text:
Label: MEMANTINE HYDROCHLORIDE capsule, extended release
Therapeutic Use
Biochemical Data Summary
View Labeling Archives
NDC Code(s): 68180-246-02, 68180-246-06, 68180-246-09, 68180-247-02, view more
68180-247-06, 68180-247-09, 68180-247-11, 68180-247-13, 68180-248-02, 68180-248-06, 68180-248-09, 68180-249-02, 68180-249-06, 68180-249-09, 68180-249-11, 68180-249-13
Packager: Lupin Pharmaceuticals, Inc.
DEA Schedule: None
Marketing Status: Abbreviated New Drug Application
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These highlights do not include all the information needed to use MEMANTINE HYDROCHLORIDE EXTENDED-RELEASE CAPSULES safely and effectively. See full prescribing information for MEMANTINE HYDROCHLORIDE EXTENDED-RELEASE CAPSULES.
MEMANTINE HYDROCHLORIDE extended-release capsules, for oral use
Memantine hydrochloride extended-release capsules are a N-methyl-D-aspartate (NMDA) receptor antagonist indicated for the treatment of moderate to severe dementia of the Alzheimer's type. (1)
The recommended starting dose of memantine hydrochloride extended-release capsules is 7 mg once daily; the dose should be increased in 7 mg increments to the recommended maintenance dose of 28 mg once daily; the minimum recommended interval between dose increases is one week. (2.1)
Patients with severe renal impairment: the recommended maintenance dose of memantine hydrochloride extended-release capsules is 14 mg once daily. (2.3)
Memantine hydrochloride extended-release capsule is available as an extended-release capsule in the following strengths: 7 mg, 14 mg, 21 mg, 28 mg (3)
Memantine hydrochloride extended-release is contraindicated in patients with known hypersensitivity to memantine hydrochloride or to any excipients used in the formulation. (4)
Conditions that raise urine pH may decrease the urinary elimination of memantine resulting in increased plasma levels of memantine. (5.1,7.1)
The most commonly observed adverse reactions occurring at a frequency of at least 5% and greater than placebo with administration of memantine hydrochloride extended-release 28 mg/day were headache, diarrhea and dizziness. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc. at 1-800-399-2561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
2.1 Recommended Dosing
2.2 Switching from Memantine hydrochloride Tablets to Memantine hydrochloride Extended-Release Capsules
2.3 Dosing in Patients with Renal Impairment
5.1 Genitourinary Conditions
6.1 Clinical Trials Experience
7.1 Drugs That Make Urine Alkaline
7.2 Use with Other N-methyl-D-aspartate (NMDA) Antagonists
8.2 Lactation
12.2 Pharmacodynamics
13.2 Animal Toxicology and /or Pharmacology
Memantine hydrochloride extended-release capsules are indicated for the treatment of moderate to severe dementia of the Alzheimer's type.
The dosage of memantine hydrochloride extended-release capsule shown to be effective in a controlled clinical trial is 28 mg once daily.
The recommended starting dose of memantine hydrochloride extended-release capsule is 7 mg once daily. The dose should be increased in 7 mg increments to the recommended maintenance dose of 28 mg once daily. The minimum recommended interval between dose increases is one week. The dose should only be increased if the previous dose has been well tolerated. The maximum recommended dose is 28 mg once daily.
Memantine hydrochloride extended-release capsules can be taken with or without food. Memantine hydrochloride extended-release capsules can be taken intact or may be opened, sprinkled on applesauce, and thereby swallowed. The entire contents of each memantine hydrochloride extended-release capsule should be consumed; the dose should not be divided.
Except when opened and sprinkled on applesauce, as described above, memantine hydrochloride extended-release capsules should be swallowed whole. Memantine hydrochloride extended-release capsules should not be divided, chewed, or crushed.
If a patient misses a single dose of memantine hydrochloride extended-release capsules, that patient should not double up on the next dose. The next dose should be taken as scheduled. If a patient fails to take memantine hydrochloride extended-release capsules for several days, dosing may need to be resumed at lower doses and retitrated as described above.
Patients treated with memantine hydrochloride tablets may be switched to memantine hydrochloride extended-release capsules as follows:
It is recommended that a patient who is on a regimen of 10 mg twice daily of memantine hydrochloride tablets be switched to memantine hydrochloride extended-release 28 mg once daily capsules the day following the last dose of 10 mg memantine hydrochloride tablets. There is no study addressing the comparative efficacy of these 2 regimens.
In a patient with severe renal impairment, it is recommended that a patient who is on a regimen of 5 mg twice daily of memantine hydrochloride tablets be switched to memantine hydrochloride extended-release 14 mg once daily capsules the day following the last dose of 5 mg memantine hydrochloride tablets.
In patients with severe renal impairment (creatinine clearance of 5 to 29 mL/min, based on the Cockcroft-Gault equation), the recommended maintenance dose (and maximum recommended dose) is 14 mg/day [see CLINICAL PHARMACOLOGY (12.3)].
Each extended-release capsule contains 7 mg, 14 mg, 21 mg, or 28 mg of memantine hydrochloride USP.
● 7 mg: Size '4' hard gelatin yellow capsule with yellow opaque cap and yellow opaque body, with black imprint "LU" on Cap and "O61" on body.
● 14 mg: Size '4' hard gelatin capsule with yellow opaque cap and dark green opaque body, with black imprint "LU" on cap and "O62" on body.
● 21 mg: Size '4' hard gelatin capsule with white opaque cap and dark green opaque body, with black imprint "LU" on cap and "O63" on body.
● 28 mg: Size '3' hard gelatin dark green capsule with black imprint "LU" on cap and "O64" on body.
Memantine hydrochloride extended-release is contraindicated in patients with known hypersensitivity to memantine hydrochloride or to any excipients used in the formulation.
Conditions that raise urine pH may decrease the urinary elimination of memantine resulting in increased plasma levels of memantine [see DRUG INTERACTIONS (7.1)].
Memantine hydrochloride extended-release was evaluated in a double-blind placebo-controlled trial in which a total of 676 patients with moderate to severe dementia of the Alzheimer's type (341 patients on memantine hydrochloride extended-release 28 mg/day and 335 patients on placebo) were treated for up to 24 weeks.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Adverse Reactions Leading to Discontinuation
In the placebo-controlled clinical trial of memantine hydrochloride extended-release, the proportion of patients in the memantine hydrochloride extended-release capsules group and the placebo group who discontinued treatment due to adverse reactions was 10% and 6%, respectively. The most common adverse reaction that led to treatment discontinuation in the memantine hydrochloride extended-release group was dizziness, at a rate of 1.5%.
Most Common Adverse Reactions
The most commonly observed adverse reactions seen in patients administered memantine hydrochloride extended-release in the controlled clinical trial, defined as those occurring at a frequency of at least 5% in the memantine hydrochloride extended-release group and at a frequency higher than placebo, were headache, diarrhea and dizziness.
Table 1 lists adverse reactions that were observed at an incidence of ≥ 2% in the memantine hydrochloride extended-release group and occurred at a rate greater than placebo.
Table 1: Adverse Reactions Observed with a Frequency of ≥ 2% in the memantine hydrochloride extended-release Group and at a Rate Greater than Placebo
Adverse Reaction
(n = 335) %
Memantine Hydrochloride Extended-Release
Weight, increased
Memantine has not been systematically evaluated in patients with a seizure disorder. In clinical trials of memantine, seizures occurred in 0.3% of patients treated with memantine and 0.6% of patients treated with placebo.
The following adverse reactions have been identified during post-approval use of memantine.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These reactions include:
agranulocytosis, leukopenia (including neutropenia), pancytopenia, thrombocytopenia, thrombotic thrombocytopenic purpura.
cardiac failure congestive.
pancreatitis.
Hepatobiliary Disorders
hepatitis.
suicidal ideation.
acute renal failure (including increased creatinine and renal insufficiency).
Stevens Johnson syndrome.
The clearance of memantine was reduced by about 80% under alkaline urine conditions at pH 8. Therefore, alterations of urine pH towards the alkaline condition may lead to an accumulation of the drug with a possible increase in adverse effects. Urine pH is altered by diet, drugs (e.g. carbonic anhydrase inhibitors, sodium bicarbonate) and clinical state of the patient (e.g. renal tubular acidosis or severe infections of the urinary tract). Hence, memantine should be used with caution under these conditions.
The combined use of memantine hydrochloride extended-release with other NMDA antagonists (amantadine, ketamine, and dextromethorphan) has not been systematically evaluated and such use should be approached with caution.
Risk Summary
There are no adequate data on the developmental risk associated with the use of memantine hydrochloride extended release in pregnant women.
Adverse developmental effects (decreased body weight and skeletal ossification) were observed in the offspring of rats administered memantine during pregnancy at doses associated with minimal maternal toxicity. These doses are higher than those used in humans at the maximum recommended daily dose of memantine hydrochloride extended release [see Data].
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.
Animal Data
Oral administration of memantine (0, 2, 6, or 18 mg/kg/day) to rats during the period of organogenesis resulted in decreased skeletal ossification in fetuses at the highest dose tested. The higher no-effect dose for adverse developmental effects (6 mg/kg) is 2 times the maximum recommended human daily dose (MRHD) of memantine hydrochloride extended release (28 mg) on a body surface area (mg/m2) basis.
Oral administration of memantine to rabbits (0, 3, 10, or 30 mg/kg/day) during the period of organogenesis resulted in no adverse developmental effects. The highest dose tested is approximately 20 times the MRHD of memantine hydrochloride extended release on a mg/m2 basis.
In rats, memantine (0, 2, 6, or 18 mg/kg/day) was administered orally prior to and throughout mating and, in females, through the period of organogenesis or continuing throughout lactation to weaning. Decreased skeletal ossification in fetuses and decreased body weight in pups were observed at the highest dose tested. The higher no-effect dose for adverse developmental effects (6 mg/kg/day) is 2 times the MRHD of memantine hydrochloride extended release on a mg/m2 basis.
Oral administration of memantine (0, 2, 6, or 18 mg/kg/day) to rats from late gestation throughout lactation to weaning, resulted in decreased pup weights at the highest dose tested. The higher no-effect dose (6 mg/kg/day) is approximately 2 times the MRHD of memantine hydrochloride extended release on a mg/m2 basis.
There are no data on the presence of memantine in human milk, the effects on the breastfed infant, or the effects of memantine hydrochloride extended release on milk production.
The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for memantine hydrochloride extended release and any potential adverse effects on the breastfed infant from memantine hydrochloride extended release or from the underlying maternal condition.
Safety and effectiveness in pediatric patients have not been established.
Memantine failed to demonstrate efficacy in two 12-week controlled clinical studies of 578 pediatric patients aged 6 to 12 years with autism spectrum disorders (ASD), including autism, Asperger's disorder and Pervasive Development Disorder -Not Otherwise Specified (PDD-NOS). Memantine has not been studied in pediatric patients under 6 years of age or over 12 years of age. Memantine treatment was initiated at 3 mg/day and the dose was escalated to the target dose (weight-based) by week 6. Oral doses of memantine 3, 6, 9, or 15 mg extended-release capsules were administered once daily to patients with weights < 20 kg, 20 to 39 kg, 40 to 59 kg and ≥ 60 kg, respectively.
In a randomized, 12-week double-blind, placebo-controlled parallel study (Study A) in patients with autism, there was no statistically significant difference in the Social Responsiveness Scale (SRS) total raw score between patients randomized to memantine (n=54) and those randomized to placebo (n=53). In a 12-week responder-enriched randomized withdrawal study (Study B) in 471 patients with ASD, there was no statistically significant difference in the loss of therapeutic response rates between patients randomized to remain on full-dose memantine (n=153) and those randomized to switch to placebo (n=158).
The overall safety profile of memantine in pediatric patients was generally consistent with the known safety profile in adults [see Adverse Reactions (6.1)].
In Study A, the adverse reactions in the memantine group (n=56) that were reported in at least 5% of patients and at least twice the frequency of the placebo group (N=58) are listed in Table 2.
Table 2: Study A Commonly Reported Adverse Reactions with a Frequency ≥ 5% and Twice That of Placebo
Memantine N=56
N=58
Rhinorrhea
Discontinuations due to Adverse Reactionsa
a Reported adverse reactions leading to discontinuation in more than one patient in either treatment group.
The adverse reactions that were reported in at least 5% of patients in the 12 to 48 week open-label study to identify responders to enroll in Study B are listed in Table 3:
Table 3: 12 to 48 Week Open Label Lead-In study to Study B Commonly Reported Adverse Reactions with a Frequency ≥ 5%
Memantine
Nasopharyngitis
Pyrexia
a At least 1% incidence of adverse reactions leading to premature discontinuation.
In the randomized withdrawal study (Study B), the adverse reaction in patients randomized to placebo (n=160) and reported in at least 5% of patients and twice that of the full-dose memantine treatment group (n=157) was irritability (5.0% vs 2.5%).
Juvenile Animal Study
In a juvenile animal study, male and female juvenile rats were administered memantine (15, 30, and 45 mg/kg/day) starting on postnatal day (PND) 14 through PND 70. Body weights were reduced at 45 mg/kg/day. Delays in sexual maturation were noted in male and female rats at doses ≥ 30 mg/kg/day. Memantine induced neuronal lesions in several areas of the brain on PND 15 and 17 at doses ≥ 30 mg/kg/day. Behavioral toxicity (decrease percent of auditory startle habituation) was noted for animals in the 45 mg/kg/day dose group. The 15 mg/kg/day dose was considered the No-Observed-Adverse-Effect-Level (NOAEL) for this study.
In a second juvenile rat toxicity study, male and female juvenile rats were administered memantine (1, 3, 8, 15, 30, and 45 mg/kg/day) starting on postnatal day (PND) 7 through PND 70. Due to early memantine-related mortality, the 30 and 45 mg/kg/day dose groups were terminated without further evaluation. Memantine induced apoptosis or neuronal degeneration in several areas of the brain on PND 8, 10, and 17 at a dose of 15 mg/kg/day. The NOAEL for apoptosis and neuronal degeneration was 8 mg/kg/day. Behavioral toxicity (effects on motor activity, auditory startle habituation, and learning and memory) was noted at doses ≥ 3 mg/kg/day during treatment, but was not seen after drug discontinuation. Therefore, the 1 mg/kg/day dose was considered the NOAEL for the neurobehavioral effect in this study.
The majority of people with Alzheimer's disease are 65 years of age and older. In the clinical study of memantine hydrochloride extended-release, the mean age of patients was approximately 77 years; over 91% of patients were 65 years and older, 67% were 75 years and older, and 14% were at or above 85 years of age. The efficacy and safety data presented in the clinical trial sections were obtained from these patients. There were no clinically meaningful differences in most adverse reactions reported by patient groups ≥ 65 years old and < 65 years old.
No dosage adjustment is needed in patients with mild or moderate renal impairment. A dosage reduction is recommended in patients with severe renal impairment [see DOSAGE AND ADMINISTRATION (2.3) and CLINICAL PHARMACOLOGY (12.3)].
No dosage adjustment is needed in patients with mild or moderate hepatic impairment. Memantine hydrochloride extended-release was not studied in patients with severe hepatic impairment [see CLINICAL PHARMACOLOGY (12.3)].
Signs and symptoms most often accompanying overdosage with other formulations of memantine in clinical trials and from worldwide marketing experience, alone or in combination with other drugs and/or alcohol, include agitation, asthenia, bradycardia, confusion, coma, dizziness, ECG changes, increased blood pressure, lethargy, loss of consciousness, psychosis, restlessness, slowed movement, somnolence, stupor, unsteady gait, visual hallucinations, vertigo, vomiting, and weakness. The largest known ingestion of memantine worldwide was 2 grams in a patient who took memantine in conjunction with unspecified antidiabetic medications. This patient experienced coma, diplopia, and agitation, but subsequently recovered.
One patient participating in a memantine hydrochloride extended-release clinical trial unintentionally took 112 mg of memantine hydrochloride extended-release daily for 31 days and experienced an elevated serum uric acid, elevated serum alkaline phosphatase, and low platelet count.
Fatal outcome has been very rarely reported with memantine, and the relationship to memantine was unclear.
Because strategies for the management of overdose are continually evolving, it is advisable to contact a poison control center to determine the latest recommendations for the management of an overdose of any drug. As in any cases of overdose, general supportive measures should be utilized, and treatment should be symptomatic.
Elimination of memantine can be enhanced by acidification of urine.
Memantine hydrochloride extended-release is an orally active NMDA receptor antagonist. The chemical name for memantine hydrochloride is 1-amino-3,5-dimethyladamantane hydrochloride with the following structural formula:
The molecular formula is C12H21N•HCl and the molecular weight is 215.76. Memantine hydrochloride occurs as a white or off-white powder and is soluble in water.
Memantine hydrochloride extended-release capsules are supplied for oral administration as 7 mg, 14 mg, 21 mg, and 28 mg capsules. Each capsule contains extended release pellets with the labeled amount of memantine hydrochloride USP and the following inactive ingredients: ethyl cellulose, gelatin, hypromellose, maize starch, sucrose, talc, titanium dioxide and triethyl citrate in hard gelatin capsules. Additionally, 7 mg strength capsules contain D&C Yellow #10 and FD&C Red #40; 14 mg strength capsules contain D&C Yellow #10, FD&C Blue #1, FD&C Red #40 and iron oxide yellow; 21 mg and 28 mg strength capsules contain FD&C Blue #1 and iron oxide yellow. The capsules are printed with edible ink containing black iron oxide, potassium hydroxide, propylene glycol and shellac.
Persistent activation of central nervous system N-methyl-D-aspartate (NMDA) receptors by the excitatory amino acid glutamate has been hypothesized to contribute to the symptomatology of Alzheimer's disease. Memantine is postulated to exert its therapeutic effect through its action as a low to moderate affinity uncompetitive (open-channel) NMDA receptor antagonist which binds preferentially to the NMDA receptor-operated cation channels. There is no evidence that memantine prevents or slows neurodegeneration in patients with Alzheimer's disease.
Memantine showed low to negligible affinity for GABA, benzodiazepine, dopamine, adrenergic, histamine and glycine receptors and for voltage-dependent Ca2+, Na+, or K+channels. Memantine also showed antagonistic effects at the 5HT3 receptor with a potency similar to that for the NMDA receptor and blocked nicotinic acetylcholine receptors with one-sixth to one-tenth the potency.
In vitro studies have shown that memantine does not affect the reversible inhibition of acetylcholinesterase by donepezil, galantamine, or tacrine.
Memantine is well absorbed after oral administration and has linear pharmacokinetics over the therapeutic dose range. It is excreted predominantly unchanged in urine and has a terminal elimination half-life of about 60 to 80 hours. In a study comparing 28 mg once daily memantine hydrochloride extended-release to 10 mg twice daily memantine hydrochloride tablets, the Cmax and AUC0-24 values were 48% and 33% higher for the XR dosage regimen, respectively.
After multiple dose administration of memantine hydrochloride extended-release, memantine peak concentrations occur around 9 to 12 hours post-dose. There is no difference in the absorption of memantine hydrochloride extended-release when the capsule is taken intact or when the contents are sprinkled on applesauce.
There is no difference in memantine exposure, based on Cmax or AUC, for memantine hydrochloride extended-release whether that drug product is administered with food or on an empty stomach. However, peak plasma concentrations are achieved about 18 hours after administration with food versus approximately 25 hours after administration on an empty stomach.
The mean volume of distribution of memantine is 9 to 11 L/kg and the plasma protein binding is low (45%).
Memantine undergoes partial hepatic metabolism. The hepatic microsomal CYP450 enzyme system does not play a significant role in the metabolism of memantine.
Memantine is excreted predominantly unchanged in the urine and has a terminal elimination half-life of about 60 to 80 hours. About 48% of administered drug is excreted unchanged in urine; the remainder is converted primarily to three polar metabolites which possess minimal NMDA receptor antagonistic activity: the N-glucuronide conjugate, 6-hydroxy memantine, and 1-nitroso-deaminated memantine. A total of 74% of the administered dose is excreted as the sum of the parent drug and the N-glucuronide conjugate. Renal clearance involves active tubular secretion moderated by pH dependent tubular reabsorption.
Specific Populations
Elderly:
The pharmacokinetics of memantine in young and elderly subjects are similar.
Following multiple dose administration of memantine hydrochloride 20 mg daily, females had about 45% higher exposure than males, but there was no difference in exposure when body weight was taken into account.
Memantine pharmacokinetics were evaluated following single oral administration of 20 mg memantine hydrochloride in 8 subjects with mild renal impairment (creatinine clearance, CLcr, > 50 to 80 mL/min), 8 subjects with moderate renal impairment (CLcr 30 to 49 mL/min), 7 subjects with severe renal impairment (CLcr 5 to 29 mL/min) and 8 healthy subjects (CLcr > 80 mL/min) matched as closely as possible by age, weight and gender to the subjects with renal impairment. Mean AUC0-∞ increased by 4%, 60%, and 115% in subjects with mild, moderate, and severe renal impairment, respectively, compared to healthy subjects. The terminal elimination half-life increased by 18%, 41%, and 95% in subjects with mild, moderate, and severe renal impairment, respectively, compared to healthy subjects.
Hepatic Impairment
Memantine pharmacokinetics were evaluated following the administration of single oral doses of 20 mg in 8 subjects with moderate hepatic impairment (Child-Pugh Class B, score 7 to 9) and 8 subjects who were age-, gender-, and weight-matched to the hepatically impaired subjects. There was no change in memantine exposure (based on Cmax and AUC) in subjects with moderate hepatic impairment as compared with healthy subjects. However, terminal elimination half-life increased by about 16% in subjects with moderate hepatic impairment as compared with healthy subjects.
Drug-Drug Interactions
Use with Cholinesterase Inhibitors:
Coadministration of memantine with the AChE inhibitor donepezil did not affect the pharmacokinetics of either compound. Furthermore, memantine did not affect AChE inhibition by donepezil. In a 24-week controlled clinical study in patients with moderate to severe Alzheimer's disease, the adverse reaction profile observed with a combination of memantine immediate-release and donepezil was similar to that of donepezil alone.
Effect of Memantine on the Metabolism of Other Drugs:
In vitro studies conducted with marker substrates of CYP450 enzymes (CYP1A2, -2A6, 2C9, -2D6, -2E1, -3A4) showed minimal inhibition of these enzymes by memantine. In addition, in vitro studies indicate that at concentrations exceeding those associated with efficacy, memantine does not induce the cytochrome P450 isozymes CYP1A2, -2C9, 2E1 and -3A4/5. No pharmacokinetic interactions with drugs metabolized by these enzymes are expected.
Pharmacokinetic studies evaluated the potential of memantine for interaction with warfarin and bupropion. Memantine did not affect the pharmacokinetics of the CYP2B6 substrate bupropion or its metabolite hydroxybupropion. Furthermore, memantine did not affect the pharmacokinetics or pharmacodynamics of warfarin as assessed by the prothrombin INR.
Effect of Other Drugs on Memantine:
Memantine is predominantly renally eliminated, and drugs that are substrates and/or inhibitors of the CYP450 system are not expected to alter the metabolism of memantine.
Drugs Eliminated via Renal Mechanisms:
Because memantine is eliminated in part by tubular secretion, coadministration of drugs that use the same renal cationic system, including hydrochlorothiazide (HCTZ), triamterene (TA), metformin, cimetidine, ranitidine, quinidine, and nicotine, could potentially result in altered plasma levels of both agents. However, coadministration of memantine and HCTZ/TA did not affect the bioavailability of either memantine or TA, and the bioavailability of HCTZ decreased by 20%. In addition, coadministration of memantine with the antihyperglycemic drug Glucovance (glyburide and metformin hydrochloride) did not affect the pharmacokinetics of memantine, metformin and glyburide. Furthermore, memantine did not modify the serum glucose lowering effect of Glucovance, indicating the absence of a pharmacodynamic interaction.
Drugs Highly Bound to Plasma Proteins:
Because the plasma protein binding of memantine is low (45%), an interaction with drugs that are highly bound to plasma proteins, such as warfarin and digoxin, is unlikely.
Carcinogenesis
There was no evidence of carcinogenicity in a 113-week oral study in mice at doses up to 40 mg/kg/day (7 times the maximum recommended human dose [MRHD] on a mg/m2basis). There was also no evidence of carcinogenicity in rats orally dosed at up to 40 mg/kg/day for 71 weeks followed by 20 mg/kg/day (14 and 7 times the MRHD on a mg/m2basis, respectively) through 128 weeks.
Mutagenesis
Memantine produced no evidence of genotoxic potential when evaluated in the in vitro S. typhimurium or E. coli reverse mutation assay, an in vitro chromosomal aberration test in human lymphocytes, an in vivo cytogenetics assay for chromosome damage in rats, and the in vivo mouse micronucleus assay. The results were equivocal in an in vitro gene mutation assay using Chinese hamster V79 cells.
Impairment of Fertility
No impairment of fertility or reproductive performance was seen in rats administered up to 18 mg/kg/day (6 times the MRHD on a mg/m2 basis) orally from 14 days prior to mating through gestation and lactation in females, or for 60 days prior to mating in males.
Memantine induced neuronal lesions (vacuolation and necrosis) in the multipolar and pyramidal cells in cortical layers III and IV of the posterior cingulate and retrosplenial neocortices in rats, similar to those which are known to occur in rodents administered other NMDA receptor antagonists. Lesions were seen after a single dose of memantine. In a study in which rats were given daily oral doses of memantine for 14 days, the no-effect dose for neuronal necrosis was 4 times the maximum recommended human dose (MRHD of 28 mg/day) on a mg/m2 basis.
In acute and repeat-dose neurotoxicity studies in female rats, oral administration of memantine and donepezil in combination resulted in increased incidence, severity, and distribution of neurodegeneration compared with memantine alone. The no-effect levels of the combination were associated with clinically relevant plasma memantine and donepezil exposures.
The relevance of these findings to humans is unknown.
The effectiveness of memantine hydrochloride extended-release as a treatment for patients with moderate to severe Alzheimer's disease was based on the results of a double-blind, placebo-controlled trial.
24-week Study of Memantine Hydrochloride Extended-Release Capsules
This was a randomized double-blind clinical investigation in outpatients with moderate to severe Alzheimer's disease (diagnosed by DSM-IV criteria and NINCDS-ADRDA criteria for AD with a Mini Mental State Examination (MMSE) score ≥ 3 and ≤ 14 at Screening and Baseline) receiving acetylcholinesterase inhibitor (AChEI) therapy at a stable dose for 3 months prior to screening. The mean age of patients participating in this trial was 76.5 years with a range of 49 to 97 years. Approximately 72% of patients were female and 94% were Caucasian.
Study Outcome Measures
The effectiveness of memantine hydrochloride extended-release was evaluated in this study using the co-primary efficacy parameters of Severe Impairment Battery (SIB) and the Clinician's Interview-Based Impression of Change (CIBIC-Plus).
The ability of memantine hydrochloride extended-release to improve cognitive performance was assessed with the Severe Impairment Battery (SIB), a multi-item instrument that has been validated for the evaluation of cognitive function in patients with moderate to severe dementia. The SIB examines selected aspects of cognitive performance, including elements of attention, orientation, language, memory, visuospatial ability, construction, praxis, and social interaction. The SIB scoring range is from 0 to 100, with lower scores indicating greater cognitive impairment.
The ability of memantine hydrochloride extended-release to produce an overall clinical effect was assessed using a Clinician's Interview Based Impression of Change that required the use of caregiver information, the CIBIC-Plus. The CIBIC-Plus is not a single instrument and is not a standardized instrument like the ADCS-ADL or SIB. Clinical trials for investigational drugs have used a variety of CIBIC formats, each different in terms of depth and structure. As such, results from a CIBIC-Plus reflect clinical experience from the trial or trials in which it was used and cannot be compared directly with the results of CIBIC-Plus evaluations from other clinical trials. The CIBIC-Plus used in this trial was a structured instrument based on a comprehensive evaluation at baseline and subsequent time-points of four domains: general (overall clinical status), functional (including activities of daily living), cognitive, and behavioral. It represents the assessment of a skilled clinician using validated scales based on his/her observation during an interview with the patient, in combination with information supplied by a caregiver familiar with the behavior of the patient over the interval rated. The CIBIC-Plus is scored as a seven point categorical rating, ranging from a score of 1, indicating "marked improvement" to a score of 4, indicating "no change" to a score of 7, indicating "marked worsening." The CIBIC-Plus has not been systematically compared directly to assessments not using information from caregivers (CIBIC) or other global methods.
In this study, 677 patients were randomized to one of the following 2 treatments: memantine hydrochloride extended-release 28 mg/day or placebo while still receiving an AChEI (either donepezil, galantamine, or rivastigmine).
Effects on Severe Impairment Battery (SIB)
Figure 1 shows the time course for the change from baseline in SIB score for the two treatment groups completing the 24 weeks of the study. At 24 weeks of treatment, the mean difference in the SIB change scores for the memantine hydrochloride extended-release 28 mg/AChEI-treated (combination therapy) patients compared to the patients on placebo/AChEI (monotherapy) was 2.6 units. Using an LOCF analysis, memantine hydrochloride extended-release 28 mg/AChEI treatment was statistically significantly superior to placebo/AChEI.
Figure 1: Time course of the change from baseline in SIB score for patients completing 24 weeks of treatment.
Figure 2 shows the cumulative percentages of patients from each treatment group who had attained at least the measure of improvement in SIB score shown on the X axis. The curves show that both patients assigned to memantine hydrochloride extended-release 28 mg/AChEI and placebo/AChEI have a wide range of responses, but that the memantine hydrochloride extended-release 28 mg/AChEI group is more likely to show an improvement or a smaller decline.
Figure 2: Cumulative percentage of patients completing 24 weeks of double-blind treatment with specified changes from baseline in SIB scores.
Figure 3 shows the time course for the CIBIC-Plus score for patients in the two treatment groups completing the 24 weeks of the study. At 24 weeks of treatment, the mean difference in the CIBIC-Plus scores for the memantine hydrochloride extended-release 28 mg/AChEI-treated patients compared to the patients on placebo/AChEI was 0.3 units. Using an LOCF analysis, memantine hydrochloride extended-release 28 mg/AChEI treatment was statistically significantly superior to placebo/AChEI.
Figure 3: Time course of the CIBIC-Plus score for patients completing 24 weeks of treatment.
Figure 4 is a histogram of the percentage distribution of CIBIC-Plus scores attained by patients assigned to each of the treatment groups who completed 24 weeks of treatment.
Figure 4: Distribution of CIBIC-Plus ratings at week 24.
7 mg Capsule
Size '4' hard gelatin yellow capsule with yellow opaque cap and yellow opaque body, with black imprint "LU" on cap and "O61" on body.
Bottle of 30: NDC 68180-246-06
Bottle of 500: NDC 68180-246-02
14 mg Capsule
Size '4' hard gelatin capsule with yellow opaque cap and dark green opaque body, with black imprint "LU" on cap and "O62" on body.
Blister of 10 X 10 Unit-Dose: NDC 68180-247-13
Size '4' hard gelatin capsule with white opaque cap and dark green opaque body, with black imprint "LU" on cap and "O63" on body.
Size '3' hard gelatin dark green capsule with black imprint "LU" on cap and "O64" on body.
Store memantine hydrochloride extended-release at 25°C (77°F); excursions permitted to 15 to 30°C (59 to 86°F) [see USP Controlled Room Temperature].
Advise the patient to read the FDA-approved patient labeling (Patient Information).
• To assure safe and effective use of memantine hydrochloride extended-release, the information and instructions provided in the patient information section should be discussed with patients and caregivers.
• Instruct patients and caregivers to take memantine hydrochloride extended-release only once per day, as prescribed.
• Instruct patients and caregivers that memantine hydrochloride extended-release capsules be swallowed whole. Alternatively, memantine hydrochloride extended-release capsules may be opened and sprinkled on applesauce and the entire contents should be consumed. The capsules should not be divided, chewed or crushed.
• Warn patients not to use any capsules of memantine hydrochloride extended-release that are damaged or show signs of tampering.
• If a patient misses a single dose of memantine hydrochloride extended-release, that patient should not double up on the next dose. The next dose should be taken as scheduled. If a patient fails to take memantine hydrochloride extended-release for several days, dosing should not be resumed without consulting that patient's healthcare professional.
• Advise patients and caregivers that memantine hydrochloride extended-release may cause headache, diarrhea, and dizziness.
Manufactured for:
Lupin Pharmaceuticals, Inc.
Lupin Limited
Pithampur (M.P.) – 454 775
Memantine Hydrochloride Extended-release Capsules
[me-MAN-teen HYE-droe-KLOR-ide]
Read this Patient Information that comes with memantine hydrochloride extended-release capsules before you start taking it and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about your medical condition or your treatment.
What are memantine hydrochloride extended-release capsules?
Memantine hydrochloride extended-release capsule is a prescription medicine used for the treatment of moderate to severe dementia in people with Alzheimer's disease. Memantine hydrochloride extended-release capsule belongs to a class of medicines called N-methyl-D-aspartate (NMDA) inhibitors.
It is not known if memantine hydrochloride extended-release capsule is safe and effective in children.
Who should not take memantine hydrochloride extended-release capsules?
Do not take memantine hydrochloride extended-release capsules if you are allergic to memantine or any of the other ingredients in memantine hydrochloride extended-release capsules. See the end of this leaflet for a complete list of ingredients in memantine hydrochloride extended-release capsules.
What should I tell my doctor before taking memantine hydrochloride extended-release capsules?
Before you take memantine hydrochloride extended-release capsules, tell your doctor if you:
have or have had seizures
have or have had problems passing urine
have or have had bladder or kidney problems
have liver problems
are pregnant or plan to become pregnant. It is not known if memantine hydrochloride extended-release will harm your unborn baby.
are breastfeeding or plan to breastfeed. It is not known if memantine passes into your breast milk. Talk to your doctor about the best way to feed your baby if you take memantine hydrochloride extended-release.
Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements.
Taking memantine hydrochloride extended-release capsules with certain other medicines may affect each other. Taking memantine hydrochloride extended-release capsules with other medicines can cause serious side effects.
Especially tell your doctor if you take:
• other NMDA antagonists such as amantadine, ketamine, and dextromethorphan
• medicines that make your urine alkaline such as carbonic anhydrase inhibitors and sodium bicarbonate
Ask your doctor or pharmacist for a list of these medicines, if you are not sure.
Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.
How should I take memantine hydrochloride extended-release capsules?
Your doctor will tell you how much memantine hydrochloride extended-release capsules to take and when to take it.
Your doctor may change your dose if needed.
Memantine hydrochloride extended-release capsules may be taken with food or without food.
Memantine hydrochloride extended-release capsules may be opened and sprinkled on applesauce before swallowing, but the contents of the entire capsule should be taken and the dose should not be divided. Except when opened and sprinkled on applesauce, memantine hydrochloride extended-release capsules must be swallowed whole and never crushed, divided or chewed.
Do not use any capsules of memantine hydrochloride extended-release that are damaged or show signs of tampering.
If you are currently taking another formulation of memantine, talk to your healthcare professional about how to switch to memantine hydrochloride extended-release capsules.
If you forget to take one dose of memantine hydrochloride extended-release capsules, do not double up on the next dose. You should take only the next dose as scheduled.
If you have forgotten to take memantine hydrochloride extended-release capsules for several days, you should not take the next dose until you talk to your doctor.
If you take too much memantine hydrochloride extended-release capsules call your doctor or poison control center at 1-800-222-1222, or go to the nearest hospital emergency room right away.
What are the possible side effects of memantine hydrochloride extended-release capsules?
Memantine hydrochloride extended-release capsules may cause side effects, including:
The most common side effects of memantine hydrochloride extended-release capsules include:
• headache
• diarrhea
These are not all the possible side effects of memantine hydrochloride extended-release capsules. For more information, ask your doctor or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
You may also report side effects to Lupin Pharmaceuticals, Inc. at 1-800-399-2561 or visit our website at www.lupinpharmaceuticals.com.
How should I store memantine hydrochloride extended-release capsules?
Store memantine hydrochloride extended-release capsules at room temperature between 68 to 77°F (20 to 25°C).
Keep memantine hydrochloride extended-release capsules and all medicines out of the reach of children.
What are the ingredients in memantine hydrochloride extended-release capsules?
Active ingredient: memantine hydrochloride USP
Inactive ingredients: ethyl cellulose, gelatin, hypromellose, maize starch, sucrose, talc, titanium dioxide and triethyl citrate in hard gelatin capsules. Additionally, 7 mg strength capsules contain D&C Yellow #10 and FD&C Red #40; 14 mg strength capsules contain D&C Yellow #10, FD&C Blue #1, FD&C Red #40 and iron oxide yellow; 21 mg and 28 mg strength capsules contain FD&C Blue #1 and iron oxide yellow. The capsules are printed with edible ink containing black iron oxide, potassium hydroxide, propylene glycol and shellac.
General information about the safe and effective use of memantine hydrochloride extended-release capsules:
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not take memantine hydrochloride extended-release capsules for a condition for which it was not prescribed. Do not give memantine hydrochloride extended-release capsules to other people, even if they have the same condition. It may harm them.
This Patient Information leaflet summarizes the most important information about memantine hydrochloride extended-release capsules. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about memantine hydrochloride extended-release capsules that was written for healthcare professionals.
This Patient Information has been approved by the U.S. Food and Drug Administration.
November 2020 ID#: 266044
PRINCIPAL DISPLAY PANEL
Memantine Hydrochloride Extended-release Capsules, 7 mg
Memantine Hydrochloride Extended-release Capsules, 14 mg
MEMANTINE HYDROCHLORIDE
memantine hydrochloride capsule, extended release
MEMANTINE HYDROCHLORIDE (UNII: JY0WD0UA60) (MEMANTINE - UNII:W8O17SJF3T) MEMANTINE HYDROCHLORIDE 7 mg
ETHYLCELLULOSES (UNII: 7Z8S9VYZ4B)
FD&C RED NO. 40 (UNII: WZB9127XOA)
FERROSOFERRIC OXIDE (UNII: XM0M87F357)
GELATIN (UNII: 2G86QN327L)
HYPROMELLOSES (UNII: 3NXW29V3WO)
POTASSIUM HYDROXIDE (UNII: WZH3C48M4T)
PROPYLENE GLYCOL (UNII: 6DC9Q167V3)
SHELLAC (UNII: 46N107B71O)
STARCH, CORN (UNII: O8232NY3SJ)
SUCROSE (UNII: C151H8M554)
TALC (UNII: 7SEV7J4R1U)
TRIETHYL CITRATE (UNII: 8Z96QXD6UM)
Color YELLOW ((YELLOW (OPAQUE))) Score no score
Shape CAPSULE Size 14mm
Flavor Imprint Code LU;O61
NDC:68180-246-06 30 in 1 BOTTLE; Type 0: Not a Combination Product 02/20/2018
NDC:68180-246-02 500 in 1 BOTTLE; Type 0: Not a Combination Product 02/20/2018
ANDA ANDA206028 02/20/2018
MEMANTINE HYDROCHLORIDE (UNII: JY0WD0UA60) (MEMANTINE - UNII:W8O17SJF3T) MEMANTINE HYDROCHLORIDE 28 mg
FERRIC OXIDE YELLOW (UNII: EX438O2MRT)
Color GREEN ((DARK GREEN)) Score no score
NDC:68180-249-13 10 in 1 CARTON 02/20/2018
NDC:68180-249-11 10 in 1 BLISTER PACK; Type 0: Not a Combination Product
Color YELLOW (YELLOW OPAQUE) , GREEN (DARK GREEN OPAQUE) Score no score
Color WHITE (WHITE OPAQUE) , GREEN (DARK GREEN OPAQUE) Score no score
Labeler - Lupin Pharmaceuticals, Inc. (089153071)
Registrant - LUPIN LIMITED (675923163)
ID/FEI
LUPIN LIMITED 863645527 MANUFACTURE(68180-246, 68180-247, 68180-248, 68180-249) , PACK(68180-246, 68180-247, 68180-248, 68180-249)
Report Adverse Events, FDA Safety Recalls, Presence in Breast Milk
Medline Plus, Clinical Trials, PubMed, Biochemical Data Summary
View Labeling Archives, RxNorm, Get Label RSS Feed, View NDC Code(s)NEW!
Number of versions: 6
1 996594 memantine HCl 14 MG 24HR Extended Release Oral Capsule PSN
2 996594 24 HR memantine hydrochloride 14 MG Extended Release Oral Capsule SCD
3 996594 memantine hydrochloride 14 MG 24 HR Extended Release Oral Capsule SY
10 996615 memantine HCl 7 MG 24HR Extended Release Oral Capsule PSN
11 996615 24 HR memantine hydrochloride 7 MG Extended Release Oral Capsule SCD
12 996615 memantine hydrochloride 7 MG 24 HR Extended Release Oral Capsule SY
https://dailymed.nlm.nih.gov/dailymed/labelrss.cfm?setid=24290655-47f3-4042-a977-a832c5161d2c
10 68180-248-06


Enter the season in style with this Heritage Check Coat by Whistles.Constructed in a classic cocoon silhouette from a decadent wool blend, this piece boasts a perennial check print. With a relaxed waist and two front slant pockets, the flattering knee length cut also has smart tailoring; with the addition of a lapel collar, three front closing buttons and slightly cropped sleeves. Layer with a favourite cosy jumper and skinny jeans.


The funny thing about the filming at Centennial High School? Las Vegas High Schools are all built the same exct way they look like two story prisons! The school was supposed to be a middle school which are 1 story with a fenced in courtyard!
Funny fact: Jerry's Motel is (was) next to 'Graceland Wedding Chapel' where Jon Bon Jovi (plays Trevor's father) was married. It's shown when Trevor leaves the motel on his bike.
I don't know how Trevor's house was remodeled because the outside view looks completely different than it did in the movie. Does anyone know any information on the remodeling and what all has changed and what it really looks like inside? I heard the interior scenes of it were shot in Los Angeles. If anyone knows please send me information to my gmail account!
The house located at 183 Spanish Drive in Las Vegas looks similar on the outside from the movie.


XtraFlex2 LED Clip-On Light features two bright white, energy efficient LEDs. Each LED lasts 100,000 hours. Use one or two LEDs by tapping button. Precisely engineered optical grade lens spreads light evenly. Flexible gooseneck. Stable free-standing base features a clip that opens extra-wide. 3 AAA batteries (included) provide 28 hours of battery life.


Welcome to the World Legal Summit Singapore!
This first part of the WLS is designed to bring disparate jurisdictions together in collaboration around building a better understanding of what is happening with technology regulation and governance world-wide. Singapore will bring a unique viewpoint to the discussion, focusing on the legislative and governance structures in the city and more broadly across Singapore.


View cart "Mopar A B & E Body Spindles" has been added to your cart.
This Mopar front suspension kit allows the use of spindles and brakes or the choice of dropped spindles and brakes for the latest in breaking technology! Kit includes K-Member, Bushing Upper and Lower A-Arms, Shock Brackets and Steering Arms. *This kit requires Coil Over Shocks and Rack and Pinion.


For vauxhall opel astra g/mk4 h/mk5 movano vivaro. Trendi oil. Exprdc-33. 70789. Wltoy xk x380. Temperature sensor engine. 4tnv88 water pump. 5.8 x 4cm / 2.28" x 1.57". Exhaust camshaft solenoid. 9015237. 6 pieces a set. For nissan micra dci 1.5 dci k9k/k9k-260/k9k-704 03 -. Stainless steel swage fittings. Harness fuel. F77z9j460ab.
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Identify the political, cultural, social and environmental trends surrounding the problem that your campaign aims to address.
This tool allows a team to foster out a collective understanding of the overall context in which a campaign is happening. Work on different chunks in small groups, and then reconvene to build it out all together.


You can download Passion Audio Player 4.0 from our software library for free. This download was checked by our built-in antivirus and was rated as virus free. Passion Audio Player relates to Multimedia Tools. The most popular versions among the software users are 3.0, 2.7 and 2.6.
The most recent setup file that can be downloaded is 4.2 MB in size. This free program is an intellectual property of George Boudouris. Passap3.exe, passap.exe and PASSAP2.exe are the most common filenames for this program's installer. This free PC software was developed to work on Windows XP, Windows Vista, Windows 7, Windows 8 or Windows 10 and is compatible with 32-bit systems.
You may want to check out more software, such as Eufony Free Audio Player, Audio Player Maker or Amazing Audio Player, which might be related to Passion Audio Player.


A nice afternoon exploring! This trip included a ferry ride, Cup and Muffin, a stop at the local Alpaca Farm, and a darling little town on the water called Port Townsend.
Be sure to check out my Washington State Travel Photography portfolio for more pictures.


text:
The Jerusalem Institute for Policy Research
Fellows Directory
Global Fellows
Google Policy Fellow
Fellows Testimonials
Financial Innovations for Economic Development
California-Israel Global Innovation Partnership
Blum Lab for Developing Economies
Green Bond Fund
Sustainable Jerusalem
Community Investment Notes Program
Financial Innovation Labs
Home » Staff » One good idea, one part community, a pinch of organization, and a spoonful money…mix well and serve
One good idea, one part community, a pinch of organization, and a spoonful money…mix well and serve
By Steven Zecher
One compelling rule in economic development is that access to capital is essential. Without it, you can have a good idea, but nothing happens. Without it, you can have a desperate need that goes unanswered.
A 2014 Milken Innovations Lab funded by Citi Foundation reported while 96 percent of all businesses in Israel are small business and employ 60 percent of the work force, they receive only 20 percent of bank credit. The banks in Israel are highly concentrated with only six traditional full-service banks operating and three have about 65 percent of the market. In addition, the Lab found limited access to affordable credit to populations in need, lacking competitive services geared to lower-income populations, and abuse of these populations by unregulated grey market lenders.
In addition to financial exclusion at the teller window, the dramatic rise in housing prices, almost doubling the average cost in 10 years, has put more of a financial crunch than ever on Israel's lower and middle classes.
With the roadmap from the Lab, and with the help of Milken Fellows based in the Bank of Israel, and other ministries involved with the targeted communities, we laid out a variety of new models, including translating the success of community development financial institutions from the US and European market into the Israeli market. In addition to regulatory relief on the capital requirements, information infrastructure technologies, and ownership and government structures, the Bank of Israel has since welcomed the creation of new community banks.
With the continuing support of Citi Foundation, Israel's Milken Innovation Center has been working with the Israel Free Loan Association, primarily a donor-supported non-profit lender with a substantial and successful track record, to become a non-profit bank, providing both deposit and credit services. IFLA has loaned over $270 million in over 60,000 loans over the last 27 years. This new bank, the first new bank in Israel in 45 years, will raise "equity" in the form of subordinated impact loans from impact investors and eventually take time and demand deposits from the community. In turn, the new social bank will provide second mortgages for qualified first-time home buyers, loans to small businesses, personal loans, and even bridge loans to non-profits (waiting for their grant receivables to arrive). The social bank will also provide financial education, low costs and fees, and promote community development and participation.
The new social bank will provide a financial and social return to impact investors, leveraging its capital by almost 12 times, provide interest on deposits, allow growth and efficient scaling, and use the existing regulatory framework (and even the same regulators).
Most importantly, the new social bank offers a new path for new money, a scalable solution that addresses a market opportunity, an impact on a population in need, and is financial viable. The new social bank is undergoing regulatory review, raising impact investment capital, and hopes to fully operational by mid-2019.
At its core, this market-based financial innovation enables community development by opening access to capital where and how it is most needed.
Steven Zecher
Steven Zecher is the project director the Milken Innovation Center at the Jerusalem Institute for Policy Research. His work focuses on financing strategies with an emphasis on public-private-philanthropic capital structures. Zecher has extensive experience in urban and regional development policy,...
Now is the time to strengthen our tourism infrastructure
Tourists lost in Jerusalem
BEYOND HOLLYWOOD: REFLECTIONS ON THE JERUSALEM FILM FESTIVAL
Robotics: What does the future hold?
Milken Innovation Center
Jerusalem Institute for Policy Research
20 Radak St.
Jerusalem 92186
Tel: +972-2-5630175 ext 34
email: Leora@jerusaleminstitute.org.il
www.jerusaleminstitute.org.il
www.milkeninstitute.org
Tweets about #financianinnovation OR #milkeninstitue OR #startupnation OR #israelinnovation

redpajama_set_name: RedPajamaCommonCrawl


text:
Hotelier Sam Nazarian scouts out NYC
Aug.August 19, 2010 11:00 AM
Sam Nazarian
Sam Nazarian, the U.S. hotelier who played himself on HBO's "Entourage," is property-hunting in New York, while he also plans to renovate the Ritz Plaza Hotel in Miami Beach, and reworks debt on a Las Vegas casino. Nazarian, 35, may strike a deal for his SLS Hotel brand in New York City within a year, as the travel industry recovers. He expects to spend $65 million in cash improving the Florida property and is also looking for locations in London, Chicago and Washington, he told Bloomberg in an Aug. 12 interview. "Six months ago, from an investment standpoint, hotels were off the radar," Nazarian said. "During the last six to eight months, leading with New York, it's changed because people really believe we hit the bottom." Nazarian, the CEO of Los Angeles-based SBE, also plans to expand his company's new high-end extended-stay brand, the Redbury. Scouts in New York are considering two locations and one possibility is converting stalled apartment projects to hotels, he said. [Bloomberg]
AccorHotels to buy half of Sam Nazarian's SBE Entertainment
Sam Nazarian gets bought out of the Mondrian Park Avenue hotel
The night manager: Sam Nazarian on the LA hotel market, branded condos and potential merger with Hakkasan Group
SBE Entertainment Group gears up for trial over hotel sale
Panelists announced for TRD's annual Miami showcase
Morgans shareholder files lawsuit over proposed SBE merger
How the SBE-Morgans deal finally came together
Securities law firm investigating Morgans-SBE deal


text:
For booking information call : (352)200-5461
Teri has been singing since she was two. Having tried several instruments she settled on guitar at the age of 12 and immediately began performing in talent shows , on a local television show, and when old enough, in lounges and restaurants. Her focus turned to theater in college where she earned a BFA in Drama at UNC-Greensboro. But after a stint in professional theater in Atlanta, GA she returned to her first love of music, playing in establishments from Florida to New England and into the mid-west.
Eventually she moved to Los Angeles where, after returning from a two month music engagement in Japan, she met Jack Justis, her 1st life partner. With his encouragement she mastered the banjo and returned to the keyboard as well. Together they performed throughout the Los Angeles area, including such well known hot spots as The Smokehouse and Chadney's across from Burbank Studios. They moved to the San Diego area in'89 performing in local clubs and on the harbor cruises.
From there they moved to the west coast of Florida north of Tampa and continued to tour in local clubs and casinos till Jack's passing in 2005.
Teri is well known in the Spring Hill area and has performed in many local places and events, among them are : Bare Bones,
The Tiki Bar,
Hernando Beach Club,
The Oasis in Homossasa, and different events for Kiwanis Club, Nature Coast Humane Society, and The Chamber of Commerce.
Teri plays guitar now with the Christian Church in the
Wildwood praise team.
Play Me
Connect and follow us on Facebook and LinkedIn.
Music by Teri Lyon
Products & Samples
Teri is still performing when she can accompanied by her new husband Chuck Houck who was the drummer for New Song Worship Center but now is in the Worship Team at Spring Hill United Methodist Church.
She makes a living as a graphic artist and Chuck is also a Webmaster and an aspiring graphic designer.
We recommend you buy your music equipment here!


You guys are the best! I brought in a cracked small black and white picture from the booths from probably the 70's. It was a picture of my Mother, they did such a wonderful job it's hanging on my wall. It will always stay there!


The Pacific Oil Company, founded in 1902, experienced rapid growth throughout the early twentieth century, expanding into north Africa and eventually the Middle East. The company became one of the successful and largest worldwide supplier and producer of industrial petrochemicals. Their central product, Vinyl Chloride Monomer (VCM), is the base ingredient in Polyvinyl Chloride (PVC) which was not readily available to all companies producing PVC products until the mid to late 1980's.
Due to the rarity of the product in 1979, Pacific Oil was able to enter into a major contract with a company called, Reliant Corp. It was written as four-year contract that resulted in the construction of a pipeline between Pacific Oil's plant in Antwerp, France, directly to Reliant's facility in Abbeville, France. At the end of the four-year contract it was understood that it would be necessary to renegotiate the contract. However, what was not taken in to consideration by Pacific Oil, was the fact that there were other companies who had begun to develop their own capabilities to produce the VCM.


text:
EARLabs Studios
Studio For Creative Mastering
Starting up with Reaper
Audio restauration
Tapage & Gareth Davis – STATES
Link movingfurniturerecords.bandcamp.com
Category stream, vinyl
Tags Moving Furniture Records
STATES started out as a live electronics setup, developed back in early 2016 by Tijs Ham. The first version combined analogue feedback with digital manipulations which resulted in a self-balancing and self-generating chaotic system, capable of producing deep, melodic and textured soundscapes. During a performance, the setup would be played until it would reach a state in which it was generating its own sonic material. The performer would then take a step back, allowing the system to run on its own. Carefully listening to the movements, progressions, noises, drones, and arpeggios until the urge to intervene took the upper hand and the system would be performed and nudged towards a new state of balance.
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Your wedding. Your daughter's Sweet 16. Your parents' anniversary party. For decades, families in Richboro have turned to The Warrington Country Club for classic events in a contemporary setting.
Spend time near our picturesque grounds and you'll hear the joyful sounds of music, laughter and celebration as friends and family gather in Richboro's premiere event facility.
Warrington Country Club is one of the leading catering services for Richboro wedding receptions. We pride ourselves in handling all the details of wedding coordination, allowing couples to focus on their big moment.
Planning an event can be daunting, but the staff at Warrington Country Club can help you ease the burden. Our Richboro banquet hall is the perfect setting for your family party or other special event. Whether you're planning an engagement party, client open house or an elaborate gala, we offer a diverse range of menu options that can be customized for you and your guests.
Come celebrate your Richboro bar mitzvah/bat mitzvah at the Warrington Country Club. Our banquet hall can be customized to suit the needs of your guests, whether you'll be hiring a band or DJ, or adding options like a photo booth or sundae bar.
From our outdoor ceremony, to cocktail hour in the Arbor Room, and our reception in the Wedgewood Ballroom, my wife and I could not have dreamed of a better wedding. Our guests continue to tell us that this was the best wedding they have ever attended. They accommodated every single one of our requests and truly provided us with an amazing wedding day. We had close to 200 people and the venue and dance floor were perfectly sized to fit everyone. The appetizers, entrees, desserts and food stations were phenomenal.
Thank you, Tyler, Linda, and all the amazing staff for making this the wedding of our dreams!
If you're looking for a little bit of history, visit Richboro Pennsylvania. This community, which is a part of the Township of Northampton, began as a farming community. There are quite a few Richboro buildings located on the national Register of Historic Places. Hampton Hill, also known as Bennet-Search House, is a historic home that was built around 1744. It is thought to have harbored slaves on the Underground Railroad. Willow Mill Complex is a complex of historic building. The buildings were built between 1800 and 1840. Also, be sure to see the John Thompson House and Twin Trees Farm.


While it's generally well known how to create physical replicas (i.e. block level copies) using the super simple and really effortless pg_basebackup tool, not so many know actually what can be done when the process is painfully slow for bigger databases. The reason for slowness can be typically linked to machine hardware (slow disks, high CPU load) or more commonly slow network between the master and replica machines – think disaster recovery, with DBs in different datacenters. So what can be done?
In the first case (slow systems) actually not too much magic can be done… hardware has it's limits after all. One could try to review/optimize the configuration, hot-swap disks to SSDs when RAID setup allows that or such. Only good news might be that when you already have a spare "high-availability" replica, that's just idling, it can be used for taking "base backup" also and things should be snappier. There are some special considerations for that use case though, so look at the pg_basebackup documentation before hitting the road.
Using pg_basebackup will be convenient in the end but the tunnel setup could get quite complex and might be "out of scope" for DBAs.
2) Local pg_basebackup (or just file level copy) compressed before copying over.
This approach requires possibly a lot of extra disk space on the master that might not be available but othwerise a good option.
3) The SSH streaming approach.
Dump pg_basebackup output to stdout on the master and stream it to the replica. We'll concentrate on this approach with this post.
So here's our quick fix to alleviate slow network – streaming "base backup" with master side compression, preferrably with multiple compression threads! Note the "master side" part – pg_basebackup already has a "–gzip/–compress" flag, but it actually only compresses things on the replica side, so that all the Postgres data files are still moved over the wire "as is", which is definitely not optimal (I wonder are there any plans to address this issue?). But ok, how much "profit" can one expect with this trick given that Postgres also has built in compression for larger strings? Well, depends heavily of course on the contents of your data and the compression/parallelization level you'll configure – but 30-50% decrease in total replica creation time are easily possible. Might not sound too much this could translate to hours already for 1TB databases. For really slow networks the gains would even bigger, when using highest levels of compression with more threads.
So to the code. A sample implementation of such approach can be found here. Some adjusting before usage is required but the main idea is that we need to combine the TAR format and compresssion on the master side and then stream over already the compressed data and then de-compress it on the replica side. For parallel compression/de-compression of the TAR stream I would recommend the "pigz" utility. NB! And not to forget about streaming the WAL files separately with pg_receivexlog as pg_basebackup does it for you only in the "plain" mode – without the WALS the whole "base backup" is later worthless.
So take a look and leave a comment when you have some thoughts on the approach or apply some other tricks. Cheers!


The Old Tree team can be booked for events throughout the year, from botanical drinks tasting events and brewery tours to small - medium sized festival workshops, foraged cocktails and botanical fermented drinks offerings. We have an Old Tree bar which can be booked for private events and collaborate with some of the best local suppliers of craft beers, such as Gun Brewery who provide world class Sussex brewed beers while we supply our craft cider, live botanical brews and soft drinks from edible landscapes.
We work with local businesses and social enterprises to offer the offer the highest quality and most ethical drinks possible, including Brighton Gin, Good Things beer and our good freinds at Brighton Permaculture Trust who provide the most delicious Sussex gleaned apple juice.
We love providing bespoke botanical drinks with stories that connect us to land and place. Whatever your event - we will be able to create or source something truly special by working with the season.
When our events take us to the West country we can also offer incredible meads, cider and perry from our network of brewers and farmers there. Look forward to hearing your desires!
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text:
May 23, 2013 by Emily
NYC Trip Diary No. 6–Once
After the Met, we went back to the apartment and Jack came to meet me. It was time for dinner and Once!
For dinner, we headed to Ellen's Stardust Diner, in Times Square. The waitstaff are all aspiring Broadway actors, so they perform during the meal, singing all sorts of songs from "I Wanna Dance With Somebody" to the Confrontation Scene from Les Miserables. (Which also involved throwing straws at each other, a nice touch.) It was REALLY loud, but also really fun. However, you do not come here if you wanted to have a conversation with the people you're eating with that evening!
The singing waitstaff, doing a Whitney Houston number.
Our waiter was a great singer (of course), and the food was surprisingly really good. I'd heard you really didn't go here for the food, you went for the entertainment, but my burger was perfectly cooked, and it came with waffle fries, which are always fun.
Since the curtain for Once is at 7–an hour earlier than most Broadway shows–we had to sort of hustle our dinner, otherwise I would have wanted to try some dessert! The theater where the show plays (The Bernard Jacobs) is only about 1/2 mile from the diner, through Times Square.
Once is a show you want to be early for, because at 6:30, the cast comes on stage and serves drinks and warms up with some great tunes. The actor who plays Da (David Patrick Kelley) came over to us during the pre-show and it was awesome. I will love him forever. 🙂 (He's a great actor, but he also seemed really sweet.) Eventually the stage hands clear the set while the cast continues to play, and the actor playing Guy (Arthur Darvil, probably best know for Dr. Who) gradually starts the first song of the show, "Leave." It was such a great way to start a show–the lights gradually went down, an d the show began.
Outside the theater
The show is unusual in a lot of respects. You really have to see it to get it, and love it. First, the actors are the orchestra, but since this show is about a song writer and a pianist, it works perfectly, and not just as a gimmick (as seen in versions of "Sweeney Todd" where they do this, or "Company"). So the cast members are always onstage, with their variety of instruments. Some of them play upwards of five instruments! (I play two. Five is like, wow.) The Girl (Joanna Christie, Mr. Selfridge) enters through the auditorium and comes up on stage while Guy is singing.
Arthur Darvill (Guy) and Joanna Christie (Girl) in "Once"
The book is what really makes this show come alive. The music is seamlessly woven in to the book and the action, and the actors are fantastic, top to bottom. It's hard to describe how great this show is. It's not sad, but it's wistful–in the end, Guy and Girl do the right things, but that doesn't mean there isn't some pain involved. It's now my new favorite show, and you must see it. It's so unique and truly special.
The only teeny note I had was that someone needs to teach Ms. Christie to use her diaphragm to breathe. She was using her upper chest a lot, and that should not be moving, so it was sort of irritating. But she does have a lovely voice, as does Mr. Darvil, who has an incredible emotional range.
Anyway, get thee to this show.
Jack and I had a great time, even buying matching Once shirts (Well, OK, his is the guy's version, and mine's the girl's crewneck, but whatever.)
We got back around 9:45, and Jack still had homework. And I had to pack. Sadly.
This entry was posted in family, food, massive excitement!, music, new things, NYC 2013, photos, theater, travel and tagged family, food, NYC 2013, Once the Musical, photos, travel. Bookmark the permalink.
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2 thoughts on "NYC Trip Diary No. 6–Once"
flatlinerbooks | May 24, 2013 at 12:35 am
We're on a vampire road trip and would like to leave a post card that we were here. See our I WANNA GO page for details. Thanks for having us 🙂
Pingback: What Emily read: May 2013 | The Literary Garden


One of the newest collections on Florida Memory is William McLeod's Civil War diary. The diary describes McLeod's experiences as a Confederate soldier from June 1864 through January 1865.
McLeod's account begins during the Atlanta Campaign and describes day-to-day siege warfare and the various engagements in which he was involved, including the Battles of Peachtree Creek, Atlanta, and Jonesboro. The diary also mentions the Battle of Dalton, Georgia in October 1864 and the subsequent advance northward into Alabama and Tennessee. McLeod provides details on the actions of the Seventh Florida Regiment at Franklin, Murfreesboro (Second Battle), and Nashville.
The diary concludes in the aftermath of the Confederate defeat at Nashville and documents the retreat into Mississippi in late 1864 and early 1865.


We loved the space & the location.
Great place!! The view of the lake is great!
The unit was great! Loved the location, access to the water, etc.
Very beautiful place, very clean even with the ability to bring pets, hot tub was hot, and pool area clean, had backup supplies to include advil.
Both the location & the amenities were great. We were not missing anything we might have needed.
What a great place for a get away! We had a little family reunion and Chateau 20 was perfect! Close to many attractions and hiking trails and a great respite to come back to. Beautiful view overlooking Superior, lovely lobby area and large main deck with fire pits, and great to have a pool and hot tub for rainy days. The staff on site were incredibly hospitable and welcoming. We would recommend Chateau 20 to others and keep it in mind ourselves for the future.
very thorough and great follow up.
Great place! Love being right on the water. Great space.
This was our 2nd year staying at the Governor's Cabin and we thoroughly enjoyed it. Great location, comfortable beds, and a true "up north at the cabin" feeling without all the issues of owning a cabin.
Fantastic cabin! Beautiful, and equipped with every thing you need for a relaxing vacation.
Second stay at this property. We really love it. Quiet and great location.
This was the perfect place for 3 girlfriends & their two small dogs to have a 4-day stay on Superior. Enjoyed the deck overlooking the lake, kitchen was well supplied, wood burning fireplace for cooler days, beds were good. The walks down to the beach were great, large deck with firepit was enjoyable, indoor pool a big plus.
Appreciate them checking in with us to make sure all was ok. Everything worked out fantastic!
The location is great - super private and TONS of space! The kitchen was fully stocked, satellite TV was great to have and all the extra movies and games and puzzles were awesome. Highly recommend this house!
The house was fine, clean and it looked like new. The location and the view are excellent.
Nice condo could use some updating but comfortable and a beautiful view.
I did have trouble using the number that was on the contract. It did not go to voice mail. It just said the office was closed. I finally wrote an email which was responded to. On the last day at first no voice mail but then got through. This would have been dicey it a pipe had broken or if something else happened.
The house was very nicely appointed and just steps away from the water's edge.
The property is beautiful. Great Lake. Very few cabins and very quiet. The cabin has everything you need. Great deck area. Nice kitchen, eating and living areas. Great dock! The bathroom needs work. It smelled bad. The floor needs to be replaced. The shower curtain was filthy. The cushion on the bench was dirty. Having to take the garbage is inconvenient but not a deal breaker. The location is great. Love the north shore!
More than we expected. Very quiet and secluded yet close to everything. Very private which was super nice. Huge manicured lawn which was fenced in with a driveway gate that really surprised us. We have a German Shepard mix and he got plenty of exercise. Nice to be able to bring him along on vacation. There were just to two of us but plenty of room for more. Well stocked kitchen and everything worked well and my wife loved the soaking bath tub with jets that soothed away aches and pains. Awesome updated bathrooms and the beds were extremely comfortable. The deck was just awesome. Spent a lot of time on it. We enjoyed the huge overhang from the house which allowed us to sit outside even in the rain. From the deck we saw seagulls, bald eagles, hummingbirds. A virtual paradise. At one point there were 6 bald eagles hovering overhead. Nice to have the telescope to view ships passing by too. We've been coming to the North Shore for years and this is at the top of our list of places to return to.
This home suited our needs perfectly. No need to bring any books as there are plenty to choose from. The piano is a very good one and was in tune. The TV is complicated to figure out, but we only used it for playing CD's so it didn't matter. The home is very private and very quiet. It is well-built and well-designed. I highly recommend it to anyone who wants to get away from it all.
Everything was perfect! It was such a beautiful cabin. We will definitely be going back!
We enjoyed our stay at Chateau LeVeaux and apartment 30. The location on the North Shore ensures easy access to many wonderful sight seeing highlights. The entire place was quiet, there was plenty to do in the game rooms and pool on sight. This apartment allows for pets and we had one. However, the apartment was very clean and well kept up. The host couple were friendly and helpful in every way we had need.
Pretty much a painless process. I was kept well informed via email.
The house was great. I came up to the Tofte for the Lutsen 99er mountain bike race with a group of guys and we absolutely loved the place. It was in great shape, it is incredibly spacious, extremely comfortable, and has stunning views of Superior. The place had everything 4 guys could possibly want for a short two night stay. The garage was key for our group, it gave us the option to storing our bikes indoor vs. leaving on the car overnight.


The San Diego metropolitan area has the 13th worst ozone pollution in the nation, but is not among the regions with the most short- term and annual particle pollution, according to a report released Wednesday by the American Lung Association.
The association's "State of the Air 2016" study noted that 16 of the nation's most-polluted cities showed their lowest levels of particle pollution in the 17-year history of the report.
California cities, however, dominated the top-10 lists of worst offenders in all three categories. Bakersfield ranked worst in the nation for short-term and annual particle pollution, and second for ozone pollution behind Los Angeles-Long Beach. The Visalia-Porterville-Hanford region ranked among the worst three in all three categories. Fresno-Madera ranked among the worst four across the board.
The report is based on readings taken at monitoring sites across the country from 2012-14.
According to the ALA, the prolonged drought and frequent heat waves caused by climate change are making it more difficult to clean up the air in San Diego.
Despite an uptick in ozone days, San Diego has experienced an overall drop of 71 percent in unhealthy ozone days since 2000, and unhealthy particle days dropped by 86 percent, the organization noted. Cleaner vehicles that produce fewer tailpipe emissions were credited with the improvement.
But air pollution continues to be a major issue nationally, according to the report's authors.
Posted in Life | Tagged air, American Lung Association, ozone, pollution, ranking, San Diego, State of the Air 2016"


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US aid to Ukraine puts pressure on Pentagon's arms stockpile
Leave a Comment / Trending / By National News Sources
WASHINGTON (AP) — The intense firefight over Ukraine has the Pentagon rethinking its weapons stockpiles. If another major war broke out today, would the United States have enough ammunition to fight?
It's a question confronting Pentagon planners, not only as they aim to supply Ukraine for a war with Russia that could stretch years longer, but also as they look ahead to a potential conflict with China.
Russia is firing as many as 20,000 rounds a day, ranging from bullets for automatic rifles to truck-sized cruise missiles. Ukraine is answering with as many as 7,000 rounds a day, firing 155 mm howitzer rounds, Stinger anti-aircraft missiles and now NASAMS air defense munitions, and thousands of rounds of small arms fire.
Much of Ukraine's firepower is being supplied through U.S. government-funded weapons that are pushed almost weekly to the front lines. On Wednesday, the Biden administration announced an additional round of aid that will provide 20 million more rounds of small arms ammunition to Kyiv.
"We've not been in a position where we've got only a few days of some critical munition left," Pentagon comptroller Michael McCord told reporters this month. "But we are now supporting a partner who is."
U.S. defense production lines are not scaled to supply a major land war, and some, like for the Stinger, were previously shut down.
That's putting pressure on U.S. reserves and has officials asking whether U.S. weapons stockpiles are big enough. Would the U.S. be ready to respond to a major conflict today, for example if China invaded Taiwan?
"What would happen if something blew up in Indo-Pacom? Not five years from now, not 10 years from now, what if it happened next week?" Bill LaPlante, the Pentagon's top weapons buyer, said, referring to the military's Indo-Pacific Command. He spoke at a defense acquisitions conference this month at George Mason University in Virginia.
"What do we have in any degree of quantity? That will actually be effective? Those are the questions we're asking right this minute," he said.
The Army uses many of the same munitions that have proven most critical in Ukraine, including High Mobility Artillery Rocket Systems, known as HIMARS, Stinger missiles and 155 mm howitzer rounds, and is now reviewing its stockpile requirements, Doug Bush, the Army's assistant secretary for acquisition, told reporters Monday.
"They're seeing what Ukraine is using, what we can produce and how fast we can ramp up, all of which are factors you would work into, 'OK, how (big) does your pre-war stockpile need to be?" Bush said. "The slower you ramp up, the bigger the pile needs to be at the start."
The military aid packages the U.S. sends either pull inventory from stockpiles or fund contracts with industry to step up production. At least $19 billion in military aid has been committed to date, including 924,000 artillery rounds for 155mm howitzers, more than 8,500 Javelin anti-tank systems, 1,600 Stinger anti-aircraft systems and hundreds of vehicles and drones. It's also provided advanced air defense systems and 38 HIMARS, although the Pentagon does not disclose how many rounds of ammunition it sends with the rocket systems.
The infusion of weapons is raising questions on Capitol Hill.
This month, the administration asked Congress to provide $37 billion more in military and humanitarian aid to Ukraine in the post-election legislative session, and to approve it before Republicans take control of the House in January. House Republican leader Kevin McCarthy of California, who is seeking to become speaker, has warned that Republicans would not support writing a "blank check" for Ukraine.
Even with fresh money, stockpiles cannot be quickly replenished. Several of the systems proving most vital in Ukraine had their production lines shut down years ago. Keeping a production line open is expensive, and the Army had other spending priorities.
The Pentagon awarded Raytheon a $624 million contract for 1,300 new Stinger missiles in May, but the company said it will not be able to increase production until next year due to parts shortages.
"The Stinger line was shut down in 2008," LaPlante said. "Really, who did that? We all did it. You did it. We did it," he said, referring to Congress and the Pentagon's decision not to fund continued production of the Army's anti-aircraft munition, which can be launched by a soldier or mounted to a platform or truck.
Based on an analysis of past Army budget documents, Center for Strategic and International Studies senior adviser Mark Cancian estimates that the 1,600 Stinger systems the U.S. has provided to Ukraine represent about one-quarter of its total arsenal.
The HIMARS system, which Ukraine has used so effectively in its counteroffensive, faces some of the same challenges, LaPlante said.
"The thing now that is saving Ukraine, and that everybody around the world wants, we stopped production of it," he said.
HIMARS production was shut down by the Army from about 2014 to 2018, LaPlante said. The Army is now trying to ramp up production to build up to eight a month, or 96 a year, Bush said.
HIMARS effectiveness in Ukraine has increased interest elsewhere, too. Poland, Lithuania and Taiwan have put in orders, even as the U.S. works to rush more to Ukraine. If the conflict drags on and more HIMARS ammunition is prioritized for Ukraine, that could potentially limit U.S. troops' access to the rounds for live-fire training.
The Pentagon this month announced a $14.4 million contract to speed production of new HIMARS to replenish its stocks.
"This conflict has revealed that munitions production in the United States and with our allies is likely insufficient for major land wars," said Ryan Brobst, an analyst at the Center on Military and Political Power at the Foundation for the Defense of Democracies.
The U.S. also recently announced it would be supplying Ukraine with four Avenger air defense systems, portable launchers that can be mounted on tracked or wheeled vehicles, to provide another shorter-range option against the Iranian drones being used by Russia's forces. But the Avenger systems rely on Stinger missiles, too.
Pentagon deputy press secretary Sabrina Singh said stockpile concerns were taken into account.
"We wouldn't have provided these Stinger missiles if we didn't feel that we could," Singh said at a recent Pentagon briefing.
Follow AP coverage of the war in Ukraine at: https://apnews.com/hub/russia-ukraine
Alanis Morissette Calls Out Rock & Roll Hall Of Fame Over 'Anti-Woman Sentiment' | HuffPost Entertainment
Olivia Culpo Was 'Left With No Sense Of Identity' After Breaking Up With Nick Jonas | HuffPost Entertainment


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Australia's got talent – or at least it could if we set our minds to it
Zoe Dattner
The inaugural Australian Financial Review Business Summit taking place yesterday and today appears, on the face of it, to be geared towards the interests of large corporates. However, the theme "Risk Takers and Growth Makers" is set squarely in the territory of SME land, and with everyone's eyes on the government's innovation agenda, discussions yesterday revolved heavily around 'the I word' and what it means.
Innovation, as a word, has been rendered largely meaningless, particularly from its use in the speeches of politicians and other individuals who, one suspects, have little intention of doing anything innovative at all.
Yet it is a word that has at its heart some noble and evocative sentiments that are hard to fake: transformation, revolution, change. Delegates at the summit agreed: if we are truly to become an innovative nation that makes the most of its capabilities in the wake of a resource-dependent economy, we need to develop, attract and maximise talent.
Speaking on the subjects of fast growth, floating a business on NASDAQ and what it's like to run a tech startup from Australia, Atlassian's Mike Cannon-Brookes gave the audience a simple plan. If Australia contributes 1% of the world's Gross Domestic Product then it should contribute 1% of the world's technology – and that means talent.
Cannon-Brookes told the summit a quarter of Atlassian's staff in Sydney have been 'imported' from overseas and are working here on 457 visas. They love their jobs, they love Australia and they're incredibly talented. Yet Australia's cost of living – which is inflated when you're on a 457 visa with rising costs such as healthcare and public education (for your children) – is hurting our ability to attract talent.
When asked how Australia's two major political parties should respond to this, Cannon-Brookes suggested politics should be asking itself: how do we have a talented workforce in 20 years? And then the major political parties should both work to present the best possible means of getting there.
The Business Council of Australia's Jennifer Westacott also sees the issue of innovation and Australia's economy as a play for talent, noting it's important we don't define innovation as purely technological; it's the ecosystem of collaboration we need to manifest.
A talent economy protects the skills we need, not just the jobs, she explained, and converts creativity at the workplace level and delivers social progress.
"It's vital that we don't assume that innovation is solely in the domain of startup companies," Westacott told the audience.
General Electric chief executive John Rice emphasised the need to make sure business leaders have the hearts and minds of all of their employees at the fore when it comes to tackling change. "Make sure all the groups are on your side," he said.
"This is a world where you're going to make changes – you have to make sure that everybody's head is in the game."
Key takeaways for SMEs striving to drive innovation
Bruce Buchanan, chief executive, Rokt
Always consider, how do I best support my team, so they can support down the line?
How can I turn my focus outward and not always be bogged down with internal systems?
Look for leaders (when recruiting) who don't have a lot of ego
Get rid of bureaucracy – it's the enemy of the entrepreneurial spirit
Celebrate along the way – facilitate camaraderie and instill a sense of achievement
Nail your communications – especially when you're operating in a geographically disperse workforce
Paul Bassat, co-founder, Square Peg Capital
On recruiting: If there are 10 candidates for a role and the best of that 10 isn't good enough, don't hire them
Hire based on a values set, rather than skills. It's achievable for someone to learn the skills, but you can't learn integrity, initiative and teamwork
Exercise a culture of honesty and transparency
Support an environment where staff think of moving their career along from within the company, rather than beyond it.
Align your values with your sense of purpose and be consistent around what the organisation says and what the organisation does, then monitor those efforts and changes every six months.
John Rice, chief executive, General Electric
"We can't have an environment where people are afraid to fail. Try something quickly and if it doesn't look like it's working then stop doing it and try something else."
Dr Larry Marshall, chief executive, CSIRO
"Managing innovation and disruption is a process of managing ambiguity". This means you need a chief executive who can listen and be attentive and not be a chest-beating hero.
Michael Cannon-Brookes, co-founder, Atlassian
"We'd love to be the second biggest tech company in Australia, because that would mean someone else is rolling past."
sam jackson
The show AGT next season, Hopefully it will be returning to Nine in next year as well. If you think you have something special to share then be prepare for it as audition about to start soon http://australia2017auditions.com/australia-got-talent-2017-auditions.html
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text:
Upper Camster is a small hamlet, which lies at the source of the Camster Burn, 4 miles north of Lybster,  in Caithness, Scottish Highlands and is in the Scottish council area of Highland.

The Grey Cairns of Camster are two large Neolithic chambered cairns located about quarter of a mile north of Upper Camster. The cairns, which are considered to be examples of the Orkney-Cromarty type of chambered cairn, were constructed in the third or fourth millennium BC in a desolate stretch of boggy peat-covered moorland in the Flow Country of Caithness.

Gallery

References

Populated places in Caithness

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