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Improvement of Negative and Positive Symptoms in Treatment-Refractory Schizophrenia: A Double-Blind, Randomized, Placebo-Controlled Trial With Memantine as Add-On Therapy to Clozapine
David de Lucena, MD; Brisa Simões Fernandes, MD; Michael Berk, PhD; Seetal Dodd, MD, PhD; Dalton W. Medeiros, PsyD; Mariana Pedrini, MD; Mauricio Kunz, MD, MSc; Fabiano Alves Gomes, MD; Larriany F. Giglio, MD; Maria Inês Lobato, MD, PhD; Paulo Silva Belmonte-de-Abreu, PhD; and Clarissa Severino Gama, MD, PhD
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Background: Glutamate deregulation may be involved in the neuropathology of schizophrenia, mainly through N-methyl-d-aspartate (NMDA) receptor dysfunction. Memantine, a drug approved by the FDA for the treatment of moderate to severe Alzheimer's disease, acts as a weak nonselective NMDA receptor antagonist. The aim of this study was to examine the efficacy of memantine as an adjunctive treatment to clozapine in patients with refractory schizophrenia.
Method: In this double-blind, placebo-controlled study, outpatients with refractory schizophrenia according to DSM-IV clinical criteria were randomly assigned, from March 2005 to February 2008, to receive either 20 mg/d memantine (n = 10) or placebo (n = 11), in addition to clozapine, for 12 weeks. The primary outcome measure was the total score on the 18-item Brief Psychiatry Rating Scale (BPRS) and BPRS subscales of positive and negative symptoms. Secondary outcomes were global severity of disease as measured by the Clinical Global Impressions scale (CGI), cognition as assessed by the Mini-Mental State Examination (MMSE), and extrapyramidal symptoms as assessed by the Simpson-Angus Scale (SAS).
Results: Twenty-one participants completed the study and were used in the analysis. Significant improvement (P < .01) on the total BPRS score, its subscales of positive (effect size [ES] = −1.38) and negative (ES = –3.33) symptoms, the CGI score (ES = 1.56), and the MMSE score was observed with memantine as compared with placebo. No significant changes in extrapyramidal symptoms were observed.
Conclusions: Memantine add-on to clozapine therapy was associated with improvement in negative and positive symptoms in refractory schizophrenia patients.
Trial Registration: clinicaltrials.gov Identifier: NCT00757978
Submitted: December 9, 2008; accepted February 23, 2009.
Corresponding author: Clarissa S. Gama, MD, PhD, Hospital de Clínicas de Porto Alegre, Laboratório de Psiquiatria Molecular, Rua Ramiro Barcelos 2350, Porto Alegre, RS, Brazil, 90035 003 (firstname.lastname@example.com).
J Clin Psychiatry 2009;70(10):1416–1423
© Copyright 2009 Physicians Postgraduate Press, Inc.
Submitted: December 9, 2008; accepted February 23, 2009 (doi:10.4088/JCP.08m04935gry).
Schizophrenia is a highly debilitating1 and multifaceted illness with positive, negative, and cognitive symptom domains. Standard treatments predominantly assist positive symptoms and may not adequately relieve other symptoms, particularly negative symptoms. Negative symptoms are a major contributor to functional impairment,2 and conventional treatments are of limited benefit.3 Clozapine, an atypical antipsychotic that is formally indicated for patients with schizophrenia whose symptoms are refractory to the other neuroleptics,4 has a pharmacologic profile that shows results against positive and negative symptoms of schizophrenia. Clozapine seems to lack the cognitive side effects that are often seen with other psychoactive drugs, and it is able to increase the ability of the person to react to his or her environment and thereby to foster social rehabilitation. Nevertheless, about one-third of patients treated with clozapine still present significant residual symptoms, especially negative symptoms.5 Adjunctive treatment, including antipsychotics, lamotrigine, antidepressants, and N-acetyl cysteine have been used to control negative symptoms.6–10
It has been suggested that glutamate deregulation may be involved in the neuropathology of schizophrenia, mainly through N-methyl-d-aspartate receptor (NMDAR) dysfunction. Memantine, a drug approved by the FDA for the treatment of moderate to severe Alzheimer's disease that acts as weak nonselective NMDAR antagonist, has been used off-label for various psychiatric disorders.11–14 Our group has reported a case-series of memantine as adjunctive therapy to antipsychotic therapy that improved the negative symptoms of schizophrenia,15 and Krivoy et al16 reported improvement in negative symptoms in an open-label study of add-on therapy. A recent randomized, placebo- controlled trial with memantine as add-on therapy to atypical antipsychotics, in a nontreatment resistant cohort, failed to show improvement in positive and negative symptoms.17
We hypothesized that memantine, as an adjunct to clozapine in a treatment-resistant sample, would be effective for the treatment of negative symptoms of schizophrenia. The need for improved therapeutic strategies that more effectively treat this domain of symptoms remains critical.
This study was a double-blind, placebo-controlled, randomized trial of memantine or placebo as adjunctive treatment to clozapine. The trial was registered with the US National Institutes of Health Clinical Trials Registry (NCT00757978).
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The sample consisted of adult outpatients with schizophrenia in the Hospital de Clinicas de Porto Alegre, Brazil, aged between 18 to 65 years, and on clozapine treatment over the last 10 years for refractory schizophrenia, with partial remission of negative symptoms. The sample had a mean ± SD age of 34.67 ± 9.04 years , and the mean ± SD duration of illness was 18.56 ± 8.59 years; 19 of the 21 patients (90.5%) were male (Table 1).
All patients fulfilled Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV),18 criteria for schizophrenia 19 on clinical interview and were treated with clozapine. Exclusion criteria included any significant medical illness, use of any additional psychotropic agent except benzodiazepines, or substance abuse; female patients who were pregnant or at reproductive age and not taking contraceptives were also excluded. The Institutional Review Board of the Hospital de Clinicas de Porto Alegre approved the study. Informed written consent was received from all participants.
Individuals were assigned using simple randomization.20 Treatment consisted of a 12-week trial of memantine or placebo, in addition to clozapine treatment as usual. Eligible patients were assigned to receive placebo or memantine (twice daily), with dosing titration as follows: week 1, 5 mg/d; week 2, 10 mg/d; week 3, 15 mg/d; weeks 4–12, 20 mg/d. Memantine was acquired from Apsen Farmaceutica S/A, Brazil (10 mg tablets). The primary domains assessed included (1) positive and negative symptoms of schizophrenia measured by the 18-item version of the Brief Psychiatry Rating Scale (BPRS),21 (2) negative symptoms and (3) positive symptoms scores of the BPRS (negative symptoms scores are the sum of scores for items 3, 9, 13, and 16, and positive symptoms scores are the sum of scores for items 8, 11, 12, and 15 of the BPRS). Secondary outcomes included severity of the disease as measured by the Clinical Global Impressions scale (CGI)22; cognition as measured by the Mini-Mental State Examination (MMSE)23; and extrapyramidal symptoms as measured by the Simpson-Angus Scale (SAS).24 All patient assessments were performed in both treatment conditions by a trained psychiatrist blinded to the patient's treatment condition. The assessments were conducted at baseline and at weeks 4, 8, and 12.
The demographic characteristics of the patients in the memantine and placebo groups were compared. Sex was examined using the χ2 test. The continuous variables from the demographic characteristics were analyzed using an unpaired t test. Between-group differences for outcome measures at baseline were calculated using unpaired t tests.
Analyses were conducted for the intent-to-treat sample (n = 21). Overall efficacy of treatment was assessed by conducting a 2-way analysis of covariance (ANCOVA), controlling for pretreatment scores on all major outcome measures by treatment condition at termination. All outcomes were assessed at baseline and at weeks 4, 8, and 12 for the memantine and placebo groups. A repeated-measures analysis of variance (ANOVA) was used to examine changes over time in the outcome measures. ANOVA was conducted on each of the outcome measures of interest; the number of time categories was the same for both groups, ranging from baseline to week 12 for all the outcomes considered. Greenhouse-Geisser estimates were used throughout to control for any sphericity. The statistical significance of the interaction between time and treatment was used to demonstrate a treatment effect. An α level of .05 (2-sided) was considered statistically significant. Post hoc data analyses were done with the Bonferroni t test, using the appropriate mean square error from the ANCOVA to establish a protected 1.25% type I error (0.05/4). Effect size (ES) d was calculated using the method of Cohen.
The required sample size was determined using the assumption that a clinically meaningful difference between the 2 treatment groups would be 10 points in total BPRS score with a pooled standard deviation of 8.0. All analyses were done using SPSS version 16.0 for Windows (SPSS Inc, Chicago, Illinois).
Of 422 schizophrenic outpatients who underwent screening from January 2006 through March 2008, 188 (44.5%) were treated with clozapine and initially eligible for baseline assessment, and 143 (33.9%) were determined to be ineligible. Thus, 45 (10.7%) of those undergoing screening were eligible and of these, 10 (22.2%) refused to participate (Figure 1). The most common reasons for refusal were related to the requirements intrinsic to a research protocol, including not wanting to be randomly assigned to placebo.
The treatment and placebo groups did not differ significantly in background demographic characteristics (Table 1). The placebo group had slightly more severe scores on the rating scales, including the BPRS, and the mean dose of clozapine was higher in the placebo group, but the differences in these baseline parameters were not significant.
Of the 22 participants initially enrolled in the study, 21 completed the full protocol (Figure 1). One patient in the memantine group discontinued the treatment during week 2 and withdrew consent. At baseline, there were no significant group differences in positive and negative symptoms on the BPRS total, BPRS positive, or BPRS negative symptom scores. On the BPRS total and on its positive symptoms and negative symptoms subscales, patients who received memantine, compared with those who received placebo, reported significantly greater decreases in BPRS total score (week 12, 19.00 vs 43.18, P = .001), positive symptoms score (week 12, 4.10 vs 9.18, P = .007), and negative symptoms score (week 12, 6.10 vs 13.55, P = .001). ESs for the differences in treatment outcomes are shown in Table 2.
The repeated-measures ANOVA showed a statistically significant interaction between treatment and time for BPRS total score, BPRS positive symptoms score, and BPRS negative symptoms score (P = .001 for all 3 outcomes). Post hoc pairwise contrasts of the treatment means at all time points revealed significant differences between mean scores, with memantine reducing the BPRS total mean score by 20.25 points more than placebo (95% CI for the difference, −27.61 to −12.89; P < .001; Figure 2). For BPRS positive and negative symptoms, the memantine groups showed reduced mean scores of 3.27 and 7.58 when compared to the placebo group (95% CI for the difference, −5.27 to −1.27, P < .003; 95% CI, −9.65 to −5.51, P < .001, respectively).
The secondary outcomes assessed were the scores on the CGI, the MMSE, the SAS, and weight. Patients receiving memantine, compared with those receiving placebo, reported significantly greater improvement in overall functioning on the CGI (P < .001) at week 12 (Table 2). At week 12, patients who received memantine as compared with those who received placebo were rated as significantly less ill. The ES for the CGI was –1.56 (95% CI, –2.54 to –0.58). The repeated-measures ANOVA showed that patterns in variation of mean global severity of disease during the 12 weeks of treatment were significantly different between the 2 conditions (treatment-by-time interaction, P = .002; Figure 3). The memantine group showed a difference of 1.25 points reduction in their mean scores compared to the placebo group (95% CI, −1.99 to −0.50; P = .002) on the CGI.
At week 12, patients who received memantine, compared with those who received placebo, showed a significantly greater improvement in their cognitive symptoms scored by the MMSE (P = .001). The repeated-measures ANOVA showed that patterns in variation of mean overall social functioning during the 12 weeks of treatment were significantly different between the 2 conditions (treatment-by-time interaction, (P < .001; Figure 3). The memantine group had a 6.12-point greater increase in mean score compared to the placebo condition (95% CI, 4.45–7.79).
The other 2 secondary outcomes, extrapyramidal symptoms as measured by the SAS score and weight, were not significantly different (Table 2). Four patients, 1 receiving memantine, and 3 placebo, complained of nausea and dizziness.
This trial supports the use of memantine as adjunctive therapy to clozapine in patients with treatment-resistant schizophrenia. Our trial successfully demonstrated significant differences in both negative and positive symptoms between the placebo and memantine groups. This study also supports the role of the NMDA system in the pathophysiology of schizophrenia.
Although clozapine is a highly effective treatment for refractory schizophrenia,4 up to one-third of patients taking clozapine remain consistently symptomatic.5 Glutamate neurotransmission has been strongly implicated in the pathophysiology of schizophrenia.25–28 Reduced activation of the NMDAR subtype may play a major role in negative symptoms of schizophrenia.29 Blocking active NMDA channels in healthy volunteers impairs cognitive functioning, creating cognitive deficits similar to those seen in schizophrenia.30,31 Studies have also demonstrated that noncompetitive NMDAR antagonists, such as dissociative anesthetics like phencyclidine and ketamine, reproduce the cardinal symptomatic features of schizophrenia.32 Alteration in peripheral glutamate receptor linkage to second messenger intracellular calcium is also reported in schizophrenia.33,34
Clozapine increases the expression of NMDARs and also glutamate metabotropic receptors (mGluRs).35 The hyperexpression of mGluR is associated with brain-derived neurotrophic factor (BDNF) production in glial neurons, increasing this neurotrophin.35,36 There is also a close relationship between NMDARs and mGluRs, particularly mGluR5, which modulates NMDA expression.35
Chronic clozapine treatment has a unique property that elevates mGluR5 expression in animal models; elevated mGluR5 expression, in turn, improves glutamatergic tonus by modeling the NMDA glutamatergic system.35 In this complex panel, chronic clozapine treatment in our sample may have prepared a special glutamatergic environment in which memantine played the main role in clinical improvement. This environment can explain both patient improvement with the memantine/clozapine association and negative results with other associations.17
Several studies suggest that clozapine interacts with the NMDAR complex.37–43 Clozapine may affect the glycine site of the NMDAR or mildly inhibit the glycine transporter. The inhibitory action of clozapine on dopaminergic neurons may account for its beneficial effects in ameliorating symptoms of schizophrenia and may suggest further studies to investigate a role for the glycine site of the NMDAR as a target for novel antipsychotics.37,40 Under a condition in which the NMDA/glycine site is saturated by the endogenous ligands (glycine or d-serine), an antagonistic action of clozapine would prevail, leading to increased firing activity.38 In contrast, when a high degree of blockade of the NMDA/glycine site is present, an agonistic action of clozapine is more prominent, thereby decreasing impulse activity.37 Thus, clozapine appears to stabilize dopaminergic neurons, dampening both hyperactivity and hypoactivity via an agonistic and antagonistic action, respectively, at the NMDA/glycine site.37–43
On the other hand, recent clinical data also support partial agonistic action at the NMDA/glycine site by clozapine. d-Cycloserine, in combination with traditional or second-generation antipsychotics, improves symptoms of schizophrenia. A unique interaction between clozapine and the glycine site of the NMDAR may explain the paradoxical worsening in negative symptoms when d-cycloserine is added to clozapine in patients with schizophrenia.39
Our results are therefore in line with the glutamatergic hypothesis of schizophrenia, according to which glutamate plays a central role in the core schizophrenic symptoms.44,45 N-Acetyl cysteine, which, in addition to increasing glutathione, increases glutamate via cysteine-glutamate exchange, improving negative symptoms of schizophrenia.46 Our study supports the initial hypothesis posited by Andreasen et al47 that improving glutamatergic tonus in some brain areas, such as prefrontal, thalamic, and cerebro-cerebellar regions,47 by NMDA partial activation could be responsible for the improvement of negative and possibly positive symptoms in our patients.
An interesting finding of this trial was the improvement of positive symptoms without worsening of psychosis in the active treatment group, suggesting that memantine has broader actions than previously realized. Improvement of positive symptoms may be due to the unique properties of memantine. Memantine is a fast off-rate (low affinity) type of uncompetitive NMDAR antagonist that blocks only pathological receptor activity and could theoretically restore abnormal neurons to a homeostatic state. Some studies indicate that memantine exerts its effect on NMDAR activity by binding at or near the Mg2+ site within the ion channel. Due to its interaction with external Mg2+, and based on mutational analysis of the NMDAR by others,48 the specific site of memantine action is assumed to be near the external Mg2+ blocking site at the selectivity filter region of the NMDAR-associated channel. This region is formed by asparagine (N) residues at the "N-site" of NR1 and "N + 1 site" of NR2 subunits. Compared with physiologic blockage by external Mg2+, a common explanation for the safety and effectiveness of memantine has been that memantine represented "better magnesium", manifesting a somewhat slower unblocking rate, moderate voltage dependence, and slightly higher affinity. Reversal of hyperactivity induced by the NMDAR antagonist MK-801 is predictive of antipsychotic activity, particularly the activity of atypical antipsychotics. MK-801–induced hyperactivity is reversed by selective 5-HT2A inverse agonists/antagonists and by atypical antipsychotic drugs having 5-HT2A inverse agonist/antagonist activity and clozapine is the masterpiece of this mechanism.49–51 Consistent with the potent clozapine interaction with 5-HT2A receptors, after systemic administration (intraperitoneally), both N-desmethylclozapine and clozapine reduced MK-801–induced hyperactivity in mice and rats, respectively.36,52
Memantine can prevent neuronal damage in several models of neurodegeneration.53 This effect has been attributed to inhibition of NMDAR activity. Meisner et al54 reported an interaction between memantine and BDNF, possibly due to an effect of memantine on nonneuronal BDNF-producing cells, activating extra synaptic NMDARs and promoting neuronal functioning.
Although there is a link between BDNF and dopamine, we cannot know if there is a causative relationship, and we cannot postulate that the effects of memantine are solely due to BDNF up-regulation, but this possibility is suggested by the novel neuroprotective pharmacologic action of memantine in neurodegenerative disorders and schizophrenia.54
There is evidence that oxidative stress is increased in patients with schizophrenia.45,55–58 As previously reported, memantine may be considered a neuroprotective drug by virtue of its increasing BDNF levels and preventing dopamine deficit. Thus, memantine may act like antipsychotics59 by chronically reducing neuronal oxidative stress in treated patients15 and decreasing neuroprogression and neuronal death.
There is no current, effective treatment for negative symptoms in schizophrenia. Considering our scarce treatment options, memantine can be considered an extremely promising medication for adjunctive treatment, in particular as an adjunct to clozapine. Lieberman et al17 did not report efficacy of memantine as adjunctive to atypical antipsychotics other than clozapine. It is nevertheless possible that there is a synergic interaction between both drugs, and treatment-refractory disease signaled by clozapine use, may respond in a differential manner with memantine as an add-on therapy to clozapine.
There are some limitations to this study. First, at baseline the placebo group had slightly more severe symptoms on the BPRS and its subscales; this discrepancy might have resulted in the overestimation of the efficacy of the memantine; to correct for this potential error, adjustment for baseline was done using ANCOVA. Second, serum clozapine levels have not been measured; the only information available was the drug daily dose. However, clozapine doses were equivalent between the 2 studied groups. As far as we are aware, clozapine metabolism is extensively hepatic,60 in contrast to memantine metabolism, in which excretion occurs in urine by active tubular secretion.61 Moreover, there is no pharmacokinetic interaction between clozapine and memantine.60 Third, since the study had only 12 weeks of follow-up, studies with a longer follow-up are necessary to determine the efficacy of memantine and its role as long-term maintenance for refractory schizophrenia adjunctive to clozapine. Fourth, the MMSE is not the most sensitive measure of cognition, and future studies should use formal cognitive testing. In addition, this was a trial of memantine add-on to clozapine in refractory schizophrenia; its positive results cannot be generalized to patients with less severe symptoms and without clozapine use. As a tautology, less refractory patients are more likely to respond to therapy, and the effects of memantine may be greater in nonrefractory individuals.
This is the first randomized clinical trial showing benefit of adjunctive treatment with memantine as add-on to clozapine therapy. This study supports the use of memantine as an adjunctive therapy for schizophrenia. However, our findings need to be replicated in a larger sample size and over a longer follow-up in order to better evaluate the potential benefits of this adjunctive treatment. Lastly, this trial adds to the evidence base supporting a key role of glutamate in the pathophysiology of schizophrenia.
Drug names: clozapine (FazaClo, Clozaril, and others), ketamine (Ketalar and others), lamotrigine (Lamictal and others), memantine (Namenda).
Author affiliations: Programa de Pós-Graduação em Medicina: Psiquiatria, Universidade Federal do Rio Grande do Sul, Brazil (Drs de Lucena, Fernandes, Kunz, Gomes, Giglio, Lobato, Belmonte-de-Abreu, and Gama); Laboratório de Psiquiatria Molecular, Centro de Pesquisas, Hospital de Clínicas de Porto Alegre, Brazil (Drs de Lucena, Fernandes, Kunz, Gomes, Giglio, Belmonte-de-Abreu, and Gama); Programa de Esquizofrenia e Demências, Hospital de Clínicas de Porto Alegre, Brazil (Drs de Lucena, Fernandes, Medeiros, Pedrini, Lobato, Belmonte-de-Abreu, and Gama); Programa de Transtornos de Humor Bipolar, Hospital de Clínicas de Porto Alegre, Brazil (Drs Fernandes, Kunz, Gomes, Giglio, and Gama); Department of Clinical and Biomedical Sciences: Barwon Health, University of Melbourne, Geelong, Australia (Drs Berk and Dodd); Orygen Research Centre, Parkville, Australia (Dr Berk).
Financial disclosure: Dr Dodd has received grant/research support from the Stanley Medical Research Foundation, the National Health and Medical Research Council (NHMRC), Beyond Blue, Geelong Medical Research Foundation, Bristol-Myers Squibb, Eli Lilly, Organon, Novartis, Mayne Pharma, Servier, and AstraZeneca; and has been a paid speaker for Eli Lilly. Dr Gama has received grant/research support from Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundo de Incentivo a Pesquisa do Hospital de Clínicas de Porto Alegre (FIPE-HCPA), and Endeavour and has been a paid speaker for Lundbeck and AstraZeneca. Dr Gomes has been a coinvestigator in clinical trials for Servier. Dr Berk has received grant/research support from the Stanley Medical Research Foundation, MBF, the NHMRC, Beyond Blue, Geelong Medical Research Foundation, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Organon, Novartis, Mayne Pharma, Servier, and Astra Zeneca; has been a paid speaker for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen Cilag, Lundbeck, Organon, Pfizer, sanofi-synthelabo, Solvay, and Wyeth; and has been a consultant for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen Cilag, Lundbeck, and Pfizer. Drs de Lucena, Fernandes, Medeiros, Pedrini, Kunz, Giglio, Lobato, and Belmonte-de-Abreu report no financial or other relationship relevant to the subject of this article.
Funding/support: This study was supported by grants from FIPE-HCPA (#05-406) to Dr Gama.
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37. Schwieler L, Linderholm KR, Nilsson-Todd LK, et al. Clozapine interacts with the glycine site of the NMDA receptor: electrophysiological studies of dopamine neurons in the rat ventral tegmental area. Life Sci. 2008;83(5-6):170–175. PubMed doi:10.1016/j.lfs.2008.05.014
38. Schwieler L, Engberg G, Erhardt S. Clozapine modulates midbrain dopamine neuron firing via interaction with the NMDA receptor complex. Synapse. 2004;52(2):114–122. PubMed doi:10.1002/syn.20008
39. Goff DC, Henderson DC, Evins AE, et al. A placebo-controlled crossover trial of D-cycloserine added to clozapine in patients with schizophrenia. Biol Psychiatry. 1999;45(4):512–514. PubMed doi:10.1016/S0006-3223(98)00367-9
40. Kessler M, Terramani T, Lynch G, et al. A glycine site associated with N-methyl-D-aspartic acid receptors: characterization and identification of a new class of antagonists. J Neurochem. 1989;52(4):1319–1328. PubMed doi:10.1111/j.1471-4159.1989.tb01881.x
41. Parsons CG, Danysz W, Quack G, et al. Novel systemically active antagonists of the glycine site of the N-methyl-D-aspartate receptor: electrophysiological, biochemical and behavioral characterization. J Pharmacol Exp Ther. 1997;283(3):1264–1275. PubMed
42. Chiodo LA, Bunney BS. Possible mechanisms by which repeated clozapine administration differentially affects the activity of two subpopulations of midbrain dopamine neurons. J Neurosci. 1985;5(9):2539–2544. PubMed
43. Arvanov VL, Wang RY. Clozapine, but not haloperidol, prevents the functional hyperactivity of N-methyl-D-aspartate receptors in rat cortical neurons induced by subchronic administration of phencyclidine. J Pharmacol Exp Ther. 1999;289(2):1000–1006. PubMed
44. Reynolds GP. Developments in the drug treatment of schizophrenia [published correction appears in Trends Pharmacol Sci. 1992;13(4):140, 184]. Trends Pharmacol Sci. 1992;13(3):116–121. PubMed
45. Aghajanian GK, Marek GJ. Serotonin model of schizophrenia: emerging role of glutamate mechanisms. Brain Res Brain Res Rev. 2000;31(2-3):302–312. PubMed doi:10.1016/S0165-0173(99)00046-6
46. Berk M, Copolov D, Dean O, et al. N-acetyl cysteine as a glutathione precursor for schizophrenia–a double-blind, randomized, placebo-controlled trial. Biol Psychiatry. 2008;64(5):361–368. PubMed doi:10.1016/j.biopsych.2008.03.004
47. Andreasen NC, Paradiso S, O'Leary DS. Cognitive dysmetria as an integrative theory of schizophrenia: a dysfunction in cortical-subcortical-cerebellar circuitry? Schizophr Bull. 1998;24(2):203–218. PubMed
48. Kashiwagi K, Masuko T, Nguyen CD, et al. Channel blockers acting at N-methyl-daspartate receptors: differential effects of mutations in the vestibule and ion channel pore. Mol Pharmacol. 2002;61(3):533–545. PubMed doi:10.1124/mol.61.3.533
49. Martin P, Waters N, Waters S, et al. MK-801-induced hyperlocomotion: differential effects of M100907, SDZ PSD 958 and raclopride. Eur J Pharmacol. 1997;335(2-3):107–116. PubMed doi:10.1016/S0014-2999(97)01188-6
50. Nilsson M, Markinhuhta KR, Carlsson ML. Differential effects of classical neuroleptics and a newer generation antipsychotics on the MK-801 induced behavioural primitivization in mouse. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30(3):521–530. PubMed doi:10.1016/j.pnpbp.2005.11.010
51. Ninan I, Kulkarni SK. Preferential blockade by clozapine of hyperlocomotion induced by non-competitive NMDA antagonist MK-801. Indian J Physiol Pharmacol. 1998;42(3):375–382. PubMed
52. Veinbergs I, Weiner DM, Olafson TM, et al. The role of M1 muscarinic receptor agonism of Ndesmethylclozapine (ACP-104) in antipsychotic and cognitive paradigms in mice. Paper presented at: 10th International Congress on Schizophrenia Research; April 2 to April 6, 2005; Savannah, GA.
53. Pietá Dias C, Martins de Lima MN, Presti-Torres J, et al. Memantine reduces oxidative damage and enhances long-term recognition memory in aged rats. Neuroscience. 2007;146(4):1719–1725. PubMed doi:10.1016/j.neuroscience.2007.03.018
54. Meisner F, Scheller C, Kneitz S, et al; German Competence Network HIV/AIDS. Memantine upregulates BDNF and prevents dopamine deficits in SIV-infected macaques: a novel pharmacological action of memantine. Neuropsychopharmacology. 2008;33(9):2228–2236. PubMed doi:10.1038/sj.npp.1301615
55. Gama CS, Salvador M, Andreazza AC, et al. Elevated serum thiobarbituric acid reactive substances in clinically symptomatic schizophrenic males. Neurosci Lett. 2008;433(3):270–273. PubMed doi:10.1016/j.neulet.2008.01.018
56. Gama CS, Salvador M, Andreazza AC, et al. Elevated serum superoxide dismutase and thiobarbituric acid reactive substances in schizophrenia: a study of patients treated with haloperidol or clozapine. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30(3):512–515. PubMed doi:10.1016/j.pnpbp.2005.11.009
57. Kunz M, Gama CS, Andreazza AC, et al. Elevated serum superoxide dismutase and thiobarbituric acid reactive substances in different phases of bipolar disorder and in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(7):1677–1681. PubMed doi:10.1016/j.pnpbp.2008.07.001
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60. Urichuk L, Prior TI, Dursun S, et al. Metabolism of atypical antipsychotics: involvement of cytochrome p450 enzymes and relevance for drug-drug interactions. Curr Drug Metab. 2008;9(5):410–418. PubMed doi:10.2174/138920008784746373
61. Schmitt F, Ryan M, Cooper G. A brief review of the pharmacologic and therapeutic aspects of memantine in Alzheimer's disease. Expert Opin Drug Metab Toxicol. 2007;3(1):135–141. PubMed doi:10.1517/17425255.3.1.135


text:
Al Darby wasn't the kind of war veteran who kept it all in. For decades before he died last month, days before he would have turned 92, he talked about what happened to him in World War II, mainly at Pearl Harbor.
Darby, who lived most of his adult life in Absecon, enlisted in the U.S. Army in early 1941. He was sent to Hawaii and stationed at the Army's Schofield Barracks when, on that Dec. 7, a massive Japanese air attack on Pearl Harbor forced America into the war.
Darby was getting out of the hospital that morning after recovering from a broken leg he got in a base football game. He had just started walking back to his unit when he saw Japanese fighters flying in, strafing him.
"He said one plane was so close, if he had a baseball, he could've hit the cockpit," said Lee Darby, of Absecon, his daughter.
Al remembered bullets hitting all around, but missing him.
"He always talked about that. My mom would say, 'Here comes another one of those gosh-darn war stories,'" Lee says — in slightly stronger language. "I think it was basically a form of PTSD," or post-traumatic stress disorder.
Al was used to hardships in his life. He was born in Atlantic City, but grew up an orphan, moving from foster home to foster home around South Jersey.
And even though all those bullets missed him at Pearl Harbor, he didn't escape the war unharmed. He got malaria from mosquito bites as he trained for an invasion of New Guinea, and episodes of the disease haunted him the rest of his life. He was more haunted because the Veterans Administration refused to acknowledge his condition, even though the family fought for compensation for years, Lee adds.
Still, he wasn't a bitter guy. He went home to Atlantic City, became a trolley driver and impressed a girl named Betty Kemmerle by being nice to her — right after a bartender was very rude to her. That meeting led to a 64-year marriage that ended only when Betty died in 2011. They had two kids, Allan Jr. and Lee.
Al Sr. joined the New Jersey State Police in 1953 and retired 25 years later as a lieutenant. But he didn't stop working. Resorts International was about to open in 1978 as Atlantic City's first casino, and Al was Resorts' first security chief. He retired for good 10 years later.
But he stayed active in the Pearl Harbor Survivors Association, whose local chapter used to be a big group.
"We had about 60 members ... maybe 30 years ago," says Al Matthews, 90, of Somers Point, Al Darby's friend since they met in Hawaii in 1941 — even though both came from Atlantic County.
Now, there's just one member of that group from Atlantic County. Matthews says he's it, since his buddy Al Darby died.
Contact Martin DeAngelis:

subset: commoncrawl


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Born to Read
In partnership with Beanstalk, our Born to Read programme is giving poorer children in the UK the reading skills they need for a better future.
We're doing that by placing volunteers in local primary schools to support children who are struggling with reading.
Learning to read unlocks a world of opportunity for children. It boosts their chances of achieving at school and, beyond that, of finding work.
But far too many boys and girls in the UK fall behind in literacy in their first few years at school. And this is even more common among children from poor or disadvantaged families.
Most of these children never catch up: 93% of those who leave primary school without basic reading skills later fail to get five good GCSEs. Without the basic qualifications they need for so many jobs, these children face a future of low pay or unemployment.
We believe that every child should have the chance to fulfil their potential - and that means being able to read with confidence.
That's why we've launched Born to Read.
How Born to Read works
We're working in partnership with Beanstalk – an organisation with over 40 years' experience in helping children learn to read.
Our programme will provide almost 8,000 more reading helper placements to support 23,000 pupils in schools across the UK.
Together we can break the cycle that keeps people poor – generation after generation.
How you can help
Are you passionate about reading? Help us to reach more children by volunteering now.
Donate now to support children in the UK:
Last updated: January 2017.


text: n. (slingks) Surreptitious web links to other good sites Slinks Julia Cho Sep 12, 2007 Share Pin It Email Share Email Share Email Dwell teams up with Fatboy and we get these!: This is no ordinary bean bag- available at Design Public. Birth Announcements that double as bookmarks: We all know they'll throw it out in a few weeks at the most- so why not give them something they can use? ABC Pillows: We are loving these pillows from Childhood Interiors- spell out their name on the bed. Share Email


text:
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Anna Nicole Smith
February 9, 2012 by staff
Anna Nicole Smith, It's been five years since Anna Nicole Smith overdosed in a Florida hotel room on February 8, 2007. It's been five years since the death of Anna Nicole Smith, the Play boy model turned reality TV star who died in her Hollywood, Fla., hotel room on Feb. 8, 2007, at age 39.
It seemed for more than a decade that Smith was in the news every other day. A few of the highlights:
At age 26, Smith married Texas oil billionaire J. Howard Marshall when he was 89. She met him while she was dancing at a strip club in Houston. After his death in 1995, a years-long battle ensued over Marshall's estate before a Supreme Court ruling in 2011 finally denied Smith's estate any part of her late husband's riches.
Smith gave birth to daughter Dannielynn on Sept. 7, 2006, in the Bahamas and three days later her son Daniel, 20, died in mysterious circumstances in her hospital room. Another lengthy battle ensued as two men — attorney/boyfriend Howard K. Stern and photographer Larry Birkhead — both claimed to be the father of Smith's new daughter.
Birkhead eventually prevailed in the custody battle and Stern faced continued legal troubles after he and two of Smith's doctors were charged with providing Smith with numerous prescription drugs before her fatal overdose.
Please feel free to send if you have any questions regarding this post , you can contact on
Disclaimer: The views expressed on this site are that of the authors and not necessarily that of U.S.S.POST.


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Can you freeze zucchini? Zucchini is a hybrid of the cucumber, but unlike it, it's mostly served cooked. It's available at stores all year round, but when winter comes, its price rises significantly. If you live a long way from a store, where you can buy fresh zucchini, or you'd simply like to have some zucchini at hand all year round, you need to have a way of extending its shelf life. Fortunately enough, you can freeze zucchini and it's a fairly simple process.
Freezing zucchini
The first step of the process is to chop the zucchini. Size and shape of zucchini's parts are of your desire. You can even grate the vegetable. Please remember that you'll probably put the frozen parts directly into your dish, so it should be chopped in convenient sizes and shapes.
Blanching is a process that deactivates some vegetable enzymes that cause vegetable to change color and become mushy after some time. This process is recommended for probably all vegetables before freezing them, or storing in the fridge for an extended period of time. The process is simple: you need to bring a pot of water into boil, put the vegetables into the boiling water for a few minutes (3 minutes should be enough [1][2]) and then quickly cool the vegetables down. A pot or a sink of cold water will allow you to cool the vegetables almost immediately.
Image used under Creative Commons from Matthew Jolly
Since zucchini shouldn't stay chopped and on air for too long, I suggest you should chop them after putting the pot on heat. After blanching the zucchini particles, you should dry them out pretty quickly. Paper towels might become very handy here. Please bear in mind that blanching is recommended but optional. You can freeze zucchini as-is if you'd like to.
Pre freezing zucchini
This step is optional. Pre freezing is used to prevent vegetable pieces from freezing to each other. If you know exactly how much zucchini you're going to need for every dish you plan to make with them, you can omit this part. If not, pre freezing might me a great idea. You simply need to put chopped zucchini individually on a plate or a baking sheet and freeze them. That takes at least a few hours, sometimes even a day. It depends on how the vegetables are chopped. After the parts are frozen, you get the plate out of the freezer and it's time for the last part of the freezing process.
Packaging chopped zucchini
Now you just need to put the chopped parts into freezer bags or containers. Remember that packaging vegetables in suitable amounts makes easy scooping vegetables from the bag as you go.If you've pre frozen chopped zucchini, it should be easy to get only a portion of vegetables out of every packaging.
Freezing zucchini – video
If you'd like to watch a short video that shows how you can freeze zucchini, check out the video below (if the video doesn't show up, watch it on Youtube):
As you can see, you can freeze zucchini and it's pretty easy to do that. The whole process is pretty similar to the process of freezing other vegetables.


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James Grayson
Biography of James Grayson
Im James and im 21, from Manchester, England. I like alot of things, writing is one of them. i like exersise, i do weights n boxing. I have bin thru alot realy, read my poems n you'll sort of see what. Ive been locked up in a mental ward, my own fault tho. When I was younger I did alot of drugs and thats what caused it. That was about 2years ago n im only just gettin back together realy, its been hard coping with everythin. Dont get me wrong tho, at the moment im realy happy, my girlfreind has realy helped me, n i realy help her. I love writing, i'll write anything i can think of. most of my is in my books, n ive got loads of it, but u'll get the new stuff mostly. Every now n then i'll put the older stuff on, one by one so i dont giv 2 much away lol. I hope you enjoy, my things about my life are true and come frm life expeiriances. Enjoy.
James Grayson's Works:
lol no... not yet anyway
James Grayson Poems
"slow Down, Sir"
When's my time up? I do not know. But I refuse to move With the worlds fast flow.
Short'N Sweet
To see the smile on Her Face, Means more to me than Gold.
Essence Of Time
Awake and arise, breathe the Essence of Time Awake and arise, breathe the Essence of Time Bare this in mind, today may be your last so Awake and arise, breathe the Essence of Time
When Death Is Near
I am dying. I can feel him breathing Down the back of my neck. I do not waste time crying,
Once again a years past by, I'm so fragile yet I haven't died. Death has smiled upon my face, Allowed me to breath and given me space.
Made Of Iron
I am a solid iron bar and I stand proud and tall. People come from afar To try and make me fall.
I Am Free
For the moment I am free. More so as I Quicken my pace.
Bobs Bad Day (May Be Found Offensive)
I'll tell you a story of a man who was coy. Bob was his name and was practically a boy. Thin was his structure and pale was his skin, Only had half a b*llock so he never had kin.
I'm Sick
I'm sick of life I'm sick of its ways I'm sick and tired Of playin these games.
I Cry
I cry. Does this mean I'm weak? Does this mean
I know exactly who I am And what I do! Im a Hoodie
Im walking. Hood up. On the phone. I shut up.
Cocaine On The Brain
As it rush's through the note And up into my nose, Theres no better feeling Every coke head knows.
I F a
PoemHunter.com Updates
Check out
Classic Poets
Footsteps of Angels
Henry Wadsworth Longfellow
A Song About Myself
John Keats
A Very Short Song
Dorothy Parker
When Death Is Near
I am dying.
I can feel him breathing
Down the back of my neck.
I do not waste time crying,
And neither should you.
Your time shall come
And mine is near
He calls my name,
I take a breath


text:
Tinaderm Anti-Tinea Spray 100g relieves the burning, itching and soreness of athletes foot or tinea within 24 hours.
It also helps to prevent reinfection when regularly dusted onto feet and into shoes and socks.
Active Ingredients:
Tolnaftate 0.9mg/g.
Wash and dry infected areas.
Shake can well.
Spray onto affected area 2-3 times daily.
Continue treatment for two weeks after symptoms disappear.
Warnings & Disclaimers:
For external use only. Do not use in the eyes.
Always read the label. Use only as directed.
If symptoms persist see your Health Care Professional.
Customer Reviews
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Delivery is FREE if your order is over $149 and weighing less than 3kg.
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Express Post is available for orders under 500g at a cost of $11.95 and between 501g – 3kg for $19.95. If your order qualifies for Express Post, this will be offered at checkout.
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text:
The St. Louis Blues hadn't given coach Ken Hitchcock many opportunities to be upset over a performance before their previous contest.
He's been much happier after their most recent games against the Nashville Predators.
St. Louis looks to beat visiting Nashville for the eighth time in nine meetings when the teams meet Saturday night.
The Blues (36-12-5) missed a chance to tie Chicago atop the Central Division with a 3-1 loss to Carolina on Friday that ended a three-game winning streak, and Hitchcock didn't hide his feelings afterward.
"Hard to find a lot of good players in our game (Friday)," Hitchcock said. "(The Hurricanes) skated. They checked. They played hard. And we looked like we had the body language like we wanted an easier game. Didn't get it."
David Backes scored for only the second time in 17 games, converting on a power play in the first period. St. Louis entered with the league's second-ranked power play unit, which has scored 23.6 percent of the time with the man advantage.
Alexander Steen's five-game point streak came to an end.
"It's nice to be back on the scoreboard, but we're more interested in winning," Backes said. "(Friday) was a game where they brought a hard-skating, tough-checking game, and we didn't have a ton of answers for it."
The Blues will look to get back on track against the Predators after winning the first two meetings this season. Steen had a goal and an assist in a 4-2 victory Oct. 3 and scored twice in a 6-1 win Oct. 26.
Nashville, though, improved to 4-1-1 over its last six with a 3-2 overtime win over New Jersey on Friday. Captain Shea Weber, who left Tuesday's win over Winnipeg with an upper-body injury, scored his second goal of the game 1:29 into OT.
Weber leads all NHL defensemen with 15 goals.
"He's one of the best at his position, plain and simple," coach Barry Trotz said. "He's our building block, and he's a difference maker in this business. There aren't too many guys at his level."
The Predators (25-23-8), hoping to avoid missing the playoffs in back-to-back seasons for the first time since 2002-03, got a goal from David Legwand with 10.8 seconds remaining in regulation to force extra time.
Legwand lauded the play of Weber.
"It's going to take a lot to keep him out of a hockey game," Legwand said. "He loves playing the game and shows that over the course of his career. He was big for us. Obviously on the first one and in overtime, two huge goals."
Carter Hutton made 24 saves, meaning Devan Dubnyk could get the start against St. Louis in the second of a back-to-back set. Dubnyk has given up nine goals while losing his first two starts for Nashville since being acquired from Edmonton on Jan. 15.
Jaroslav Halak stopped 28 shots Friday for the Blues, leaving the door open for Brian Elliott to get the nod for this contest. Elliott has lost three straight starts while posting a 3.69 goals-against average, but he's 3-2-0 with a 1.80 GAA in five career starts against Nashville.
Dubnyk has a 4.72 GAA while losing all seven of his starts against the Blues.


text:
Letters Home
Letters Home puts the wars in Afghanistan & Iraq front and center by
bringing to life actual letters written by soldiers serving in the
Middle East. The play gives audiences a powerful portrait of the soldier
experience. Although the title of the play implies that all the
letters are from soldiers, the piece includes a small number of
correspondences from parents – their words, being no less important.
These letters were written under the most difficult of circumstances;
the disorientation of training, deployment, separation from family and
loved ones and combat, and occupation duties in Afghanistan and Iraq.
They help define for the audience—patriotism and what it means to serve
our country today, through acts of bravery, compassion, social
responsibility, sense of community and brotherhood.
Collectively the production gives a voice to a generation that went to war against terror in Afghanistan and to war in Iraq. More importantly, the play reveals the humanity that lies within the war as seen through the eyes of the men and women fighting it.
Our Veterans Organization Partner for this performance is Dryhootch of America. Learn more about Dryhootch.


text:
Hey there, time traveller!
This article was published 25/9/2013 (1425 days ago), so information in it may no longer be current.
One more player is on his way to the AHL's St. John's IceCaps, the Winnipeg Jets announced this afternoon.
Goalie Eddie Pasquale, who fared well during his two pre-season appearanced in this training camp, we re-assigned this afternoon.
It leaves the Jets training camp at 26 players. The NHL team will need to cut it to 23 by next Monday.
Pasquale, 22, played 43 games for the IceCaps last season, going 15-23-4 as the No. 1 man in net.


text:
At election time in Massachusetts every voter gets a copy of the state produced 'Information Guide.' Inside this guide, with the usual pros and cons, are URLs for the folks leading the support or opposition. An interested voter clicked on the VoteNoOnQuestion3.org website, the listed opposition to a current medical marijuana initiative, only to discover THEY FORGOT TO REGISTER IT.
Now a parody site with a ton of fake "facts" about marijuana lives in its place. Did you know that "No marijuana smoker has ever been successful?"
It's a well known fact that smoking marijuana can lead to a dependency on Twinkies. If medical marijuana were legalized in Massachusetts, the increase in Twinkie consumption could possibly lead to shortages of Twinkies across the Bay State...Thanks Joe!


text:
The first intercollegiate debate for the current academic year will be held with Princeton at Princeton, probably on December 12. Princeton will choose the question and Harvard the side. The trials to select the Harvard team will be held during the first two weeks in November. The Yale debate will be held in Cambridge in the latter part of March.
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Read more in NewsCarlisle Game Tickets.


text:
It's a reality for most religious leaders: To keep congregations vibrant, you've got to refresh the flock with a steady stream of young adults. Many people leave after high school, no longer under the control of their faithful parents. They go to college, get jobs and move to a new city. Intentionally or not, life blocks their spiritual path.
But forward-thinking leaders are increasingly finding a place for these adults, ages 18 to 35. It's often not the church their grandmother grew up in — fun, lively, even hip. Scripture still tells the truth, but usually over pizza, coffee and (imagine!) beer.
In recognition of Easter and Passover, tbt* reached out to active young adult groups in Tampa Bay, and to people under age 40 in notable religious roles.
Socializing, not Scripture
They put together happy hours at SoHo bars, Mahjong nights and volunteer projects. When an issue about Scripture comes up, they defer to local synagogues.
The JCC's Young Adult Division acts as a gateway to Jewish life in Tampa for people ages 21 to 45. Its events, many of them social, aim to strengthen Jewish identity and reinforce core values.
The group targets young Jewish professionals new to the area and operates nationwide. People often hear about it while in other cities and seek it out when they land here.
"Many people move to Tampa because of jobs," said director Iris Pastor. "They don't have family, they don't have connections. They look around and get concerned."
The group organizes happy hours the third Thursday of the month at the Lime and Lodge bars on Howard Avenue. Upward of 60 people attend. Nervous about not knowing anyone? The group connects newbies with a regular who will meet up with them ahead of time to ease the introduction.
JCC events are open to anyone, regardless of their affiliation to a synagogue. It often teams up with the 20s and 30s group at Congregation Schaarai Zedek in South Tampa led by Joel Simon.
The group does monthly philanthropic activities, from cleaning a nature reserve to volunteering at the Weinberg Village, an assisted-living center for Jewish seniors. Its six-month leadership training program places professionals on the boards and committees of Jewish nonprofit groups.
Central to everything is finding connections with like-minded people.
"We're very social," said Pastor, who has five children who are young adults. "We really stay away from Scripture and are not a religious institution. We leave that to the temples and synagogues."
Easing transition to 'adult' church
Ryan Marr, an associate pastor at Calvary Chapel St. Petersburg, sees it all the time. After graduating from high school, young people don't transition well to the "adult" church. They become too old for youth programs but can't relate to the main services.
That's where Remnant comes in. Marr and other church leaders started the ministry a year ago to give 18- to 30-year-olds a place of their own.
"I've found that unless you're 24 or 25, you don't do really well with people over 30," Marr said. "We want them to get plugged in relationally."
The group mirrors the traditional church, but in a smaller package with acoustic music. At the end of each Sunday evening service, they break into small "community groups" to share what's going on in their lives and pray for one another. Every few weeks, they go to Starbucks.
The majority are in college or their early 20s. Many live at home and, to the disbelief and even chagrin of some older members, admittedly spend more time playing Xbox than finding a job, Marr said.
"The new 18-year-old is 25," he said.
Remnant members serve throughout the Pinellas Park church and run a coffee bar during regular services to raise money for their Starbucks trips. Chris Gibson, who does the group's sermons, was a church intern and works in the preschool. He's 24.
Remnant began with about 140 people and has settled into a comfortable 50 to 60 weekly. Many didn't like opening up to others, Marr said. Those who have stayed find it uplifting and encouraging in their walk with Christ.
"Our goal is to have genuine community," Marr said. "We're not into the light show. We just want to be honest with you and see what the Bible says and deal with the truth."
For single Christians seeking their purpose … and maybe a date
Gary Taylor measures success not in how many single young professionals show up to South Tampa Fellowship's weekly services, but how many of them find their life's calling.
He views faith as a verb that extends beyond going to church.
Taylor is the singles pastor for 97West, which meets Tuesday nights at the church's Davis Islands campus. The name has nothing to do with Scripture or even music, although it can be confused for the rock station, 97X. It's simply the address of the meeting place, 97 W Biscayne Ave., where, hopefully, lives are changed.
Taylor, 43, joined the ministry more than two years ago to help singles develop a relationship with God and discover their purpose.
About 150 to 200 people attend each week for live music, a Bible-based message and Christian camaraderie. Less than half are members of South Tampa Fellowship, which holds Sunday services at its main building along Bayshore Boulevard.
"The goal is not to grow the group bigger," he said. "It's about, go from here and fulfill your mission."
Unlike many young adult groups, 97West attracts more 25- to 30-year-olds than college students and has gradually shifted older as more people delay marriage. If someone comes to find a date, so be it. Hasn't everyone's mom suggested going to church to meet Mr. or Mrs. Right?
The latest message series focuses on the plight of the homeless and working poor. Taylor challenged members to "Walk A Mile In My Shoes" by wearing the same pair of sneakers for more than three weeks. He hasn't liked it.
It culminates April 26 when people will spend the night in the fellowship hall. Charity groups will distribute information on how to help . Rather than eat after the meeting, like they usually do, they will go to bed hungry.
Throughout church, youth movement spreads
When Countryside Christian Center set out to target college students and young adults, leaders knew traditional wouldn't work.
They had to try something new.
For starters, they needed cutting-edge music, food during services and condensed messages. But don't water down the material. This age group wants it Scripture-based.
Their formula worked. Encounter, a ministry for 18- to 29-year-olds, began seven years ago with three people. Today, it has 100, with new people coming every week.
The concept worked so well that leaders incorporated many of the principles throughout the Clearwater church.
"The church started taking notice and saying, 'We like the way they are reaching this age group,' " said Pastor Tim O'Fallon, who oversees Encounter. "Now Countryside Christian Center looks very much like Encounter did a few years ago."
The Thursday evening services start with food and fellowship over basketball, air hockey or Wii. A live band plays on the stage, followed by Bible study and prayer time. When everything is said and done, a big group heads to Applebee's.
Encounter welcomes married couples and people with children, who often end up as mentors for college students and those seeking their first jobs. Aside from weekly services, they do cookouts, pool parties and other activities, as well as join the church's community projects.
A good percentage of first-time visitors call themselves nonreligious. They come to see what Christians are like, O'Fallon said. Often, they find they aren't so bad.
Seeking out God in everything
At Bible-Based Fellowship Church, leaders set high expectations for young adults and involve them in all aspects of church life.
They evangelize in housing projects, feed the homeless and pick produce for seniors. They come to regular church services in full force, sometimes representing more than a third of the congregation. The second Sunday of every month, their New Generation choir sings during the service.
The senior pastor, the Rev. Arthur T. Jones, considers them the new generation of leaders.
The church calls its 19- to 35-year-old members Young Adults Living Eternally, or Y.A.L.E, a nod to top-achieving Ivy leaguers. The group meets the second Sunday of the month at 1 p.m.
More of an informational session than a church service, the Y.A.L.E. meetings provide an overview of the upcoming month and introduce new members to the predominantly black church in North Tampa. When conversations turn to careers, relationships and even the nightclub scene, coordinators Rodney and Desiree Allmond put the emphasis on God.
"When we talk about careers, we talk about not forgetting about Christ," Rodney Allmond said. "We just don't live day to day. We live for Christ in the workplace, in our home and in our relationships."
The ministry has about 500 members, from college age to those with children. About 50 attend the monthly meetings. Others take part in a faith-based book club or Bible study.
"Other churches have forgotten about young adult," Rodney Allmond said. "They'll join a church but leave because they don't feel like there's a role for them. We have opportunities for them and can provide skills with a spiritual twist."


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Basketball roundup: Gonzaga nips Oklahoma St. in anticipated contest
Updated 11:02 pm, Monday, December 31, 2012
Kevin Pangos scored 23 points and hit the clinching free throws with 4.3 seconds left, Kelly Olynyk scored all 21 of his points in the second half and No. 10 Gonzaga edged No. 22 Oklahoma State 69-68 on Monday night in Stillwater, Okla.
The victory by Gonzaga (13-1) spoiled one of the Cowboys' most anticipated nonconference games at Gallagher-Iba Arena in decades.
Marcus Smart led Oklahoma State (10-2) with 23 points but missed two free throws with 8.7 seconds left with the Cowboys trailing by two. Elias Harris grabbed the rebound on Smart's second miss, and Pangos was fouled in the backcourt before stepping to the line to drill both free throws.
Sports Channel
Gonzaga was the first ranked team outside of the Big Eight or Big 12 to visit Stillwater since Memphis in 1989.
(5) Indiana 69, Iowa 65: At Iowa City, Iowa, Cody Zeller had 15 of his 19 points in the second half, and the Hoosiers (13-1, 1-0 Big Ten) opened Big Ten play by holding off the Hawkeyes (11-3, 0-1).
(7) Syracuse 96, Central Connecticut 62: In Syracuse, N.Y., Michael Carter-Williams scored a career-high 18 points and added 13 assists as the Orange (12-1) defeated the Blue Devils (4-7) to give coach Jim Boeheim his 902nd career win, tying him with Bob Knight for second all-time among Division I men's coaches.
(9) Minnesota 76, (18) Michigan State 63: In Minneapolis, Andre Hollins had 22 points and six assists and Rodney Williams added 15 points and six rebounds to lift the Golden Gophers (13-1, 1-0 Big Ten) over the Spartans (11-3, 0-1). Michigan State had won 13 of the previous 15 meetings between the teams.
(14) Cincinnati 70, (24) Pittsburgh 61: In Pittsburgh, Cashmere Wright scored 18 points, and the Bearcats (13-1, 1-0 Big East) surged past the Panthers (12-2, 0-1).
(25) Kansas State 70, South Dakota 50: In Manhattan, Kan., Nino Williams scored 16 points, and the Wildcats (11-2) pulled away late to defeat the Coyotes (6-9).
Texas Tech 70, Florida A&M 56: In Lubbock, Trency Jackson and Josh Gray scored 10 points apiece to lead the Red Raiders (7-4) over the Rattlers (4-9).
Utah State 81, Texas State 57: In San Marcos, Preston Medlin scored 21 points, Spencer Butterfield had 18 and nine assists, and the Aggies (11-1, 2-0 WAC) shot 63.3 percent in the second half to roll past the Bobcats (4-10, 0-2).
UTSA 57, San Jose State 54: In San Jose, Calif., Simone Young scored 12 points, all on four 3-pointers, and Cori Cooper added 11 points to lift the Roadrunners (7-6, 1-1 WAC) past the Spartans (4-9, 1-1).
Trinity 72, Texas Lutheran 48: Murphy Burns scored 19 points as the Tigers (7-4) snapped a three-game win streak by the Bulldogs' (4-8). Trinity shot 53 percent from the field in the first half in building a 21-point halftime advantage at Sams Gym.


text: 1 photos $499,900 40 acres 3 Beds | 3 Baths | 2200 sqft 1444 Creek Channel Lane, Saint Germain, WI 54558 - Vilas County Big St. Germain Condominium A Life Style in itself, Bradford Point Condominiums, enjoy carefree living on one of the prime lakes in the area Big St.Germain, excellent fishing, along with being a great all around sport lake. You will love paddleboarding, canoeing and kayaking into Fawn and Content Lakes for quiet beauty. This 3 bedroom 3 bath home offers room for your family and friends,a large great room, patio doors to spacious lakeside deck and has a large unfinished lower level if additional room is desired. You will love the screened porch off the dining area and also access from the master bedroom. Open your bedroom patio doors to enjoy those beautiful lake breezes.The St. Germain area located between Eagle River, Boulder Junction and Minocqua offers some scenic Adam Redman Redman Realty Group, LLC


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Five hotbeds of biodiversity
Biodiversity is biological diversity - an area having a large number of varied life forms. Biologists and conservation groups are concerned with regions deemed 'biodiversity hotspots,' which are threatened. Hotspots require two main criteria: at least 1500 vascular plant species(that have a system to transport nutrients and water) with over half endemic to the region, or found only there. They also have lost over 70% of their original habitat. Here are five of the highest biodiversity ecologies still over 70% intact in the world as identified by Conservation International, a nonprofit environmental organization based in Arlington, VA.
Sources: Conservation International, Infoplease.com, and Permanent Mission of the Congo to the United Nations
1. Amazon Rain Forest
The Amazon wilderness, which spans nine countries, is renowned for its superlatives: 40,000 plant species, of which the majority are not found anywhere else. It is also home to more primate species anywhere in the world, possibly more insects as well. The Brazilian government said in December 2011 that deforestation rates in the Amazon, the world's largest rainforest, had fallen to the lowest levels since 1988.
1 of 5


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Kiribati Move
March 10, 2012 by staff
Kiribati Move, Fears that rising sea levels due to climate change could soon wipe out their entire Pacific archipelago has forced the leaders of Kiribati to look at the option of moving their entire nation to neighbouring Fiji.
The Republic of Kiribati, is an island nation in the central tropical Pacific Ocean with a population just over 100,000. The entire nation is composed of 32 atolls and one coral island, scattered over 3.5 million square kilometres. The nation straddles the equator, and borders the International Date Line.
AP reports that the president of Kiribati Anote Tong, said on Friday that his Cabinet has endorsed a plan to buy nearly 6,000 acres of land on Fiji's main island, Viti Levu. He said the land is being sold by a church group for about $9.6 million, and could provide insurance policy for the entire population of Kiribati of about 103, 000 people.
But meanwhile, the people of Kiribati are hoping that the move will never become necessary. Tong said: "We would hope not to put everyone on one piece of land, but if it became absolutely necessary, yes, we could do it. It wouldn't be for me, personally, but would apply more to a younger generation. For them, moving won't be a matter of choice. It's basically going to be a matter of survival."
Kiribati is one country often cited as evidence of climate change, as its atolls are at the risk of being submerged as sea levels rise. The country is expected to be the first country in which land territory disappears due to global climate change. In June 2008, President Anote Tong said the country has reached "the point of no return." He said: "To plan for the day when you no longer have a country is indeed painful but I think we have to do that."
Please feel free to send if you have any questions regarding this post , you can contact on
Disclaimer: The views expressed on this site are that of the authors and not necessarily that of U.S.S.POST.


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After 11 amazing years of business, I have decided to close the doors of Urban Roots. I will be in the studio from Jan. 3-25 and hope to see you.
Teren is becoming a salon owner at Wednesdae Salon in Russian Hill. I encourage you to follow her there.
Wednesdae Salon
1538 Pacific Ave #103, San Francisco, CA. 94109


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Timothy J. Walton, PGA
Main Address:
PO Box 1889
Sioux Falls, SD 57101-1889
(605) 782-0316
Sioux Falls, SD 57101-1889
(605) 782-0316
3400 W 22nd St
Sioux Falls, SD 57105-0107
Sioux Falls, SD 57105-0107
(605) 336-3766
3400 W 22nd St
Sioux Falls, SD 57105-0107
Sioux Falls, SD 57105-0107
(605) 336-3766
Timothy Walton is a PGA Professional in Sioux Falls, SD. The PGA of America comprises 27,000 men and women professionals with one singular goal in mind - to make the game of golf more enjoyable for you.
Services Offered:
- Instruction
- Play Golf of America Participant
Welcome to Golf Month
Professional has not entered award information.
Home » Golf Courses » South Dakota » Sioux Falls » Timothy J. Walton, PGA
PGA of America Championships
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Duke men's tennis nearly upsets Virginia
The team aspect of collegiate tennis was very apparent in the Blue Devils' narrow loss to No. 1 Virginia (13-0, 3-0 in the ACC) Friday.
Despite a stellar performance from junior Fred Saba to defeat the top-ranked player in the nation, Alex Domjian, No. 8 Duke (15-3, 3-1) could not convert one of the final two singles matches and fell to the Cavaliers 4-3.
"We put ourselves in position to win— we were up 3-2," Blue Devil head coach Ramsey Smith said. "But it just didn't work out for us."
The day started off well for Duke, with the top-ranked doubles team of senior Henrique Cunha and sophomore Raphael Hemmeler defeating the second-ranked Virginia pair of Jarmere Jenkins and Mac Styslinger. In a sign of things to come, however, the higher-ranked Blue Devil teams could not take either of the next two matches and dropped the doubles point to the Cavaliers.
Duke did not get on the board until Hemmeler won his singles match 6-3, 6-2 to bring the score to 2-1. Cunha continued his unbeaten run this season and defeated fifth-ranked Jenkins 6-4, 6-0 to tie the score at 2-2.
"[Cunha]'s been incredible. He hasn't lost a match in singles," Smith said. "He's had times when he hasn't hit the ball great, but he finds a way to win. His win over Jenkins was huge, he's had trouble with him in the past, but he dominated Jenkins [Friday]. He's had an incredible senior season."
Saba then gave the Blue Devils the lead for the first time with what he describes as "the biggest win" of his collegiate career. Smith said his victory against the nation's top player was evidence of Saba's improvement, especially in the mental aspect of the game.
"It was a great win, but it's not just one match—it's a long process for me to continue improving on the court," Saba said. "It's been a result of all the hard work I've been putting in on and off the court."
At this point Duke needed only one of Chris Mengel or Jason Tahir to win their matches to hand Virginia its first loss of the season, but it was not to be.
Mengel fought back from a demoralizing 6-1 loss in the first set but could not push the match to a third set, falling narrowly in a second-set tiebreaker 7-6 (9-7). Tahir also fell victim to the tiebreaker, dropping the first set 7-6 (8-6) before a tight 6-4 loss in the second set.
"They've been the best for a bunch of years now. They've been dominant in the ACC," Smith said. "This sends a message that we're obviously right there. We've got a long way to go, but hopefully we'll get another chance at them at the ACC Tournament."
Sunday, the Blue Devils responded by demolishing Virginia Tech (10-5, 2-1) 7-0, losing only two sets in the process.
Duke swept the doubles matches, though by the slimmest of margins. Tahir teamed up with Daniel McCall and Cunha with Hemmeler to secure the doubles point for the Blue Devils with tiebreaker wins, following an 8-6 victory by the pair of Mengel and Saba.
Tahir and Michael Redlicki both bounced back from their losses against the Cavaliers to give Duke a commanding 3-0 lead. Hemmeler then recorded his team-leading 26th win of the season 6-2, 6-4 to clinch the contest which meant the team would not return to Durham empty-handed.
"We did a really good job bouncing back, from what was certainly a tough loss [against Virginia]," Smith said. "A lot of times it's tough to bounce back after losing an opportunity like that."
Smith said this performance during the weekend shows his team is playing as well as Virginia, which has won the previous six conference titles, and they will now also be considered the team to beat.
"We've just got to make sure we turn up for every single ACC match," Smith said. "We've got a bull's eye on our back, and teams will always give us their best shot."
The Chronicle is your source for Duke news, sports, culture and dialogue.
Subscribe to the Chronicle: Newsletter | The Dirt | Overtime


text:
Effortless repair Secrets - Updated
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text:
Re: [mythsoc] From the Council of Stewards
Expand Messages
- I think that Joan has done such a good job of warning us when things go
off-topic that we could trust her as well to rebuke the ad-hominem, or to
suggest that some subjects be taken off-list. Perhaps a periodic message
reminding of "good mythie manners" could be posted.
I would prefer not to see any of the recently announced rules imposed.
Second post of the day.
Diamond Proudbrook
- Hi Bill how's the coffee? Mine's not so great lately.
Yes, I would like to see more about other authors. I do love Tolkien,
honestly the man was a genius, but I want to hear more about today too.
And I especially want to know who else reads Kazantzakis, or knows people
who do. I am behind in my reading, but he's one of my favorites, and I'd
really like some insights.
Do you know that there are rats with curly coats? I have never seen one.
Do you think they would have better insulation when they had to swim away
from the ship?
Lizzie (squeak)
Elizabeth Apgar Triano
amor vincit omnia
> [Original Message]about
> From: Bill West <lunacy2@...>
> To: <email@example.com>
> Date: 5/11/2005 2:31:44 PM
> Subject: Re: [mythsoc] From the Council of Stewards
> In the interest of full disclosure, let me say upfront that I am
> co-moderator of the
> other list with Lizzie.
> This might be rambling. I slept in late and my first cup of coffee
> hasn't quite
> taken hold as yet. Apologies in advance.
> While I am not one of the listmembers who has written Joan privately
> the list, I have expressed similiar opinions in posts here. I wasn'ttheir
> certain
> how many others might feel the same way until folks began joining the
> Disaffected
> List. There's a lot of people on this list who never post and while I'm
> sure there's
> many who are see no problem, I'm equally sure there are others who do
> but
> prefer not to voice it and deal with the fall out after.
> For example, those who've written Joan offlist have been labeled
> "malcontents".
> It makes them sound like sailors downbelow decks plotting mutiny.
> Why should anyone who raises a legitmate concern about the tone and
> content
> of the list be stuck with such a label?
> It points to the reason why they took it in private to Joan.
> I think I've been on this list three or four years now, and for the
> most part,
> it's usually the same group of about a dozen folks involved in the
> discussions.
> I know from being on other lists that not everyone on a mail list
> participates
> but I would have thought I'd see some others out of 310 members
> occasionally
> over a three or four year span. A good portion of them most likely simply
> agree with the opinions the others expressed and see no reason to add
> comments.in
> And others..and I readily concede they may be few...might not agree but
> don't speak because they've seen how some others who've advanced an
> idea contrary to the active group are sometimes treated.
> The other list was started after the last go round over Lewis
> because it became
> exactly that..a go-round..with the tone becoming..umm..shall we
> say...acidic? Liz
> and I emailed back and forth about it and then started the Disaffected
> list as a place
> where some of the issues raised here could be continued a bit more
> civily and other
> authors outside of the Inklings could be discussed. We hope people will
> feel able to
> raise any issue for spirited debate without fear of unkind commentary.
> Now..all that being said..
> I must disagree respectfully with the proposed Rule change. I'm a
> bookseller.
> I deal in ideas. Limiting how many posts a person can make a day (except
> cases of abuse, such as flooding or spamming) seems a form of censorship.I
> think that Joan has done a great job and I trust her to continue to do so
> without the imposing of any barriers to the flow of ideas.
> I know I have more to say but that first cup of coffee has come and
> gone
> and I think I'm going to go make another.
> Bill
Your message has been successfully submitted and would be delivered to recipients shortly.


text:
Staff at the Russell Offices could refuse to work outside standard business hours and some are planning to seek jobs at other Defence sites when paid parking is introduced.
Workers at the Russell defence complex who responded to an online union survey were overwhelming opposed to the introduction of paid parking without financial compensation.
The federal government plans to introduce fees for using public car parks in the Parliamentary Triangle, Barton, Russell and Acton. More than 500 Russell Offices staff participated in a survey by Professionals Australia, with 93 per cent saying that they were opposed to paid parking being introduced without compensation.
Staff wanted the issue raised in enterprise bargaining negotiations and most agreed compensation was also needed for military personnel who worked at Russell.
Professionals Australia ACT director David Smith said staff were unhappy at the claim that paid parking was needed to make it easier for tourists to visit national institutions.
''No one accessing the public institutions would do so by parking at Russell,'' Mr Smith said.
Respondents to the survey said that if paid parking was introduced they would be reluctant to work outside standard business hours because of poor evening public transport options.
One respondent wrote: ''The last bus to Gungahlin, where I live, is proposed to leave just after 7pm on weekdays. ''I have been required to work well past this time on many occasions so does this mean I have to pay almost $60 for a taxi?''
Mr Smith said his union would not wait until enterprise bargaining negotiations to raise the issue with management.
''We're seeking meetings with Defence before then to try and to get the issue resolved before it gets into bargaining,'' he said. ''Obviously this affects uniformed personnel as well as civilian personnel.''
Mr Smith said charging staff to park at Russell raised equity issues because there was free parking at other Defence sites in Canberra.
The department paid for staff car parks at Brindabella Park.
''There's going to be a whole issue with consistency,'' Mr Smith said.


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Remaining Fall Healthy Hikes
You have three more weeks to join us on a walk and see the beautiful fall leaves during our 2-mile walk. All hikes start at 1pm (sorry no pets).
Oct 13: Blendon Woods Metro Park
Oct 20: Chestnut Ridge Metro Park
Oct 27: Highbanks Metro Park


text:
Reads: The 4-Hour Workweek, The War of Art, Meditations by Marcus Aurelius, Stephen King books, The Hobbit, The Road, Outliers, Random other books that are interesting, Wired Magazine
Shows: Nathan For You, Breaking Bad, Louie, It's Always Sunny, Boston sports, especially Bruins hockey dude
Movies: Interstellar, Inglourious Basterds, Reservoir Dogs, Inception, Dumb and Dumber, Happy Gilmore, the Sandlot, Donnie Darko, The Truman Show, Superbad, Jurassic Park, Pineapple Express, Back to the Future, Random good finds on Netflix
Musics: Led Zeppelin, Red Hot Chili Peppers, Coheed and Cambria, The Dear Hunter, deadmau5, Eminem, Kid Cudi... Don't listen to country much.
Foodstuffs: Lobster, raw oysters, sushi, chinese, my nonnas homemade italian food, crab legs, steak, mexican...food is good.
A future with many possibilities
Hot and cold showers
Sleep and dreaming
Music that fits the scene perfectly


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ok, then 90's can't be worth 10 ft. either or my chimney would be -7 ft. functionally.
i have also considered coming out of the stove collar with a "T" laying flat, going into a 90 on each end, with a bit of pipe, then 2 more 90's coming back to a "T" and into the wall thimble.
i've seen this construction on european stoves that were actually cast as part of the stove body.
might be an extra heat radiator too.


text:
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Every purchase supports National Museums Liverpool
A single Christmas card from Liverpool with the phrase "Sleigh Bells Ring are yuh listenin' Buggar Lugs?".
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Dimensions: 12.5 x 12.5cm
Brand: Scouse Stuff
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text:
In a move meant to advance and fund his nationalism agenda, Venezuelan President Hugo Chavez on Tuesday nationalized the remaining privately operated oil fields valued at $30 billion. Continue reading
Venezuelan President Hugo Chavez was sworn in for a second six-year term Wednesday, vowing "socialism or death" in a move reminiscent of Cuban leader Fidel Castro, as he pledged to continue the country's movement toward a socialist state. Continue reading


text:
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Two flight attendants were stabbed in the head and face when a man tried to force his way into the cockpit of a Qantas flight from Melbourne to Launceston this afternoon.
A Melbourne ambulance official said that the two - a 38-year-old man and a 25-year-old woman - had sustained facial injuries from the passenger wielding two small wooden stakes.
The injured pair have since been taken to the Royal Melbourne Hospital where they are in a stable condition, Metropolitan Ambulance spokesman James Howe said.
One passenger was also reported to have sustained minor lacerations and was treated on the scene by paramedics.
Australian Federal Police said a 40-year-old man was detained shortly after the flight returned to Melbourne.
Federal agent Stephen Cato said the man made his attempt to take control of the Qantas plane after it left Melbourne for Launceston today.
"We believe he was trying to take over the plane," Agent Cato said.
The incident took place onboard Qantas Flight 1737, shortly after it left Melbourne at 2.50pm this afternoon. The plane returned to Tullamarine Airport shortly after take off.
Transport Minister John Anderson told reporters there was no evidence the attack was an act of terrorism, or premeditated.
He said the attacker "was headed for the cabin to force a nasty outcome."
"As I understand, if you call an attempt to crash an aircraft, you might call that a hijacking."
However, Qantas chief executive Geoff Dixon, refused to describe the incident as a hijacking. He said it was a "very, very serious incident."
Mr Dixon said that approximately ten minutes after the flight left Tullamarine Airport for Launceston, a male passenger sitting in row seven became agitated and made his way towards the front of the plane.
He produced two small wooden stakes, Dixon said, and in an ensuing scuffle was subdued by passengers and air crew.
Mr Dixon said the two crew members sustained head and facial injuries, and one passenger was slightly injured.
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