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BioMed Research International
Volume 2014, Article ID 109786, 11 pages
Targeting the Glutamatergic System to Treat Pathological Gambling: Current Evidence and Future Perspectives
1Institute of Psychiatry and Psychology, Catholic University of the Sacred Heart, Largo Agostino Gemelli 8, 00168 Rome, Italy
2Department of Neuroscience and Imaging, "G. d'Annunzio" University, Chieti, Italy
Received 28 February 2014; Accepted 22 May 2014; Published 12 June 2014
Academic Editor: Sophia Achab
Copyright © 2014 Mauro Pettorruso et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Pathological gambling or gambling disorder has been defined by the DSM-5 as a behavioral addiction. To date, its pathophysiology is not completely understood and there is no FDA-approved treatment for gambling disorders. Glutamate is the principal excitatory neurotransmitter in the nervous system and it has been recently involved in the pathophysiology of addictive behaviors. In this paper, we review the current literature on a class of drugs that act as modulating glutamate system in PG. A total of 19 studies have been included, according to inclusion and exclusion criteria. Clinical trial and case series using glutamatergic drugs (N-acetylcysteine, memantine, amantadine, topiramate, acamprosate, baclofen, gabapentin, pregabalin, and modafinil) will be presented to elucidate the effectiveness on gambling behaviors and on the related clinical dimensions (craving, withdrawal, and cognitive symptoms) in PG patients. The results have been discussed to gain more insight in the pathophysiology and treatment of PG. In conclusion, manipulation of glutamatergic neurotransmission appears to be promising in developing improved therapeutic agents for the treatment of gambling disorders. Further studies are required. Finally, we propose future directions and challenges in this research area.
1. Background
Pathological gambling (PG) is characterized by persistent and maladaptive gambling behavior, whereby individuals engage in frequent and repeated episodes of gambling despite serious adverse consequences [1]. Gambling disorder affects 0.2–5.3% of adults worldwide; the devastating consequences of this behavioral disturbance often entail severe damage to the lives of patients and their families. To date, there is no FDA-approved treatment for PG, despite almost a decade of intense research, and effective treatment strategies remain very challenging. Recently, PG has been included in the diagnostic category of substance use and addictive disorders in the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V).
Glutamate (Glu) is the principal excitatory neurotransmitter in the nervous system. It has been recently proposed that addiction can be viewed as the result of an impaired ability to inhibit drug seeking in response to environmental contingencies, due to alterations in Glu homeostasis, with combined activation of sensitized dopamine (DA) and N-methyl-d-aspartate (NMDA) glutamatergic receptors [2]. Blocking the release of Glu has prevented drug seeking behaviors in animals as well as patients with substance use disorders [3, 4]. The clinical and biological similarities between PG and drug addiction [5] suggest that PG patients may benefit from medication used to treat drug addiction and that pathophysiological models for drug addiction may be relevant to PG as well.
In this paper, we review the current literature on drugs that modulate glutamatergic neurotransmission in PG. We also elucidate current hypotheses on the neurobiology of PG, focusing on glutamatergic neurotransmission and its interactions with other neurotransmitters. Clinical trials and case series using glutamatergic drugs will be presented to elucidate the effectiveness on gambling behaviors and on the related clinical dimensions (craving, withdrawal, and cognitive symptoms) in PG patients. The results will be discussed to gain more insight into the pathophysiology and treatment of PG. Finally, we propose future directions and challenges in this research area.
2. Methods
Two reviewers were separately engaged in this review, following the same bibliographic search and data extraction protocol. Bibliographic search consisted of a computerized screening of Medline, Scopus, and Google Scholar database in January 2014. Only English language studies published in the last ten years were reviewed. We used the following queries: "gambl*" combined with "glutamate" and with a list of glutamatergic neurotransmission-modulating agents including N-acetylcysteine, memantine, amantadine, acamprosate, topiramate, lamotrigine, baclofen, gabapentin, pregabalin, modafinil, riluzole, dizocilpine, LY354740, D-cycloserine, methadone, and dextromethorphan. The search initially yielded 99 results. We then hand-searched relevant references of each article, including earlier studies on the topic.
Of the 99 potential articles, 19 were included (Figure 1) according to the following criteria: (a) the target problem is PG; (b) the abstract is available; (c) the publication is an original paper, excluding reviews; (d) the study is a neurobiological or a clinical research on PG subjects.
Table 1 shows relevant data from the articles included in the study: drug used, dosage, study design, sample size and targeted population, methods, cognitive outcome, and main finding on gambling outcome.
3. Glutamatergic Transmission in Addictive Behaviors: Relevance for Pathological Gambling
Glu is the most prevalent excitatory neurotransmitter in the CNS and its action is regulated by two types of receptors: the ionotropic (iGlu) and metabotropic (mGlu) receptors. The ionotropic receptors are ion channels that, upon Glu binding, increase the influx of sodium and potassium cations causing depolarization of the membrane [19]. They are divided into three subtypes: N-methyl-D-aspartate (NMDA), -amino-3-hydroxy-5-methyl-4-isoazole-propionic acid (AMPA), and kainate. The metabotropic receptors are G protein-coupled receptors and are divided into three groups (I, II, and III) based on the homology of the sequences, the mechanism of signal transduction, and their pharmacological selectivity [20]. The metabotropic receptors are located primarily in the limbic and frontal areas, which are specifically involved in the mechanisms of addiction. In particular, receptors of group I seem to have an important role in the regulation of the reinforcing effects of drugs, while type II receptors are implicated in synaptic changes that occur as a result of prolonged exposure to the drug and in withdrawal syndromes [21]. Following abuse of any substance, increased glutamatergic transmission occurs in the limbic system and the prefrontal cortex which seems to be responsible, first and foremost, a greater release of DA, and also DA-dependent effects. In particular, while phenomena such as sensitization, craving, relapse, and reinforcement are linked to changes in both dopaminergic and glutamatergic systems, specific context and conditioned behaviors related to substance use primarily depend on glutamatergic mechanisms [22]. Summarily, the glutamatergic-dopaminergic system (in the nucleus accumbens) is responsible for the onset of "drug seeking," while relapse only involves the glutamatergic system [23]. Reduction of extracellular glutamate levels in the limbic areas seems to be closely related to the withdrawal syndrome from psychostimulants; metabotropic glutamate receptor agonists seem to be able to reduce craving and prevent relapse via a compensation mechanism. Also, antagonists of metabotropic receptors hinder the behavioral effects of cocaine, nicotine, and alcohol, and NMDA antagonists are potential candidates for the treatment of opiate, alcohol, and sedative withdrawal syndromes [24].
PG has been presumed to be modulated mainly by brain DA and Glu, though findings are contrasting. DA is implicated in rewarding, reinforcing, and addictive behaviors. In drug addiction, data support the existence of a hypodopaminergic state at both the presynaptic and postsynaptic levels [25]. While DA release may reinforce learning [26, 27], Glu may be implicated in long-lasting neuroadaptations in the corticostriatal circuitry that represents the putative neural substrate of enduring vulnerability to relapse [2]. Glu is involved in learning and memory and may activate different types of Glu receptors, including NMDA receptors expressed in brain regions comprising reward circuitry [2]. Levels of Glu within the nucleus accumbens mediate reward-seeking behavior [2]. Pathological gamblers report euphoric feelings during gambling episodes, comparable to the "high" in substance use, thus making them more prone to continued gambling. In addition, preliminary reports showed a reduction of hedonic capacity in response to stimuli usually perceived as rewarding [28]. By continued gambling, the salience attribution to the behavior is strengthened and induces cue reactivity which can result in craving phenomena and potentially further enhancement of DA neurotransmission. Finally, continued gambling and subsequent altered DA neurotransmission could lead to neuroadaptation in mesolimbic-prefrontal glutamatergic pathways [29]. Chronic drug intake is associated with neuroadaptation of glutamatergic neurotransmission in the ventral striatum and limbic cortex [30]. In addition, cue exposure has been found to depend on strong projections of glutamatergic neurons from the prefrontal cortex to the nucleus accumbens [31]. Repetitive behaviors closely followed by rewards increase extracellular Glu levels [32]. In one study, cerebrospinal fluid (CSF) levels of glutamic and aspartic acid, both of which bind to NMDA receptors, were elevated among PG patients as compared to control subjects [33]. The imbalance in Glu homeostasis engenders changes in neuroplasticity which impair communication between the prefrontal cortex and the nucleus accumbens, thus favoring engagement in reward-seeking behaviors, such as PG [34].
4. Glutamatergic Treatment Strategies in Pathological Gambling
Manipulation of glutamatergic neurotransmission is a relatively young but promising avenue for the development of improved therapeutic agents for the treatment of drug and behavioral addictions [10, 35]. Substantial evidence has accumulated indicating that ligands acting on glutamatergic transmission are also of potential utility in the treatment of drug addiction, as well as various behavioral addictions such as pathological gambling. Growing evidence suggests that the glutamatergic system is central to the neurobiology and treatment of mood disorders [36] and that it could represent a valuable target in PG with comorbid conditions [37].
4.1. N-Acetylcysteine
N-Acetylcysteine (NAC), a cysteine prodrug and amino acid, can increase extracellular levels of Glu concentration in the nucleus accumbens and has shown preliminary efficacy in treating substance addictions [38, 39]. NAC may stimulate inhibitory metabotropic Glu receptors, possibly causing a reduction in synaptic release of glutamate. Studies in rat populations show that NAC is effective in reducing reward-seeking behavior [40] and preliminary data in PG are encouraging.
NAC was found to be effective in reducing gambling urges and behavior (lower scores on the Yale-Brown Obsessive Compulsive Scale modified for PG (PG-YBOCS)) in a small clinical trial [14]. Twenty-seven PG subjects (12 women) were treated for 8 weeks with NAC (mean dose was 1476.9 ± 311.3 mg/day). Responders were randomized in a 6-week double-blind discontinuation trial (NAC vs placebo). A significantly higher percentage of subjects treated with NAC still meet responder criteria at the end of the study (83.3% in NAC versus 28.6% in placebo group). In addition, a recent RCT confirmed the efficacy of NAC augmentation of behavioral therapy in the treatment of PG [15]. The study was conducted on 28 subjects with cooccurring nicotine dependence and PG. They received behavioral therapy and were randomized to augmentation with NAC (up to 3,000 mg/day) or placebo in a double-blind trial. During the final 3-month followup, there was a significant additional benefit for NAC versus placebo on gambling severity measures (PG-YBOCS).
Several matters remain unresolved. The optimal dose of NAC for PG is still unknown. The dose used in the augmentation-RCT was notably higher than that used in the previous study. According to preclinical data in rats, lower concentrations of NAC inhibit Glu transmission in the nucleus accumbens core while higher concentrations countermand this effect [41]. Given NAC glutamatergic properties and glutamate's role in learning and memory in addictive processes [42], its use has been proposed for patients who report craving to gamble and for those who are also undergoing an exposure-based psychosocial intervention.
4.2. Memantine
Memantine, a noncompetitive antagonist at the NMDA receptor with neuroprotective properties, is approved for Alzheimer's disease and is increasingly being studied in a variety of psychiatric disorders [43]. In PG patients memantine decreased PG-YBOCS scores and time spent gambling, also improving neurocognitive function related to cognitive flexibility [11]. Twenty-nine subjects were enrolled in a 10-week open-label trial. After memantine treatment (10–30 mg/day), PG-YBOCS scores and hours spent gambling decreased significantly. In addition, subjects underwent pre- and posttreatment cognitive assessment using the stop-signal task and the intradimensional/extradimensional (IDED) set shift task to assess impulsivity and cognitive flexibility, respectively. At study endpoint, a significant improvement in IDED performance was found, probably due to memantine modulation of glutamatergic transmission in PFC [44]. Nonetheless, the extent to which memantine exerts its influences on gambling behaviors through effects on impulsivity or compulsivity is still unclear [45].
A clinical case study reports effectiveness of memantine in the treatment of a 23-year-old patient with obsessive-compulsive disorder, body dysmorphic disorder, and severe PG [12]. A clinical response was observed after 8 weeks of memantine treatment, with more control over gambling and less anticipatory tension and excitation.
Memantine seems to reduce Glu excitability and improve impulsive decision-making. In addition, it shows promise in the treatment of cognitive and compulsive symptoms in PG patients [11, 45].
4.3. Amantadine
Amantadine, an antiglutamatergic drug with additional actions on dopaminergic neurotransmission, has been evaluated in treating PG and other compulsive behaviors in individuals with Parkinson's disease [9, 46]. Conflicting data have been reported regarding use of amantadine among Parkinson's disease patients [47]. It was found to be safe and effective in 17 patients with PG, reducing or stopping gambling urges and behaviors [9]. In a cross-sectional study amantadine was associated with PG and other impulse control disorders [48].
In addition, a case study suggested the possible utility in the treatment of PG patients [8]. A significant improvement on gambling symptoms suggests that simultaneous pharmacological modulation of the glutamatergic and dopaminergic systems may reduce gambling in PG, possibly reversing neuroplasticity-based pathological changes determined by addictive behaviors [2].
4.4. Topiramate
Topiramate is a glutamatergic antagonist and pro-GABAergic drug that significantly reduces impulsive behavior and compulsiveness. It has been tested and found to be effective versus placebo in disorders in which impulsivity and craving represent core features, such as alcohol dependence, cocaine dependence, bulimia nervosa, and binge eating disorder. In addition, it has recently been proposed that topiramate is also an antagonist of AMPA receptors, a Glu receptor subtype that mediates relapse-like behaviors and is implicated in the neuroadaptive changes produced by drugs of abuse as well [49].
A 14-week, randomized, double-blind, placebo-controlled trial investigated topiramate in PG [17]. Though no significant differences between the placebo group and the topiramate-treated group were observed with respect to primary outcome measures (change in the obsessions subscale of the PG-YBOCS), topiramate reduced impulsivity (particularly, motor and nonplanning impulsivity), as measured with the Barratt Impulsiveness Scale (BIS). The authors suggest that topiramate could be useful in PG subgroups characterized by high levels of impulsivity. Dannon et al. [16] compared the effectiveness of topiramate versus fluvoxamine in the treatment of PG in a 12-week, blind-rater comparison trial. Though the authors conclude that both topiramate and fluvoxamine monotherapies may be effective in the treatment of PG, improvement on the PG-CGI for fluvoxamine did not quite reach statistical significance. Also, a smaller number of dropouts were reported in the topiramate group.
In addition, in a patient with bipolar disorder and comorbid PG, Nicolato et al. [18] reported full remission of gambling craving and behavior after topiramate was added to standard lithium treatment.
4.5. Acamprosate
Acamprosate (calcium acetylhomotaurinate) is a taurine derivative and a nonspecific GABA agonist that promotes a balance between excitatory and inhibitory neurotransmitters (Glu and GABA). It binds specifically to GABAB receptors and appears to block Glu receptors and inhibit hyperactive glutamatergic signaling [50]. Although there is accumulated evidence suggesting that acamprosate interferes with the Glu system by antagonizing NMDA receptor activity [51], its mechanism of action still remains unclear. Recent findings suggest the involvement of calcium-mediated pathways [52]. These inconsistencies are perhaps related to factors such as brain region examined, NMDA receptor subunit composition, state of neuronal excitation, and the presence of various endogenous NMDA receptor neuromodulators such as polyamines [50, 53]. Acamprosate has been approved by the FDA for alcohol dependence. Restoring the imbalance between excitatory and inhibitory neurotransmissions caused by chronic alcohol exposure [53], it has been found to raise the continuous alcohol abstinence rate and double the days of cumulative abstinence from alcohol [54].
Contrasting results have been reported on its use in PG treatment [55]. In an 8-week, open-label trial following a 2-week observation, acamprosate significantly improved PG-YBOCS and Gambling Severity Assessment Scale (G-SAS) scores, both CGI scales, and number of gambling episodes [6]. Twenty-six patients received the medication (1,998 mg/day). The primary efficacy measure was the PG-YBOCS. Secondary efficacy measures included the G-SAS, the Clinical Global Impression (CGI) Improvement and Severity scales, a patient self-rated global rating, the Hamilton Depression Rating Scale (HDRS), the Sheehan Disability Scale (SDS), and the timeline follow back (TLFB).
In contrast, a parallel study failed to confirm its effectiveness on gambling behavior [7]. In this open-label study, 8 pathological gamblers treated with acamprosate 999 mg/day were evaluated monthly for 6 months to assess relapse. None of the patients attained 6 months of abstinence, defined as the absence of any gambling behavior during the month preceding the follow-up visit. VAS scores at baseline, after 1 month, and at relapse showed no statistically significant differences. No validated scales were employed to determine the effectiveness of acamprosate on gambling urges and craving.
4.6. Baclofen
Baclofen (beta-(4-chlorophenyl)-GABA) is a GABAB receptor agonist that has been found to suppress both acquisition of alcohol drinking behaviors in rats and daily alcohol intake in alcohol experienced rats. By inhibiting multivesicular release from the presynaptic terminal, it decreases synaptic Glu signaling [56] and inhibits Ca2+ permeability of NMDA receptors. In rats, it also suppresses alcohol-stimulated dopamine release in the shell of the nucleus accumbens [57].
In an open-label trial [7], 9 patients receiving baclofen were evaluated on a monthly basis in order to assess measures of sustained improvement (i.e., abstinence) and relapse. None of the patients attained 6 months of abstinence, defined as the absence of any gambling behavior during the month preceding the follow-up visit; only one patient receiving baclofen attained 4 months of abstinence. VAS scores at baseline, after 1 month, and at relapse showed no statistically significant differences.
4.7. Gabapentin and Pregabalin
Anticonvulsants, like gabapentin and pregabalin, have multiple mechanisms of action, including inhibition of presynaptic voltage-gated Na+ and Ca2+ channels, thereby inhibiting the relapse of neurotransmitters including glutamate. Gabapentin modulates both GABAergic and glutamatergic neurotransmissions. Several authors have explored the use of gabapentin in substance use disorders. Gabapentin reverses GABA deficits and Glu excess thought to underlie alcohol withdrawal and early abstinence. It reduces alcohol consumption and craving, thereby facilitating abstinence [58]. Pregabalin is a structural analog of GABA, similar to gabapentin. It also reduces excitatory neurotransmitter release and postsynaptic excitability. The FDA has approved pregabalin for partial epilepsy, neuropathic pain, and generalized anxiety disorders. In addition, pregabalin has been extensively studied in alcohol and benzodiazepine dependence [59]. A 6-month pilot trial preliminarily investigated the potential utility of their use in PG patients (6 patients received pregabalin; 4 patients received gabapentin), with a reduction of gambling craving as measured by G-SAS [10]. Also, pregabalin has been used to treat a case of citalopram-associated gambling onset [60]. Future studies should investigate the use of gabapentin and pregabalin in the treatment of PG, given that this drug seems to specifically target the central features of impulsivity, anxiety, and craving.
4.8. Modafinil
Modafinil is an atypical stimulant, originally designed to enhance wakefulness and vigilance in the treatment of narcolepsy and sometimes prescribed as an off-label treatment for attention-deficit/hyperactivity disorder (ADHD). Although its mechanisms of action are not completely understood, modafinil does not appear to act as a monoamine releaser as is the case for amphetamine-like stimulants. Rather, modafinil may act by stimulating -adrenoceptors, suppressing GABA release, weakly inhibiting the dopamine transporter, or stimulating hypothalamic orexin-containing neurons [61, 62]. While most studies suggest a dopaminergic basis for its stimulant effects [63], modafinil has been shown to elevate extracellular levels of glutamate in numerous brain regions including the dorsal striatum, hippocampus, and diencephalon without affecting glutamate synthesis [35, 64]. Numerous clinical reports have shown that modafinil demonstrates potential efficacy in the treatment of cocaine addiction [62].
Zack and Poulos [13], in a placebo-controlled double-blind trial, tried to determine if modafinil (mean dose 200 mg/day) reduces the reinforcing effects of slot machine gambling in PG subjects and if this effect is stronger in high versus low impulsivity subjects (). Bet size declined uniformly in both high and low impulsivity participants taking modafinil. In high impulsivity participants, modafinil decreased desire to gamble, salience of gambling words, disinhibition, and risky decision-making. In low impulsivity participants, modafinil increased scores on these indices. The results showed that modafinil had bidirectional effects in the two groups. The same sample of patients was reevaluated in a prospective study, with clinical results highlighting that modafinil may discourage pathological gamblers from chasing losses but also encourage them to continue betting, rather than quitting while they are ahead [65]. Also, it has been reported a case of clear-cut temporal relationship between modafinil treatment and pathological gambling in a 39-year-old patient with a history of narcolepsy and associated cataplexy [66].
5. Discussion
There is substantial evidence indicating that pharmacological treatments targeting glutamatergic transmission are of potential utility in the treatment of drug addiction. Given that neurobiological findings indicate that PG and drug addiction share common etiopathological pathways [5, 45], drugs targeting glutamatergic transmission could be of use for the treatment of behavioral addictions (i.e., PG) as well.
The data seem to confirm the utility of targeting the glutamatergic system for the treatment of PG, in particular by acting on craving and increasing treatment retention [10, 15]. Glutamatergic medications may, in fact, offer some advantages in preventing relapse [4]. It has been recently proposed that addiction can be viewed as the result of an impaired ability to inhibit drug seeking in response to environmental contingencies, due to alterations in Glu homeostasis, with combined activation of sensitized DA and NMDA glutamatergic receptors [2]. Glutamatergic drugs may regulate the complex interactions between the glutamatergic and dopaminergic systems, acting simultaneously on both systems, in ways that need to be better explored.
Studies discussed are not homogeneous with respect to the criteria used to evaluate the effectiveness of pharmacological treatments for PG. In fact, some studies consider the absence of gambling behavior as the primary outcome while overlooking important clinical dimensions including craving and withdrawal symptoms. Interestingly, research on glutamatergic drugs highlights the importance of pointing clinical attention to the detection and treatment of cognitive symptoms [29]. Pathological gamblers exhibit a pattern of decision-making that repeatedly ignores long-term negative consequences in order to obtain immediate gratification or relief from uncomfortable states associated with their addiction. A variety of cognitive and emotional processes influence decision-making [11]. These alterations (i.e., cognitive inflexibility) may contribute to deviant choice in PG patients and to the maintenance of the disorder, as indirectly confirmed by the potential efficacy of cognitive therapy focused on altering irrational gambling cognition [67]. Targeting this clinical dimension, throughout the pharmacological modulation of the glutamatergic system, could be a useful treatment perspective and needs further study.
Drugs that enhance decision-making and executive function abilities are less well known because of the complexity of these functions which comprise different subprocesses (i.e., reward, punishment sensitivity, and impulsivity). However, it can be argued that agents targeting these subprocesses may improve decision-making as well. In addition, cognitive enhancers such as modafinil might also have beneficial effects, particularly in high impulsivity subjects [13].
6. Future Perspectives
The data seem to confirm the utility of targeting the glutamatergic system for the treatment of PG, in particular by acting on craving and cognitive domains (impulsivity and cognitive inflexibility). While empirically validated treatments for PG have varying degrees of support, little is known about their mechanisms of action or how specific therapies might work better for specific individuals. Several studies have been conducted to test the efficacy of opioid antagonists in the treatment of the disorder, and a genetic predisposition or a family history of alcoholism has been hypothesized to regulate response to opioid antagonists across diagnostic groups [68]. Similarly, future studies should investigate the biological and psychological features of PG patients for whom glutamatergic treatment is appropriate. Based on current knowledge, we suggest clinical domains and comorbidity issues that may help guide the clinicians in the selection of appropriate glutamatergic treatment strategies (Figure 2). This model may provide the basis and rationale to guide the selection of pharmacotherapies in some groups of PG patients. Further investigations are certainly needed to confirm the treatment algorithm we propose.
Following cocaine administration, disrupted Glu homeostasis of nucleus accumbens core has been observed. A hallmark of disrupted homeostasis is a decrease in expression and function of the major Glu transporter, GLT-1 [69]. Future studies should investigate its role in PG and the potential utility of drugs that act to modulate the expression of Glu neurotransmitter transporters via gene activation (i.e., ceftriaxone) [70].
Besides Glu and DA, other factors, like brain-derived neurotrophic factor (BDNF), can be involved in the action of glutamatergic agents in PG [71]. Neurotrophic factors have been shown to be modulated by environmental events in various psychopathological conditions [72], and their role has been confirmed in the pathophysiology of PG [73]. Future studies should help understand the potential role of glutamatergic modulation on neurotrophins levels in PG patients.
Future investigations would benefit from placebo-controlled clinical trials to outline the true benefits of glutamatergic drugs for the treatment of PG. In addition, future research could profit from pharmacological challenges in combination with neuroimaging techniques to shed light on Glu role in the pathophysiology of PG. New neurobiological PG research should include matched controls, account for comorbidity issues, and differentiate between gambling preferences. Investigations in specific subgroups, therefore, are expected to give more insight into the pathophysiology of the disorder in these groups and perhaps lead to more tailored and efficient therapies. Future studies should also focus on the functional connections between dopaminergic and glutamatergic systems, in order to shed light upon the complex neurobiological mechanisms underlying the development of maladaptive gambling behavior.
|Pathological gambling
|α-amino-3-hydroxy-5-methyl-4-isoazole- propionic acid
|Gamma-aminobutyric acid
|Cerebrospinal fluid
|Randomized-controlled trial
|Yale-Brown Obsessive Compulsive Scale modified for PG
|Gambling Severity Assessment Scale.
Conflict of Interests
The authors declare that there is no conflict of interests regarding the publication of this paper.
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text:
Elementar.io Strategy
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subset: commoncrawl


text:
|Lance Stout
|★ (1)
What steps will reproduce the problem? 1. Using Prosody trunk, create a non-persistent MUC room 2. Have several users join the room 3. Explicitly send a room destroy command What is the expected output? What do you see instead? Expected result is that the `muc-room-destroyed` event will fire once. Instead it fires for every occupant in the room. What version of the product are you using? On what operating system? Prosody trunk (for new muc), Debian Please provide any additional information below. Looks to be caused by how these two handlers are interacting: https://hg.prosody.im/trunk/file/tip/plugins/muc/muc.lib.lua#l811 https://hg.prosody.im/trunk/file/tip/plugins/muc/mod_muc.lua#l123 The clear() method in muc.lib is emptying out the room occupants, and afterward triggering a muc-occupant-left event for each occupant. This muc-occupant-left handler in mod_muc is checking if the room is now empty, and firing muc-room-destroyed if so. Except that we just cleared out all of the occupants, so the room appears empty to all of the previous occupants.
Fixed in https://hg.prosody.im/trunk/rev/695904638cfa Thanks for the report. I stumbled upon this due to #1182Changes


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Sunday, March 1, 2009
One more administrative thing
Annoyed that another batch of images got slightly cut off in the display, I have fiddled around the with display parameters for the blog. Hopefully the changes should make it look more readable, but if they mess anything up for anyone or frightfully impinge upon your aesthetic sense, please let me know.
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Wednesday, October 9, 2013
Hearthstone Beta Key Giveaway!
107 comments:
Oooooh gimmie :D GLHFReplyDeleteReplies
Thanks for doing this :) My facebook is name is "Sarah C"ReplyDelete
Thanks for the chance at a key :)ReplyDelete
My facebook name is : Clément De Branches Pichon
- AnonymousOctober 9, 2013 at 1:08 PM
lets see who winsReplyDelete
FaceBook Akakai Thao
- Shawn McGawlseyOctober 9, 2013 at 1:09 PM
Would love a key, gl to everyone!ReplyDelete
Facebook name is Shawn McGawlsey
My Facebook is Peter R, I have been dreaming of playing this game since I first heard of it. Good luck to all!!ReplyDelete
Thank you for the chance :) my facebook name is Vitor CostaReplyDelete
Liked, Facebook name is Casey Schlegelmilch Email is email@example.com :)ReplyDelete
- AnonymousOctober 9, 2013 at 1:11 PM
Heres me:ReplyDelete
Facebook name is "Ben Swisegood". I have liked and commented, please, please, please pick me. :)ReplyDelete
Thanks for the opportunity my friend! I liked it and am hoping for the best :DReplyDelete
My facebook name is Donte Burgese. I have it locked up pretty tight so if you can't find it email me at firstname.lastname@example.com
- AnonymousOctober 9, 2013 at 1:13 PM
Liked and commented. Hope I win!ReplyDelete
Facebook: https://www.facebook.com/charon.skolovik
Hearthstone Forums: Mouserug
Thanks for the chance to get a key!
- AnonymousOctober 9, 2013 at 1:14 PM
Hi! Really like the page! Wish you and all other participants best of luck :) My FB name is Juraj Grega (im from US ;) ).ReplyDelete
I liked, really hoping to get this key. My friend got one yesterday, whereas I sadly didn't. Name is Jack Haveman, if you want to give the key wants to play for all aspects, lore and Warcraft history as well as for the gameplay, then im your guy!ReplyDeleteReplies
As i said below, my facebook profile page is:Delete
I am passionate about Warcraft: its lore, its characters, and its games. I want to TEST this beta as well as play it ASAP. You won't go wrong giving the key to someone like me, who is so enthralled with the Shaman lore, its cards (Bloodlust and Windfury speak to my Enhancement Shaman heart!). Btw no pun intended with the "enThralled" part of my post. Definitely looking forward to building my Shaman deck!
- AnonymousOctober 9, 2013 at 1:17 PM
Thank you for the opportunity!ReplyDelete
Liked this website and my facebook name is "Jeong Michael Heo"
- AnonymousOctober 9, 2013 at 1:17 PM
Wouldnt mind winning the key :PReplyDelete
my FB: https://www.facebook.com/benjamin.presutti
- AnonymousOctober 9, 2013 at 1:25 PM
Fingers crossedReplyDelete
Solar McFallon
(Yes it is my gaming facebook, it takes a bit more than a key to get into my personal facebook's pants)
This comment has been removed by the author.ReplyDelete
- AnonymousOctober 9, 2013 at 1:28 PM
Thanks for the giveaway, been waiting since the announciment!ReplyDelete
Facebook = Henrique Pesci
I am not going to beg like some of the people on the Blizzard forum. If I get the key hooray, if not o well.ReplyDelete
Douglas Toms
Facebook is Will Dixon, thanks for doing this :)ReplyDelete
I would love one for my husband! Thank you for the chance! My fb name is Kyla PattonReplyDelete
My Facebook is Anton Van Metre. Hope I win!!! It would mean a lot :DReplyDelete
Thank you for the chance to win a key!ReplyDelete
Liked you on Facebook as Jason Crooks
Hey, Buddy Patton here, would love to play.ReplyDelete
Hope to get in, cool offer.ReplyDelete
Nice website, Chris.ReplyDelete
- Jerome QuintinOctober 9, 2013 at 2:33 PM
Hopefully this is it for meReplyDelete
- Kote LockeOctober 9, 2013 at 2:48 PM
liked, name is Kote LockeReplyDelete
You're very lucky! ~ Sally SmithReplyDelete
- Jared HowardOctober 9, 2013 at 6:33 PM
Well ive pretty much given up hope for ever getting a key for this game but maybe this is the time!ReplyDelete
- AnonymousOctober 9, 2013 at 9:38 PM
Liked. FB name is Wk Trail.ReplyDelete
This comment has been removed by the author.ReplyDelete
I wish I could win this key so I can play with my Brother who lives in america, its the only way we connect :(ReplyDelete
Carlo Carbone on Facebook
Thank you for your generosityReplyDelete
FB name: Jason Chiang
- GrystorOctober 9, 2013 at 9:51 PM
I would love to win this key, been waiting with no luck so far, so it seems giveaway's are probably my best chance of actually seeing one....ReplyDelete
facebook name is Jon Morley.
- AnonymousOctober 9, 2013 at 9:55 PM
Would really love it!ReplyDelete
Facebook name is Travis Caryofilles
Would love the key.ReplyDelete
Facebook name is Matt Neubauer
Liked. My Facebook name is Ron AccettulloReplyDelete
Thanks for the opportunity...name on FB is James ClarkReplyDelete
Thanks for giving this away and not selling it, good luck to everyone! FB is https://www.facebook.com/russell.story.5?fref=ts.ReplyDelete
- AnonymousOctober 9, 2013 at 10:31 PM
Dying to get a chance to play, thanks for being generous and keeping it in community! My facebook account is Wil HowellReplyDelete
Thanks for the quick and short giveaway! All of us that don't have a key yet really appreciate it.ReplyDelete
This comment has been removed by the author.ReplyDelete
This comment has been removed by the author.ReplyDelete
My facebook name is Joe Nguyen. I'm here for the beta key. Thank you so much.ReplyDeleteReplies
Liked you on facebook. Names Jason C.ReplyDelete
good luck everyone!
- AnonymousOctober 9, 2013 at 11:27 PM
would love to be able to play with my friend and stop him shit talking me for not having it.
well good luck everyone :)ReplyDeleteReplies
my facebook account is email@example.com i use that because i do not like my private info on places like facebook :)Delete
- AnonymousOctober 9, 2013 at 11:53 PM
Liked the facebook page. Thanks for the giveaway!
Thanks for this appreciate the giveaway facebook name is Esteban GuillenReplyDelete
Thank you for creating a fair giveaway that anyone can participate in.ReplyDelete
Hope to see you in the beta or full game~ Good luck to everyone else too! :)
- Patrick Morre (https://www.facebook.com/patrick.morre.3)
- Colby OlsonOctober 10, 2013 at 12:36 AM
Thanks for doing a fair giveaway.ReplyDelete
Colby Olson(https://www.facebook.com/colby.olson.9)
Pick me, pick me! :DReplyDelete
- AnonymousOctober 10, 2013 at 5:03 AM
Mine is Bruce Johnson. Best of luck to everyone.ReplyDelete
- AnonymousOctober 10, 2013 at 5:28 AM
Kerbi OkillerReplyDelete
- AnonymousOctober 10, 2013 at 5:51 AM
I'm desperate for a key! My FB is Svetoslav AntovReplyDelete
Thank you for doing this, your power level is OVER 9000!!!!!!!! :) FB - Rick StenslienReplyDelete
Hope the key goes to someone who really appreciate the good will from the art of Rince =)ReplyDelete
My name is Tiew Jin Jie
Hope be to lucky this time
- Bob BeachOctober 10, 2013 at 7:35 AM
I enjoy seeing people do this. Thanks for giving someone a chance and not selling the key!ReplyDelete
Here's hoping.
- AnonymousOctober 10, 2013 at 7:51 AM
I have tried so many different ways to get a key its kinda sad....but whats one more lol hit me up shaun canfield or email firstname.lastname@example.com
- Jacob SkowronekOctober 10, 2013 at 9:57 AM
Thanks for doing this!ReplyDelete
- AnonymousOctober 10, 2013 at 10:25 AM
I'd be very happy to finally get in :)ReplyDelete
Thanks for the chance to win!ReplyDelete
I'd be very grateful if I won the beta key. My graduation is coming up and I hope I get this as my grad gift! :)ReplyDelete
My name on FB is Joseph Stanley Sy
This comment has been removed by the author.ReplyDelete
gl everyone i would love to play this gameReplyDelete
David ChampouxReplies
from Earth with love <3 https://www.facebook.com/kudryavtsev.vladimir.9ReplyDelete
Thank you for doing this! Facebook name is: Adam SordahlReplyDelete
- AnonymousOctober 10, 2013 at 11:51 AM
Would love to win a beta key.ReplyDelete
Facebook name is Jay Tee
At least it's not being sold.ReplyDeleteReplies
Adding FaceBook linkDelete
- AnonymousOctober 10, 2013 at 11:54 AM
Liked you on FB... Come on beta keyReplyDelete
Facebook name is Chris Egan
Woop! For pony!ReplyDelete
Hope I win, but gl to all nonetheless and grats to whoever gets it!
- AnonymousOctober 10, 2013 at 11:56 AM
Good luck to all!ReplyDelete
My name is Stefan Bauer: https://www.facebook.com/stefan.bauer.35762
If you didnt get my Facebook page (I posted as Kaveman) then here it is:ReplyDelete
So good to see a nice guy who is whiling to giveaway a key and not justReplyDelete
sell it on ebay. Thank you sir, for making 1 person happier.
- AnonymousOctober 10, 2013 at 11:58 AM
gg DANIEL RAUCHReplyDelete
- AnonymousOctober 10, 2013 at 12:01 PM
comment 'Candi Rush' on fb!ReplyDelete
Michael Zazzaro on Facebook and liked your page. Thanks for the opportunity and goodluck everyone.ReplyDelete
- Replies
Any update on who won?ReplyDelete
Hope I can get a win. https://www.facebook.com/majormayoReplyDelete
- AnonymousOctober 10, 2013 at 12:16 PM
Thanks for this. Liked. name in link.
This comment has been removed by the author.ReplyDelete
Winner on the front page: http://rince-art.blogspot.com/ReplyDelete


text:
New Fresh Content, Different word, keywords everything help
Diversification is the Top SEO Tip for Local Businesses
By: Sarah Beth
For small businesses to be able to keep pace with the competition and comprehensive campaigns on SEO, they must learn to optimize the local search strategy. Local search is particularly effective for drawing in customers using a mobile device. Use of proper keywords can be a useful tool.
Your first step in developing a local SEO strategy should be to diversify your online presence. Although Google+ Local is clearly the heavyweight of local search engines, a marketing campaign that relies solely on Google+ is in danger. If anything goes wrong with your Google+ listing, your entire campaign is instantly gone!
There is a plethora of smaller, more specialized search sites that reward a more organic style of promotion. Consider what kinds of link neighborhoods will work best with your business, and then optimize your presence in those neighborhoods in any…
View original post 91 more words


text:
Be Successful…Be Yourself! In business being yourself is important. Using your tool and passion are also important. In the video below I talk about where you find your victory. Thank you for stopping by!
Category Archive: Online Business
Jun 19
Be Successful…Be Yourself!
Jun 18
What are you Focusing on?
What are you Focusing on? So often we are so focus on the circumstance we can not see away out. I want to encourage you and focus God and on the outcome you want to see and I hope that is to overcome the situation. Please take a minute to listen to this video on something I …
Jun 04
How to Find Your Encouragement For Victory!
May 21
8 Step To Overcoming Procrastination
Things you leave for another day sit in your mind as clutter. -Amanda Schroter Please take a couple of minute to learn 8 step to Overcoming Procrastination Procrastination is a pothole on the road to success! – Bob Harrison Designing your success, Amanda Schroter Subcribe to my YouTube …
Apr 11
Think and Grow Rich by Napoleon Hill
Found this today on a archive website and thought I would share it. "Set your mind on a definite goal and observe how quickly the world stands aside to let you pass." ― Napoleon Hill, Think and Grow Rich Audio Book of Think and Grow Rich by Napoleon Hill Read by Michael McConnohie It only show one …
Apr 10
What's Your Brand?
What are you known for? and The Power of Your Name Just some of the thing talk about in this video. Take sometime and listen to Terri Savelle Foy talk about "What's Your Brand?" Each of us have passions and interests. I would love to hear from you. Name three things you think you are known …
Apr 04
Leadership and Success Tips
Below is a video with Bod Harrison. I have mention him in a couple of videos I have done, so I thought I would put a video on my blog to introduce to him to you. Some of the question they talk about in this short clip are, How should …
Apr 03
Self Talk
What are you saying? I found this great pod-cast with Jeffery Combs, There's something about listening to Jeffrey that will get you instantly productive and completely honest with yourself. Please take sometime and listen, he makes some great point on mindset and this creates success! Below is the embed audio of the podcast. Enjoy! The topics he talks about! 1. What do you …
Mar 28
Design Your BEST Life – Goal, Dreams and Values
Time. We all want more of it and We all only have 168 hours an week. How will you use them? You have goals, but do they line up with your values and dreams? Take a couple of minutes and listen as I talk about Design Your BEST Life – Create Lifestyle Freedom! Designing your success, …
Mar 25
What are you known for ~ Create your legacy now Pt 2
Mar 21
Principle Of Mortgaged Time
Principle Of Mortgaged Time – Intentions Vlog Challenge day 3 What are you lending your time to? Are these activities helping you reach your goals or keeping you from them? Questions to ask yourself…. Please watch this short video below as I talk about Principle Of Mortgaged Time Watch~Like~Comment ~Share Time is Free, but it's priceless. …
Mar 20
What Are You Saying About Yourself ?
What are you saying about yourself – Intentions day 2 So I change the name of my personal video challenge to Intentions. But it will still have a "Golden Nugent" in the video. Never say anything about yourself you don't want to come true… ~Rick Godwin Designing your success, Amanda Schroter Subcribe to …
Mar 04
Don't Give Up, Don't Give In!
A short video clip of a movie coming out that is inspiring story. Unbroken – Olympics Preview "I'd made it this far and refused to give up because all my life I had always finished the race." ― Louis Zamperini, Devil at My Heels : A Heroic Olympian's Astonishing Story of Survival as a Japanese POW …
Feb 10
Never, Ever Give Up on Your Dreams!
Never, Ever Give Up on Your Dreams! Another video from my video project. Watch as I talk on pursing your dreams! Sometimes the dream seems impossible, but failure is not an option, just getting back up trying again. Maybe not the same way as you have tried before. Problems will arise when pursue your dreams …
Feb 08
In the video below is the calmest dog I have ever seen around a squirrel. I know it says the squirrel is a pet but there is no way my dog would allows us to own a pet squirrel. Sport is getting older now (15 years old) and he does not see as well as …


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What happens when a GRAMMY award-winning artist/DJ/producer doesn't agree with the current state of affairs? He organizes a killer line-up for a concert benefitting the ACLU in Los Angeles, California. The EDM artist, Zedd, took to twitter and announced his fundraiser/concert in response to the recent immigration bans in the US. He then called upon his fellow colleagues, friends, mentors and musicians for a once in a lifetime "stick it to you" concert, with all proceeds going to the ACLU.
Appropriately titled, Welcome!, this benefit concert and fundraiser will take place at the Staples Center in Los Angeles on April 3rd, 2017. Some of the biggest names in music are coming together collectively in protest of President Trump's immigration ban. Among the impressive and diverse line up are Skrillex, Bebe Rexha, Tinashe, Daya, Halsey, Imagine Dragons, Incubus, Macklemore, and Zedd, just to name a few. Celebrities such as Judd Apatow, Sia, Grimes, and Rosie O'Donnell have also been actively donating and raising money for this cause.
All locals, tourists and guests of Ayres Hotels are welcomed to get tickets here to the star-studded event, as well as become members of the American Civil Liberties Union (ACLU). The Staples Center in Los Angeles is perfectly situated near both Ayres Hotels LA locations. Stay either at the Ayres Hotel Manhattan Beach/Hawthorne, just 24 miles from Welcome! or Ayres Suites Diamond Bar, only 34 miles away from your favorite artists and activists.


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25 players / 30 plays
Report this game if it's content is inappropriate. Misuse of this feature may cause your account to be suspended.
No próprio jogo o aluno coloca uma janela de instruções.
🚫 Game author has disabled embedding for this game
Link to this game with these dynamically updating game cards!
by hctatuape
First published on 7th July, 2017
Jogo LOKO É POCO, produzido por Heitor de Azevedo Gomes aluno da Happy Code - Unidade Tatuapé. Escola de Tecnologia e Inovação para Crianças e Adolescentes.
30 total plays
26 guest plays
4 Scirra member plays
25 unique players
23 unique guests
2 Scirra members
Game stats last updated 0.000780001666666667 minutes ago
18 minutes 39 seconds total play time
1 minute 42 seconds average play length
3 highest number of simultaneous players
Friday, July 07, 2017
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Thursday, October 15, 2015
QuickBooks Pro Tech Support Contact Help Desk Phone Number solve QuickBooks Remote Desktop Services Issues
6 comments:
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This mirrors my own sentiments rather well. I've been waiting for Diablo 3 since...well... Diablo 2. Announcing one class at Blizzcon? No release date in sight? A testament to how successful they are, that they can announce a class for a game and count that as major news.
I shouldn't really complain; it is a convention, so it is mainly targeted to people who bought tickets and showed. I hear it was a blast from that point of view.


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Mail Chime
Unless you live in an apartment where all mail is delivered to a sheltered collection of mailboxes, those living in a house with plenty of ground space can identify with the chore of walking out from the warm comfort of your home and braving the chilly winds outside just to check whether the postman has left anything behind for you. More often than not, the cold, lonely walk will prove fruitless, or you will be cursing under your breath as you clutch the latest bills and tax notices in your hand.
The Mail Chime is no chump as is offers a way to know whether you have some snail mail, regardless of the type of mailbox you use. This nifty device has a range of 300-feet, so unless you own a huge mansion with sprawling grounds, any incoming mail will immediately result in an alert. The Mail Chime is compatible with a mail slot, a curbside box, or even a wall-mounted mailbox.
Installation is child's play – all you need to do is to mount the sensor on your mailbox door by taping it with the double-face tape provided, and plug the receiver into any available electrical outlet in your home. The battery-powered sensor will send a wireless signal to the Mail Chime whenever the mailbox door opens, which will subsequently result in a red LED light and a quartet of beeps.
Once you have retrieved your mail, press the reset button for the next impending delivery. The sensor is powered by a single 12V A23 battery (included) and measures 4.25″ x 1.5″ x 1″ while the receiver is slightly larger at 4.25" x 3.25" x 1". You can pick up the Mail Chime for $44.99 from Smart Home.


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In my studio I can dream, watch movies, listen to radio plays, listen to music, paint, draw, glue, cut wood, cut paper, work with clay, sew, laugh, enjoy life and create!
I work on scale dollhouses and related projects, use watercolours and acrylic paints, Zentangle and draw Zentangle Inspired Art and prepare classes for students of Zentangle. I make cards of thanks, wishes, sympathy and congratulations. I work on making altered books and sewing paper, material and anything else that will fit under a needle.
And what does all this look like? Well, I would need to do some heavy cleaning to make it into a magazine, but then, do those clean organized studios every get used? I mean really used? My studio is my comfort zone. It is my place to make a mess and leave it until the project is finished. Granted I do sweep about 3-4 times a day when really making a mess on the floor and I empty my trash 1-2 times a week depending on the projects.
I usually have a small space that I do the actual work. And I am finding that this is typical of most crafters (except Gina K, whom I adore!).
So here is my studio.
|Enter. Back of door is filled with supplies. All paint bottles are on the wall. I try to use my vertical space since the room is only 10x12.
|I use the Billy Bookshelves from IKEA (I love that store and it's a 4 hr drive to the nearest one) I have sections for scrapbooking and cards, miniatures, Zentangle, painting, and miscellaneous. I had to add a small table to hold overflow and this gives me an easier area to work on things not miniature related (as you will see in the next picture.
|Moving around the room is my trusty computer, printer and die cut area. I store my special papers, 12x12 papers and die cut supplies in the Billy System flat file. More vertical storage and cabinets hang above the desk to hold printer supplies and who knows what else.
|And finally the closet. We installed an adjustable shelving unit in the closet to hold miniature supplies, landscaping materials, fabrics, trimmings, dollhouse furniture and so much more. I can pull the curtains and everything looks lovely again.
If you want to see other great studios please visit Seth's website The Altered Page:Studio Table Revealed


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Political Mother choreographed and composed by Hofesh Shechter. Presented by Canadian Stage at the Bluma Appel (27 Front East). Runs to October 28, Thursday-Saturday 8 pm, matinees Saturday-Sunday 2 pm. $24-$99. 416-368-3110, canadianstage.com. Rating: NNNN
With presidential debates dominating the zeitgeist south of the border and tomfoolery by assorted levels of government in the news closer to home, political machinery is much in evidence these days.
So the arrival of UK-based choreographer and composer Hofesh Shechter's Political Mother is timely. It's a scathing dance depiction of society's love/hate relationship with the political mechanisms it creates. The show's in-your-face blend of irony and menace has earned the company raves as it tours the world.
Shechter tips his hand in the opening scene. With the title of the work projected overhead, a knight in leather armour slowly draws his sword and then falls on it. A few shocked giggles ripple through the audience and are quickly stifled as he noisily expires. Fade to black. Hold.
Shechter has no problem making his audience wait for what comes next: a duet that introduces a slouchy, slinky, vaguely simian movement vocabulary, a row of drummers that keep the beat with military precision as a figure yells into a microphone from high on a pedestal, his voice distorted, his polemic indecipherable.
The latter morphs into a backdrop featuring rock guitars and a shrieking vocalist. These twin symbols of influence and power - the civic and the secular - alternate throughout, overlooking a sea of thrashing, stumbling humanity.
The 12 dancers in the company embody his ideas with mostly simple steps drawn from Shechter's background in folk dance and as a dancer with Ohad Naharin's Batsheva Dance Company in Israel, where he grew up. Certain gestures recur: simple spins with arms up, whole body convulsions, a crossover step performed in a circle, a kind of knees-out low jump/shuffle with both arms raised straight up - a move a non-dancer might make when asked to imitate a gorilla.
The rhythm and emphasis of the movement is often unexpected, and occasionally it's performed double-time. It looks far more casual than it is - this is loose, fluid movement that expresses anger, despair, hesitation, aggression, non-engagement, tenderness, intensity, trance, ecstasy and even goofiness, whatever the dancer needs to bring to the stage at any given moment.
Yet dance is only one element in this assault of a show.
The carefully crafted series of moving tableaux owe much of their power to bold visual and aural decisions. A lot's been made of the loudness of Shechter's score (he's moonlighted as a drummer in a rock band), which reaches peak volume when the guitars and drums are in full effect.
But I'm enchanted by his ease with the vocabularies of contemporary popular culture. It's a relief to drink in the massive drumbeats and guitar licks sourced from diverse parts of the world as they drive the dance.
Similarly, it's exhilarating to watch a dance work that confidently nods at cinema, employing jump cuts and fades and imagery from films like Metropolis and Triumph Of The Will to reference our collective cultural catalogue.
If the choreography itself doesn't quite keep up (I greedily wanted yet more depth and range), it definitely has its own integrity. The work feels longer than its requires - it noticeably loses momentum in a couple of places. But overall, Political Mother is a convincing and oddly entertaining theatrical indictment of political indoctrination and manipulation.
That message sounds bleak, but Shechter cleverly infuses the show with moments of strange and jarring beauty. In one section the entire company performs spinning steps together, arms raised in submission, or is it supplication? As the music transitions from ear-splitting rock licks into a sublimely lovely Bach violin concerto, and most of the dancers head for the wings, a quartet of knights in leather armour continue spinning in a kind of historical time line gone mad.
For all civilization's suffering, oppression and stupidity, this persistent lyricism, too, is part of the human project, Shechter might be suggesting. As is dance itself.
The profound/funny statement "Where there is pressure there is folk dance" written in lights across the back wall of the stage near the end of the piece drives home the point. People dance for a reason. Dance is both conformity and defiance, and perhaps we dance when there is nothing left to be said or done.


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I finished up the binding on Maddie's quilt today. It never takes as long as I am dreading that it will. I've got the label printed up and am waiting for it to dry before I sew it on. Maddie is looking forward to giving it to her friend tomorrow morning.
The quilting always ends up being much denser than I imagined - but Maddie was thrilled with it - so I'm happy!
And here is the quilter herself. I can't figure out why - but she hates having her picture taken. Silly girl!
Looking forward to getting to do some of my own sewing next week!


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James Taylor, Bonnie Raitt to perform at Summerfest June 28
Posted: Feb 1, 2018 5:35 AM CDT
MILWAUKEE (CBS 58) – James Taylor and his All Star Band will headline the American Family Insurance Amphitheater during Summerfest on June 28.
Taylor will be joined by Bonnie Raitt and her band.
Over the course of his career, Taylor has sold more than 100 million albums. Some of his hits include "Sweet Baby James" and "October Road".
Raitt is known for her hits, "Something To Talk About" and "I Can't Make You Love Me".
Tickets go on sale January 19 at 10 a.m.
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Parents, though I know many of your girls will be attending camps home and abroad, there may be those times when you require some non-screen time activities to keep them occupied, especially during rainy days!
Here are a few that I found while browsing.
Good old fashioned board games are always an amazing way to have fun as a family or group of friends. Most of all, kids just want to spend quality time with their loved ones, even if it means having to put their iPads or smart phones down for a little bit. They'll thank you when they're older!
In closing, I want wish all of the Seisen community a happy & safe summer. See you all in August!
~Ms. Carnright


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From September 6-9, Joshua Tree will be the venue for Bhakti Fest 2012, a combination music festival, yoga, and meditation retreat. This family friendly event features activities for adults and children (kids under 12 can participate for free) including workshops, swimming pools, crafts, and ecologically responsible vendors. Attendees can look forward to over 80 hours of music on two stages with performers such as Krishna Das, MC Yogi, Dave Stringer, Jai Uttal, and Deva Premal & Miten. Top yoga teachers, such as Janet Stone, Saul David Raye, Bryan Kest, and Sarah Ivanhoe will be leading sessions that will stretch body and mind. Bodyworkers trained in Shiatsu, acupuncture, massage, and Reiki will be available to heal and restore.
Celebrating the disciplines of mediation, yoga, and kirtan, this gathering combines ancient and modern wisdom in pursuit of spiritual awakening. Each guest is selected for their commitment to expanding human consciousness and furthering the heart-centered revolution in devotional worship of the divine. A bulk of the proceeds are donated to a variety of non-profit organizations that provide food, shelter, medication, and environmental services across the globe.
Based in the idea of "seva", the sankrit word for service without the expectation of reward, Bhakti Fest offers a work exchange program for those who are not able to afford tickets. Lodging is provided through either the Joshua Tree Retreat Center or campsites within the park. For more information, visit the festival's website.


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UK Edition. Click here for US version.
Active substance(s): GUAIFENESIN
PDF options: View Fullscreen Download PDF
PDF Transcript
Do NOT take this medicine if you
100 mg/5 ml Oral Solution
Read all of this leaflet carefully because it
contains important information for you.
This medicine is available without prescription.
However, you still need to use it carefully to get the
best results from it.
■ Keep this leaflet. You may need to read it again.
■ Ask your pharmacist if you need more information
or advice.
■ Contact a doctor if your symptoms worsen or do
not improve within 7 days.
■ If any of the side-effects gets serious, or if you notice
any side-effects not listed in this leaflet, please tell
your doctor or pharmacist.
In this leaflet:
1. What the medicine is and what it is used for.
2. Before you take this medicine.
3. How to take this medicine.
4. Possible side effects.
5. How to store this medicine.
6. Further information.
1 What the medicine is and
what it is used for
Benylin Mucus Cough Menthol flavour 100 mg/5 ml
oral solution contains guaifenesin which is a type of
medicine called an expectorant. It helps to relieve
chesty (productive) coughs by loosening phlegm
(mucus), making it easier to cough up and the cough
more productive.
The medicine is for use in adults and adolescents aged
12 years and over.
are allergic (hypersensitive) to guaifenesin or
any of the other ingredients (see Section 6 and
Section 2).
Take special care with this medicine
Talk with your doctor or pharmacist before taking
this medicine if you:
■ have had a cough for more than 7 days or your
cough recurs or is accompanied by a fever, rash
or persistent headache.
■ have a persistent cough that may be caused by
■ have a cough which brings up a lot of mucus
■ suffer from liver or kidney problems.
■ are taking alcohol.
Interference with laboratory tests
If you are undergoing urine tests it is important to tell
the doctor or nurse you are taking, or have recently
taken, this medicine as it can affect some results.
Taking other medicines
Always tell your doctor or pharmacist if you are
taking, or have recently taken, any other medicine,
including medicines obtained without a prescription.
■ It is not recommended that you take this
medicine with other cough medicines intended
to stop you from coughing (antitussives or cough
suppressants) as they may interfere with the
action of this medicine.
Taking with food or drink
You can take this medicine with or without food or
Pregnancy and breast-feeding
If you are pregnant or think you may be pregnant,
tell your doctor or pharmacist. This medicine
should not be used during pregnancy unless
advised by a doctor.
■ Do not take this medicine if you are breastfeeding until you speak with a doctor or
Driving and using machines
Benylin Mucus Cough Menthol flavour 100 mg/
5 ml oral solution is not expected to affect your
ability to drive or operate machinery. However, if
you do feel unwell, do not drive or use machinery.
Important information on some of
the other ingredients in this
4.7 vol % ethanol (alcohol), i.e. up to
400 mg per dose, equivalent to approximately
10 ml beer, 4 ml wine per 10 ml dose. This can
be harmful for those suffering from alcoholism.
The ethanol content should be taken into
account in pregnant or breast-feeding women,
children and high-risk groups such as patients
with liver or kidney disease or epilepsy.
■ Ponceau 4R (E124) - red colouring - may
cause allergic reactions.
■ 17.6 mg sodium per 10 ml dose. This should
be taken into consideration by those on a
controlled sodium diet.
■ Glucose and fructose. If you have been told
by your doctor that you have an intolerance
to some sugars, contact your doctor before
taking this medicine.
3 How to take this
Always take this medicine exactly as described in
this leaflet or as your pharmacist has told you. You
should check with your doctor or pharmacist if you
are not sure.
■ This solution is for oral use only.
■ Do not use more than the stated dose
turn over c
3 How to take this
medicine (continued)
Adults and
adolescents over
12 years
Take two 5 ml spoonfuls
(total of 10 ml) 4 times
a day
As for adults
Children under 12
Do not give
Patients with liver
or kidney problems
Speak to a doctor or
Do NOT take more than 4 doses (40 ml) in 24
■ Contact a doctor if your symptoms worsen or
do not improve within 7 days.
If you take too much of this
If anyone has too much, contact a doctor
or your nearest Accident and Emergency
Department taking this leaflet and pack with you.
If you take too much of this medicine you may
develop kidney stones.
Symptoms may include:
■ Upset stomach, nausea and drowsiness.
If you forget to take this medicine
You should only take this medicine as required
following the dosage instructions carefully. If you
forget to take a dose, take the next dose when
needed. Do not take a double dose to make up
for the forgotten dose. Do not take more than
4 doses (40 ml) in 24 hours.
4 Possible side-effects
6 Further information
Like all medicines, Benylin Mucus Cough Menthol
flavour 100 mg/5 ml oral solution can cause sideeffects, although not everybody gets them.
What Benylin Mucus Cough Menthol
flavour 100 mg/5 ml oral solution
If you experience any of the following
STOP using the medicine and seek
medical help immediately:
The active substance is guaifenesin. Each ml of oral
solution contains 20 mg of guaifenesin. Each 10 ml of
oral solution contains 200 mg of guaifenesin.
Other ingredients: Xanthan gum, sodium
chloride, saccharin sodium, ammonium
glycyrrhizate, citric acid, sodium citrate, macrogol
glycerol hydroxystearate 40, levomenthol, raspberry
flavour (includes ethanol, glucose and fructose),
glycerol, macrogol 1500, propylene glycol, ethanol,
purified water, sodium benzoate (E211), Ponceau 4R
(E124), caramel (E150)(includes glucose).
Allergic reactions including skin rashes (which
may be severe and include blistering and peeling of
the skin) and itching.
Mild effects that may occur include:
Nausea or vomiting.
Stomach pain and diarrhoea.
If you get any side-effects, talk to your doctor,
pharmacist or nurse. This includes any possible sideeffects not listed in this leaflet. You can also report
side-effects directly via the Yellow Card Scheme at:
By reporting side-effects you can help provide more
information on the safety of this medicine.
5 How to store this
Keep this medicine out of the reach and sight
of children.
■ Do not store this medicine above 25°C.
■ Keep the product in the original packaging
(bottle in a carton) to protect from light.
Do not use if bottle seal is broken when
■ Do not use this medicine after the expiry date
which is stated on the bottle and outer carton
after 'EXP'. The expiry date refers to the last
day of that month.
■ Use within 4 weeks of opening.
■ Medicines should not be disposed of via
wastewater or household waste. Ask your
pharmacist how to dispose of medicines no
longer required. These measures will help to
protect the environment.
(for further information on some of the ingredients see Section 2).
What Benylin Mucus Cough Menthol
flavour 100 mg/5 ml oral solution looks
like and contents of the pack
Benylin Mucus Cough Menthol flavour 100 mg/
5 ml oral solution is a clear to slightly opalescent red
solution for oral use only. It is available in a 150 ml
brown glass bottle fitted with a plastic child resistant
cap. A plastic dosing cup marked with a 10 ml
graduation may be provided in the pack.
Marketing authorisation holder: McNeil Products Ltd,
Maidenhead, Berkshire, SL6 3UG, UK.
Manufacturer: Famar Orléans, 5 avenue de Concyr,
45071 Orleans, Cedex 2, France.
This package leaflet was prepared January 2014.
Benylin is a registered trade mark.
Further information
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.


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West is the river
flowing like stop-
light-less traffic
and it murmurs a gentle
riddle to you
standing alone on its profitless bank:
Tomorrow is a
slender boat
sailing beyond your
purposeless grasp.
Just then a casual breeze touches
your sunlit face
and all that you want to believe in
holds sudden truth. – Susan Scutti


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Baby Portrait Harrogate 2
Local Harrogate Portrait Photographers based at the Zone, Hornbeam Park, Harrogate, HG2 8QT. Pete & Sheryl specialise in Baby Portrait Harrogate at their professional photography studio. They were awarded Portrait Photographer of the Year 2014 with the Master Photographers Association. They pride ourselves on the quality of our work which can clearly be seen in their images. Why not contact them for your family portrait on 01423 202027.
Contact Information To book an appointment at Bristo Photography's professional studio call on 01423 202027. Speak to Sheryl Bristo who will advice you about your family portrait. Whether it's chatting about what to wear or what to bring.Your portrait session will take around 60 – 90 minutes. Whether your prefer classical, fun or contemporary portrait photography they would love to hear from you.
Babies grow and develop so quickly. It's so important to capture them at various stages. Whether that is Newborn photography. Ideally as soon as Mum is able to visit the studio. Less than two weeks of age is ideally the time. Then next ideal age is around six months, when you baby is able to sit. Then at around one year old is perfect for recording their first Birthday. There are no strict rules as babies all develop differently.
Baby Portrait Harrogate
For Newborn photography consider skin to skin photography. The wow factor is achieved with black and white imagery with a touch of sepia. The images create a wonderful feeling of intimacy. This is particularly evident with dad and baby photos. At around six months baby photography will capture your babies smiles and expressions that you know and love. This is a great time for your family portrait and your baby may be at the sitting stage. Later at one year old this is a great time not just for family portraits. But capturing some fun dressing up photos and that all important cake smash.


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Tools and Utilities
Maintain your Android Tablet with major file editing tools like Astro, ES File Explorer and much more! Download Astro File Manager and ES File Explorer.
Click on the title of this section to expand the list and show you every app in our system!
GOWidget Theme SteelBlue-Free« Personalization & Tools « Downloads
|September 18, 2013
|27 times
|Personalization & Tools
*** BEFORE YOU COMMENT THAT YOU CAN'T USE ITOR IT DOESN'T OPEN, CHECK OUT THE VIDEOGUIDE ON HOW TO APPLY THE WIDGET THEMES ***https://www.youtube.com/watch?v=-MZ4ihAIuts
A SteelBlue Theme from Team Carbon
=== SteelBlue Transparent Widgets ===
=== GoWidget Theme ===
=== by TeamCarbon ===
This Theme matches other SteelBlue themes by TeamCarbon, such as GOLauncher Ex, GoSMS Pro, and CM7 Themechooser.
We also have other colors available, please check them out.
This is a free version of this theme, hope you enjoy it, if you really like it, please consider buying and downloading the paid version, to support us.
Please remember to rate/comment on our themes, it all helps
Any suggestions get in touch via our email
Thanks, TeamCarbon…
Please check us out on:
Twitter : @TeamCarboneam
Facebook (search TeamCarbon)
Website: www.team-carbon.com
?This is not a stand alone app, Make sure you have already installed GO Launcher EX whose version is higher than 2.39. You should also update your widget to latest version.
How to Change GOWidgets'theme?
-Long press on your GOWidget, press the Skin option and choose the SteelBlue Theme.
Theme supports the following GOWidget:
-GO Calendar Widget V2.3 or higher
-GO Contacts Widget V1.5 or higher
-GO Message Widget V1.5 or higher
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text:
Practice Statement
Dr. Ofori-Awuah earned her medical degree from the University of Ghana followed by a rigorous internal medicine residency at the Good Samaritan Hospital. She
has admitting privileges at Good Samaritan Hospital, Franklin Square Hospital and Upper Chesapeake Medical Campus.
For over eight years, Lorraine Ofori-Awuah, MD PA (LO-A MD PA) has provided first class primary care for patients in Baltimore County. LO-A MD PA's three-part mission of preventative, acute management and rehabilitative care has formed an important core which ultimately brings the highest customized standard of care to the patients in our practice.
5430 Campbell Blvd
Suite 214
Nottingham, MD 21236
- Primary Care Doctor
- Internist
In-Network Insurances
- Aetna
- AmeriHealth
- View all


text: I noticed my 15" MPB (C2D) makes louder noise when taking in DVD disks (or any optical disk) and ejecting DVD disks. My PBs and iBook do not make this type of noise during those in-and-out processes. The noise is only when DVD disks are putting in and being ejected. It is as quiet as my other Macs when it is reading DVD disks. Is your MBP (C2D) making louder noises? Edit: I am referring to any optical disk (DVD movie, DVD software, CD RW, CD, and what-not). Noise is only when you put in the disk and taking out the disk. Any optical drive makes noise; but, compared to my PBs, this MBP seems to make louder noise.