretreated with 100 nM plasmin for 6 hr, washed, and then cultured for 24-48 hr in the absence of plasmin. To identify substrates of plasmin, the expression of three major components of ECM, laminin, fibronectin, and type IV collagen, was investigated by immunofluorescence imaging. The three ECM components were widely distributed in the hippocampus, and only laminin was degraded by plasmin pretreatment. The expression level of laminin returned to normal levels when the slices were cultured for 24-48 hr after washout of plasmin. Furthermore, preincubation with anti-laminin antibodies prevented both the degradation of laminin and the impairment of LTP maintenance by plasmin. These results suggest that the laminin-mediated cell-ECM interaction may be necessary for the maintenance of LTP.

  7. Maternal Postsecondary Education Associated With Improved Cerebellar Growth After Preterm Birth.

    PubMed

    Stiver, Mikaela L; Kamino, Daphne; Guo, Ting; Thompson, Angela; Duerden, Emma G; Taylor, Margot J; Tam, Emily W Y

    2015-10-01

    The preterm cerebellum is vulnerable to impaired development impacting long-term outcome. Preterm newborns (<32 weeks) underwent serial magnetic resonance imaging (MRI) scans. The association between parental education and cerebellar volume at each time point was assessed, adjusting for age at scan. In 26 infants, cerebellar volumes at term (P = .001), but not birth (P = .4), were associated with 2-year volumes. For 1 cm(3) smaller cerebellar volume (4% total volume) at term, the cerebellum was 3.18 cm(3) smaller (3% total volume) by 2 years. Maternal postsecondary education was not associated with cerebellar volume at term (P = .16). Maternal postsecondary education was a significant confounder in the relationship between term and 2-year cerebellar volumes (P = .016), with higher education associated with improved volumes by 2 years. Although preterm birth has been found to be associated with smaller cerebellar volumes at term, maternal postsecondary education is associated with improved growth detectable by 2 years.

  8. Effects of long-term treatment on brain volume in patients with obstructive sleep apnea syndrome.

    PubMed

    Kim, Hosung; Joo, EunYeon; Suh, Sooyeon; Kim, Jae-Hun; Kim, Sung Tae; Hong, Seung Bong

    2016-01-01

    We assessed structural brain damage in obstructive sleep apnea syndrome (OSA) patients (21 males) and the effects of long-term continuous positive airway pressure (CPAP) treatment (18.2 ± 12.4 months; 8-44 months) on brain structures and investigated the relationship between severity of OSA and effects of treatment. Using deformation-based morphometry to measure local volume changes, we identified widespread neocortical and cerebellar atrophy in untreated patients compared to controls (59 males; Cohen's D = 0.6; FDR < 0.05). Analysis of longitudinally scanned magnetic resonance imaging (MRI) scans both before and after treatment showed increased brain volume following treatment (FDR < 0.05). Volume increase was correlated with longer treatment in the cortical areas that largely overlapped with the initial atrophy. The areas overlying the hippocampal dentate gyrus and the cerebellar dentate nucleus displayed a volume increase after treatment. Patients with very severe OSA (AHI > 64) presented with prefrontal atrophy and displayed an additional volume increase in this area following treatment. Higher impairment of working memory in patients prior to treatment correlated with prefrontal volume increase after treatment. The large overlap between the initial brain damage and the extent of recovery after treatment suggests partial recovery of nonpermanent structural damage. Volume increases in the dentate gyrus and the dentate nucleus possibly likely indicate compensatory neurogenesis in response to diminishing oxidative stress. Such changes in other brain structures may explain gliosis, dendritic volume increase, or inflammation. This study provides neuroimaging evidence that revealed the positive effects of long-term CPAP treatment in patients with OSA.

  9. Lateralized cognitive deficits in children following cerebellar lesions.

    PubMed

    Scott, R B; Stoodley, C J; Anslow, P; Paul, C; Stein, J F; Sugden, E M; Mitchell, C D

    2001-10-01

    The aim of this preliminary study was to examine the developing cognitive profiles of children with cerebellar tumours in a consecutive series of clinical patients. MRI and longitudinal intellectual profiles were obtained on seven children (two females, five males; mean age 3 years at diagnosis; mean age 7 years at first assessment). Tumours in three of the children were astrocytomas; of the remaining tumours, two were medulloblastomas, one low-grade glioma, and one ependymoma. In right-handed children, we observed an association between greater damage to right cerebellar structures and a plateauing in verbal and/or literacy skills. In contrast, greater damage to left cerebellar structures was associated with delayed or impaired non-verbal/spatial skills. Long-term cognitive development of the children studied tentatively supports a role for the cerebellum in learning/development. These findings suggest that lateralized cerebellar damage may selectively impair the development of cognitive functions subserved by the contralateral cerebral hemisphere and, in addition, that all children with cerebellar lesions in early childhood should routinely undergo long-term monitoring of their intellectual development. PMID:11665825

  10. The Womanly World of Long Term Care: The Plight of the Long Term Care Worker. Gray Paper.

    ERIC Educational Resources Information Center

    Older Women's League, Washington, DC.

    Long-term care workers (those who are paid to provide custodial care for long-term patients in nursing homes or at home) must care for a growing number of increasingly disabled or dependent persons. They are working for agencies and institutions under growing pressure to increase productivity. They face new training and competency requirements,…

  11. Dopamine favours the emergence of long-term depression versus long-term potentiation in slices of rat prefrontal cortex.

    PubMed

    Law-Tho, D; Desce, J M; Crepel, F

    1995-03-24

    In the present study, we have investigated possible interactions between dopamine and long-term changes in synaptic efficacy induced in layer V pyramidal cells by tetanization of afferents from layer I-II. In the absence of dopamine, we confirmed that high frequency stimulation of excitatory afferents induced long-term potentiation, long-term depression or no change. Inversely, in the presence of dopamine, we have found that the same tetanus led to long-term depression in synaptic transmission in a majority of cells, but no more long-term potentiation. These results suggest that in rat prefrontal cortex, dopamine may determine the direction of activity dependent changes in synaptic efficacy and therefore, plays a functional role in the physiology of this structure.

  12. Role of healthcare in Korean long-term care insurance.

    PubMed

    Kang, Im-Oak; Park, Chong Yon; Lee, Yunhwan

    2012-05-01

    With the rapid aging of the population, Korea introduced public long-term care insurance for older people in 2008. The long-term care insurance was designed as a separate scheme from the national health insurance, with eligibility qualifications and the certification process based on functional disability, benefits and coverage of community-based and institutional care, and a financing structure through multi-party contributions. Delivering appropriate health services to long-term care beneficiaries who manifest a high prevalence of comorbid chronic conditions with rising healthcare costs, however, presents a particular challenge. The lack of coordination between the health and long-term care sectors, limited consideration of physicians' assessments in the certification process, inadequate provision of health services in long-term care facilities, and overlapping and inefficient use of care resources act as barriers to providing comprehensive healthcare for older beneficiaries. Through active participation in the long-term care system, health professionals can help older patients navigate through the complex long-term care terrain to obtain quality healthcare.

  13. Long-Term Stewardship Baseline Report and Transition Guidance

    SciTech Connect

    Kristofferson, Keith

    2001-11-01

    Long-term stewardship consists of those actions necessary to maintain and demonstrate continued protection of human health and the environment after facility cleanup is complete. As the Department of Energy’s (DOE) lead laboratory for environmental management programs, the Idaho National Engineering and Environmental Laboratory (INEEL) administers DOE’s long-term stewardship science and technology efforts. The INEEL provides DOE with technical, and scientific expertise needed to oversee its long-term environmental management obligations complexwide. Long-term stewardship is administered and overseen by the Environmental Management Office of Science and Technology. The INEEL Long-Term Stewardship Program is currently developing the management structures and plans to complete INEEL-specific, long-term stewardship obligations. This guidance document (1) assists in ensuring that the program leads transition planning for the INEEL with respect to facility and site areas and (2) describes the classes and types of criteria and data required to initiate transition for areas and sites where the facility mission has ended and cleanup is complete. Additionally, this document summarizes current information on INEEL facilities, structures, and release sites likely to enter long-term stewardship at the completion of DOE’s cleanup mission. This document is not intended to function as a discrete checklist or local procedure to determine readiness to transition. It is an overarching document meant as guidance in implementing specific transition procedures. Several documents formed the foundation upon which this guidance was developed. Principal among these documents was the Long-Term Stewardship Draft Technical Baseline; A Report to Congress on Long-Term Stewardship, Volumes I and II; Infrastructure Long-Range Plan; Comprehensive Facility Land Use Plan; INEEL End-State Plan; and INEEL Institutional Plan.

  14. Consensus Paper: Radiological Biomarkers of Cerebellar Diseases

    PubMed Central

    Baldarçara, Leonardo; Currie, Stuart; Hadjivassiliou, M.; Hoggard, Nigel; Jack, Allison; Jackowski, Andrea P.; Mascalchi, Mario; Parazzini, Cecilia; Reetz, Kathrin; Righini, Andrea; Schulz, Jörg B.; Vella, Alessandra; Webb, Sara Jane; Habas, Christophe

    2016-01-01

    Hereditary and sporadic cerebellar ataxias represent a vast and still growing group of diseases whose diagnosis and differentiation cannot only rely on clinical evaluation. Brain imaging including magnetic resonance (MR) and nuclear medicine techniques allows for characterization of structural and functional abnormalities underlying symptomatic ataxias. These methods thus constitute a potential source of radiological biomarkers, which could be used to identify these diseases and differentiate subgroups of them, and to assess their severity and their evolution. Such biomarkers mainly comprise qualitative and quantitative data obtained from MR including proton spectroscopy, diffusion imaging, tractography, voxel-based morphometry, functional imaging during task execution or in a resting state, and from SPETC and PET with several radiotracers. In the current article, we aim to illustrate briefly some applications of these neuroimaging tools to evaluation of cerebellar disorders such as inherited cerebellar ataxia, fetal developmental malformations, and immune-mediated cerebellar diseases and of neurodegenerative or early-developing diseases, such as dementia and autism in which cerebellar involvement is an emerging feature. Although these radiological biomarkers appear promising and helpful to better understand ataxia-related anatomical and physiological impairments, to date, very few of them have turned out to be specific for a given ataxia with atrophy of the cerebellar system being the main and the most usual alteration being observed. Consequently, much remains to be done to establish sensitivity, specificity, and reproducibility of available MR and nuclear medicine features as diagnostic, progression and surrogate biomarkers in clinical routine. PMID:25382714

  15. Space ventures and society long-term perspectives

    NASA Technical Reports Server (NTRS)

    Brown, W. M.

    1985-01-01

    A futuristic evaluation of mankind's potential long term future in space is presented. Progress in space will not be inhibited by shortages of the Earth's physical resources, since long term economic growth will be focused on ways to constrain industrial productivity by changing social values, management styles, or government competence. Future technological progress is likely to accelerate with an emphasis on international cooperation, making possible such large joint projects as lunar colonies or space stations on Mars. The long term future in space looks exceedingly bright even in relatively pessimistic scenarios. The principal driving forces will be technological progress, commercial and public-oriented satellites, space industrialization, space travel, and eventually space colonization.

  16. Earth's Long-Term Warming Trend, 1880-2015

    NASA Video Gallery

    This visualization illustrates Earth’s long-term warming trend, showing temperature changes from 1880 to 2015 as a rolling five-year average. Orange colors represent temperatures that are warmer th...

  17. Malaria prophylaxis in long-term expatriate mineworkers in Ghana.

    PubMed

    Fegan, D; Glennon, J

    1993-08-01

    The role of malaria chemoprophylaxis for long-term expatriates has not been re-evaluated since the emergence of widespread multidrug resistance. A survey of 106 expatriates working in a mine in Ghana (holoendemic for malaria) was conducted to determine the compliance with malaria chemoprophylaxis. Overall 64 per cent took regular chemoprophylaxis. Of the long-term expatriates (5 or more years in areas with holoendemic malaria), 48.4 per cent either took malaria prophylaxis very irregularly or not at all. The main reasons for failing to comply were fear of long-term side effects and conflicting advice on prophylaxis. This reluctance to take long-term chemoprophylaxis highlights the need to re-emphasise the importance of anti-mosquito measures, prompt treatment of fevers, and perhaps consider abandoning chemoprophylaxis in those expatriate workers with ready access to hospital care.

  18. Biogeochemistry: Long-term effects of permafrost thaw

    NASA Astrophysics Data System (ADS)

    Zona, Donatella

    2016-09-01

    Carbon emissions from the Arctic tundra could increase drastically as global warming thaws permafrost. Clues now obtained about the long-term effects of such thawing on carbon dioxide emissions highlight the need for more data.

  19. Long-term Outcomes of Childhood Onset Nephrotic Syndrome

    PubMed Central

    Hjorten, Rebecca; Anwar, Zohra; Reidy, Kimberly Jean

    2016-01-01

    There are limited studies on long-term outcomes of childhood onset nephrotic syndrome (NS). A majority of children with NS have steroid-sensitive nephrotic syndrome (SSNS). Steroid-resistant nephrotic syndrome (SRNS) is associated with a high risk of developing end-stage renal disease. Biomarkers and analysis of genetic mutations may provide new information for prognosis in SRNS. Frequently relapsing and steroid-dependent NS is associated with long-term complications, including dyslipidemia, cataracts, osteoporosis and fractures, obesity, impaired growth, and infertility. Long-term complications of SSNS are likely to be under-recognized. There remain many gaps in our knowledge of long-term outcomes of childhood NS, and further study is indicated. PMID:27252935

  20. Long-Term Quiescent Fibroblast Cells Transit into Senescence

    PubMed Central

    Marthandan, Shiva; Priebe, Steffen; Hemmerich, Peter; Klement, Karolin; Diekmann, Stephan

    2014-01-01

    Cellular senescence is described to be a consequence of telomere erosion during the replicative life span of primary human cells. Quiescence should therefore not contribute to cellular aging but rather extend lifespan. Here we tested this hypothesis and demonstrate that cultured long-term quiescent human fibroblasts transit into senescence due to similar cellular mechanisms with similar dynamics and with a similar maximum life span as proliferating controls, even under physiological oxygen conditions. Both, long-term quiescent and senescent fibroblasts almost completely fail to undergo apoptosis. The transition of long-term quiescent fibroblasts into senescence is also independent of HES1 which protects short-term quiescent cells from becoming senescent. Most significantly, DNA damage accumulates during senescence as well as during long-term quiescence at physiological oxygen levels. We suggest that telomere-independent, potentially maintenance driven gradual induction of cellular senescence during quiescence is a counterbalance to tumor development. PMID:25531649

  1. Long-term memories in online users' selecting activities

    NASA Astrophysics Data System (ADS)

    Pan, Xue; Hou, Lei; Stephen, Mutua; Yang, Huijie

    2014-07-01

    In this paper, we investigate the long-term memory effect in the behavior of online users. Two user-oriented online movie systems are used in this study. Due to the short length of the series, the balanced estimation of diffusion entropy approach is used to evaluate scaling-invariance in selecting activities of users in the two online movie systems. Our results indicate that persistence (long-term memory) exists widely in the movie selecting series. However, there is generally significant difference between a user's objective and subjective behaviors. Additionally, statistically, the long-term memory depends on activity levels, as results show that the much more active a users' group, the stronger the long-term memory will be. These findings provide a new criterion for constructing reasonable models, and can help understand how individuals' behaviors form a collective behavior of an online society.

  2. Long-Term Ecological Monitoring Field Sampling Plan for 2007

    SciTech Connect

    T. Haney R. VanHorn

    2007-07-31

    This field sampling plan describes the field investigations planned for the Long-Term Ecological Monitoring Project at the Idaho National Laboratory Site in 2007. This plan and the Quality Assurance Project Plan for Waste Area Groups 1, 2, 3, 4, 5, 6, 7, 10, and Removal Actions constitute the sampling and analysis plan supporting long-term ecological monitoring sampling in 2007. The data collected under this plan will become part of the long-term ecological monitoring data set that is being collected annually. The data will be used t determine the requirements for the subsequent long-term ecological monitoring. This plan guides the 2007 investigations, including sampling, quality assurance, quality control, analytical procedures, and data management. As such, this plan will help to ensure that the resulting monitoring data will be scientifically valid, defensible, and of known and acceptable quality.

  3. Long-term monitoring for nanomedicine implants and drugs

    NASA Astrophysics Data System (ADS)

    Kendall, Michaela; Lynch, Iseult

    2016-03-01

    Increasing globalization means that traditional occupational epidemiological approaches may no longer apply, suggesting a need for an alternative model to assess the long-term impact of nanomaterial exposure on health.

  4. The market for long-term care services.

    PubMed

    Grabowski, David C

    2008-01-01

    Although a large literature has established the importance of market and regulatory forces within the long-term care sector, current research in this field is limited by a series of data, measurement, and methodological issues. This paper provides a comprehensive review of these issues with an emphasis on identifying initiatives that will increase the volume and quality of long-term care research. Recommendations include: the construction of standard measures of long-term care market boundaries, the broader dissemination of market and regulatory data, the linkage of survey-based data with market measures, the encouragement of further market-based studies of noninstitutional long-term care settings, and the standardization of Medicaid cost data. PMID:18524292

  5. Examining Long-Term Global Climate Change on the Web.

    ERIC Educational Resources Information Center

    Huntoon, Jacqueline E.; Ridky, Robert K.

    2002-01-01

    Describes a web-based, inquiry-oriented activity that enables students to examine long-term global climate change. Supports instruction in other topics such as population growth. (Contains 34 references.) (DDR)

  6. The Long Term Agroecosystem Research Network - Shared research strategy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Agriculture faces tremendous challenges in meeting multiple societal goals, including a safe and plentiful food supply; climate change adaptation and mitigation; supplying sources of bioenergy; improving water, air, and soil quality; and maintaining biodiversity. The Long Term Agroecosystem Research...

  7. Long-term Career Goals for Professional Women in Agriculture.

    ERIC Educational Resources Information Center

    Klepper, Betty

    1986-01-01

    Encourages the formation of long-term career goals for women in agronomy. Offers perspectives and practical suggestions for obtaining positions, maintaining professional credentials, and managing personal and career related obligations. (ML)

  8. Endoscopic Management of Attic Cholesteatoma: Long-Term Results.

    PubMed

    Alicandri-Ciufelli, Matteo; Marchioni, Daniele; Kakehata, Seiji; Presutti, Livio; Villari, Domenico

    2016-10-01

    The main application of endoscopic surgery relies on the middle ear cholesteatoma surgical treatment, although for a definitive validation and acceptance by scientific community, long-term results are needed about recurrent and residual rates of the pathology. The aim of the present paper was to analyze the single institution experience with the long-term results of surgical treatment of attic cholesteatoma. PMID:27565391

  9. Long-term effects of sludge application to land

    SciTech Connect

    Geertsema, W.S. ); Knocke, W.R.; Novak, J.T.; Dove, D. . Dept. of Civil Engineering)

    1994-11-01

    The purpose of this study was to evaluate the long-term environmental effects of applying alum sludge to land. Investigations at the original field site included soil analysis, soil water monitoring, groundwater monitoring, and analysis of tissues from pine needles. No long-term (30 months) effects were observed, and the authors conclude that alum coagulant sludges can be applied to forest lands at loading rates of at least 1.5 to 2.5% by dry weight without adverse effect.

  10. Influenza in long-term care facilities: preventable, detectable, treatable.

    PubMed

    Mossad, Sherif B

    2009-09-01

    Influenza in long-term care facilities is an ever more challenging problem. Vaccination of residents and health care workers is the most important preventive measure. Although vaccine efficacy has been questioned, the preponderance of data favors vaccination. Antiviral resistance complicates postexposure chemoprophylaxis and treatment. Factors that limit the choice of antiviral agents in this patient population include limited vaccine supplies and impaired dexterity and confusion in long-term care residents. PMID:19726556

  11. Maintaining Engagement in Long-term Interventions with Relational Agents

    PubMed Central

    Bickmore, Timothy; Schulman, Daniel; Yin, Langxuan

    2011-01-01

    We discuss issues in designing virtual humans for applications which require long-term voluntary use, and the problem of maintaining engagement with users over time. Concepts and theories related to engagement from a variety of disciplines are reviewed. We describe a platform for conducting studies into long-term interactions between humans and virtual agents, and present the results of two longitudinal randomized controlled experiments in which the effect of manipulations of agent behavior on user engagement was assessed. PMID:21318052

  12. Cerebellar circuitry as a neuronal machine.

    PubMed

    Ito, Masao

    2006-01-01

    Shortly after John Eccles completed his studies of synaptic inhibition in the spinal cord, for which he was awarded the 1963 Nobel Prize in physiology/medicine, he opened another chapter of neuroscience with his work on the cerebellum. From 1963 to 1967, Eccles and his colleagues in Canberra successfully dissected the complex neuronal circuitry in the cerebellar cortex. In the 1967 monograph, "The Cerebellum as a Neuronal Machine", he, in collaboration with Masao Ito and Janos Szentágothai, presented blue-print-like wiring diagrams of the cerebellar neuronal circuitry. These stimulated worldwide discussions and experimentation on the potential operational mechanisms of the circuitry and spurred theoreticians to develop relevant network models of the machinelike function of the cerebellum. In following decades, the neuronal machine concept of the cerebellum was strengthened by additional knowledge of the modular organization of its structure and memory mechanism, the latter in the form of synaptic plasticity, in particular, long-term depression. Moreover, several types of motor control were established as model systems representing learning mechanisms of the cerebellum. More recently, both the quantitative preciseness of cerebellar analyses and overall knowledge about the cerebellum have advanced considerably at the cellular and molecular levels of analysis. Cerebellar circuitry now includes Lugaro cells and unipolar brush cells as additional unique elements. Other new revelations include the operation of the complex glomerulus structure, intricate signal transduction for synaptic plasticity, silent synapses, irregularity of spike discharges, temporal fidelity of synaptic activation, rhythm generators, a Golgi cell clock circuit, and sensory or motor representation by mossy fibers and climbing fibers. Furthermore, it has become evident that the cerebellum has cognitive functions, and probably also emotion, as well as better-known motor and autonomic functions

  13. Commentary: The Broader Context of Long-Term Care Ethics.

    PubMed

    Lesandrini, Jason; O'Connell, Carol

    2016-07-01

    Ethical issues in long-term care settings, although having received attention in the literature, have not in our opinion received the appropriate level they require. Thus, we applaud the Cambridge Quarterly for publishing this case. We can attest to the significance of ethical issues arising in long-term care facilities, as Mr. Hope's case is all too familiar to those practicing in these settings. What is unique about this case is that an actual ethics consult was made in a long-term care setting. We have seen very little in the published literature on the use of ethics structures in long-term care populations. Our experience is that these healthcare settings are ripe for ethical concerns and that providers, patients, families, and staff need/desire ethics resources to actively and preventively address ethical concerns. The popular press has begun to recognize the ethical issues involved in long-term care settings and the need for ethics structures. Recently, in California a nurse refused to initiate CPR for an elderly patient in a senior residence. In that case, the nurse was quoted as saying that the facility had a policy that nurses were not to start CPR for elderly patients. 1 Although this case is not exactly the same as that of Mr. Hope, it highlights the need for developing robust ethics program infrastructures in long-term care settings that work toward addressing ethical issues through policy, education, and active consultation.

  14. Private Financing Options for Long-term Care

    PubMed Central

    Brody, Barbara L.; Simon, Harold J.; Smallwood, Dennis E.

    1987-01-01

    Private financing for long-term care now comes almost exclusively from out-of-pocket payments. Long-term-care costs quickly impoverish most elderly, resulting in Medicaid dependency. The consequences are profound for the western Sun Belt with its rapidly growing elderly population. Key private financing options are long-term-care individual retirement accounts (LTC/IRAs), home equity conversion, social-health maintenance organizations and long-term-care insurance. Study of data from the past half century suggests that the LTC/IRA approach would prove unsatisfactory for the purpose despite the intuitive appeal of this mechanism. Experience with home equity conversions is still very limited, and unresolved questions limit this approach to the role of a reserve option for now. While promising, social-health maintenance organizations are still in the experimental stages and not yet commercially available. Long-term-care insurance is currently sold on a thin market and emphasizes nursing home coverage. New approaches to private financing through long-term-care insurance seem to offer the best approach for immediate implementation. PMID:3118576

  15. Mitochondrial myopathy caused by long-term zidovudine therapy.

    PubMed

    Dalakas, M C; Illa, I; Pezeshkpour, G H; Laukaitis, J P; Cohen, B; Griffin, J L

    1990-04-19

    Both infection with the human immunodeficiency virus type 1 (HIV) and zidovudine (formerly called azidothymidine [AZT]) cause myopathy. To identify criteria for distinguishing zidovudine-induced myopathy from that caused by primary HIV infection, we reviewed the histochemical, immunocytochemical, and electron-microscopical features of muscle-biopsy specimens from 20 HIV-positive patients with myopathy (15 of whom had been treated with zidovudine) and compared the findings with the patients' clinical course and response to various therapies. Among the zidovudine-treated patients, the myopathy responded to prednisone in four, to the discontinuation of zidovudine in eight, and to nonsteroidal anti-inflammatory drugs in two. Numerous "ragged-red" fibers, indicative of abnormal mitochondria with paracrystalline inclusions, were found in the biopsy specimens from the zidovudine-treated patients but not in those from the other patients. The number of these fibers appeared to correlate with the severity of the myopathy. All the patients, regardless of whether they had been treated with zidovudine, had inflammatory myopathy characterized by degenerating fibers, cytoplasmic bodies, and endomysial infiltrates consisting of CD8+ cells (mean +/- SD, 60.7 +/- 6.4 percent) and macrophages (39.2 +/- 6.4 percent) associated with Class I major histocompatibility complex (MHC-I) antigens (HLA-A, -B, and -C antigens) in the muscle fibers. The numbers and percentages of CD8+ cells and macrophages were similar in both the zidovudine-treated and the untreated HIV-positive patients. Specimens obtained on repeat muscle biopsy from two patients in whom the myopathy responded to the discontinuation of zidovudine showed remarkable histologic improvement. We conclude that long-term therapy with zidovudine can cause a toxic mitochondrial myopathy, which coexists with a T-cell-mediated inflammatory myopathy that is restricted to MHC-I antigen, and is indistinguishable from the myopathy

  16. Long-term care insurance in Japan: implications for U.S. long-term care policy.

    PubMed

    Houde, Susan Crocker; Gautam, Ramraj; Kai, Ichiro

    2007-01-01

    The purpose of this article is to review the long-term care insurance program in Japan and the present system of payment of long-term care services in the United States. The long-term care insurance system in Japan was implemented in 2001 for the purpose of promoting independence in older adults with functional disability. It reimburses for both home and institutional care. Several concerns expressed about the Japanese system include increasing applications for nursing home placement, lower use of home care services than anticipated, limited coverage for disabilities for those under 65, regional variations in service, educational preparation for case managers, and access to care for older adults. Revisions to the Japanese system and implications for U.S. long-term care policy are discussed.

  17. Short-Term and Long-Term Effects of Orthopedic Biodegradable Implants

    PubMed Central

    Amini, Ami R.; Wallace, James S.; Nukavarapu, Syam P.

    2012-01-01

    Presently, orthopedic and oral/maxillofacial implants represent a combined $2.8 billion market, a figure expected to experience significant and continued growth. Although traditional permanent implants have been proved clinically efficacious, they are also associated with several drawbacks, including secondary revision and removal surgeries. Non-permanent, biodegradable implants offer a promising alternative for patients, as they provide temporary support and degrade at a rate matching tissue formation, and thus, eliminate the need for secondary surgeries. These implants have been in clinical use for nearly 25 years, competing directly with, or maybe even exceeding, the performance of permanent implants. The initial implantation of biodegradable materials, as with permanent materials, mounts an acute host inflammatory response. Over time, the implant degradation profile and possible degradation product toxicity mediate long-term biodegradable implant-induced inflammation. However, unlike permanent implants, this inflammation is likely to cease once the material disappears. Implant-mediated inflammation is a critical determinant for implant success. Thus, for the development of a proactive biodegradable implant that has the ability to promote optimal bone regeneration and minimal detrimental inflammation, a thorough understanding of short- and long-term inflammatory events is required. Here, we discuss an array of biodegradable orthopedic implants, their associated short- and long- term inflammatory effects, and methods to mediate these inflammatory events. PMID:22043969

  18. Long-term enhancement (LTE) of postsynaptic potentials following neural conditioning, in mammalian sympathetic ganglia.

    PubMed

    Libet, B; Mochida, S

    1988-11-15

    Orthodromic, preganglionic conditioning stimulation can consistently induce long-term enhancement (LTE) (greater than 3 h) of the muscarinically mediated slow excitatory postsynaptic potential and the slow inhibitory postsynaptic potential. This was shown for superior cervical ganglia of rabbit and rat. Effective conditioning stimuli are in a physiologically observed range (3/s for 7 min, 5/s for 4 min, 10/s for 2 min, 20/s for 1 min). LTE was producible both homosynaptically and heterosynaptically. LTE can thus be associative, with conditioning synaptic input in one line inducing long-term changes in postsynaptic responses to another (heterosynaptic) input. The dopamine antagonist butaclamol depressed LTE, particularly that following the initial postconditioning period of 30 min. Adrenergic antagonists had no effect. This pharmacological evidence, coupled with the heterosynaptic induction of LTE, supports the view that neurally induced LTE may be at least partly mediated by endogenous dopamine. Another non-cholinergic but non-adrenergic transmitter (possibly a peptide) might contribute to the LTE seen in the initial 30 min postconditioning. The present, orthodromically induced LTE is clearly different from the long-term potentiation widely studied in hippocampus, etc., in the modes of induction and synaptic mediation.

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

    PubMed

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

    2013-10-01

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

  20. The interaction of short-term and long-term memory in phonetic category formation

    NASA Astrophysics Data System (ADS)

    Harnsberger, James D.

    2002-05-01

    This study examined the role that short-term memory capacity plays in the relationship between novel stimuli (e.g., non-native speech sounds, native nonsense words) and phonetic categories in long-term memory. Thirty native speakers of American English were administered five tests: categorial AXB discrimination using nasal consonants from Malayalam; categorial identification, also using Malayalam nasals, which measured the influence of phonetic categories in long-term memory; digit span; nonword span, a short-term memory measure mediated by phonetic categories in long-term memory; and paired-associate word learning (word-word and word-nonword pairs). The results showed that almost all measures were significantly correlated with one another. The strongest predictor for the discrimination and word-nonword learning results was nonword (r=+0.62) and digit span (r=+0.51), respectively. When the identification test results were partialed out, only nonword span significantly correlated with discrimination. The results show a strong influence of short-term memory capacity on the encoding of phonetic detail within phonetic categories and suggest that long-term memory representations regulate the capacity of short-term memory to preserve information for subsequent encoding. The results of this study will also be discussed with regards to resolving the tension between episodic and abstract models of phonetic category structure.

  1. Creature comforts: personal communities, pets and the work of managing a long-term condition

    PubMed Central

    Brooks, Helen L; Rogers, Anne; Kapadia, Dharmi; Pilgrim, Jack; Reeves, David; Vassilev, Ivaylo

    2013-01-01

    Objectives: To explore in the context of peoples’ personal social networks, the contribution that pets make to ‘the work’ associated with the management of long-term conditions. Method: Mixed methods survey with nested parallel qualitative study; 300 participants were drawn from diabetes and chronic heart disease registers of General Practices across Greater Manchester in the North West of England. Notions of ‘work’ were used to describe the illness and everyday activities associated with chronic illness. Results: Nineteen percent of participants identified at least one pet within their network. Pets contributed mostly to managing emotions (emotional work), to enhancing a sense of self identity (biographical work) and to a lesser extent practical tasks (everyday work). There were indicators that pets mediated relationships for people living with a long-term condition through very weak ties with others in domestic and community settings. Conclusion: The findings suggest that pets have unique qualities and are not simply substitutes for human relationships in long-term condition management. The study has potential implications for furthering a social contextual analysis of chronic illness, the understanding of relationships, and the meaning and the role of companion animals in long-term condition management. PMID:22777565

  2. Histidine provides long-term neuroprotection after cerebral ischemia through promoting astrocyte migration

    PubMed Central

    Liao, Ru-jia; Jiang, Lei; Wang, Rong-rong; Zhao, Hua-wei; Chen, Ying; Li, Ya; Wang, Lu; Jie, Li-Yong; Zhou, Yu-dong; Zhang, Xiang-nan; Chen, Zhong; Hu, Wei-wei

    2015-01-01

    The formation of glial scar impedes the neurogenesis and neural functional recovery following cerebral ischemia. Histamine showed neuroprotection at early stage after cerebral ischemia, however, its long-term effect, especially on glial scar formation, hasn’t been characterized. With various administration regimens constructed for histidine, a precursor of histamine, we found that histidine treatment at a high dose at early stage and a low dose at late stage demonstrated the most remarkable long-term neuroprotection with decreased infarct volume and improved neurological function. Notably, this treatment regimen also robustly reduced the glial scar area and facilitated the astrocyte migration towards the infarct core. In wound-healing assay and transwell test, histamine significantly promoted astrocyte migration. H2 receptor antagonists reversed the promotion of astrocyte migration and the neuroprotection provided by histidine. Moreover, histamine upregulated the GTP-bound small GTPase Rac1, while a Rac1 inhibitor, NSC23766, abrogated the neuroprotection of histidine and its promotion of astrocyte migration. Our data indicated that a dose/stage-dependent histidine treatment, mediated by H2 receptor, promoted astrocyte migration towards the infarct core, which benefited long-term post-cerebral ischemia neurological recovery. Therefore, targeting histaminergic system may be an effective therapeutic strategy for long-term cerebral ischemia injury through its actions on astrocytes. PMID:26481857

  3. Long-term effects of manipulated natal brood size on metabolic rate in zebra finches.

    PubMed

    Verhulst, Simon; Holveck, Marie-Jeanne; Riebel, Katharina

    2006-09-22

    Long-term effects of developmental conditions on health, longevity and other fitness components in humans are drawing increasing attention. In evolutionary ecology, such effects are of similar importance because of their role in the trade-off between quantity and quality of offspring. The central role of energy consumption is well documented for some long-term health effects in humans (e.g. obesity), but little is known of the long-term effects of rearing conditions on energy requirements later in life. We manipulated the rearing conditions in zebra finches (Taeniopygia guttata) using brood size manipulation and cross-fostering. It has previously been shown in this species that being reared in a large brood has negative fitness consequences, and that such effects are stronger in daughters than in sons. We show that, independent of mass, standard metabolic rate of 1-year-old birds was higher when they had been reared in a large brood, and this is to our knowledge the first demonstration of such an effect. Furthermore, the brood size effect was stronger in daughters than in sons. This suggests that metabolic efficiency may play a role in mediating the long-term fitness consequences of rearing conditions. PMID:17148435

  4. Long-term effects of manipulated natal brood size on metabolic rate in zebra finches

    PubMed Central

    Verhulst, Simon; Holveck, Marie-Jeanne; Riebel, Katharina

    2006-01-01

    Long-term effects of developmental conditions on health, longevity and other fitness components in humans are drawing increasing attention. In evolutionary ecology, such effects are of similar importance because of their role in the trade-off between quantity and quality of offspring. The central role of energy consumption is well documented for some long-term health effects in humans (e.g. obesity), but little is known of the long-term effects of rearing conditions on energy requirements later in life. We manipulated the rearing conditions in zebra finches (Taeniopygia guttata) using brood size manipulation and cross-fostering. It has previously been shown in this species that being reared in a large brood has negative fitness consequences, and that such effects are stronger in daughters than in sons. We show that, independent of mass, standard metabolic rate of 1-year-old birds was higher when they had been reared in a large brood, and this is to our knowledge the first demonstration of such an effect. Furthermore, the brood size effect was stronger in daughters than in sons. This suggests that metabolic efficiency may play a role in mediating the long-term fitness consequences of rearing conditions. PMID:17148435

  5. Rural long-term care work, gender, and restructuring.

    PubMed

    Leach, Belinda; Joseph, Gillian

    2011-06-01

    Restructuring--the introduction of changes that alter the way health care is delivered for maximum efficiency and least cost--layered with rurality and with rural gender ideologies and practices, results in rural long-term care settings that have particular consequences for the women working in them, and for the residents and communities that they serve. This research investigated how rurality affects the implementation of patient classification in Ontario long-term care homes. Methods involved interviews and focus groups with front-line long-term care workers, administrators, and key participants. The findings revealed that rural long-term care delivery takes place when a restructured work environment intersects with gender ideologies and practices that take on particular characteristics when developed and sustained in a rural context. These factors shape the labor market and working conditions for rural women. We argue that this produces a uniquely rural experience for long-term care workers and conclude that those implementing classification systems must consider contextual factors as well as practical and financial exigencies. PMID:24650670

  6. Wnt signaling is required for long-term memory formation

    PubMed Central

    Tan, Ying; Yu, Dinghui; Busto, Germain U.; Wilson, Curtis; Davis, Ronald L.

    2013-01-01

    SUMMARY Wnt signaling regulates synaptic plasticity and neurogenesis in the adult nervous system, suggesting a potential role in behavioral processes. Here, we probed the requirement for Wnt signaling during olfactory memory formation in Drosophila using an inducible RNA interference approach. Interfering with β-catenin expression in the adult mushroom body neurons specifically impaired long-term memory without altering short-term memory. The impairment was reversible, rescued with expression of a wild-type β-catenin transgene, and correlated with a disruption of a cellular long-term memory trace. Inhibition of wingless, a Wnt ligand, and arrow, a Wnt co-receptor, also impaired long-term memory. Wingless expression in wild type flies was transiently elevated in the brain after long-term memory conditioning. Thus, inhibiting three key components of the Wnt signaling pathway in the adult mushroom bodies impairs long-term memory, collectively indicating that this pathway mechanistically underlies this specific form of memory. PMID:24035392

  7. The relationship between interannual and long-term cloud feedbacks

    DOE PAGES

    Zhou, Chen; Zelinka, Mark D.; Dessler, Andrew E.; Klein, Stephen A.

    2015-12-11

    The analyses of Coupled Model Intercomparison Project phase 5 simulations suggest that climate models with more positive cloud feedback in response to interannual climate fluctuations also have more positive cloud feedback in response to long-term global warming. Ensemble mean vertical profiles of cloud change in response to interannual and long-term surface warming are similar, and the ensemble mean cloud feedback is positive on both timescales. However, the average long-term cloud feedback is smaller than the interannual cloud feedback, likely due to differences in surface warming pattern on the two timescales. Low cloud cover (LCC) change in response to interannual andmore » long-term global surface warming is found to be well correlated across models and explains over half of the covariance between interannual and long-term cloud feedback. In conclusion, the intermodel correlation of LCC across timescales likely results from model-specific sensitivities of LCC to sea surface warming.« less

  8. Epilepsy-related long-term amnesia: anatomical perspectives.

    PubMed

    Butler, Chris; Kapur, Narinder; Zeman, Adam; Weller, Roy; Connelly, Alan

    2012-11-01

    There are few clues as to the neural basis of selective long-term amnesia. We report group and single-case data to shed light on this issue. In a group study of patients with transient epileptic amnesia, there were no significant correlations between volumetric measures of the hippocampus and indices of accelerated long-term forgetting or longer-term autobiographical memory loss. Post-mortem investigations in a patient with temporal lobe epilepsy who showed accelerated long-term forgetting, together with a degree of autobiographical memory loss, yielded evidence of neuronal loss and gliosis in regions of both the right and the left hippocampus. Neuronal loss and gliosis were more evident in anterior than posterior hippocampus. These results indicate that the unusual forms of long-term forgetting seen in some patients with temporal lobe epilepsy have no gross anatomical correlate. The findings leave open the possibilities that subtle structural damage or subtle functional disturbance, perhaps in the form of subclinical epileptiform activity, underly epilepsy-related long-term amnesia.

  9. Characteristics of Long-Term Survivors of Epithelial Ovarian Cancer

    PubMed Central

    Cress, Rosemary D.; Chen, Yingjia S.; Morris, Cyllene R.; Petersen, Megan; Leiserowitz, Gary S.

    2015-01-01

    Objective To identify characteristics associated with long-term survival forepithelial ovarian cancer patients using the California Cancer Registry. Methods A descriptive analysis of survival of all California residents diagnosed with epithelial ovarian cancer between 1994 and 2001 was conducted using patients identified through the cancer registry with follow up through 2011. Characteristics of the patients who survived more than 10 years (long-term survivors) were compared to three other cohorts: patients who survived less than 2 years, those who survived at least 2 but no more than 5 years, and those who survived at least 5 but no more than 10 years. Results A total of 3,582 out of 11,541 (31% CI=30.2%, 31.8%) of the patients survived more than 10 years. Younger age, early stage, low-grade, and non-serous histology were significant predictors of long-term survival, but long-term survivors also included women with high-risk cancer. Conclusion Long-term survival is not unusual in patients with epithelial ovarian cancer, even in those with high-risk disease. Many of the prognostic factors are well known, but it remains to be determined why some patients with advanced stage high-grade cancers survive longer than others with the same histology. These findings are important for patient counseling. PMID:26244529

  10. Method for Water Management Considering Long-term Probabilistic Forecasts

    NASA Astrophysics Data System (ADS)

    Hwang, J.; Kang, J.; Suh, A. S.

    2015-12-01

    This research is aimed at predicting the monthly inflow of the Andong-dam basin in South Korea using long-term probabilistic forecasts to apply long-term forecasts to water management. Forecasted Cumulative Distribution Functions (CDFs) of monthly precipitation are plotted by combining the range of monthly precipitation based on proper Probability Density Function (PDF) in past data with probabilistic forecasts in each category. Ensembles of inflow are estimated by entering generated ensembles of precipitation based on the CDFs into the 'abcd' water budget model. The bias and RMSE between averages in past data and observed inflow are compared to them in forecasted ensembles. In our results, the bias and RMSE of average precipitation in the forecasted ensemble are bigger than in past data, whereas the average inflow in the forecasted ensemble is smaller than in past data. This result could be used for reference data to apply long-term forecasts to water management, because of the limit in the number of forecasted data for verification and differences between the Andong-dam basin and the forecasted regions. This research has significance by suggesting a method of applying probabilistic information in climate variables from long-term forecasts to water management in Korea. Original data of a climate model, which produces long-term probabilistic forecasts should be verified directly as input data of a water budget model in the future, so that a more scientific response in water management against uncertainty of climate change could be reached.

  11. Wastewater treatment by soil infiltration: Long-term phosphorus removal.

    PubMed

    Eveborn, David; Kong, Deguo; Gustafsson, Jon Petter

    2012-10-01

    Phosphorus (P) leaching from on-site wastewater treatment systems may contribute to eutrophication. In developed countries the most common on-site treatment technique is septic systems with soil infiltration. However, the current knowledge about long term P removal in soil treatment systems is not well developed and the data used for estimation of P losses from such systems are unreliable. In this study we sampled four filter beds from community-scale soil treatment systems with an age of between 14 and 22years to determine the long-term P removal and to investigate the chemical mechanisms behind the observed removal. For one site the long-term P removal was calculated using a mass balance approach. After analysis of the accumulated P, it was estimated that on average 12% of the long-term P load had been removed by the bed material. This indicates a low overall capacity of soil treatment systems to remove phosphorus. Batch experiments and chemical speciation modelling indicated that calcium phosphate precipitation was not an important long-term P removal mechanism, with the possible exception of one of the sites. More likely, the P removal was induced by AlPO(4) precipitation and/or sorption to poorly ordered aluminium compounds, as evidenced by strong relationships between oxalate-extractable Al and P. PMID:22982614

  12. Long-Term Prognosis of Ischemic Stroke in Young Adults

    PubMed Central

    Varona, Jose F.

    2011-01-01

    There is limited information about long-term prognosis of ischemic stroke in young adults. Giving the potentially negative impact in physical, social, and emotional aspects of an ischemic stroke in young people, providing early accurate long-term prognostic information is very important in this clinical setting. Moreover, detection of factors associated with bad outcomes (death, recurrence, moderate-to-severe disability) help physicians in optimizing secondary prevention strategies. The present paper reviews the most relevant published information concerning long-term prognosis and predictors of unfavorable outcomes of ischemic stroke affecting young adults. As a summary, we can conclude that, in the long term, stroke in the young adult increases slightly the risk of mortality, implies higher risk of future cardiovascular events, and determines functional limitations in a significant percentage of patients. Nevertheless, in every individual case the prognosis has to be considered depending on several factors (stroke subtype, initial severity, cardiovascular risk factors) that determine the long-term outcomes. PMID:21197408

  13. Long-Term Stewardship Program Science and Technology Requirements

    SciTech Connect

    Joan McDonald

    2002-09-01

    Many of the United States’ hazardous and radioactively contaminated waste sites will not be sufficiently remediated to allow unrestricted land use because funding and technology limitations preclude cleanup to pristine conditions. This means that after cleanup is completed, the Department of Energy will have long-term stewardship responsibilities to monitor and safeguard more than 100 sites that still contain residual contamination. Long-term stewardship encompasses all physical and institutional controls, institutions, information, and other mechanisms required to protect human health and the environment from the hazards remaining. The Department of Energy Long-Term Stewardship National Program is in the early stages of development, so considerable planning is still required to identify all the specific roles and responsibilities, policies, and activities needed over the next few years to support the program’s mission. The Idaho National Engineering and Environmental Laboratory was tasked with leading the development of Science and Technology within the Long-Term Stewardship National Program. As part of that role, a task was undertaken to identify the existing science and technology related requirements, identify gaps and conflicts that exist, and make recommendations to the Department of Energy for future requirements related to science and technology requirements for long-term stewardship. This work is summarized in this document.

  14. Common Calibration Source for Monitoring Long-term Ozone Trends

    NASA Technical Reports Server (NTRS)

    Kowalewski, Matthew

    2004-01-01

    Accurate long-term satellite measurements are crucial for monitoring the recovery of the ozone layer. The slow pace of the recovery and limited lifetimes of satellite monitoring instruments demands that datasets from multiple observation systems be combined to provide the long-term accuracy needed. A fundamental component of accurately monitoring long-term trends is the calibration of these various instruments. NASA s Radiometric Calibration and Development Facility at the Goddard Space Flight Center has provided resources to minimize calibration biases between multiple instruments through the use of a common calibration source and standardized procedures traceable to national standards. The Facility s 50 cm barium sulfate integrating sphere has been used as a common calibration source for both US and international satellite instruments, including the Total Ozone Mapping Spectrometer (TOMS), Solar Backscatter Ultraviolet 2 (SBUV/2) instruments, Shuttle SBUV (SSBUV), Ozone Mapping Instrument (OMI), Global Ozone Monitoring Experiment (GOME) (ESA), Scanning Imaging SpectroMeter for Atmospheric ChartographY (SCIAMACHY) (ESA), and others. We will discuss the advantages of using a common calibration source and its effects on long-term ozone data sets. In addition, sphere calibration results from various instruments will be presented to demonstrate the accuracy of the long-term characterization of the source itself.

  15. Wastewater treatment by soil infiltration: Long-term phosphorus removal

    NASA Astrophysics Data System (ADS)

    Eveborn, David; Kong, Deguo; Gustafsson, Jon Petter

    2012-10-01

    Phosphorus (P) leaching from on-site wastewater treatment systems may contribute to eutrophication. In developed countries the most common on-site treatment technique is septic systems with soil infiltration. However, the current knowledge about long term P removal in soil treatment systems is not well developed and the data used for estimation of P losses from such systems are unreliable. In this study we sampled four filter beds from community-scale soil treatment systems with an age of between 14 and 22 years to determine the long-term P removal and to investigate the chemical mechanisms behind the observed removal. For one site the long-term P removal was calculated using a mass balance approach. After analysis of the accumulated P, it was estimated that on average 12% of the long-term P load had been removed by the bed material. This indicates a low overall capacity of soil treatment systems to remove phosphorus. Batch experiments and chemical speciation modelling indicated that calcium phosphate precipitation was not an important long-term P removal mechanism, with the possible exception of one of the sites. More likely, the P removal was induced by AlPO4 precipitation and/or sorption to poorly ordered aluminium compounds, as evidenced by strong relationships between oxalate-extractable Al and P.

  16. Effects of maternal cigarette smoking during pregnancy on long-term physical and cognitive parameters of child development.

    PubMed

    Lassen, K; Oei, T P

    1998-01-01

    The negative impact of maternal cigarette smoking during pregnancy on the growth and development of the foetus has been well documented. However, the long-term effects of the subsequent cognitive and physical development of the child are less clearly understood. This article presents a critical review of the literature on this topic. The review shows that the effects of prenatal exposure to smoking on children's physical development are mediated by a dose-response relationship. Although the observed effects are long term, they are small and may have no major functional importance. The evidence on the long-term consequences of intellectual function is still unclear. One reason is that very few studies have looked at the long-term consequences of maternal smoking on both physical and cognitive development. More effort is needed to investigate this important issue.

  17. Consensus Paper: Revisiting the Symptoms and Signs of Cerebellar Syndrome.

    PubMed

    Bodranghien, Florian; Bastian, Amy; Casali, Carlo; Hallett, Mark; Louis, Elan D; Manto, Mario; Mariën, Peter; Nowak, Dennis A; Schmahmann, Jeremy D; Serrao, Mariano; Steiner, Katharina Marie; Strupp, Michael; Tilikete, Caroline; Timmann, Dagmar; van Dun, Kim

    2016-06-01

    The cerebellum is involved in sensorimotor operations, cognitive tasks and affective processes. Here, we revisit the concept of the cerebellar syndrome in the light of recent advances in our understanding of cerebellar operations. The key symptoms and signs of cerebellar dysfunction, often grouped under the generic term of ataxia, are discussed. Vertigo, dizziness, and imbalance are associated with lesions of the vestibulo-cerebellar, vestibulo-spinal, or cerebellar ocular motor systems. The cerebellum plays a major role in the online to long-term control of eye movements (control of calibration, reduction of eye instability, maintenance of ocular alignment). Ocular instability, nystagmus, saccadic intrusions, impaired smooth pursuit, impaired vestibulo-ocular reflex (VOR), and ocular misalignment are at the core of oculomotor cerebellar deficits. As a motor speech disorder, ataxic dysarthria is highly suggestive of cerebellar pathology. Regarding motor control of limbs, hypotonia, a- or dysdiadochokinesia, dysmetria, grasping deficits and various tremor phenomenologies are observed in cerebellar disorders to varying degrees. There is clear evidence that the cerebellum participates in force perception and proprioceptive sense during active movements. Gait is staggering with a wide base, and tandem gait is very often impaired in cerebellar disorders. In terms of cognitive and affective operations, impairments are found in executive functions, visual-spatial processing, linguistic function, and affective regulation (Schmahmann's syndrome). Nonmotor linguistic deficits including disruption of articulatory and graphomotor planning, language dynamics, verbal fluency, phonological, and semantic word retrieval, expressive and receptive syntax, and various aspects of reading and writing may be impaired after cerebellar damage. The cerebellum is organized into (a) a primary sensorimotor region in the anterior lobe and adjacent part of lobule VI, (b) a second sensorimotor

  18. Cerebellar and Brainstem Malformations.

    PubMed

    Poretti, Andrea; Boltshauser, Eugen; Huisman, Thierry A G M

    2016-08-01

    The frequency and importance of the evaluation of the posterior fossa have increased significantly over the past 20 years owing to advances in neuroimaging. Conventional and advanced neuroimaging techniques allow detailed evaluation of the complex anatomic structures within the posterior fossa. A wide spectrum of cerebellar and brainstem malformations has been shown. Familiarity with the spectrum of cerebellar and brainstem malformations and their well-defined diagnostic criteria is crucial for optimal therapy, an accurate prognosis, and correct genetic counseling. This article discusses cerebellar and brainstem malformations, with emphasis on neuroimaging findings (including diagnostic criteria), neurologic presentation, systemic involvement, prognosis, and recurrence. PMID:27423798

  19. Local and descending circuits regulate long-term potentiation and zif268 expression in spinal neurons.

    PubMed

    Rygh, Lars Jørgen; Suzuki, Rie; Rahman, Wahida; Wong, Yuk; Vonsy, Jean Laurent; Sandhu, Hardip; Webber, Mark; Hunt, Stephen; Dickenson, Anthony H

    2006-08-01

    Long-term potentiation (LTP), a use dependent long-lasting modification of synaptic strength, was first discovered in the hippocampus and later shown to occur in sensory areas of the spinal cord. Here we demonstrate that spinal LTP requires the activation of a subset of superficial spinal dorsal horn neurons expressing the neurokinin-1 receptor (NK1-R) that have previously been shown to mediate certain forms of hyperalgesia. These neurons participate in local spinal sensory processing, but are also the origin of a spino-bulbo-spinal loop driving a 5-hydroxytryptamine 3 receptor (5HT3-R)- mediated descending facilitation of spinal pain processing. Using a saporin-substance P conjugate to produce site-specific neuronal ablation, we demonstrate that NK1-R expressing cells in the superficial dorsal horn are crucial for the generation of LTP-like changes in neuronal excitability in deep dorsal horn neurons and this is modulated by descending 5HT3-R-mediated facilitatory controls. Hippocampal LTP is associated with early expression of the immediate-early gene zif268 and knockout of the gene leads to deficits in long-term LTP and learning and memory. We found that spinal LTP is also correlated with increased neuronal expression of zif268 in the superficial dorsal horn and that zif268 antisense treatment resulted in deficits in the long-term maintenance of inflammatory hyperalgesia. Our results support the suggestion that the generation of LTP in dorsal horn neurons following peripheral injury may be one mechanism whereby acute pain can be transformed into a long-term pain state. PMID:16930406

  20. Stirling engine - Approach for long-term durability assessment

    NASA Technical Reports Server (NTRS)

    Tong, Michael T.; Bartolotta, Paul A.; Halford, Gary R.; Freed, Alan D.

    1992-01-01

    The approach employed by NASA Lewis for the long-term durability assessment of the Stirling engine hot-section components is summarized. The approach consists of: preliminary structural assessment; development of a viscoplastic constitutive model to accurately determine material behavior under high-temperature thermomechanical loads; an experimental program to characterize material constants for the viscoplastic constitutive model; finite-element thermal analysis and structural analysis using a viscoplastic constitutive model to obtain stress/strain/temperature at the critical location of the hot-section components for life assessment; and development of a life prediction model applicable for long-term durability assessment at high temperatures. The approach should aid in the provision of long-term structural durability and reliability of Stirling engines.

  1. Long-term Synoptic Observations of the Sun.

    NASA Astrophysics Data System (ADS)

    Pevtsov, Alexei

    2015-08-01

    Does the solar activity vary with time, or it remains constant? How systematic or intermittent solar cycles are? Long-term observations of the Sun are the reason we know answers to these questions. Ultimately, the development of a better understanding of stellar cycles will require similar long-term observations of other sun-like stars. To facilitate international collaboration on synoptic long-term solar observations, IAU created a working group on “Coordination of Synoptic Observations of the Sun.” The working group provides a forum for discussion of all issues relevant to past, current, and future synoptic programs, preservation, calibration, and access to synoptic solar data products. This talk will provide a summary of recent activity by this IAU WG. It will also present a brief overview of recent research on sun-as-a-star conducted at the US National Solar Observatory.

  2. Forecasting demand for long-term care services.

    PubMed Central

    Lane, D; Uyeno, D; Stark, A; Kliewer, E; Gutman, G

    1985-01-01

    This article analyzes three methods used to forecast the transition of long-term care clients through a variety of possible home and facility placements and levels of care. The test population (N = 1,653) is derived from the larger population of clients admitted in 1978 to British Columbia's newly established Long-Term Care program. The investigators have accumulated 5 years of service-generated data on moves, discharges, and deaths of these clients. Results show that the first-order Markov chain with stationary transition probabilities yields a superior forecast to state-by-state moving average growth and state-by-state regression analyses. The results of these analyses indicate that the Markov method should receive serious consideration as a tool for resource planning and allocation in long-term care. PMID:3932260

  3. Winning market positioning strategies for long term care facilities.

    PubMed

    Higgins, L F; Weinstein, K; Arndt, K

    1997-01-01

    The decision to develop an aggressive marketing strategy for its long term care facility has become a priority for the management of a one-hundred bed facility in the Rocky Mountain West. Financial success and lasting competitiveness require that the facility in question (Deer Haven) establish itself as the preferred provider of long term care for its target market. By performing a marketing communications audit, Deer Haven evaluated its present market position and created a strategy for solidifying and dramatizing this position. After an overview of present conditions in the industry, we offer a seven step process that provides practical guidance for positioning a long term care facility. We conclude by providing an example application. PMID:10179063

  4. Long-term RNA persistence in postmortem contexts

    PubMed Central

    2013-01-01

    Ribonucleic acids (RNA) are generally considered fragile molecules that are readily degraded. However, there is growing documentation of long-term (from days to centuries) RNA persistence in a variety of contexts and tissue types, and as such a number of academic disciplines are beginning to exploit degraded RNA. While the reasons for its survival are not fully understood, there are several plausible mechanisms that would safeguard this molecule against degradation. However, after examining the literature available on the postmortem instability and decay mechanisms of RNA, it has become clear that limited experimental studies and no reviews offer an overview of these mechanisms. Hence in this review we outline molecular reasons for RNA surviving long-term postmortem, and provide specific examples of RNA survival in forensic, archival and archaeological contexts. A better understanding of the mechanisms of RNA decay will be crucial for developing expectations on its long-term survival. PMID:23618361

  5. Long-term Internship through Cooperative Education with Regional Industries

    NASA Astrophysics Data System (ADS)

    Takahashi, Kenzo; Hase, Hiroyuki

    The long term internship is one of special educational programs for graduate students of Graduate School of Engineering in University of Fukui. This is a collaborative program between university and industries where selected post-graduate students are dispatched to companies for a long term and educated in real business environments. It is the final goal of the program to develop sophisticated specialists who would be able to catch the business strategy in industries and solve any problems by themselves. The program is managed in a semester (6 months) and contains 1.5 month prior education of preliminary special knowledge, ethics and secrecy, about 3 month dispatch with long-term internship, and 1.5 month post-education for complementary education and presentation. This paper presents the effect of this program which has been evolving since 2005.

  6. Marijuana effects on long-term memory assessment and retrieval.

    PubMed

    Darley, C F; Tinklenberg, J R; Roth, W T; Vernon, S; Kopell, B S

    1977-05-01

    The ability of 16 college-educated male subjects to recall from long-term memory a series of common facts was tested during intoxication with marijuana extract calibrated to 0.3 mg/kg delta-9-tetrahydrocannabinol and during placebo conditions. The subjects' ability to assess their memory capabilities was then determined by measuring how certain they were about the accuracy of their recall performance and by having them predict their performance on a subsequent recognition test involving the same recall items. Marijuana had no effect on recall or recognition performance. These results do not support the view that marijuana provides access to facts in long-term storage which are inaccessible during non-intoxication. During both marijuana and placebo conditions, subjects could accurately predict their recognition memory performance. Hence, marijuana did not alter the subjects' ability to accurately assess what information resides in long-term memory even though they did not have complete access to that information.

  7. An approach to long-term sedative-hypnotic use

    PubMed Central

    Shahid, Azmeh; Chung, Sharon A; Phillipson, Ron; Shapiro, Colin M

    2012-01-01

    Insomnia is a common, often chronic medical disorder with significant medical and socioeconomic repercussions. However, unlike other medical conditions, there is intense debate as to whether the long-term treatment of insomnia is clinically appropriate. The perceived deleterious side effect of sedative-hypnotic medications may result in patients remaining untreated or undertreated. This review proposes that a more subtle approach needs to be taken in the management of patients with chronic insomnia and that long-term use of the newer sedative-hypnotics may be a feasible and effective treatment option when used in conjunction with thorough medical assessment and regular patient follow-up. This review discusses these issues and discusses the pros and cons of long-term sedative-hypnotic use. PMID:23620678

  8. Sexuality and Physical Intimacy in Long Term Care

    PubMed Central

    Lichtenberg, Peter A.

    2015-01-01

    Sexuality and sexual needs in older adults remains a neglected area of clinical intervention, particularly so in long term care settings. Because older adults in medical rehabilitation and long term care beds present with significant frailties, and often significant neurocognitive disorders it makes it difficult for occupational therapists and other staff to evaluate the capacity of an older adult resident to participate in sexual relationships. The current paper reviews the current literature on sexuality and aging, examines some of the clinical practices and guidelines regarding sexual expression in long term care and presents two case examples. A semi-structured interview and decision tree is presented to assist therapists in making careful and informed decisions and thereby balancing needs for protection with needs for autonomy. PMID:24354331

  9. Long-term management of patients with multiple sclerosis.

    PubMed

    Weightman, Cherie

    2006-07-01

    This article explores the challenges of long-term case management for patients who have multiple sclerosis (MS). Currently there is scant research into district nursing input into long-term management of patients who have MS. Until now the role of the community nurses has been confined to palliation or terminal care, focusing on the more physical manifestations of MS. The contemporary role of district nurse is going to evolve to include proactive approaches. Governmental initiatives demand proactive services, and place emphasis on self-care for patients with MS. Themes that emerge from this article relate to the pre-existing skills--such as managing patients with complex needs and the advanced assessment skills--that will be required to achieve this. What is clear is that community nurses already possess many of the prerequisite skills needed for long-term management, and they should not be daunted by this prospect.

  10. Long-term Use of Opioids for Complex Chronic Pain

    PubMed Central

    Von Korff, Michael R.

    2014-01-01

    Increased opioid prescribing for back pain and other chronic musculoskeletal pain conditions has been accompanied by dramatic increases in prescription opioid addiction and fatal overdose. Opioid-related risks appear to increase with dose. While short-term randomized trials of opioids for chronic pain have found modest analgesic benefits (a one-third reduction in pain intensity on average), the long-term safety and effectiveness of opioids for chronic musculoskeletal pain is unknown. Given the lack of large, long-term randomized trials, recent epidemiologic data suggests the need for caution when considering long-term use of opioids to manage chronic musculoskeletal pain, particularly at higher dosage levels. Principles for achieving more selective and cautious use of opioids for chronic musculoskeletal pain are proposed. PMID:24315147

  11. Data Analysis in the LOFAR Long Term Archive

    NASA Astrophysics Data System (ADS)

    Holties, H. A.; van Diepen, G.; van Dok, D.; Dijkstra, F.; Loose, M.; Renting, G. A.; Schrijvers, C.; Vriend, W.-J.

    2012-09-01

    The LOFAR Long Term Archive (LTA) is a distributed information system that provides integrated services for data analysis as well as long term preservation of astronomical datasets and their provenance. The data analysis capabilities are provided by a federated system that integrates a central catalog and client user interfaces provided by Astro-Wise with processing pipelines running on Grid based and University HPC clusters. The framework used for data analysis ensures that proper authorization and access rules are applied and that generated data products are ingested into the storage part of the Long Term Archive. The ingest process includes information about data provenance. This paper presents the architecture of the processing framework of the LTA.

  12. Inflammatory markers in relation to long-term air pollution.

    PubMed

    Mostafavi, Nahid; Vlaanderen, Jelle; Chadeau-Hyam, Marc; Beelen, Rob; Modig, Lars; Palli, Domenico; Bergdahl, Ingvar A; Vineis, Paolo; Hoek, Gerard; Kyrtopoulos, Soterios Α; Vermeulen, Roel

    2015-08-01

    Long-term exposure to ambient air pollution can lead to chronic health effects such as cancer, cardiovascular and respiratory disease. Systemic inflammation has been hypothesized as a putative biological mechanism contributing to these adverse health effects. We evaluated the effect of long-term exposure to air pollution on blood markers of systemic inflammation. We measured a panel of 28 inflammatory markers in peripheral blood samples from 587 individuals that were biobanked as part of a prospective study. Participants were from Varese and Turin (Italy) and Umea (Sweden). Long-term air pollution estimates of nitrogen oxides (NOx) were available from the European Study of Cohorts for Air Pollution Effects (ESCAPE). Linear mixed models adjusted for potential confounders were applied to assess the association between NOx and the markers of inflammation. Long-term exposure to NOx was associated with decreased levels of interleukin (IL)-2, IL-8, IL-10 and tumor necrosis factor-α in Italy, but not in Sweden. NOx exposure levels were considerably lower in Sweden than in Italy (Sweden: median (5th, 95th percentiles) 6.65 μg/m(3) (4.8, 19.7); Italy: median (5th, 95th percentiles) 94.2 μg/m(3) (7.8, 124.5)). Combining data from Italy and Sweden we only observed a significant association between long-term exposure to NOx and decreased levels of circulating IL-8. We observed some indication for perturbations in the inflammatory markers due to long-term exposure to NOx. Effects were stronger in Italy than in Sweden, potentially reflecting the difference in air pollution levels between the two cohorts.

  13. Morphodynamic length scale and long term river meandering dynamics

    NASA Astrophysics Data System (ADS)

    Lanzoni, S.; Frascati, A.

    2009-12-01

    The fully nonlinear simulation of the lateral migration of meandering channels, combined with an analytical description of the linearized flow field, gives a powerful and yet computationally accessible tool to investigate short and long term evolution of alluvial rivers. In the present contribution we focus on the long term behavior of meandering rivers. This class of dynamical systems is driven by the coexistence of various intrinsically nonlinear mechanisms which determine the possible occurrence of two different morphodynamic regimes: the sub-resonant and the super-resonant regime. Investigating the full range of morphodynamic conditions, we end up with a new morphodynamic length scale associated with spatially oscillating disturbances, accounting for both curvature-forced variations in velocity and depth and alternate bars. Once normalized with this length scale, the relevant morphologic features of the simulated long term patterns (i.e. the probability density function of the local channel curvature and the geometric characteristics of the oxbow lakes) tend to collapse on two distinct behaviors, depending on the dominant morphologic regime. The long term river meandering dynamics is then investigated. The occurrence of cutoff events is a key mechanism in the dynamics of these systems. They introduce a strong source of nonlinearity in the evolution of river meandering, which strongly contributes to the formation of the complex planform patterns usually observed in nature. To detect the possible signatures of a chaotic behavior or a self-organized criticality state triggered in river meandering dynamics by the repeated occurrence of cutoffs, some robust nonlinear methodologies have been applied to both the spatial series of local curvatures and the time series of long term channel sinuosity. The temporal distribution of cutoff inter-arrivals is also investigated. The results are consistent and show that, at least from a modelling point of view, no evidence of

  14. A basic strategy for financing long term care.

    PubMed

    Greenberg, J A; Leutz, W N

    1984-02-01

    As pressure mounts to contain Medicaid long term care spending, short-range "quick fixes" must be avoided. Three such false solutions in particular have shortcomings that may actually exacerbate long term care's financial dilemma because they are based on inadequate definitions of the problem. Two of these proposals--legislation to broaden family responsibility toward institutionalized elders on Medicaid and expanded state power to put liens on such elders' real property--err by trying to mandate "caring" and are predicated on a misunderstanding of the "spend-down" problem. The other proposal--to provide tax incentives to family members who care for elders--requires a large administrative apparatus, assumes an elasticity of supply that may not exist, and could disrupt the "gift relationship" on which family exchanges are often based. What is needed is a strategy with short term, intermediate, and long term objectives that move toward an insurance approach. The short term plan should lay the groundwork for intermediate strategy and control costs by changing rate-setting methods and putting limits on facility construction. The intermediate plan should change the problem's definition from one of merely controlling Medicaid long term care expenditures to one of efficiently managing state resources for the elderly through the development of state financing and local delivery systems that target older persons in greatest need. An effective means of doing this is through the creation of social/HMOs, which have five key features: integration of service responsibility and authority; flexibility in organizational design; balanced clientele; pooled prepaid funding; and financial risk for the provider organization. Finally, the long term strategy should transfer much of the long term care financial burden from individuals and state Medicaid agencies to insurance mechanisms. Many individuals would thus avoid impoverishment caused by health care spending and Medicaid would

  15. 18. Uniform cost accounting in long-term care.

    PubMed

    Sorensen, J E

    1976-05-01

    Uniform cost data are essential for managing health services, establishing billing and reimbursement rates, and measuring effectiveness and impact. Although it is especially difficult in the case of long-term health care to develop standard cost accounting procedures because of the varied configurations of inpatient, intermediate, and ambulatory services, the overall approaches to cost accounting and its content can be made more uniform. With this purpose in mind, a general model of cost accounting is presented for a multilevel program of long-term services, together with a special method for ambulatory services using "hours accounted for" as the basic measure.

  16. Long-term results after intentional tooth reimplantation in monkeys.

    PubMed

    Caffesse, R G; Nasjleti, C E; Castelli, W A

    1977-11-01

    The purpose of this study was to evaluate histologically the long-term response to intentional tooth reimplantation in six rhesus monkeys. The study revealed that cervical and apical root resorption is a universal complication after tooth reimplantation and that arrested areas of resorption will show repair by deposition of cementum. A highly cellular periodontal membrane usually will develop. Periodontal fibers will reattach to reparative bone and cementum but seldom regain functional orientation. Partial or complete ankylosis may result. A further complication is progressive undermining resorption of the ankylosed teeth. Long-term studies are mandatory to evaluate the response to intentional tooth reimplantation.

  17. Leadership: the Winnipeg Community and Long-Term Care Authority.

    PubMed

    Suski, M; Hack, T; Heaman, M

    1999-01-01

    The Winnipeg Community and Long Term Care Authority (WCA) was established in 1998 under the Regional Health Authorities Act of the Province of Manitoba. The WCA's role is to provide for the successful integration of Winnipeg's community-based healthcare delivery services through its three main portfolios: Community Care and Public Health, Home Care and Mental Health, and Long Term Care and Specialized Services. The WCA is dedicated to building a quality health future for Winnipeg. Various initiatives undertaken in the pursuit of quality are described.

  18. Neurohumoral reactions to long-term vestibular stimulation in man.

    PubMed

    Nichiporuk, I A; Rapotkov, A N; Orlov, O I; Grigoriev, A I

    1993-02-01

    The main purposes of present work were: 1) to examine neurohumoral reactions to long-term vestibular stimulation provocative for MS symptoms in man; 2) to compare the peculiarities of neuroendocrine reactions to short-term and to long-term vestibular stimulation; 3) to analyze the received results from the position of neuroendocrine adaptive reactions biological conformity to natural laws, and its physiological importance for human organisms; 4) to make some prognostic points of neurohumoral reaction changes on health and capacity for work in subjects influenced by professional conditions, provocative for MS manifestation development.

  19. Long-term stability test of a triple GEM detector

    NASA Astrophysics Data System (ADS)

    Adak, R. P.; Biswas, S.; Das, S.; Ghosal, D.; Ghosh, S. K.; Mondal, A.; Nag, D.; Nayak, T. K.; Patra, R. N.; Prasad, S. K.; Raha, S.; Sahu, P. K.; Sahu, S.; Swain, S.

    2016-10-01

    The main aim of the study is to perform the long-term stability test of gain of the single mask triple GEM detector. A simple method is used for this long-term stability test using a radioactive X-ray source with high activity. The test is continued till accumulation of charge per unit area > 12.0 mC/mm2. The details of the chamber fabrication, the test set-up, the method of measurement and the test results are presented in this paper.

  20. Intrahepatic haematoma in a patient on long-term haemodialysis.

    PubMed

    Lai, K N; Disney, A P; Mathew, T H

    Spontaneous intrahepatic haematoma is an uncommon potentially fatal complication in uraemic patients receiving long-term haemodialysis, particularly in those taking anticoagulant and antiplatelet drugs. Prompt diagnosis, withdrawal of anticoagulant and antiplatelet therapy, cautious transfusion, and careful dialysis with regional heparinisation are essential in the management and may help to avoid surgical intervention in the presence of a tendency to bleed. Noninvasive organ imaging such as ultrasonography and computerised axial tomography are helpful in diagnosis and monitoring of progress. A case of intrahepatic haematoma in a 37-year-old man who had been receiving long-term haemodialysis since 1976 is described.

  1. Human sperm chromosomes. Long-term effect of cancer treatment

    SciTech Connect

    Genesca, A.; Caballin, M.R.; Miro, R.; Benet, J.; Bonfill, X.; Egozcue, J. )

    1990-06-01

    The long-term cytogenetic effect of radio- or chemotherapy or both on male germ cells was evaluated by study of the chromosomal abnormalities in spermatozoa of four men treated for cancer 5-18 years earlier. The cytogenetic analysis of 422 sperm metaphases showed no differences in the aneuploidy rate. The incidence of structural chromosome aberrations was 14.0%, however, which is much higher than in controls. Thus, the high incidence of structurally aberrant spermatozoa observed in our long-term study indicates that antitumoral treatments affect stem-cell spermatogonia and that aberrant cells can survive germinal selection and produce abnormal spermatozoa.

  2. Thermospheric density long-term trend at high latitude

    NASA Astrophysics Data System (ADS)

    Yamazaki, Yosuke; Kosch, Michael

    2016-07-01

    We present a novel technique that has been recently developed to estimate the thermospheric oxygen density using ionospheric measurements from EISCAT radars. The technique is based on an ion momentum equation, which takes into account the collisional interaction between neutrals and ions. We apply the technique to a 30-year long data set from the Tromso UHF radar, which for the first time allows us to evaluate the thermospheric density long-term trend at high latitude. The results are compared with the trend derived from satellite drag, which represents the long-term trend at lower latitudes.

  3. 18. Uniform cost accounting in long-term care.

    PubMed

    Sorensen, J E

    1976-05-01

    Uniform cost data are essential for managing health services, establishing billing and reimbursement rates, and measuring effectiveness and impact. Although it is especially difficult in the case of long-term health care to develop standard cost accounting procedures because of the varied configurations of inpatient, intermediate, and ambulatory services, the overall approaches to cost accounting and its content can be made more uniform. With this purpose in mind, a general model of cost accounting is presented for a multilevel program of long-term services, together with a special method for ambulatory services using "hours accounted for" as the basic measure. PMID:819732

  4. [Long-term-management of organ transplant recipients].

    PubMed

    Bürger, Christin; Schmidt, Martina; Maschmeier, Miriam; Stella, Jaqueline; Hüsing, Anna; Wilms, Christian; Schmidt, Hartmut Hans-Jürgen; Kabar, Iyad

    2016-07-01

    Due to advances in immunosuppressive therapy and surgical techniques, survival rates after solid organ transplantation have constantly improved over the last decades. In long-term care after transplantation, physicians need to focus as much on diagnosis and treatment of allograft-related complications as they should consider comorbidities and evaluate risk-factors and adverse events of immunosuppressive agents to prevent secondary diseases. In particular, cardiovascular and metabolic diseases, malignancy and infection play a major role in long-term survival. Therefore, screening of organ transplant recipients in regard to these complications and adverse events is a crucial part of follow up in these patients. PMID:27359310

  5. Long-term Outcomes in Youth with Diabetes Mellitus

    PubMed Central

    White, Neil H.

    2015-01-01

    Synopsis In this chapter, I will review the long-term outcomes and their precursors of type 1 diabetes (T1D) starting in youth. I will also contrast the changing incidence of these long-term complications as we have moved from the pre-DCCT to the post-DCCT standard of care and will review the emerging data related to complications in youth with type 2 diabetes (T2D). Finally, I will review the recent understanding related to the effects of diabetes on the brain and cognition. PMID:26210623

  6. Elder rights and the Long-Term Care Ombudsman Program.

    PubMed

    Netting, F E; Huber, R; Paton, R N; Kautz, J R

    1995-05-01

    Since 1975 the Long-Term Care Ombudsman Program has grown and developed under the Older Americans Act (OAA) of 1965. With the passage of the Older Americans Act Amendments of 1992, this program was combined with other advocacy functions and placed in Title VII--Vulnerable Elder Rights Protection Activities. This article provides a historical overview of the policy, programmatic, and research issues that surround OAA and explains the activities of ombudsmen in their local communities and the roles many social workers perform under the auspices of long-term care ombudsman programs.

  7. Cerebellar vermis plays a causal role in visual motion discrimination.

    PubMed

    Cattaneo, Zaira; Renzi, Chiara; Casali, Stefano; Silvanto, Juha; Vecchi, Tomaso; Papagno, Costanza; D'Angelo, Egidio

    2014-09-01

    Cerebellar patients have been found to show deficits in visual motion discrimination, suggesting that the cerebellum may play a role in visual sensory processing beyond mediating motor control. Here we show that triple-pulse online transcranial magnetic stimulation (TMS) over cerebellar vermis but not over the cerebellar hemispheres significantly impaired motion discrimination. Critically, the interference caused by vermis TMS on motion discrimination did not depend on an indirect effect of TMS over nearby visual areas, as demonstrated by a control experiment in which TMS over V1 but not over cerebellar vermis significantly impaired orientation discrimination. These findings demonstrate the causal role of the cerebellar vermis in visual motion processing in neurologically normal participants.

  8. Dissociation of short- and long-term face memory: evidence from long-term recency effects in temporal lobe epilepsy.

    PubMed

    Bengner, T; Malina, T

    2007-07-01

    We tested whether memory deficits in temporal lobe epilepsy (TLE) are better described by a single- or dual-store memory model. To this aim, we analyzed the influence of TLE and proactive interference (PI) on immediate and 24-h long-term recency effects during face recognition in 16 healthy participants and 18 right and 21 left non-surgical TLE patients. PI in healthy participants or TLE erased the long-term recency effect, but left the immediate recency effect unaffected. Although the immediate recency effect was still visible in right TLE patients, the number of detected recency items during immediate recognition was decreased in right TLE compared to left TLE. Right TLE was also related to decreased detection of pre-recency items during delayed recognition compared to left TLE, and decreased detection of pre-recency items during immediate recognition under PI. The results show that the temporal lobes are necessary for the long-term recency effect, but not for the immediate recency effect, and thus speak for a dissociation of short- and long-term memory for faces. Right TLE is related to more severe long-term memory deficits than left TLE and is also related to additional short-term memory deficits for faces.

  9. 42 CFR 412.536 - Special payment provisions for long-term care hospitals and satellites of long-term care...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... hospitals and satellites of long-term care hospitals that discharged Medicare patients admitted from a hospital not located in the same building or on the same campus as the long-term care hospital or satellite... payment provisions for long-term care hospitals and satellites of long-term care hospitals that...

  10. 42 CFR 412.536 - Special payment provisions for long-term care hospitals and satellites of long-term care...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... hospitals and satellites of long-term care hospitals that discharged Medicare patients admitted from a hospital not located in the same building or on the same campus as the long-term care hospital or satellite... payment provisions for long-term care hospitals and satellites of long-term care hospitals that...

  11. 42 CFR 412.536 - Special payment provisions for long-term care hospitals and satellites of long-term care...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... hospitals and satellites of long-term care hospitals that discharged Medicare patients admitted from a hospital not located in the same building or on the same campus as the long-term care hospital or satellite... payment provisions for long-term care hospitals and satellites of long-term care hospitals that...

  12. 42 CFR 412.536 - Special payment provisions for long-term care hospitals and satellites of long-term care...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... hospitals and satellites of long-term care hospitals that discharged Medicare patients admitted from a hospital not located in the same building or on the same campus as the long-term care hospital or satellite... payment provisions for long-term care hospitals and satellites of long-term care hospitals that...

  13. 42 CFR 412.536 - Special payment provisions for long-term care hospitals and satellites of long-term care...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... hospitals and satellites of long-term care hospitals that discharged Medicare patients admitted from a hospital not located in the same building or on the same campus as the long-term care hospital or satellite... payment provisions for long-term care hospitals and satellites of long-term care hospitals that...

  14. Long-term Exposure to Air Pollution and Markers of Inflammation, Coagulation, and Endothelial Activation

    PubMed Central

    Hajat, Anjum; Allison, Matthew; Diez-Roux, Ana V.; Jenny, Nancy Swords; Jorgensen, Neal W.; Szpiro, Adam A.; Vedal, Sverre; Kaufman, Joel D.

    2015-01-01

    Background Air pollution is associated with cardiovascular disease, and systemic inflammation may mediate this effect. We assessed associations between long- and short-term concentrations of air pollution and markers of inflammation, coagulation, and endothelial activation. Methods We studied participants from the Multi-Ethnic Study of Atherosclerosis from 2000 to 2012 with repeat measures of serum C-reactive protein (CRP), interleukin-6 (IL-6), fibrinogen, D-dimer, soluble E-selectin, and soluble Intercellular Adhesion Molecule-1. Annual average concentrations of ambient fine particulate matter (PM2.5), individual-level ambient PM2.5 (integrating indoor concentrations and time–location data), oxides of nitrogen (NOx), nitrogen dioxide (NO2), and black carbon were evaluated. Short-term concentrations of PM2.5 reflected the day of blood draw, day prior, and averages of prior 2-, 3-, 4-, and 5-day periods. Random-effects models were used for long-term exposures and fixed effects for short-term exposures. The sample size was between 9,000 and 10,000 observations for CRP, IL-6, fibrinogen, and D-dimer; approximately 2,100 for E-selectin; and 3,300 for soluble Intercellular Adhesion Molecule-1. Results After controlling for confounders, 5 µg/m3 increase in long-term ambient PM2.5 was associated with 6% higher IL-6 (95% confidence interval = 2%, 9%), and 40 parts per billion increase in long-term NOx was associated with 7% (95% confidence interval = 2%, 13%) higher level of D-dimer. PM2.5 measured at day of blood draw was associated with CRP, fibrinogen, and E-selectin. There were no other positive associations between blood markers and short- or long-term air pollution. Conclusions These data are consistent with the hypothesis that long-term exposure to air pollution is related to some markers of inflammation and fibrinolysis. PMID:25710246

  15. Long-term functional recovery and compensation after cerebral ischemia in rats

    PubMed Central

    Girard, Sylvie; Murray, Katie N.; Rothwell, Nancy J.; Metz, Gerlinde A.S.; Allan, Stuart M.

    2014-01-01

    Cerebral ischemia is one of the most common causes of disabilities in adults and leads to long-term motor and cognitive impairments with limited therapeutic possibilities. Treatment options have proven efficient in preclinical models of cerebral ischemia but have failed in the clinical setting. This limited translation may be due to the suitability of models used and outcomes measured as most studies have focused on the early period after injury with gross motor scales, which have limited correlation to the clinical situation. The aim of this study was to determine long-term functional outcomes after cerebral ischemia in rats, focusing on fine motor function, social and depressive behavior as clinically relevant measures. A secondary objective was to evaluate the effects of an anti-inflammatory treatment (interleukin-1 receptor antagonist (IL-1Ra)) on functional recovery and compensation. Infarct volume was correlated with long-term (25 days) impairments in fine motor skills, but not with emotional components of behavior. Motor impairments could not be detected using conventional neurological tests and only detailed analysis allowed differentiation between recovery and compensation. Acute systemic administration of IL-1Ra (at reperfusion) led to a faster and more complete recovery, but delayed (24 h) IL-1Ra treatment had no effect. In summary functional assessment after brain injury requires detailed motor tests in order to address long-term impairments and compensation processes that are mediated by intact tissues. Functional deficits in skilled movement after brain injury represent ideal predictors of long-term outcomes and should become standard measures in the assessment of preclinical animal models. PMID:24821402

  16. Commitment and the Long-Term Marriage Relationship.

    ERIC Educational Resources Information Center

    Swensen, Clifford H.; Trahaug, Geir

    1985-01-01

    Examined the relationship of commitment in marriage and change in commitment over marriage to the expression of love and marriage problems among long-term Norwegian married couples. Results indicated that those who were committed to their spouses as persons had significantly fewer marriage problems. Those whose commitment increased expressed more…

  17. The Jornada Basin long term ecological research program

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chihuahuan Desert landscapes exemplify the ecological conditions, vulnerability, and management challenges in arid and semi-arid regions around the world. The goal of the Jornada Basin Long Term Ecological Research program (JRN LTER) established in 1982 is to understand and quantify the key factors ...

  18. Case Management Takes Hold in Long-Term Care.

    ERIC Educational Resources Information Center

    Rose, Stephen M.; And Others

    1992-01-01

    Includes "Empowering Case Management Clients" (Rose); "Case Management in Rural Japan" (Maeda, Takahashi); "Coordinated-Care Teams" (Brodsky, Sobol); "Comparing Practice in the United States and the United Kingdom" (Sturges); "Business of Case Management Flourishing in the U.S." (Cress); and "Community Options Bring Change to Long-Term Care in…

  19. Transfer of Information from Short- to Long-Term Memory

    ERIC Educational Resources Information Center

    Modigliani, Vito; Seamon, John G.

    1974-01-01

    The present study examined current hypotheses concerning information transfer from short-term memory (STM) to long-term memory (LTM) using a Peterson STM task with word triplets presented over retention intervals of 0, 3, 6, 9, and 18 sec. (Editor)

  20. Long-Term Ecological Research and Network-Level Science

    NASA Astrophysics Data System (ADS)

    Collins, Scott L.; Childers, Daniel L.

    2014-08-01

    With every passing year, the effects of global environmental change are becoming more pervasive and are occurring at a more accelerated pace. Climate change, land use change, atmospheric nitrogen deposition, ocean acidification and sea level rise, loss of biodiversity, and homogenization of Earth's ecosystems are all manifestations of human activities. These short- and long-term effects of environmental changes continue to mount.

  1. Going Solar Yields Long-Term Economical, Educational Benefits

    ERIC Educational Resources Information Center

    von Moos, Brian

    2009-01-01

    Going solar is not an easy decision, but a long-term investment with a potentially substantial up-front cost. While some schools have enough capital in reserve, can raise bond money, or can solicit sufficient donations, many schools rely on creative financial programs to make a solar energy system economically feasible. Thinking about going solar…

  2. Review of "The Long-Term Impacts of Teachers"

    ERIC Educational Resources Information Center

    Ballou, Dale

    2012-01-01

    A new report titled "The Long-Term Impacts of Teachers" concludes that teachers whose students tend to show high gains on their test scores (called "high value-added teachers") also contribute to later student success in young adulthood, as indicated by outcomes such as college attendance and future earnings. To support this claim, it is not…

  3. A Conditioning Analysis of Infant Long-Term Memory.

    ERIC Educational Resources Information Center

    Sullivan, Margaret W.; And Others

    1979-01-01

    Assesses the long-term retention of conditioned operant footkicks by three-month-old infants. Views a conditioning analysis as a logical means by which to bridge the gap between animal and adult human models of memory. (Author/RH)

  4. Global, long-term surface reflectance records from Landsat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Global, long-term monitoring of changes in Earth’s land surface requires quantitative comparisons of satellite images acquired under widely varying atmospheric conditions. Although physically based estimates of surface reflectance (SR) ultimately provide the most accurate representation of Earth’s s...

  5. Making Wise Decisions for Long-Term Care.

    ERIC Educational Resources Information Center

    American Association of Retired Persons, Washington, DC.

    This booklet offers simple descriptions of each of the long-term care services that may be available to individuals needing such care, identifies where in the community services might be located, and explains what portions of the costs for each type of service will be paid by Medicare, Medicaid or private supplementary insurance policies. This…

  6. Areas of Marital Dissatisfaction among Long-Term Couples

    ERIC Educational Resources Information Center

    Duba, Jill D.; Hughey, Aaron W.; Lara, Tracy; Burke, Monica G.

    2012-01-01

    To better understand relational dissatisfaction and duration of long-term married couples, this study surveyed 30 couples married at least 40 years with the Marital Satisfaction Inventory. Findings suggest various areas of dissatisfaction (e.g., affective communication, conflict over child rearing) and relationship among and link to other areas of…

  7. Long-Term Sensitization Training Primes "Aplysia" for Further Learning

    ERIC Educational Resources Information Center

    Cleary, Leonard J.; Byrne, John H.; Antzoulatos, Evangelos G.; Wainwright, Marcy L.

    2006-01-01

    Repetitive, unilateral stimulation of "Aplysia" induces long-term sensitization (LTS) of ipsilaterally elicited siphon-withdrawal responses. Whereas some morphological effects of training appear only on ipsilateral sensory neurons, others appear bilaterally. We tested the possibility that contralateral morphological modifications may have…

  8. A Plea for Long-term Orientation in Organizations

    NASA Astrophysics Data System (ADS)

    Schwaninger, Markus; Ambroz, Kristjan

    2010-11-01

    The stress field between short- and long-term orientations is the epitome of organizational problematics: In many enterprises the latter is dominated by the former. The consequences of a dominant short-term orientation are negative in the best case, but the cases that result in destruction and catastrophe are legion. Few sustainable solutions for the conflict between the short- and long-term perspectives have been developed, and among those concerned many have not sufficiently reflected on this shortfall, or even become aware of it. Frequently, practical constraints obstruct a balance between short- and long-term orientations. The aim of this contribution is to enquire into this dilemma and to find a way of coping with it. Any progress in that direction would help to further the viability of organizations and the quality of life within them. As a pertinent contribution we present the Model of Systemic Control, a framework with a long-term view for the governance of organizations. Even though we are emphasizing the conceptual aspect, our theoretical statement is underpinned by an empirical approach and simulation experiments.

  9. Long-term care offers opportunity for revenue.

    PubMed

    Dixon, R D

    1991-06-01

    Hospital administrators already know that diversification will be a key to success in the future. Applying that philosophy to long-term care of the elderly is just one way to capture a growing consumer market. In the following article, the author addresses three potential variations for delivering such care by the hospital to this group. PMID:10113608

  10. Mutual Support Groups for Long-Term Recipients of TANF

    ERIC Educational Resources Information Center

    Anderson-Butcher, Dawn; Khairallah, Angela Oliver; Race-Bigelow, Janis

    2004-01-01

    This study examined the effect of involvement in mutual support groups on long-term recipients of Temporary Assistance for Needy Families (TANF) and other vulnerable individuals. From qualitative interviews with nine group members, the study identified key themes, benefits, and barriers related to involvement in the groups. Content analysis of the…

  11. 26 CFR 1.460-1 - Long-term contracts.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... as the provision of architectural, design, engineering, and construction management services, and the... to design and manufacture a satellite and to develop computer software enabling B to operate the... the manufacture, building, installation, or construction of property is a long-term contract...

  12. 26 CFR 1.460-1 - Long-term contracts.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... as the provision of architectural, design, engineering, and construction management services, and the... to design and manufacture a satellite and to develop computer software enabling B to operate the... the manufacture, building, installation, or construction of property is a long-term contract...

  13. 26 CFR 1.460-1 - Long-term contracts.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... architectural, design, engineering, and construction management services, and the development or implementation... to design and manufacture a satellite and to develop computer software enabling B to operate the..., building, installation, or construction of property is a long-term contract under section 460 and...

  14. 26 CFR 1.460-1 - Long-term contracts.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... as the provision of architectural, design, engineering, and construction management services, and the... to design and manufacture a satellite and to develop computer software enabling B to operate the... the manufacture, building, installation, or construction of property is a long-term contract...

  15. Phototherapy for Neonatal Hyperbilirubinemia: Long-Term Implications.

    ERIC Educational Resources Information Center

    Brown, Audrey K., Ed.; Showacre, Jane, Ed.

    This book contains 16 papers from the 1974 conference held by the Pregnancy and Infancy Branch of the National Institute of Child Health and Human Development to: (1) assess the photobiological processes involved in phototherapy used in treatment of neonatal hyperbilirubinemia, and (2) to document long term clinical experience with the treatment…

  16. Infection Control in the Long Term Care Facility.

    ERIC Educational Resources Information Center

    Morris, Sara

    This booklet is intended to increase the awareness of persons working in long-term care facilities regarding the danger of infectious disease and the ways in which it can be spread. Materials in this booklet include: (1) a brief discussion of historical events in the study of microorganisms; (2) information about how microorganisms cause infection…

  17. Long-term prognosis of depression in primary care.

    PubMed Central

    Simon, G. E.

    2000-01-01

    This article uses longitudinal data from a primary care sample to examine long-term prognosis of depression. A sample of 225 patients initiating antidepressant treatment in primary care completed assessments of clinical outcome (Hamilton Depression Rating Scale and the mood module of the Structured Clinical Interview for DSM-IIIR) 1, 3, 6, 9, 12, 18 and 24 months after initiating treatment. The proportion of patients continuing to meet criteria for major depression fell rapidly to approximately 10% and remained at approximately that level throughout follow-up. The proportion meeting criteria for remission (Hamilton Depression score of 7 or less) rose gradually to approximately 45%. Long-term prognosis (i.e. probability of remission at 6 months and beyond) was strongly related to remission status at 3 months (odds ratio 3.65; 95% confidence interval, 2.81-4.76) and only modestly related to various clinical characteristics assessed at baseline (e.g. prior history of recurrent depression, medical comorbidity, comorbid anxiety symptoms). The findings indicate that potentially modifiable risk factors influence the long-term prognosis of depression. This suggests that more systematic and effective depression treatment programmes might have an important effect on long-term course and reduce the overall burden of chronic and recurrent depression. PMID:10885162

  18. Autonomy and Acceptance of Long-Term Care

    ERIC Educational Resources Information Center

    Hsu, Hui-Chuan; Ting, Yu-Shan; Jiang, Ting-Wen; Chien, Ming-Chih; Chien, Chih-Hsin

    2009-01-01

    This study explored the relationship between four types of autonomy (health autonomy, informational autonomy, living autonomy, and financial autonomy) and the acceptance of five types of long-term care (adult day care, respite care, assisted living, unit care, and group home) for the elderly in Taiwan. Data were collected from 167 middle-aged and…

  19. Long-term Enhancements in Solar Wind Speed

    NASA Technical Reports Server (NTRS)

    Gazis, P. R.; Cuzzi, Jeff (Technical Monitor)

    1995-01-01

    Long-term enhancements in solar wind speed over timescales on the order of a year appear to be a common feature throughout the heliosphere over heliocentric distances that range from less than 0.72 AU to greater than 60. The origin of these events remains to be determined, but they are almost certainly associated with long-term variations at the solar wind source, in contrast with smaller-scale structures such as CIRs, MIRs, and GMIRs which are dynamical in origin. We present a survey of the long-term speed enhancements observed at the Pioneer Venus Orbiter (PVO), IMP 8, Voyager 2, and Pioneer 10 between 1974 and 1994 and compare this with published reports of smaller-scale events such as MIRs. We examine several of these long-term speed enhancements in detail to identify and characterize aspects of their structure, then describe how that structure evolves with heliocentric distance. Finally we discuss some of the implications of these events.

  20. The Insider's Experience of Long-Term Peer Victimisation

    ERIC Educational Resources Information Center

    Mackay, Graham J.; Carey, Timothy A.; Stevens, Bruce

    2011-01-01

    Bullying in schools continues to be a problem despite the best efforts of educators, researchers, and clinicians. Of most concern for the present study is that some children experience long-term victimisation by their peers. To improve our understanding in this area, the phenomenology of being bullied over the course of the school year was…

  1. Continental diatoms as indicators of long-term environmental change

    USGS Publications Warehouse

    Bradbury, J. Platt

    1999-01-01

    It is curious that diatoms, whose short lifespans and capacity for rapid regeneration make them especially suitable for short-term paleoenvironmental studies, would also have a significant role as indicators of long-term environmental change. This chapter explores the nature of long diatom records, their relation to global environmental changes, guidelines for their interpretation, and problems common to such records.

  2. Idaho National Laboratory Site Long-Term Stewardship Implementation Plan

    SciTech Connect

    B. E. Olaveson

    2006-07-27

    The U.S. Department of Energy has established long-term stewardship programs to protect human health and the environment at sites where residual contamination remains after site cleanup. At the Idaho National Laboratory Site, Comprehensive Environmental Response, Compensation, and Liability Act (CERLA) long-term stewardship activities performed under the aegis of regulatory agreements, the Federal Facility Agreement and Consent Order for the Idaho National Laboratory, and state and federal requirements are administered primarily under the direction of the Idaho Cleanup Project. It represents a subset of all on-going environmental activity at the Idaho National Laboratory Site. This plan provides a listing of applicable CERCLA long-term stewardship requirements and their planned and completed implementation goals. It proffers the Long-Term Stewardship Environmental Data Warehouse for Sitewide management of environmental data. This plan will be updated as needed over time, based on input from the U.S. Department of Energy, its cognizant subcontractors, and other local and regional stakeholders.

  3. Incidental Biasing of Attention from Visual Long-Term Memory

    ERIC Educational Resources Information Center

    Fan, Judith E.; Turk-Browne, Nicholas B.

    2016-01-01

    Holding recently experienced information in mind can help us achieve our current goals. However, such immediate and direct forms of guidance from working memory are less helpful over extended delays or when other related information in long-term memory is useful for reaching these goals. Here we show that information that was encoded in the past…

  4. Consolidation of Long-Term Memory: Evidence and Alternatives

    ERIC Educational Resources Information Center

    Meeter, Martijn; Murre, Jaap M. J.

    2004-01-01

    Memory loss in retrograde amnesia has long been held to be larger for recent periods than for remote periods, a pattern usually referred to as the Ribot gradient. One explanation for this gradient is consolidation of long-term memories. Several computational models of such a process have shown how consolidation can explain characteristics of…

  5. Children's Long-Term Memory for Autobiographical Events.

    ERIC Educational Resources Information Center

    Peterson, Carole

    2002-01-01

    Traces the origins of children's autobiographical memories, discussing research on infantile amnesia and young children's memory skills. Focuses on studies of children's long-term memory for autobiographical events that investigate delays of 1-2 years and delays of 4 years or more. Reports that a few studies have documented remarkably robust…

  6. 40 CFR 52.29 - Visibility long-term strategies.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 3 2012-07-01 2012-07-01 false Visibility long-term strategies. 52.29... strategies. (a) Plan disapprovals. The provisions of this section are applicable to any State implementation plan which has been disapproved for not meeting the requirements of 40 CFR 51.306 regarding...

  7. 40 CFR 52.29 - Visibility long-term strategies.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 3 2013-07-01 2013-07-01 false Visibility long-term strategies. 52.29... strategies. (a) Plan disapprovals. The provisions of this section are applicable to any State implementation plan which has been disapproved for not meeting the requirements of 40 CFR 51.306 regarding...

  8. 40 CFR 52.29 - Visibility long-term strategies.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 3 2014-07-01 2014-07-01 false Visibility long-term strategies. 52.29... strategies. (a) Plan disapprovals. The provisions of this section are applicable to any State implementation plan which has been disapproved for not meeting the requirements of 40 CFR 51.306 regarding...

  9. Long-Term Effects of First-Grade Multitier Intervention

    ERIC Educational Resources Information Center

    Al Otaiba, Stephanie; Kim, Young-Suk; Wanzek, Jeanne; Petscher, Yaacov; Wagner, Richard K.

    2014-01-01

    The purpose of this study was to compare the long-term effects of 2 first-grade Response to Intervention (RTI) models (Dynamic and Typical RTI) on the reading performance of students in second and third grade. Participants included 419 first-grade students (352 in second grade and 278 in third grade after attrition). Students were classified based…

  10. Long term agro-ecosystem research: The Southern Plains partnership

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The USDA Agricultural Research Service (ARS) is coordinating ten well-established research sites as a Long Term Agro-ecosystem Research (LTAR) Network. The goal of the LTAR is to sustain a land-based infrastructure for research, environmental management testing, and education, that enables understan...

  11. Security basics for long-term care facilities.

    PubMed

    Green, Martin

    2015-01-01

    The need for Long-Term Care (LTC) facilities is growing, the author reports, and along with it the need for programs to address the major security concerns of such facilities. In this article he explains how to apply the IAHSS Healthcare Security Industry Guidelines and the Design Guidelines to achieve a safer LTC facility. PMID:26647503

  12. SBUV/2 Long-Term Measurements of Solar Spectral Variability

    NASA Technical Reports Server (NTRS)

    DeLand, Matthew T.; Cebula, Richard P.

    1997-01-01

    The NOAA-11 SBUV/2 spectral solar data have been corrected for long-term instrument changes to produce a 5.5 year data record during solar cycle 22 (December 1988 - October 1994). Residual drifts in the data at long wavelengths are +/- 1% or less. At 200-205 nm, where solar variations drive stratospheric photochemistry, these data indicate long-term solar changes of 5-7% from the maximum of Cycle 22 in April 1991 through the end of the NOAA-11 data record. Comparisons of NOAA-11 data with UARS SUSIM and SOLSTICE for the period October 1991 - October 1994, when all 3 instruments were operating simultaneously, show that the observed long-term variations in 200-205 nm irradiance agree to within 2%. This result is consistent with predictions from the Mg-2 proxy index. The SBUV/2 instruments represent a valuable resource for long-term solar UV activity studies because of their overlapping data records. In addition to the NOAA-11 data presented here, the NOAA-9 SBUV/2 instrument began taking data in March 1985 and is still operating, providing a complete record of Cycle 22 behavior from a single instrument. Three additional SBUV/2 instruments are scheduled to be launched between 1997 and 2003, which should permit full coverage of solar cycle 23.

  13. The Long-Term Effects of Youth Unemployment

    ERIC Educational Resources Information Center

    Mroz, Thomas A.; Savage, Timothy H.

    2006-01-01

    Using NLSY data, we examine the long-term effects of youth unemployment on later labor market outcomes. Involuntary unemployment may yield suboptimal investments in human capital in the short run. A theoretical model of dynamic human capital investment predicts a rational "catch-up" response. Using semiparametric techniques to control for the…

  14. Long-Term Psychosomatic Effects of Biofeedback vs. Relaxation Training.

    ERIC Educational Resources Information Center

    Nowlis, David P.; Borzone, Ximena C.

    Differences were compared in the short-term and long-term responses of subjects with headache, insomnia, or hypertension to biofeedback training, relaxation, or a combination of both. Headache sufferers, insomniacs, and hypertensives were randomly assigned in equal numbers to biofeedback, relaxation training or a record-keeping control. Over 2…

  15. Effects of Acute Exercise on Long-Term Memory

    ERIC Educational Resources Information Center

    Labban, Jeffrey D.; Etnier, Jennifer L.

    2011-01-01

    In this study, we tested the effect of acute exercise on long-term memory, specifically the timing of exercise relative to the memory challenge. We assessed memory via paragraph recall, in which participants listened to two paragraphs (exposure) and recounted them following a 35-min delay. Participants (n = 48) were randomly assigned to one of…

  16. Long-Term Effects of Neurofeedback Treatment in Autism

    ERIC Educational Resources Information Center

    Kouijzer, Mirjam E. J.; de Moor, Jan M. H.; Gerrits, Berrie J. L.; Buitelaar, Jan K.; van Schie, Hein T.

    2009-01-01

    Previously we demonstrated significant improvement of executive functions and social behavior in children with autism spectrum disorders (ASD) treated with 40 sessions of EEG neurofeedback in a nonrandomized waiting list control group design. In this paper we extend these findings by reporting the long-term results of neurofeedback treatment in…

  17. The Basics of Long-Term Debt Issuance and Management

    ERIC Educational Resources Information Center

    Van Meter, Christine M.

    2011-01-01

    Issuing long-term debt can be a complex, multifaceted process. Although the process varies by stare, typically the school business official and the district solicitor work with the financing ream, which includes a financial adviser, bond counsel, underwriter, raring agency, and possibly a bond insurance agent, paying agent, and architect.…

  18. Long-term Toxicity of Cancer Treatment in Older Patients.

    PubMed

    Shahrokni, Armin; Wu, Abraham J; Carter, Jeanne; Lichtman, Stuart M

    2016-02-01

    With earlier cancer diagnosis among older patients with cancer, the possibility of curing cancer increases. However, cancer treatment may have a long-lasting impact on older cancer survivors. It is vital to screen, diagnose, and properly manage the long-term toxicities of cancer treatment in order to maintain the quality of life of older cancer survivors. PMID:26614861

  19. Weight-Loss Surgery Sheds Pounds Long Term

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_160719.html Weight-Loss Surgery Sheds Pounds Long Term 10-year follow- ... 31, 2016 WEDNESDAY, Aug. 31, 2016 (HealthDay News) -- Weight-loss surgery helps people drop a significant amount of ...

  20. Predictors of Home Based Long-Term Care Services.

    ERIC Educational Resources Information Center

    Luppens, Jean; And Others

    An attempt was made to determine predictors of service need, use, and outcome among chronically impaired adults and aged who were living in the community and using the home-based, long term care services of the Chronic Illness Center (CIC) of the Cuyahoga County Hospitals (Ohio). Randomly selected consumer service records (N=200) were coded for…

  1. Investment in Skills Must Be for the Long Term

    ERIC Educational Resources Information Center

    Field, John

    2009-01-01

    Since the 1980s, researchers have formed a much better understanding of how unemployment scars people's lives, not just in the short term, but sometimes for years ahead. Researchers differ on the details, but no one disagrees that the negative effects are serious and long term. In the recession of the 1980s, government schemes to improve people's…

  2. European Agency Leader Urges Long-Term Environmental Policy

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    2014-11-01

    A 23 October agreement by European Union (EU) leaders to reduce domestic greenhouse gas emissions is a good example of developing and implementing a needed long-term, sustainable environmental policy agenda for Europe. So says Hans Bruyninckx, executive director of the European Environment Agency (EEA), an EU agency.

  3. Gender-Based Violence in India: Long-Term Trends

    ERIC Educational Resources Information Center

    Simister, John; Mehta, Parnika S.

    2010-01-01

    This article examines long-term trends in Indian society regarding domestic violence between husband and wife, and attitudes to such violence. This article analyzes crime data and uses data from several Indian household surveys: "Work Attitudes and Spending" surveys (1992 to 2007); "World Values Survey" (1990, 1995, 2001, and 2006); and…

  4. Long-Term Adaptation to Institutionalization in Dementia Caregivers

    ERIC Educational Resources Information Center

    Gaugler, Joseph E.; Pot, Anne Margriet; Zarit, Steven H.

    2007-01-01

    Purpose: Longitudinal research in dementia has acknowledged the importance of transitions during the course of family caregiving. However, long-term adaptation to institutionalization has received little attention. This study attempts to describe caregivers' adaptation (changes in stress, well-being, and psychosocial resources) to placement up to…

  5. Neural correlates of long-term intense romantic love.

    PubMed

    Acevedo, Bianca P; Aron, Arthur; Fisher, Helen E; Brown, Lucy L

    2012-02-01

    The present study examined the neural correlates of long-term intense romantic love using functional magnetic resonance imaging (fMRI). Ten women and 7 men married an average of 21.4 years underwent fMRI while viewing facial images of their partner. Control images included a highly familiar acquaintance; a close, long-term friend; and a low-familiar person. Effects specific to the intensely loved, long-term partner were found in: (i) areas of the dopamine-rich reward and basal ganglia system, such as the ventral tegmental area (VTA) and dorsal striatum, consistent with results from early-stage romantic love studies; and (ii) several regions implicated in maternal attachment, such as the globus pallidus (GP), substantia nigra, Raphe nucleus, thalamus, insular cortex, anterior cingulate and posterior cingulate. Correlations of neural activity in regions of interest with widely used questionnaires showed: (i) VTA and caudate responses correlated with romantic love scores and inclusion of other in the self; (ii) GP responses correlated with friendship-based love scores; (iii) hypothalamus and posterior hippocampus responses correlated with sexual frequency; and (iv) caudate, septum/fornix, posterior cingulate and posterior hippocampus responses correlated with obsession. Overall, results suggest that for some individuals the reward-value associated with a long-term partner may be sustained, similar to new love, but also involves brain systems implicated in attachment and pair-bonding.

  6. Security basics for long-term care facilities.

    PubMed

    Green, Martin

    2015-01-01

    The need for Long-Term Care (LTC) facilities is growing, the author reports, and along with it the need for programs to address the major security concerns of such facilities. In this article he explains how to apply the IAHSS Healthcare Security Industry Guidelines and the Design Guidelines to achieve a safer LTC facility.

  7. Long-Term Teacher Effects on Pupils' Learning Gains

    ERIC Educational Resources Information Center

    Bressoux, Pascal; Bianco, Maryse

    2004-01-01

    Many studies have demonstrated that a teacher has a substantial impact on how much pupils learn. However, research on the long-term effects of teachers is scarce, and the results obtained so far are inconsistent. Some studies have concluded that teacher effects are relatively permanent, while others claim that they fade away more or less rapidly…

  8. PLUME-SCALER-EVALUATING LONG-TERM MONITORING WELL NETWORKS

    EPA Science Inventory

    EPA's Subsurface Protection and Remediation Division is developing a new computer application called PLUME-SCALER to evaluate long term monitoring well networks using typically available historical site water level data. PLUME-SCALER can be used to determine if there are enough ...

  9. An Empirical Study of Long Term Effects of Education.

    ERIC Educational Resources Information Center

    Harnqvist, Kjell

    A large-scale study of Swedish men and women, each of whose intelligence level at age 13 was above the 25th percentile and whose father's education was only at the elementary level, was conducted in order to determine what educational level the participants had achieved and to study long-term effects of schooling. Subjects were sent questionnaires…

  10. 41 CFR 51-6.3 - Long-term procurements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 41 Public Contracts and Property Management 1 2010-07-01 2010-07-01 true Long-term procurements. 51-6.3 Section 51-6.3 Public Contracts and Property Management Other Provisions Relating to Public... ensure stability of employment and development of job skills for persons who are blind or have...

  11. Long-Term Impact of Service Learning in Environmental Studies

    ERIC Educational Resources Information Center

    MacFall, Janet

    2012-01-01

    Long-term impacts from a senior course in Environmental Studies were evaluated by a survey of program graduates (36 respondents, 50% response rate) who had participated in the course over an 8-year permiod. Each year, the Senior Seminar used a service-learning pedagogy with a different environmentally focused project ranging from web resource…

  12. Increasing long term response by selecting for favorable minor alleles

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Long-term response of genomic selection can be improved by considering allele frequencies of selected markers or quantitative trait loci (QTLs). A previous formula to weight allele frequency of favorable minor alleles was tested, and 2 new formulas were developed. The previous formula used nonlinear...

  13. 24 CFR 971.5 - Long-term viability.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Long-term viability. 971.5 Section...-term viability. (a) Reasonable investment. (1) Proposed revitalization costs for viability must be... ensure viability and to sustain the operating costs that are described in paragraph (a)(2) of...

  14. 40 CFR 52.29 - Visibility long-term strategies.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... plan which has been disapproved for not meeting the requirements of 40 CFR 51.306 regarding the... ascribed to them in the Clean Air Act, or in the protection of visibility program (40 CFR 51.301). (c) Long... 40 Protection of Environment 3 2011-07-01 2011-07-01 false Visibility long-term strategies....

  15. Experimental protocols and preparations to study respiratory long term facilitation

    PubMed Central

    Mateika, Jason H.; Sandhu, Kulraj S.

    2011-01-01

    Respiratory long-term facilitation is a form of neuronal plasticity that is induced following exposure to intermittent hypoxia. Long-term facilitation is characterized by a progressive increase in respiratory motor output during normoxic periods that separate hypoxic episodes and by a sustained elevation in respiratory activity for up to 90 min after exposure to intermittent hypoxia. This phenomenon is associated with increases in phrenic, hypoglossal or carotid sinus nerve inspiratory-modulated discharge. The examination of long-term facilitation has been steadily ongoing for approximately 3 decades. During this period of time a variety of animal models (e.g. cats, rats and humans), experimental preparations and intermittent hypoxia protocols have been used to study long-term facilitation. This review is designed to summarize the strengths and weaknesses of the models, preparations and protocols that have been used to study LTF over the past 30 years. The review is divided into two primary sections. Initially, the models and protocols used to study LTF in animals other than humans will be discussed, followed by a section specifically focused on human studies. Each section will begin with a discussion of various factors that must be considered when selecting an experimental preparation and intermittent hypoxia protocol to examine LTF. Model and protocol design recommendations will follow, with the goal of presenting a prevailing model and protocol that will ultimately ensure standardized comparisons across studies. PMID:21292044

  16. Long-Term Parental Illness and Children: Perils and Promises.

    ERIC Educational Resources Information Center

    Johnston, Mona; And Others

    1992-01-01

    Discusses effects of long-term parental illness, focusing on effects on children. Describes effects on family homeostasis and family coping mechanisms. Discusses school counselor's role in bringing about a more balanced viewpoint of power and sharing within the family. Recommends establishing a strong therapeutic bond, assessing what the child is…

  17. Long-Term Marriage and Late-Life Divorce.

    ERIC Educational Resources Information Center

    Peters, Elana

    Projections, based on current rates, are that 40% of recent marriages will end in divorce. To investigate the factors associated with long term marriage stability and satisfaction among elderly persons, 60 California older adults (30 married, 30 divorced) were interviewed about their perceptions of the role of companionship, alternatives to…

  18. Sexuality and Aging: Implications for Long Term Care.

    ERIC Educational Resources Information Center

    Hinkley, Nancy E.

    With increasing emphasis on treating the whole person, on the maintenance of an individual's former life style, and on patients' rights, long-term care personnel need to become aware that many nursing home residents experience needs related to their sexuality. A model two-day workshop is presented wlth a focus on the following topics: (1) a broad…

  19. Long Term Treatment Concepts and Proactive Therapy for Atopic Eczema

    PubMed Central

    Ehmann, Laura Maximiliane

    2012-01-01

    Atopic eczema, also known as atopic dermatitis, is a frequent, highly pruritic, chronic skin disease, which is typically running in flares. The traditional treatment mainly consists of the reactive application of topical anti-inflammatory agents such as topical corticosteroids and topical calcineurin inhibitors. The short term benefit of this approach is well known, but long term remission between flares is difficult to achieve. Therefore, innovative long-term treatment strategies targeting flare prevention and skin barrier stabilization are needed. We and others have shown that normal looking, non-lesional skin of atopic dermatitis patients is immunobiologially not normal but characterized by an invisible inflammation and barrier defect. This has led to the novel concept of proactive therapy, which is defined as long-term, low-dose intermittent application of anti-inflammatory therapy to the previously affected skin, together with an ongoing emollient treatment of unaffected skin. This review article describes the most important long-term treatment options for atopic dermatitis, which includes emollient therapy, the novel concept of proactive treatment, the different ultraviolet light modalities and a selection of systemic immunosuppressive drugs and biologics. Current trial data, licensed indications, off-label use and relevant side effects of the different treatment modalities are summarized. PMID:22879707

  20. Long term management practices influenced soil aggregation and carbon dynamics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Soil aggregation protects soil organic C (SOC) against rapid decomposition, improves soil quality, and reduces soil erosion potential. The objectives of this study are to evaluate the effects of long-term (21 yrs.) management practices on SOC, water stable aggregate (WSA), and aggregate-associated ...