text:
Generic Name: tizanidine
Brand Name: Zanaflex
Last reviewed on RxList: 1/4/2021
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What is Zanaflex and how is it used?
Zanaflex is a prescription medicine used to treat the symptoms of muscle stiffness (spasticity) associated with conditions such as Cerebral palsy or other neurological disorders. Zanaflex may be used alone or with other medications.
Zanaflex belongs to a class of drugs called Central Alpha-2-Adrenergic Agonist.
It is not known if Zanaflex is safe and effective in children.
What are the possible side effects of Zanaflex?
Zanaflex may cause serious side effects including:
low blood pressure,
abnormal liver function tests,
drowsiness,
hallucinations,
excessive drowsiness,
slow heartrate,
tiredness, and
Get medical help right away, if you have any of the symptoms listed above.
The most common side effects of Zanaflex include:
tiredness,
speech disorder,
lazy eye (amblyopia),
urinary frequency,
flu symptoms,
uncontrolled muscle movements,
sore throat, and
Tell the doctor if you have any side effect that bothers you or that does not go away.
These are not all the possible side effects of Zanaflex. 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.
Zanaflex® (tizanidine hydrochloride) is a central alpha2-adrenergic agonist. Tizanidine HCl is a white to off-white, fine crystalline powder, which is odorless or with a faint characteristic odor. Tizanidine is slightly soluble in water and methanol; solubility in water decreases as the pH increases. Its chemical name is 5-chloro-4-(2- imidazolin-2-ylamino)-2,1,3-benzothiadiazole monohydrochloride. Tizanidine's molecular formula is C9H8ClN5S-HCl, its molecular weight is 290.2 and its structural formula is:
Zanaflex Capsules® are supplied as 2, 4, and 6 mg capsules for oral administration. Zanaflex Capsules® contain the active ingredient, tizanidine hydrochloride (2.29 mg equivalent to 2 mg tizanidine base, 4.58 mg equivalent to 4 mg tizanidine base, and 6.87 mg equivalent to 6 mg tizanidine base), and the inactive ingredients, hypromellose, silicon dioxide, sugar spheres, titanium dioxide, gelatin, and colorants.
Zanaflex® tablets are supplied as 4 mg tablets for oral administration. Zanaflex® tablets contain the active ingredient, tizanidine hydrochloride (4.58 mg equivalent to 4 mg tizanidine base), and the inactive ingredients, colloidal silicon dioxide, stearic acid, microcrystalline cellulose and anhydrous lactose.
Zanaflex is a central alpha-2-adrenergic agonist indicated for the management of spasticity. Because of the short duration of therapeutic effect, treatment with Zanaflex should be reserved for those daily activities and times when relief of spasticity is most important [see DOSAGE AND ADMINISTRATION].
Zanaflex Capsules® or Zanaflex® tablets may be prescribed with or without food. Once the formulation has been selected and the decision to take with or without food has been made, this regimen should not be altered.
Food has complex effects on tizanidine pharmacokinetics, which differ with the different formulations. Zanaflex Capsules and Zanaflex tablets are bioequivalent to each other under fasting conditions (more than 3 hours after a meal), but not under fed conditions (within 30 minutes of a meal). These pharmacokinetic differences may result in clinically significant differences when switching administration of tablet and capsules and when switching administration between the fed or fasted state. These changes may result in increased adverse events, or delayed or more rapid onset of activity, depending upon the nature of the switch. For this reason, the prescriber should be thoroughly familiar with the changes in kinetics associated with these different conditions [see CLINICAL PHARMACOLOGY].
The recommended starting dose is 2 mg. Because the effect of Zanaflex peaks at approximately 1 to 2 hours post-dose and dissipates between 3 to 6 hours post-dose, treatment can be repeated at 6 to 8 hour intervals, as needed, to a maximum of three doses in 24 hours.
Dosage can be gradually increased by 2 mg to 4 mg at each dose, with 1 to 4 days between dosage increases, until a satisfactory reduction of muscle tone is achieved. The total daily dose should not exceed 36 mg. Single doses greater than 16 mg have not been studied.
Dosing in Patients with Renal Impairment
Zanaflex should be used with caution in patients with renal insufficiency (creatinine clearance < 25 mL/min), as clearance is reduced by more than 50%. In these patients, during titration, the individual doses should be reduced. If higher doses are required, individual doses rather than dosing frequency should be increased [see WARNINGS AND PRECAUTIONS].
Dosing in Patients with Hepatic Impairment
Zanaflex should be used with caution in patients with any hepatic impairment. In these patients, during titration, the individual doses should be reduced. If higher doses are required, individual doses rather than dosing frequency should be increased. Monitoring of aminotransferase levels is recommended for baseline and 1 month after maximum dose is achieved, or if hepatic injury is suspected. [see Use In Specific Populations]
Drug Discontinuation
If therapy needs to be discontinued, particularly in patients who have been receiving high doses (20 mg to 36 mg daily) for long periods (9 weeks or more) or who may be on concomitant treatment with narcotics, the dose should be decreased slowly (2 mg to 4 mg per day) to minimize the risk of withdrawal and rebound hypertension, tachycardia, and hypertonia [see Drug Abuse and Dependence].
2 mg: Light blue opaque body with a light blue opaque cap with "2 MG" printed on the cap
4 mg: White opaque body with a blue opaque cap with "4 MG" printed on the cap
6 mg: Blue opaque body with a white stripe and blue opaque cap with "6 MG" printed on the cap
4 mg white, uncoated tablets with a quadrisecting score on one side and debossed with "A594" on the other side
Zanaflex Capsules®
Zanaflex Capsules® (tizanidine hydrochloride) capsules are available in three strengths as two-piece hard gelatin capsules containing tizanidine hydrochloride 2.29 mg, 4.58 mg and 6.87 mg, equivalent to 2 mg, 4 mg and 6 mg tizanidine base.
The 2 mg capsules have a light blue opaque body with a light blue opaque cap with "2 MG" printed on the cap: bottles of 150 capsules (NDC 10144-602-15)
The 4 mg capsules have a white opaque body with a blue opaque cap with "4 MG" printed on the cap: bottles of 150 capsules (NDC 10144-604-15)
The 6 mg capsules have a blue opaque body with a white stripe and blue opaque cap with "6 MG" printed on the capsules: bottles of 150 capsules (NDC -10144-606-15)
Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) [see USP Controlled Room Temperature]. Dispense in containers with child resistant closure.
Zanaflex® Tablets
Zanaflex® (tizanidine hydrochloride) tablets are available as 4 mg white, uncoated tablets containing tizanidine hydrochloride 4.58 mg, equivalent to 4 mg tizanidine base. The tablets have a quadrisecting score on one side and are debossed with "A594" on the other side. Tablets are provided as follows: bottles of 150 tablets (NDC -10144-594-15).
Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) [see USP Controlled Room Temperature].
Dispense in containers with child resistant closure .
Marketed and Distributed by: Acorda Therapeutics Inc. Ardsley, NY 10502. Revised: November 2013.
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The following adverse reactions are described elsewhere in other sections of the prescribing information:
Hypotension [see WARNINGS AND PRECAUTIONS]
Liver Injury [see WARNINGS AND PRECAUTIONS]
Sedation [see WARNINGS AND PRECAUTIONS]
Hallucinosis/Psychotic-Like Symptoms [see WARNINGS AND PRECAUTIONS]
Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice.
Three double-blind, randomized, placebo controlled -clinical studies were conducted to evaluate the effect of tizanidine on spasticity control. Two studies were conducted in patients with multiple sclerosis and one in patients with spinal cord injury. Each study had a 13-week active treatment period which included a 3-week titration phase to the maximum tolerated dose up to 36 mg/day in three divided doses, a 9-week plateau phase where the dose of tizanidine was held constant and a 1- week dose tapering. In all, 264 patients received tizanidine and 261 patients received placebo. Across the three studies patient ages ranged from 15–69 years and 51.4 percent were women. The median dose during the plateau phase ranged from 20–28 mg/day.
The most frequent adverse reactions reported in multiple dose, placebo-controlled clinical studies involving 264 patients with spasticity were dry mouth, somnolence/sedation, asthenia (weakness, fatigue and/or tiredness) and dizziness. Three-quarters of the patients rated the events as mild to moderate and one-quarter of the patients rated the events as being severe. These events appeared to be dose related.
Table 1 lists signs and symptoms that were reported in greater than 2% of patients in three multiple dose, placebo-controlled studies who received Zanaflex where the frequency in the Zanaflex group was greater than the placebo group. For comparison purposes, the corresponding frequency of the event (per 100 patients) among placebo treated patients is also provided.
Table 1: Multiple Dose, Placebo-Controlled Studies—Frequent ( > 2%) Adverse Reactions Reported for Which Zanaflex Tablets Incidence is Greater than Placebo
Event Placebo
N = 261
% Zanaflex Tablet
Dry mouth 10 49
Somnolence 10 48
Asthenia* 16 41
Dizziness 4 16
UTI 7 10
Infection 5 6
Liver test abnormality 2 6
Speech disorder 0 3
Amblyopia (blurred vision) < 1 3
Urinary frequency 2 3
Flu syndrome 2 3
Dyskinesia 0 3
Nervousness < 1 3
Pharyngitis 1 3
Rhinitis 2 3
*(weakness, fatigue, and/or tiredness)
In the single dose, placebo-controlled study involving 142 patients with spasticity due to multiple sclerosis (Study 1) [see Clinical Studies], the patients were specifically asked if they had experienced any of the four most common adverse reactions: dry mouth, somnolence (drowsiness), asthenia (weakness, fatigue and/or tiredness) and dizziness. In addition, hypotension and bradycardia were observed. The occurrence of these reactions is summarized in Table 2. Other events were, in general, reported at a rate of 2% or less.
Table 2: Single Dose, Placebo-Controlled Study—Common Adverse Reactions Reported
% Zanaflex Tablet, 8mg,
% Zanaflex Tablet, 16 mg,
Somnolence 31 78 92
Dry mouth 35 76 88
Asthenia* 40 67 78
Dizziness 4 22 45
Hypotension 0 16 33
Bradycardia 0 2 10
Post-Marketing Experience
The following adverse reactions have been identified during post approval use of Zanaflex. 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.
Certain events, such as somnolence, dry mouth, hypotension, decreased blood pressure, bradycardia, dizziness, weakness or asthenia, muscle spasms, hallucinations, fatigue, liver function test abnormality and hepatotoxicity, have been observed in post marketing and clinical trials and are discussed in previous sections of this document.
The following adverse reactions have been identified as occurring in the post marketing experience of Zanaflex. Based on the information provided regarding these reactions, a causal relationship with Zanaflex cannot be entirely excluded. The events are listed in order of decreasing clinical significance; severity in the post marketing setting is not reported.
Exfoliative Dermatitis
Concomitant use of fluvoxamine and Zanaflex is contraindicated. Changes in pharmacokinetics of tizanidine when administered with fluvoxamine resulted in significantly decreased blood pressure, increased drowsiness, and increased psychomotor impairment. [see CONTRAINDICATIONS and CLINICAL PHARMACOLOGY]
Concomitant use of ciprofoxacin and Zanaflex is contraindicated. Changes in pharmacokinetics of tizanidine when administered with ciprofloxacin resulted in significantly decreased blood pressure, increased drowsiness, and increased psychomotor impairment [See CONTRAINDICATIONS and CLINICAL PHARMACOLOGY]
CYP1A2 Inhibitors other than Fluvoxamine and Ciprofloxacin
Because of potential drug interactions, concomitant use of Zanaflex with other CYP1A2 inhibitors, such as zileuton, fluoroquinolones other than strong CYP1A2 inhibitors (which are contraindicated), antiarrythmics (amiodarone, mexiletine, propafenone, and verapamil), cimetidine, famotidine, oral contraceptives, acyclovir, and ticlopidine) should be avoided. If their use is clinically necessary, therapy should be initiated with 2 mg dose and increased in 2–4 mg steps daily based on patient response to therapy. If adverse reactions such as hypotension, bradycardia, or excessive drowsiness occur, reduce or discontinue Zanaflex therapy. [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY]
Concomitant use of Zanaflex with oral contraceptives is not recommended. However, if concomitant use is clinically necessary, initiate Zanaflex with a single 2 mg dose and increase in 2–4 mg steps daily based on patient response to therapy. If adverse reactions such as hypotension, bradycardia, or excessive drowsiness occur, reduce or discontinue Zanaflex therapy. [see CLINICAL PHARMACOLOGY]
Alcohol increases the overall amount of drug in the bloodstream after a dose of Zanaflex. This was associated with an increase in adverse reactions of Zanaflex. The CNS depressant effects of Zanaflex and alcohol are additive. [see CLINICAL PHARMACOLOGY]
Other CNS Depressants
The sedative effects of Zanaflex with CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants) may be additive. Monitor patients who take Zanaflex with another CNS depressant for symptoms of excess sedation. [see CLINICAL PHARMACOLOGY]
α2-adrenergic agonists
Because hypotensive effects may be cumulative, it is not recommended that Zanaflex be used with other α2-adrenergic agonists. [see WARNINGS AND PRECAUTIONS]
Abuse potential was not evaluated in human studies. Rats were able to distinguish tizanidine from saline in a standard discrimination paradigm, after training, but failed to generalize the effects of morphine, cocaine, diazepam, or phenobarbital to tizanidine.
Tizanidine is closely related to clonidine, which is often abused in combination with narcotics and is known to cause symptoms of rebound upon abrupt withdrawal. Three cases of rebound symptoms on sudden withdrawal of tizanidine have been reported. The case reports suggest that these patients were also misusing narcotics. Withdrawal symptoms included hypertension, tachycardia, hypertonia, tremor, and anxiety. Withdrawal symptoms are more likely to occur in cases where high doses are used, especially for prolonged periods, or with concomitant use of narcotics. If therapy needs to be discontinued, the dose should be decreased slowly to minimize the risk of withdrawal symptoms [see DOSAGE AND ADMINISTRATION].
Monkeys were shown to self-administer tizanidine in a dose-dependent manner, and abrupt cessation of tizanidine produced transient signs of withdrawal at doses > 35 times the maximum recommended human dose on a mg/m² basis. These transient withdrawal signs (increased locomotion, body twitching, and aversive behavior toward the observer) were not reversed by naloxone administration.
Included as part of the PRECAUTIONS section.
Tizanidine is an α2-adrenergic agonist that can produce hypotension. Syncope has been reported in the post marketing setting. The chance of significant hypotension may possibly be minimized by titration of the dose and by focusing attention on signs and symptoms of hypotension prior to dose advancement. In addition, patients moving from a supine to fixed upright position may be at increased risk for hypotension and orthostatic effects.
Monitor for hypotension when Zanaflex is used in patients receiving concurrent antihypertensive therapy. It is not recommended that Zanaflex be used with other α2- adrenergic agonists. Clinically significant hypotension (decreases in both systolic and diastolic pressure) has been reported with concomitant administration of either fluvoxamine or ciprofloxacin and single doses of 4 mg of Zanaflex. Therefore, concomitant use of Zanaflex with fluvoxamine or with ciprofloxacin, potent inhibitors of CYP1A2, is contraindicated [see CONTRAINDICATIONS and DRUG INTERACTIONS].
Risk of Liver Injury
Zanaflex may cause hepatocellular liver injury. Zanaflex should be used with caution in patients with any hepatic impairment.. Monitoring of aminotransferase levels is recommended for baseline and 1 month after maximum dose is achieved, or if hepatic injury is suspected. [see DOSAGE AND ADMINISTRATION and Use In Specific Populations]
Zanaflex can cause sedation, which may interfere with everyday activity. In the multiple dose studies, the prevalence of patients with sedation peaked following the first week of titration and then remained stable for the duration of the maintenance phase of the study. The CNS depressant effects of Zanaflex with alcohol and other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants) may be additive. Monitor patients who take Zanaflex with another CNS depressant for symptoms of excess sedation. [see DRUG INTERACTIONS]
Hallucinosis/Psychotic-Like Symptoms
Zanaflex use has been associated with hallucinations. Formed, visual hallucinations or delusions have been reported in 5 of 170 patients (3%) in two North American controlled clinical studies. Most of the patients were aware that the events were unreal. One patient developed psychosis in association with the hallucinations. One patient among these 5 continued to have problems for at least 2 weeks following discontinuation of tizanidine. Consider discontinuing Zanaflex in patients who develop hallucinations.
Interaction with CYP1A2 Inhibitors
Because of potential drug interactions, Zanaflex is contraindicated in patients taking potent CYP1A2 inhibitors, such as fluvoxamine or ciprofloxacin. Adverse reactions such as hypotension, bradycardia, or excessive drowsiness can occur when Zanaflex is taken with other CYP1A2 inhibitors, such as zileuton, fluoroquinolones other than ciprofloxacin (which is contraindicated), antiarrythmics (amiodarone, mexiletine, propafenone), cimetidine, famotidine, oral contraceptives, acyclovir, and ticlopidine ). Concomitant use should be avoided unless the necessity for Zanaflex therapy is clinically evident. In such a case, use with caution. [see DRUG INTERACTIONS and CLINICAL PHARMACOLOGY]
Hypersensitivity Reactions
Zanaflex can cause anaphylaxis. Signs and symptoms including respiratory compromise, urticaria, and angioedema of the throat and tongue have been reported. Patients should be informed of the signs and symptoms of severe allergic reactions and instructed to discontinue Zanaflex and seek immediate medical care should these signs and symptoms occur. [see CONTRAINDICATIONS]
Increased Risk of Adverse Reactions in Patients with Renal Impairment
Zanaflex should be used with caution in patients with renal insufficiency (creatinine clearance < 25 mL/min), as clearance is reduced by more than 50%. In these patients, during titration, the individual doses should be reduced. If higher doses are required, individual doses rather than dosing frequency should be increased. These patients should be monitored closely for the onset or increase in severity of the common adverse events (dry mouth, somnolence, asthenia and dizziness) as indicators of potential overdose. [see DOSAGE AND ADMINISTRATION and Use In Specific Populations]
Withdrawal Adverse Reactions
Withdrawal adverse reactions include rebound hypertension, tachycardia, and hypertonia. To minimize the risk of these reactions, particularly in patients who have been receiving high doses (20 to 28 mg daily) for long periods of time (9 weeks or more) or who may be on concomitant treatment with narcotics, the dose should be decreased slowly (2 to 4 mg per day). [see DOSAGE AND ADMINISTRATION]
Nonclinical Toxicology
Tizanidine was administered to mice for 78 weeks at oral doses up to 16 mg/kg/day, which is 2 times the maximum recommended human dose (MRHD) on a mg/m² basis. Tizanidine was administered to rats for 104 weeks at oral doses up to 9 mg/kg/day, which is 2.5 times the MRHD on a mg/m² basis. There was no increase in tumors in either species.
Tizanidine was negative in in vitro (bacterial reverse mutation [Ames] , mammalian gene mutation, and chromosomal aberration test in mammalian cells) and in vivo (bone marrow micronucleus, and cytogenetics) assay.
Oral administration of tizanidine resulted in reduced fertility in male and female rats following doses of 30 and 10 mg/kg/day, respectively. No effect on fertility was observed at doses of 10 (male) and 3 (female) mg/kg/day, which are approximately 8 and 3 times, respectively, the MRHD on a mg/m² basis).
Pregnancy Category C
Zanaflex has not been studied in pregnant women. Zanaflex should be given to pregnant women only if the benefit outweighs the risk to the unborn fetus. Reproduction studies performed in rats at a dose of 3 mg/kg, equal to the maximum recommended human dose on a mg/m² basis, and in rabbits at 30 mg/kg, 16 times the maximum recommended human dose on a mg/m² basis, did not show evidence of teratogenicity. Tizanidine at doses that are equal to and up to 8 times the maximum recommended human dose on a mg/m² basis increased gestation duration in rats. Prenatal and postnatal pup loss was increased and developmental retardation occurred. Post-implantation loss was increased in rabbits at doses of 1 mg/kg or greater, equal to or greater than 0.5 times the maximum recommended human dose on a mg/m² basis.
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Zanaflex is administered to a nursing woman.
Zanaflex is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Clinical studies of Zanaflex did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently than younger subjects. Crossstudy comparison of pharmacokinetic data following single dose administration of 6 mg Zanaflex showed that younger subjects cleared the drug four times faster than the elderly subjects. In elderly patients with renal insufficiency (creatinine clearance < 25 mL/min), tizanidine clearance is reduced by more than 50% compared to healthy elderly subjects; this would be expected to lead to a longer duration of clinical effect. During titration, the individual doses should be reduced. If higher doses are required, individual doses rather than dosing frequency should be increased. Monitor elderly patients because they may have an increased risk for adverse reactions associated with Zanaflex.
Impaired Renal Function
Zanaflex is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. In patients with renal insufficiency (creatinine clearance < 25 mL/min) clearance was reduced by more than 50%. In these patients, during titration, the individual doses should be reduced. If higher doses are required, individual doses rather than dosing frequency should be increased. These patients should be monitored closely for the onset or increase in severity of the common adverse events (dry mouth, somnolence, asthenia and dizziness) as indicators of potential overdose. [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY]
Impaired Hepatic Function
The influence of hepatic impairment on the pharmacokinetics of tizanidine has not been evaluated. Because tizanidine is extensively metabolized in the liver, hepatic impairment would be expected to have significant effects on pharmacokinetics of tizanidine. [see DOSING AND ADMINISTRATION, WARNINGS AND PRECAUTIONS, and CLINICAL PHARMACOLOGY].
A review of the safety surveillance database revealed cases of intentional and accidental Zanaflex overdose. Some of the cases resulted in fatality and many of the intentional overdoses were with multiple drugs including CNS depressants. The clinical manifestations of tizanidine overdose were consistent with its known pharmacology. In the majority of cases a decrease in sensorium was observed including lethargy, somnolence, confusion and coma. Depressed cardiac function is also observed including most often bradycardia and hypotension. Respiratory depression is another common feature of tizanidine overdose.
Should overdose occur, basic steps to ensure the adequacy of an airway and the monitoring of cardiovascular and respiratory systems should be undertaken. Tizanidine is a lipid-soluble drug, which is only slightly soluble in water and methanol. Therefore, dialysis is not likely to be an efficient method of removing drug from the body. In general, symptoms resolve within one to three days following discontinuation of tizanidine and administration of appropriate therapy. Due to the similar mechanism of action, symptoms and management of tizanidine overdose are similar to that following clonidine overdose. For the most recent information concerning the management of overdose, contact a poison control center.
Zanaflex is contraindicated in patientstaking potent inhibitors of CYP1A2, such as fluvoxamine or ciprofloxacin [see DRUG INTERACTIONS].
Tizanidine is a central alpha-2-adrenergic receptor agonist and presumably reduces spasticity by increasing presynaptic inhibition of motor neurons. The effects of tizanidine are greatest on polysynaptic pathways. The overall effect of these actions is thought to reduce facilitation of spinal motor neurons.
Following oral administration, tizanidine is essentially completely absorbed. The absolute oral bioavailability of tizanidine is approximately 40% (CV = 24%), due to extensive first-pass hepatic metabolism. Tizanidine is extensively distributed throughout the body with a mean steady state volume of distribution of 2.4 L/kg (CV = 21%) following intravenous administration in healthy adult volunteers. Tizanidine is approximately 30% bound to plasma proteins.
Differences between Zanaflex Capsules® and Zanaflex® Tablets
Zanaflex Capsules® and Zanaflex® tablets are bioequivalent to each other under fasting conditions, but not under fed conditions. A single dose of either two 4 mg tablets or two 4 mg capsules was administered under fed and fasting conditions in an open label, four period, randomized crossover study in 96 human volunteers, of whom 81 were eligible for the statistical analysis. Following oral administration of either the tablet or capsule (in the fasted state), peak plasma concentrations of tizanidine occurred 1.0 hours after dosing with a half-life of approximately 2 hours. When two 4 mg tablets were administered with food, the mean maximal plasma concentration was increased by approximately 30%, and the median time to peak plasma concentration was increased by 25 minutes, to 1 hour and 25 minutes. In contrast, when two 4 mg capsules were administered with food, the mean maximal plasma concentration was decreased by 20%, the median time to peak plasma concentration was increased 2 to 3 hours. Consequently, the mean Cmax for the capsule when administered with food is approximately 66% the Cmax for the tablet when administered with food.
Food also increased the extent of absorption for both the tablets and capsules. The increase with the tablet (~30%) was significantly greater than with the capsule (~10%). Consequently when each was administered with food, the amount absorbed from the capsule was about 80% of the amount absorbed from the tablet. Administration of the capsule contents sprinkled on applesauce was not bioequivalent to administration of an intact capsule under fasting conditions. Administration of the capsule contents on applesauce resulted in a 15%–20% increase in Cmax and AUC of tizanidine and a 15 minute decrease in the median lag time and time to peak concentration compared to administration of an intact capsule while fasting.
Figure 1: Mean Tizanidine Concentration vs. Time Profiles For Zanaflex Tablets and Capsules (2 × 4 mg) Under Fasted and Fed Conditions
Tizanidine has linear pharmacokinetics over the doses studied in clinical development (1–20 mg). Tizanidine has a half-life of approximately 2.5 hours (CV=33%). Approximately 95% of an administered dose is metabolized. The primary cytochrome P450 isoenzyme involved in tizanidine metabolism is CYP1A2. Tizanidine metabolites are not known to be active; their half-lives range from 20 to 40 hours.
Following single and multiple oral dosing of 14C-tizanidine, an average of 60% and 20% of total radioactivity was recovered in the urine and feces, respectively.
Age Effects
No specific pharmacokinetic study was conducted to investigate age effects. Cross study comparison of pharmacokinetic data following single dose administration of 6 mg Zanaflex showed that younger subjects cleared the drug four times faster than the elderly subjects. Zanaflex has not been evaluated in children. [see Use in Specific Populations]
The influence of hepatic impairment on the pharmacokinetics of tizanidine has not been evaluated. Because tizanidine is extensively metabolized in the liver, hepatic impairment would be expected to have significant effects on pharmacokinetics of tizanidine. Zanaflex is not recommended in this patient population [see Use in Specific Populations]
Tizanidine clearance is reduced by more than 50% in elderly patients with renal insufficiency (creatinine clearance < 25 mL/min) compared to healthy elderly subjects; this would be expected to lead to a longer duration of clinical effect. Zanaflex should be used with caution in renally impaired patients [see WARNINGS AND PRECAUTIONS and Use In Specific Populations].
Gender Effects
No specific pharmacokinetic study was conducted to investigate gender effects. Retrospective analysis of pharmacokinetic data, however, following single and multiple dose administration of 4 mg Zanaflex showed that gender had no effect on the pharmacokinetics of tizanidine.
Race Effects
Pharmacokinetic differences due to race have not been studied.
CYP1A2 Inhibitors
The interaction between Zanaflex and either fluvoxamine or ciprofloxacin is most likely due to inhibition of CYP1A2 by fluvoxamine or ciprofloxacin. The effect of fluvoxamine on the pharmacokinetics of a single 4 mg dose of Zanaflex was studied in 10 healthy subjects. The Cmax, AUC, and half-life of tizanidine increased by 12- fold, 33-fold, and 3-fold, respectively. The effect of ciprofloxacin on the pharmacokinetics of a single 4 mg dose of Zanaflex was studied in 10 healthy subjects. The Cmax and AUC of tizanidine increased by 7-fold and 10-fold, respectively. [see CONTRAINDICATIONS]
Although there have been no clinical studies evaluating the effects of other CYP1A2 inhibitors on tizanidine, other CYP1A2 inhibitors, such as zileuton, other fluoroquinolones, antiarrythmics (amiodarone, mexiletine, propafenone and verapamil), cimetidine, famotidine oral contraceptives, acyclovir and ticlopidine, may also lead to substantial increases in tizanidine blood concentrations [see WARNINGS AND PRECAUTIONS].
In vitro studies of cytochrome P450 isoenzymes using human liver microsomes indicate that neither tizanidine nor the major metabolites are likely to affect the metabolism of other drugs metabolized by cytochrome P450 isoenzymes.
No specific pharmacokinetic study was conducted to investigate interaction between oral contraceptives and Zanaflex. Retrospective analysis of population pharmacokinetic data following single and multiple dose administration of 4 mg Zanaflex, however, showed that women concurrently taking oral contraceptives had 50% lower clearance of tizanidine compared to women not on oral contraceptives [see WARNINGS AND PRECAUTIONS].
Tizanidine delayed the Tmax of acetaminophen by 16 minutes. Acetaminophen did not affect the pharmacokinetics of tizanidine.
Alcohol increased the AUC of tizanidine by approximately 20%, while also increasing its Cmax by approximately 15%. This was associated with an increase in side effects of tizanidine. The CNS depressant effects of tizanidine and alcohol are additive.
Tizanidine's capacity to reduce increased muscle tone associated with spasticity was demonstrated in two adequate and well controlled studies in patients with multiple sclerosis or spinal cord injury (Studies 1 and 2).
Single-Dose Study in Patients with Multiple Sclerosis with Spasticity
In Study 1, patients with multiple sclerosis were randomized to receive single oral doses of drug or placebo. Patients and assessors were blind to treatment assignment and efforts were made to reduce the likelihood that assessors would become aware indirectly of treatment assignment (e.g., they did not provide direct care to patients and were prohibited from asking questions about side effects). In all, 140 patients received placebo, 8 mg or 16 mg of Zanaflex.
Response was assessed by physical examination; muscle tone was rated on a 5 point scale (Ashworth score), with a score of 0 used to describe normal muscle tone. A score of 1 indicated a slight spastic catch while a score of 2 indicated more marked muscle resistance. A score of 3 was used to describe considerable increase in tone, making passive movement difficult. A muscle immobilized by spasticity was given a score of 4. Spasm counts were also collected. Assessments were made at 1, 2, 3 and 6 hours after treatment. A statistically significant reduction of the Ashworth score for Zanaflex compared to placebo was detected at 1, 2 and 3 hours after treatment. Figure 2 below shows a comparison of the mean change in muscle tone from baseline as measured by the Ashworth scale. The greatest reduction in muscle tone was 1 to 2 hours after treatment. By 6 hours after treatment, muscle tone in the 8 and 16 mg Zanaflex groups was indistinguishable from muscle tone in placebo treated patients. Within a given patient, improvement in muscle tone was correlated with plasma concentration. Plasma concentrations were variable from patient to patient at a given dose. Although 16 mg produced a larger effect, adverse events including hypotension were more common and more severe than in the 8 mg group. There were no differences in the number of spasms occurring in each group.
Figure 2: Single Dose Study—Mean Change in Muscle Tone from Baseline as Measured by the Ashworth Scale ± 95% Confidence Interval (A Negative Ashworth Score Signifies an Improvement in Muscle Tone from Baseline)
Seven-Week Study in Patients with Spinal Cord Injury with Spasticity
In a 7-week study (Study 2), 118 patients with spasticity secondary to spinal cord injury were randomized to either placebo or Zanaflex. Steps similar to those taken in the first study were employed to ensure the integrity of blinding.
Patients were titrated over 3 weeks up to a maximum tolerated dose or 36 mg daily given in three unequal doses (e.g., 10 mg given in the morning and afternoon and 16 mg given at night). Patients were then maintained on their maximally tolerated dose for 4 additional weeks (i.e., maintenance phase). Throughout the maintenance phase, muscle tone was assessed on the Ashworth scale within a period of 2.5 hours following either the morning or afternoon dose. The number of daytime spasms was recorded daily by patients.
At endpoint (the protocol-specified time of outcome assessment), there was a statistically significant reduction in muscle tone and frequency of spasms in the Zanaflex treated group compared to placebo. The reduction in muscle tone was not associated with a reduction in muscle strength (a desirable outcome) but also did not lead to any consistent advantage of Zanaflex treated patients on measures of activities of daily living. Figure 3 below shows a comparison of the mean change in muscle tone from baseline as measured by the Ashworth scale.
Figure 3: Seven Week Study—Mean Change in Muscle Tone 0.5–2.5 Hours After Dosing as Measured by the Ashworth Scale ± 95% Confidence Interval (A Negative Ashworth Score Signifies an Improvement in Muscle Tone from Baseline)
Serious Drug Interactions
Advise patients they should not take Zanaflex if they are taking fluvoxamine or ciprofloxacin because of the increased risk of serious adverse reactions including severe lowering of blood pressure and sedation. Instruct patients to inform their physicians or pharmacists when they start or stop taking any medication because of the risks associated with interaction between Zanaflex and other medicines.
Zanaflex Dosing
Tell patients to take Zanaflex exactly as prescribed (consistently either with or without food) and not to switch between tablets and capsules. Inform patients that they should not take more Zanaflex than prescribed because of the risk of adverse events at single doses greater than 8 mg or total daily doses greater than 36 mg. Tell patients that they should not suddenly discontinue Zanaflex, because rebound hypertension and tachycardia may occur.
Effects of Zanaflex
Warn patients that they may experience hypotension and to be careful when changing from a lying or sitting to a standing position. Tell patients that Zanaflex may cause them to become sedated or somnolent and they should be careful when performing activities that require alertness, such as driving a vehicle or operating machinery. Tell patients that the sedation may be additive when Zanaflex is taken in conjunction with drugs (baclofen, benzodiazepines) or substances (e.g., alcohol) that act as CNS depressants. Remind patients that if they depend on their spasticity to sustain posture and balance in locomotion, or whenever spasticity is utilized to obtain increased function, that Zanaflex decreases spasticity and caution should be used.
Back Pain Resources
Life With Ankylosing Spondylitis
Is Your Back Pain Ankylosing Spondylitis?
Pain Management for Your Back
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Zanaflex Drug Imprint
round, white, imprinted with E 34
round, white, imprinted with M 722
capsule, blue, imprinted with 2 mg
capsule, blue/white, imprinted with 4 mg
round, white, imprinted with A594
capsule, blue, imprinted with APO, T2
capsule, green/white, imprinted with APO, T4
oval, white, imprinted with RDY 179
oval, white, imprinted with RDY, 180
round, white, imprinted with 503
round, white, imprinted with APO TI-2
capsule, blue/white, imprinted with APO, T4
Tizanidine 2 mg 707101111
capsule, blue, imprinted with 1111
Tizanidine 2 mg-PAR
oval, white, imprinted with R179
Tizanidine 2 mg-TEV
round, white, imprinted with 93 5163
capsule, purple/white, imprinted with 1112
Tizanidine 4mg 009046898
capsule, purple, imprinted with 1113
Zanaflex 4 mg
round, white, imprinted with A 594
Celebrex Dolobid Flexeril Norflex Norgesic Reprexain Ultram Ultram ER Vicoprofen
Chronic Pain Pain Management Back Pain FAQs
Robaxin vs. Zanaflex Zanaflex vs. Flexeril Zanaflex vs. Norflex Zanaflex vs. Soma Zanaflex vs. Ultram
Zanaflex User Reviews


Looking for the perfect piece of silver jewelry for your baby, toddler, or teenage girl? We have plenty of 925 jewelry options to choose from, including animal necklaces, silver name bracelets and unique pretty earrings, so there is sure to be something your special little girl or you will love!
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We create all of our own designs and source all of our materials ourselves, so you can rest assured that you are getting real 925 silver jewelry at the lowest possible price. Our rings, earrings, bracelets, and necklaces will last a lifetime for your little girl.


text:
The Clinical Problem
The iDTECT Dx Test
Quality and Regulatory
Clinical Study
iDTECT Database and Software
Biologics Genomic Service
Meetings and Congresses
Contact Form Page
Proof-of-concept study published in Clinical Microbiology and Infection reports the benefit of PathoQuest NGS-based metagenomics test
Feb 22, 2017 | Press Release
Click here to view French version of this release
PathoQuest, a biotechnology company spun out from Institut Pasteur, announced today the on-line publication of results from the PATHOQUEST-1 study. The full manuscript, titled "Untargeted next-generation sequencing-based first-line diagnosis of infection in immunocompromised adults: a multicentre, blinded, prospective study", is available in Clinical Microbiology and Infection. PATHOQUEST-1 (NCT02007642) is an observational, proof-of-concept study conducted in 2 reference hospitals; Necker-Enfants Malades and Européen-Georges Pompidou Hospitals (Paris, France). It enrolled 101 immunocompromised patients suspected of infection, and compared the performance of PathoQuest's NGS-based metagenomics test and the conventional diagnostic pipeline to identify pathogens.
The results demonstrated two key findings:
on samples collected at inclusion in the trial, a clinically relevant pathogen -virus or bacteria- was identified in 3 times more patients with the metagenomics test than with the conventional tests
the statistically significant higher performance of PathoQuest's test was maintained when comparing the metagenomics results obtained at inclusion to those cumulatively obtained with the conventional pipeline over 30 days (resp. 36% patients with a clinically relevant pathogen versus 19%)
PATHOQUEST-1 was run with a prototype version of the CE-IVD iDTECT Blood™ test. The 3 key components of the test (i.e. sample preparation, sequencing and data analysis) have been improved to reach the level of performance and validation required for CE marking. Specific steps of the test process have been patented or copyrighted and are proprietary.
"This study demonstrates that the metagenomic test identified a relevant pathogen in more patients in a difficult-to-diagnose population than the conventional pipeline," said Marc Eloit, PhD, Pathogen Discovery Laboratory at Institut Pasteur, Paris, France, a study investigator and founder and scientific advisor for PathoQuest. "These data underscore the potential of NGS to improve detection and identification of pathogens in routine diagnostic testing of biological samples including blood which is technically challenging."
"With the broader availability of sequencing platforms in clinical microbiology laboratories, metagenomics-based testing will increase our chances of identifying pathogens in infected patients and allow a better management of infectious diseases, especially in immunocompromised patients where the current diagnostic pipeline frequently fails to identify a responsible pathogen." added Xavier Nassif, MD, PhD, Head of the Clinical Microbiology Laboratory, Necker-Enfants Malades Hospital, Paris, France, and a study investigator. "These study results should pave the way for such developments".
About infections in immunocompromised patients
Immunocompromised patients have an impaired or weakened immune system resulting in an increased susceptibility to infection and reduced ability to efficiently respond to such situations. This inability to fight infections can be caused by a number of diseases (such as cancer or leukemia), or drugs (such as anti-cancer therapies or long term immune-suppressants used to prevent organ rejection). Prevalence of these conditions is increasing. Identifying the causative pathogen(s) in immunocompromised patients suspected of infection can be challenging. For instance, only 20 to 30% of blood cultures, the conventional diagnostic test in this clinical situation, are positive for a pathogen in patients developing febrile neutropenia following chemotherapy or stem cell transplantation (1-3). In most other cases, the infection remains of unknown origin, leading to the systematic use of broad spectrum instead of targeted antibiotics. Moreover, these patients are more susceptible to viruses or other microorganisms which have limited or no pathogenicity for non-immunocompromised subjects. Many also receive prophylactic or recurrent courses of antibiotics, making their pathogens difficult to grow in the lab.
1. Gyamarti et al, Scientific Reports, 2016
2. Freifeld et al, CID 2011
3. Gea-Banacloche, Hematology Am Soc Hematol Educ Program. 2013
About PathoQuest
PathoQuest, a spin out of Institut Pasteur, is a biotechnology company offering a game changing metagenomics approach to improving pathogen detection in biological samples that overcomes the current limitation associated with pathogen detection.
PathoQuest's technology combines a Next-Generation Sequencing (NGS) platform and a proprietary sample preparation process which is applicable to several types of samples with a proprietary pathogen genome sequence database and automated analysis pipeline. The company's solution provides microbiologists and clinicians with a comprehensive analysis covering all known clinically relevant human pathogens.
PathoQuest has developed iDTECT™ Blood Test, the first and only clinical CE IVD metagenomic test in infectious disease. Using a single blood sample, the test provides clinicians and microbiologists with an improved method for detecting pathogens, particularly for immunocompromised patients with suspected infections. This new molecular diagnostic test should improve antibiotic stewardship and lead to better patient care through precision medicine.
Based on the company's technological platform, PathoQuest also offers biopharmaceutical companies a disruptive approach to secure production of biologics like vaccines and recombinant proteins. PathoQuest's solution is currently being utilized by several major biopharma companies for this purpose.
PathoQuest to exhibit at the 4th Edition Bioproduction of Immunotherapies – 24th September 2019 in Romainville, France
View our 2019 PathoQuest Workshop highlights video
PathoQuest announces publication in Biologicals reporting on a new RNA-based NGS approach for adventitious viruses detection
PathoQuest to exhibit at the 2019 European Antibody Congress – 15th to 17th October 2019 in Basel, Switzerland
Copyright © 2018 PathoQuest. All rights reserved.
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redpajama_set_name: RedPajamaCommonCrawl


Unlike many of my works, Heavy is not programmatic, nor does it evoke some extra-musical topic. The title is inspired by the instrumentation of Levels, the commissioning ensemble, comprised of instruments with heavy and dark timbres. I sought to exploit those dark timbres throughout the piece through sharp accents, drawn-out motivic processes, pulsing grooves, and a deeply emotional slow section.
Heavy was commissioned by Levels, a student ensemble based at Lawrence University, my alma mater.


text:
Ian McKellen: "I Feel Euphoric" After Receiving First Part of Covid Vaccine
McKellen received round one of the shot in his native England.
(© David Gordon)
Sir Ian McKellen, 81, has taken the first of the two-part Covid vaccine in England, and says he feels "euphoric" having done so.
Posing for pictures posted by the NHS England on social media today, McKellen gave a big thumbs up as he received his first jab. The vaccine roll-out began in earnest earlier this month, with those either working on the front line or the most elderly receiving the initial batch of vaccines.
McKellen was in the West End onstage barely a week or so ago in the West End production of The Comeback, which has had to pause its run while the pandemic continues and stronger tier restrictions are in place. He will have to return to the second part of the jab in a few weeks' time.
Chatting after receiving the first shot, McKellen said, "It's a very special day, I feel euphoric...Anyone who has lived as long as I have is alive because they have had previous vaccinations...I really hope that, as more people get vaccinated, we will move further along the path back to a more normal way of life."
'I really hope that, as more people get vaccinated, we will move further along the path back to a more normal way of life.'
⁰Sir @IanMcKellen joins the thousands of people who have now safely received the first dose of the #CovidVaccine. https://t.co/1e3nCAUFcB pic.twitter.com/FFW6jrKqEg
— NHS England and NHS Improvement (@NHSEngland) December 16, 2020


Christmas is beginning its take-over at Circuit Makati.
There's no such thing as celebrating too early or having too much holiday spirit, especially when Makati's premier go-to entertainment district is starting to get into a festive mood. What better way to kick off the season of giving than by getting started with your holiday shopping and feasting in the Metro's biggest entertainment district!
This holiday season, Circuit Makati will be hosting a special three-day sale that puts the spotlight on top brands with homegrown and handcrafted items.
"It's a great way to spend time with the family and to start the Christmas gift shopping season right especially before the rush gets too overwhelming. This year is very special because we've also emphasized on supporting local, with more booths supporting local made products and young entrepreneurs." says Shiella Aguilar, Makati Project Development Head for Ayala Land.
A Circuit Holiday Night Market co-presented by Mastercard, makes Christmas bazaars bigger and better! Now on its fifth year, Ayala Land ups the ante with six standout Christmas district concepts for visitors to shop and dine in and tops it off with acoustic performances for the whole night!
If you've ever wanted to dress and eat like a celebrity, the Celebrity District is a great place to start! Your favorite local celebs will have their personally curated pre-loved items for sale and their culinary skills will be put on display with their personally baked and home-cooked fare. Charities such as Purple Centers Foundation, Hineleban Foundation and Glenn's Cookies will also be a part of this district, giving you more reasons to drop by!
For the first time this year, SSI will delight all Mastercard holders with an exclusive raffle when they use their Mastercard in the Lifestyle District. Every P1,000 worth of receipts (single or accumulated) from the Lifestyle District entitles the shopper to one (1) raffle coupon for the A Circuit Holiday Night Market Raffle Promo. Get a chance to win as you shop among the best brands like High Sierra, Cache Cache, Oka-B, Joe Fresh, Marks & Spencer's and Gap!
The youth are the future, and the future looks bright, especially in the Student District led by The UP Organization of Business Economics Majors (UP OBEM). Through its commitment to provide its members with the exposure to the business and economic environment, UP OBEM frequently holds business conventions and lifestyle bazaars for small to medium-scale concessionaires.
The Student District offers a wide selection of booths that feature one-of-a-kind homemade finds and craft items that showcase the creativity of the next generation. Support these budding entrepreneurs and get unique gifts for your loved ones!
Explore thoughtfully curated items in the Artisan District organized by The Common Good Market! There are gifts and products for everyone on your list, may it be for the youngsters or the oldies. Spend a little time and you'll be surprised at what you'll find with the wide range of options to take home and gift to loved ones this holiday season.
Famed dining destination, Mercato Centrale and online foodie website Zomato, team up to create an extensive and mouthwatering selection of gastronomic treats at the Cuisine District. Browse through dry food items and a wide selection of baked and packed goods that are perfect for the holidays. And take a break from all that shopping with up to 50 amazing food booths!
For the first time ever, Circuit Makati will be holding a Landscape Festival to brighten everyone's home. Whether you're starting to appreciate those little succulents, or are an avid gardener, the Green District will have everything you need to get started or keep going!
With all the unique and diverse Districts styled and lighted by Firefly you will surely find what you're looking for may it be for yourself or anyone this holiday season. To make the celebration more meaningful, Circuit Makati will again light up the tallest Christmas Tree in the city, bringing light to the Makati community and its guests. Watch out for Circuit Makati's other events like the Manila Hip-hop Festival on November 30, OpenAir Cinema One: Music By Day, Movies by Night on December 15 and Playground 3.0 on December 22.
Create fun and exciting memories to remember this Yuletide season, drop by #ACircuitHolidayNightMarket co-presented by Mastercard on November 16, 17, and 18 from 5PM to 12MN. Entrance of P100 with a discounted rate of P50 for students, Senior Citizens PWD and pregnant women. Mastercard users enter for free when they show their card at the entrance. See you in #CircuitMakati in the place where Christmas comes alive, #MakeItMakati.


text:
Jeff Corwin (Photographer); William Shakespeare, D.H. Lawrence, Henry David Thoreau, and John Keats (Quotes)
"A series of original prints depicting our interaction with the earth": The Earth, The Client's Shoes, Tools, [and] Challenges
1986: The Earth Technology Corporation, Long Beach, California. Corwin, Jeff. Limited Edition. No binding. Four limited-edition photographs, each one of 500, each numbered, signed and dated by the photographer, with corresponding text. A series of four black-and-white photographs, each photograph signed, dated, and numbered below the image by the artist..... More
Graves, Robert
Good-Bye to All That; An Autobiography by Robert Graves
London: Jonathan Cape, (1929). First Edition. Hardcover. First issue (see details below), octavo size, 448 pp., in publisher's dust jacket. Robert von Ranke Graves (1895-1985) was born into a literary family and showed literary genius from a young age. Although the horrors of "The Great War" and subsequent difficulties had..... More
Yeats, W.B.
Early Poems and Stories
New York: The Macmillan Company, 1925. Limited Edition. Hardcover. No. 131 of 250 copies, octavo size, 538 pp., signed by Yeats. William Butler Yeats (1865-1939) is acknowledged by many as "supreme among modern Irish poets". He was awarded the Nobel Prize in Literature in 1923 (the first Irish to be..... More
[Medieval Legends]; Caxton, William (Translator)
Barlaam and Josephat; A Christian Legend of the Buddha
Greenbrae, California: The Allen Press, 1986. Limited Edition. Hardcover. One of 140 copies, quarto size, [53] pp., with prospectus. A spiritual romance themed around a man's fight to attain eternal life, with parables and stories to spark the imagination. Based on the original text written around 100 A.D. in India..... More
Olmstead, Duncan H.
[LEAF BOOK] Bartolomeus Zanni; Printer at Venice 1486-1518 and at Portese 1489-90, A monograph Compiled from Various Sources, Together with a Leaf from Jacobus de Voragine's "Legendario de Sancti" Printed by Zanni at Venice, 1503
Berkeley: Tamalpais Press, 1962. Limited Edition. Wraps. No. 58 of 135 copies, folio size, 7 pp. Bartolomeus Zanni, while not as well known as some of his contemporaries who were inventing the art of printing using movable type as they went, was one of about 150 printers working in Venice..... More
Saroyan, William (Note / Afterword); Dean, Mallette (Artist)
Farewell Speech of King Edward the Eighth Broadcast from Windsor Castle the Tenth Day of December, MCMXXXVI; With the Instrument of Abdication & A Note by William Saroyan
San Francisco: Ransohoffs [Printed at the Grabhorn Press], 1938. Dean, Mallette. Limited Edition. Hardcover. Limited edition, one of 200 copies, folio size, unpaginated [28] pp. Edward VIII (1894-1972), Prince of Wales, then King Edward VIII, and then the Duke of Windsor, made history when he abdicated the British throne in..... More
Carson, Anne
Plainwater
New York: Alfred A. Knopf, 1995. First Edition. Hardcover. First printing, octavo size, 270 pp. Anne Carson (b. 1950) is one of today's most highly-regarded poets; a New York Times reviewer wrote: "In the small world of people who keep up with contemporary poetry...[Carson] has been cutting a large swath..... More
Crane, Hart; Cowley, Malcolm (Introduction)
New York: The Limited Editions Club [printed by Michael & Winifred Bixler], 1981. Benson, Richard. Limited Edition. Hardcover. No. 351 of 2000 copies, folio size, 97 pp., signed by Richard Benson, with LEC Monthly Letter, announcement, and slipcase. Hart Crane (1899-1932) tragically died by committing suicide at the age of..... More
Smart, Adam [pseudonym of Alfred Sutro]; Davenport, W. R. (Illustrations)
[San Francisco]: [The Grabhorn Press], [1939]. Davenport, W. R. Limited Edition. Hardcover. One of 500 copies, folio size, [44] pp., with a short ANS from Alfred Sutro (Adam Smart) to Aurelia Henry Reinhardt. Alfred Sutro (1869-1945), a lawyer residing in San Francisco, was an avid book lover and collector, and..... More
Stahlecker, Karen
A Rainbow from the Earth
Alaska, Arizona & California: Karen Stahlecker, 1995. Limited Edition. String Binding. No. 8 of 30 copies (total edition 45), miniature book, 53 leaves (14 with text), signed by Karen Stahlecker. Karen Stahlecker (b. 1954) is an environmental artist who produces handmade paper using a process derived from traditional Japanese methods;..... More
Poe, Edgar Allen; Soyer, Raphael (Appreciation of the Artist); Neel, Alice (Artist)
New York: The Limited Editions Club, 1985. Neel, Alice. Limited Edition. Hardcover. No. 351 of 1500 copies, folio size, 33 pp., signed by both Alice Neel and Raphael Soyer, with LEC Monthly Newsletter, in the clamshell box. This lovely edition of Edgar Allan Poe's (1809-1849) narrative short story "The Fall..... More
Heebner, Mary (Book Artist)
Island: Journal from Iceland, September 1995
[Santa Barbara, CA]: [Simplemente Maria Press], [1999]. Heebner, Mary. Limited Edition. No binding. No. 44 of 60 copies (total edition), folio size, with twelve giclée prints each encased in a letterpress-printed folio, signed by Mary Heebner on the verso of each print and at the colophon. Mary Heebner founded her..... More
Randle, John et al
Vance Gerry and the Weather Bird Press. With contributions by Vance Gerry, Simon Lawrence, David Butcher, Patrick Reagh, James Lorson, and John Randle. With a checklist of publications compiled by David Butcher.
[Risbury, Herefordshire]: The Whittington Press, 2018. First and Limited Edition. Leather bound. No. 14 of 40 copies of the "A" edition with accompaniments (see below); folio size, 100 pp., in a leather-backed solander case. In his typical fashion, John Randle has done a masterful job presenting insights into the life..... More
Burnett, Frances Hodgson; Birch, Reginald B. (Illustrations)
Little Lord Fauntleroy
New York: Charles Scribner's Sons, 1886. First Edition. Hardcover. First printing in book form, the first issue, octavo size, 236 pp. The work of Frances Hodgson Burnett (1849-1924) captured the imaginations of readers, with her enduring novels such as "The Secret Garden" and "Sara Crewe". "Little Lord Fauntleroy" was intially..... More
Wallace, David Foster; Robbins, Matthew (Photographs)
Consider the Lobster
[South Freeport, Maine]: Ascensius Press, 2011. Robbins, Matthew. Limited Edition. Hardcover. Lettered copy "J" of 26 copies (total edition), folio size, 24 pp., signed by Matthew Robbins and Scott Vile, with prospectus. David Foster Wallace (1962-2008) committed suicide at the tragically young age of 46, after battling anxiety and depression..... More
Hawthorne, Nathaniel
Boston: Ticknor, Reed, and Fields, 1851. First Edition. Hardcover. First printing, duodecimo size, 347 pp. "The House of Seven Gables", being part fictionalized history, part literature, and part supernatural, was immediately acclaimed upon publication and has remained both widely read and influential. H.P. Lovecraft called it "New England's greatest contribution..... More
Lemström, S[elim], Professor
Electricity In Agriculture and Horticulture
London: "The Electrician" Printing & Publishing Company, Ltd., 1904. First Edition. Hardcover. First printing, octavo size, 96 pp. Finnish geophysicist Karl Selim Lemström (1838-1904) is perhaps best remembered today for his studies on the aurora borealis; he has been described as the "forgotten pioneer of northern light studies" and his..... More
Macdonald, Charles Blair
Scotland's Gift: Golf; Reminiscences by Charles Blair Macdonald, 1872-1927
New York: Charles Scribner's Sons, 1928. First and Limited Edition. Hardcover. No. 234 of 260 copies, quarto size, 358 pp. plus folding map, signed by Charles B. Macdonald. Charles Blair Macdonald (1855-1939) is revered (rightly) among fans of the great game of golf, and is referred to as the "Father..... More
John Wieners, Jack Hirschman, David Meltzer
First Poem After Silence Since Thanksgiving [with] Two Triangles Foursquared, or, Dark Tong [and with] Yod Beth Letter; Butterfly Broadsides Nos. 1, 2, and3
San Francisco: The Brownstone Press, 1970-1971. No binding. A series of three broadsides, the "Butterfly Broadsides", printed by The Brownstone Press during the years 1970 to 1971. While we cannot be certain whether or not additional broadsides in the series were published, it appears likely that these three constitute the..... More
Partridge, Eric
[LEAF BOOK] An Original Issue of "The Spectator", Together with The Story of the Famous Periodical and of its Founders, Joseph Addison & Richard Steele
San Francisco: The Book Club of California [printed by The Grabhorn Press], 1939. Limited Edition. Hardcover. One of 455 copies, folio size, 58 pp., with original leaf from "The Spectator" tipped in, with Ex-Libris of Alfred Sutro and postcard addressed to him written and signed by Eric Partridge. "The Spectator"..... More
Yeats, W.B.; Yeats, J.B. (Frontispiece)
The Celtic Twilight; Men and Women, Dhouls and Faeries
London: Lawrence and Bullen, 1893. Yeats, J.B. First Edition. Hardcover. First printing, duodecimo size, 224 pp. William Butler Yeats (1865-1939) is acknowledged by many as "supreme among modern Irish poets". He was awarded the Nobel Prize in Literature in 1923 (the first Irish to be so recognized), at which time..... More
New York: The Macmillan Company, 1924. Limited Edition. Hardcover. No. 9 of 250 copies, octavo size, 548 pp., with the slipcase, signed by Yeats. William Butler Yeats (1865-1939) is acknowledged by many as "supreme among modern Irish poets". He was awarded the Nobel Prize in Literature in 1923 (the first..... More
Kroeber, Theodora; Le Guin, Ursula K. (Foreword); Wikstrom, Karin (Illustrations)
The Inland Whale
[Covelo, California]: The Yolla Bolly Press, (1987). Wikstrom, Karin. Limited Edition. Hardcover. No. 94 of 135 copies, folio size (oblong), 103 pp., with prospectus, signed by Karin Wikstrom. Theodora Kroeber (1887-1979) was a writer and anthropologist, best known for writing the biography of Ishi, the last member of the Yahi..... More


text:
Lilly Ledbetter (Jacksonville (Alabama), 14 april 1938) is een Amerikaans activist die zich inzet voor gelijke rechten voor vrouwen. Ook is ze spreker en auteur. Ze richt zich vooral op gelijk salaris voor mannen en vrouwen. Ledbetter is opgenomen in de National Women's Hall of Fame.

In 1989 spande ze een rechtszaak aan tegen haar werkgever, de bandenfabrikant Goodyear, wegens discriminatie, omdat ze minder betaald had gekregen dan haar mannelijke collega's. Deze rechtszaak, Ledbetter v. Goodyear Tire & Rubber Co., bereikte het Hooggerechtshof, dat in 2007 tegen haar besloot. Het Hooggerechtshof besloot niet dat geen discriminatie had plaatsgevonden, maar dat de rechtszaak te lang na de salarisbeslissing was aangespannen. De rechtbank besloot dat werknemers geen rechtszaak tegen hun werknemer mogen aanspannen op basis van de Civil Rights Act of 1964 over salarisbeslissingen die meer dan 180 dagen daarvoor hebben plaatsgevonden.

In reactie op de beslissing van het Hooggerechtshof nam het Amerikaans Congres in 2009 een wet aan, die naar haar vernoemd werd: de Lilly Ledbetter Fair Pay Act of 2009.

In 2012 kwam een autobiografie van Ledbetter uit, Grace and Grit: My Fight for Equal Pay and Fairness at Goodyear and Beyond.

Zie ook
 Vrouwendiscriminatie
 Loonkloof

Amerikaans feminist
Seksisme

redpajama_set_name: RedPajamaWikipedia


Elvis Presley is the single biggest entertainment personality in the history of American popular culture.
He remains the undisputed king of Rock 'n' Roll, known the world over by his first name alone.
He is the foremost iconic figure in popular music.
This superb book has more than 400 pages, featuring a wealth of firsthand interviews, and previously unpublished material to give the definitive detailed account of Elvis Presley's fantastic life.


text:
News & Politics » The Straight Dope
by Cecil Adams
What is the deal with cousins marrying each other? In most states it's against the law. Yet where I am working, in a West African francophone country, there is a saying, "Cousins are made for cousins." Is this practice really genetically unsound, or is that just an American old wives' tale? --Jay Davidson, Peace Corps volunteer, Mauritania
Among the many things Americans just know, without ever having thought about it, is that if first cousins marry, their children will be drooling half-wits. The handful who wonder if there's any logic to this belief probably think: Royal inbreeding. Prince Charles. Case closed.
As recent events have shown, however, a lot of things we Yanks just know aren't so. The supposed evils of cousin marriage may not be the first one that comes to mind, but it's definitely on the list. In his impressive dissection of the issue, Forbidden Relatives: The American Myth of Cousin Marriage (1996), anthropologist Martin Ottenheimer points out the following little-known facts--little-known, that is, here in the U.S.:
The U.S. is virtually alone among developed nations in outlawing marriage among first cousins. European countries have no such prohibition. In some cultures, particularly Islamic ones, first-cousin marriage is encouraged. Even in the U.S. laws forbidding the practice are far from universal. First-cousin marriage is currently illegal or restricted in 31 states. (Some states allow it if there's no chance of procreation--interesting in light of conservative opposition to gay marriage on the grounds that the institution's function is to produce children.) It's legal in the rest--and no, Kentucky and West Virginia aren't among the permissive ones. Try California and New York.
First-cousin marriage isn't a surefire recipe for congenital defects. True, marriage among close kin can increase the chance of pathological recessive genes meeting up in some unlucky individual, with dire consequences. The problem isn't cousin marriage per se, however, but rather how many such genes are floating around in the family pool. If the pool's pretty clean, the likelihood of genetic defects resulting from cousin marriage is low. A recent review (Bennett et al, Journal of Genetic Counseling, 2002) says that, on average, offspring of first-cousin unions have a 2 to 3 percent greater risk of birth defects than the general population, and a little over 4 percent greater risk of early death. While those margins aren't trivial, genetic testing and counseling can minimize the danger. An argument can be made that marriages of first cousins descended from strong stock can produce exceptional children. Charles Darwin, for example, married his first cousin Emma, which wasn't at all unusual in their prominent and successful family--their common grandparents were cousins too. Three of Charles and Emma's ten kids died in childhood, it's true, but that was standard for Victorian England; the others went on to productive and in some cases distinguished careers.
All kidding aside, the formerly high incidence of congenital defects, specifically hemophilia, among European royal families isn't the classic demonstration of the perils of inbreeding that everybody thinks it is. The short explanation is that hemophilia is an X-chromosome-related characteristic, transmitted only through the female line. The children of royal female carriers would have been at risk no matter whom their mothers had married.
Why are Americans and their legal system so phobic about first-cousin marriage while Europeans aren't? Ottenheimer blames several factors. First, bad research in the 19th century greatly exaggerated the dangers of imbecility, blindness, etc, among children of close kin. This research was eventually discredited in Europe, but Americans and their state legislators never got the word. Second, cousin marriage in the U.S. was considered a sign of barbarism (probable translation: hillbillies did it). In Europe, on the other hand, particularly in Mediterranean cultures, cousin marriage had a long and reasonably respectable history, although it's rare today. Finally, European deep thinkers contended that certain forms of cousin marriage increased social cohesion. No such positive arguments were advanced in the States.
Let me emphasize we're talking strictly about cousin marriage here. The incest taboo regarding parent-child and sibling unions is still strong in Europe and most other places. Setting aside the issue of exploitation where minor children are concerned, such unions have a much higher risk of "adverse medical outcome"--7 to 31 percent, according to Bennett et al.
As for cousin marriage--admit it, you admire me for keeping the word "kissin'" out of this discussion--Ottenheimer thinks U.S. laws against it ought to be repealed. I don't see it happening: Jerry Lee Lewis got a buttload of flak for marrying his first cousin once removed in 1957, and the uproar over gay marriage suggests that rewriting the rules about whom one may properly wed is likely to be a tough sell now. Still, the issue reminds us of the importance of asking, when confronted with some instance of conventional wisdom: Says who?
Art accompanying story in printed newspaper (not available in this archive): illustration/Slug Signorino.


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Special Protection Waters
Chapter 93 of the Pennsylvania Code sets forth water quality standards for surface waters of the Commonwealth, including wetlands. These standards are based upon water uses which are to be protected and will be considered by the Department of Environmental Protection in implementing its authority under The Clean Streams Law and other statutes that authorize protection of surface water quality.
According to Chapter 93, the following are water uses which shall be protected, and upon which the development of water quality criteria shall be based, are set forth, accompanied by their identifying symbols:
Protected Use
CWF
Cold Water Fishes—Maintenance or propagation, or both, of fish species including the family Salmonidae and additional flora and fauna which are indigenous to a cold water habitat.
Warm Water Fishes—Maintenance and propagation of fish species and additional flora and fauna which are indigenous to a warm water habitat.
Migratory Fishes—Passage, maintenance and propagation of anadromous and catadromous fishes and other fishes which ascend to flowing waters to complete their life cycle.
Trout Stocking—Maintenance of stocked trout from February 15 to July 31 and maintenance and propagation of fish species and additional flora and fauna which are indigenous to a warm water habitat.
Potable Water Supply—Used by the public as defined by the Federal Safe Drinking Water Act, 42 U.S.C.A. § 300F, or by other water users that require a permit from the Department under the Pennsylvania Safe Drinking Water Act (35 P. S. § § 721.1—721.18), or the act of June 24, 1939 (P. L. 842, No. 365) (32 P. S. § § 631—641), after conventional treatment, for drinking, culinary and other domestic purposes, such as inclusion into foods, either directly or indirectly.
IWS
Industrial Water Supply—Use by industry for inclusion into nonfood products, processing and cooling.
Livestock Water Supply—Use by livestock and poultry for drinking and cleansing.
Wildlife Water Supply—Use for waterfowl habitat and for drinking and cleansing by wildlife.
Irrigation—Used to supplement precipitation for growing crops.
Recreation and Fish Consumption
Boating—Use of the water for power boating, sail boating, canoeing and rowing for recreational purposes when surface water flow or impoundment conditions allow.
Fishing—Use of the water for the legal taking of fish. For recreation or consumption.
Water Contact Sports—Use of the water for swimming and related activities.
Esthetics—Use of the water as an esthetic setting to recreational pursuits.
Special Protection
High Quality Waters—Surface waters having quality which exceeds levels necessary to support propagation of fish, shellfish, and wildlife and recreation in and on the water by satisfying § 93.4b(a).
Exceptional Value Waters—Surface waters of high quality which satisfy § 93.4b(b) (relating to antidegradation).
Navigation—Use of the water for the commercial transfer and transport of persons, animals and goods.
Perry County has streams in the Aquatic life and Special Protection designations within its boundaries. These waters fall under anti-degradation requirements and are protected in such a way that existing in stream water uses and the level of water quality necessary to protect the existing uses shall be maintained and protected. You can check out Perry County stream designations at the following website. Perry's streams are in the Susquehanna River Basin (93.9M, 93.9N and 93.9O).
To view a Pennsylvania map that includes identification information on Special Protection waters (high quality and exceptional value) in Perry County visit Emap on the Department of Environmental Protection's website.


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Q: MongoDB aggregation, find number of distinct values in documents' arrays Reading the docs, I see you can get the number of elements in document arrays. For example given the following documents:
{ "_id" : 1, "item" : "ABC1", "description" : "product 1", colors: [ "blue", "black", "red" ] }
{ "_id" : 2, "item" : "ABC2", "description" : "product 2", colors: [ "purple" ] }
{ "_id" : 3, "item" : "XYZ1", "description" : "product 3", colors: [ ] }

and the following query:
db.inventory.aggregate([{$project: {item: 1, numberOfColors: { $size: "$colors" }}}])

We would get the number of elements in each document's colors array:
{ "_id" : 1, "item" : "ABC1", "numberOfColors" : 3 }
{ "_id" : 2, "item" : "ABC2", "numberOfColors" : 1 }
{ "_id" : 3, "item" : "XYZ1", "numberOfColors" : 0 }

I've not been able to figure out if and how you could sum up all the colors in all the documents directly from a query, ie:
{ "totalColors": 4 }

A: You can use the following query to get the count of all colors in all docs:
db.inventory.aggregate([
  { $unwind: '$colors' } , // expands nested array so we have one doc per each array value
  { $group: {_id: null, allColors: {$addToSet: "$colors"} } }  , // find all colors
  { $project: { totalColors: {$size: "$allColors"}}} // find count of all colors
 ])

A: Infinitely better is is to simply $sum the $size:
db.inventory.aggregate([
  { "$group": { "_id": null, "totalColors": { "$sum": { "$size": "$colors" } } }
])

If you wanted "distinct in each document" then you would instead:
db.inventory.aggregate([
  { "$group": {
    "_id": null,
    "totalColors": {
      "$sum": {
        "$size": { "$setUnion": [ [], "$colors" ] }
      }
    }
  }}
])

Where $setUnion takes values likes ["purple","blue","purple"] and makes it into ["purple","blue"] as a "set" with "distinct items".
And if you really want "distinct across documents" then don't accumulate the "distinct" into a single document. That causes performance issues and simply does not scale to large data sets, and can possibly break the 16MB BSON Limit. Instead accumulate naturally via the key:
db.inventory.aggregate([
  { "$unwind": "$colors" },
  { "$group": { "_id": "$colors" } },
  { "$group": { "_id": null, "totalColors": { "$sum": 1 } } }
])

Where you only use $unwind because you want "distinct" values from the array as combined with other documents. Generally $unwind should be avoided unless the value contained in the array is being accessed in the "grouping key" _id of $group. Where it is not, it is better to treat arrays using other operators instead, since $unwind creates a "copy" of the whole document per array element.
And of course there was also nothing wrong with simply using .distinct() here, which will return the "distinct" values "as an array", for which you can just test the Array.length() on in code:
var totalSize = db.inventory.distinct("colors").length;

Which for the simple operation you are asking, would be the overall fastest approach for a simple "count of distinct elements". Of course the limitation remains that the result cannot exceed the 16MB BSON limit as a payload. Which is where you defer to .aggregate() instead.

redpajama_set_name: RedPajamaStackExchange


text:
Please Note All County Government Offices closed on Monday, January 18th Read On...
Departments Q - Z
Transportation Council
Orange County is a vital point of connection for transportation in the New York City Metropolitan Area, the Hudson Valley, New York State and the Eastern Seaboard. In Orange County, 13% of residents in the workforce commute to New York City, and 27.6% commute out of the County for work. Orange County also has the 7th-highest commute time in New York State, with an average commute of 33.5 minutes compared to the national average of 26.6 minutes.
The Orange County Transportation Council is dedicated to reducing air pollution in our region and minimizing the negative effects of congestion. This can be done by reducing the number of Single Occupancy Vehicles (SOV) on our roads. Orange County has many options available, including Carpooling and Vanpooling programs, Park and Ride Lots, Regional Bus Service, and MTA Metro-North Service on the Port Jervis Line.
Commuter Graphic from Transportation Chapter of Orange County Comprehensive Plan (2019)
Commuting and COVID-19
As New York State and our community in Orange County responds to the COVID-19 Pandemic, it is important to maintain the most up-to-date health regulations. To stay informed, check resources like the www.Coronavirus.gov, Centers for Disease Control and Prevention (CDC), New York State Department of Health (NYSDOH), and Orange County Department of Health regularly. Protect yourself from COVID-19 when using transportation including: public transit, rideshares and taxis, micro-mobility devices, and personal vehicles by following these general principles:
Stay up-to-date on information concerning COVID-19
Practice hand hygiene and respiratory etiquette
Avoid touching surfaces
Practice safe social distance
Avoid riding with unmasked drivers or passengers
Clean and disinfect surfaces
Improve ventilation
Stay home when appropriate
For more information regarding COVID-19 and transportation, visit https://www.cdc.gov/coronavirus/2019-ncov/daily-life-coping/using-transportation.html
Carpooling and Vanpooling
Carpools and vanpools are ride-sharing programs where 2+ people in a car, or 7-15 people in a van, travel to and from work together. Carpooling and Vanpooling are a convenient, cost-effective, and efficient way to commute.
511NY Rideshare
The 511NY platform allows you to find other commuters, close to your home or work address, or those along your route. 511NY Rideshare offers ridematching for carpools and vanpools, a Guaranteed Ride Program, so regular users are never left stranded, as well as resources for transit, park and ride lots, bicycling, walking, and telework. Use the "Find a Carpool Quick Match" tool below to see your options.
Find a Carpool Quick Match: Find potential carpool partners by entering your start and destination addresses in the tool below. You will be brought to your Carpool Matches page to view your match results. Once you receive your matches, simply log in or create an account to contact them and start ridesharing.
Follow 511NY Rideshare on Facebook, Instagram and Twitter for the latest information and updates on commuting and traveling in New York.
Commuter bus service in Orange, which leaves from the many park & ride lots throughout the county, typically provides service between Orange County and New York City. Coach USA/ShortLine, the intercity carrier, provides significant local service throughout the county (not to all communities,) as well as other regional service. These commuter and regional transit services provide the majority of trips for Orange County with approximately two million passengers annually.
For the most up-date information, visit the Transit Orange Website.
Orange County is served by MTA Metro-North Railroad's Port Jervis Line through a service contract with New Jersey Transit (NJT) and by the Metro-North Hudson Line on the East side of the Hudson River. The Port Jervis train line operated by Metro-North is the only passenger rail line in the County. Service currently runs from seven stations in Orange County to Hoboken and the Secaucus Transfer Station (as well as other rail station stops in New Jersey). From the new station in Secaucus, passengers may connect with other New Jersey Transit service to NY Penn Station in midtown Manhattan (or to other NJT services, including a connection for Amtrak service at Newark Penn Station). Port Jervis Line passengers may also connect with the Port Authority Trans-Hudson (PATH) service or NY Waterway ferry service in Hoboken for access to lower Manhattan.
If you have a disability and would like help getting on or off a Metro-North train, Metro-North offers a complimentary Call Ahead Program. You may request help by dialing 511 at least 15 minutes before your trip. Customers can learn more about accessible stations by visiting https://new.mta.info/accessibility/stations
Due to its location at the crossing of Interstates 84, 87, and Route 17 (future I-86), together with the rivers, airports, and rail lines, Orange County is an important center and conduit for freight movements. The majority of freight traffic in Orange County is shipped by trucks. There are 48 local freight movers and 36 long distance freight companies located within the County.
Commercial Routing Assistance Tool
The Cybersecurity and Infrastructure Security Agency (CISA) and Idaho National Laboratory (INL) launched a new Commercial Routing Assistance (CRA) tool for truckers and other commercial drivers in the U.S. This free app incorporates coordinated data streams and plots multiple routing options so commercial operators can plan and manage vehicle movements across multiple states quickly in times of disasters or other restrictions. This app leverages coordinated data streams provided by the All Hazards Consortium (AHC) Sensitive Information Sharing Environment (SISE) to visualize and streamline commercial vehicle movement across multiple states by aggregating documents, information, and data relevant to the logistics industry in times of restricted operations.For more information and access to the Commercial Routing Assistance (CRA) tool landing page, visit https://cra.inl.gov .
Non-Motorized Transportation
Steven M. Neuhaus
Orange County Government Center
FOIL Information
Property/Tax Information
History and Genealogy


text:
MABEL SANMANN
Mabel Sanmann, age 98, of St. Charles, formerly of Plano and Big Rock, IL, passed away peacefully on September 22, 2020.
She was born January 15, 1922 in Aurora, IL, to loving parents, John and Edith (Baker) Cooper.
Mabel grew up in the communities of Kaneville and Big Rock, Illinois, graduating from Big Rock High School as the class of 1940 valedictorian.
Following her graduation, Mabel served as the secretary of her alma mater for about a decade before becoming a homemaker, assisting the parents of her future husband, Leonard. United in marriage on Valentine's Day 1952, they began their new life together and Mabel quickly took on the role of a farmer's wife and mother to their two daughters, Charlene and Marlene. Retiring from farm life in 1973, Mabel and Leonard made their first and only home purchase on Sears Road where Leonard lived until his death in 1984 and Mabel resided until moving to The Bickford of St. Charles in 2015. In 1987 Mabel was fortunate enough to meet Jim Sanmann, and a year later they were married on what Mabel would deem "the hottest June 25th ever" in 1988. In recent years she has made a name for herself at the Bickford in St. Charles where she found a family of friends and made many memories over countless games of bingo.
Mabel was a "social butterfly" and attended as many events as she could including going to the movies, The Arcada and Rialto Theatres, local play productions, and Lake Geneva for Oktoberfest to listen to polka music. Marking her calendar for other social events such as Huntley Brown concerts, Golden Harvester meetings, the Sandwich Fair, and craft shows, Grandma still made time to go antiquing and catch reruns of Lawrence Welk. Had it not been canceled, Mabel would have attended her 80th high school reunion this year in conjunction with the Big Rock Plowing Match. As the family matriarch, Mabel lived for holiday and birthday celebrations, insisting on decorating and cooking for everything she could until the last few years of her life. Another constant in Mabel's life was writing to her cousin in England and favorite pen pal, Frances Andrews.
Mabel is survived by her daughters: Charlene (Dennis) Ryan and Marlene (Kurt Fitzgerald) Bartl; granddaughters: Colleen (Joshua Sherman) Ryan and Samantha Quiles; great-grand daughter Lacey; a special step-daughter, Tina (Tim) Nichols; one brother, George Cooper; many nieces, nephews, and beloved family friends, Regina Bartl, Darwin and Louise Classon, and Kelly Fey.
Mabel is preceded in death by her parents, John and Edith Cooper; husbands Leonard Hubbard and Jim Sanmann; three siblings: Alice Davis, Shirley Leadbetter, and C.J. Cooper; sister-in-law Jean Penczek; son-in-law, Don Bartl; and her 100 year-old cousin, Francis Andrews.
Visitation will be from 4-6 pm, Friday, September 25, 2020 at Conley Funeral Home, 116 W. Pierce St., Elburn, IL, 60119. Masks will be required to enter and social distancing will be in effect. Private family burial will follow at a later date.
In lieu of flowers, a memorial has been established in Mabel's name. Checks may be made to the "Mabel Sanmann Memorial" and mailed in care of P.O. Box 66, Elburn, 60119. Tributes and memories may also be forwarded to the same address, the Conley Funeral Home Facebook Page, or at www.conleycare.com. The family would also like to extend special thanks to the staff of Bickford Assisted Living in St. Charles as well as many healthcare workers over the years.


text:
Manhattan Toy Company at Nook
We've teamed up with Manhattan Toy Company to bring you an immersive experience of their most beloved toy collections. For a short time, you'll have the chance to see what happens when a play space that sets out to elevate the standard for family-friendly joins forces with a toy company that recognizes that "we are profoundly influenced by the toys we play with."
When we partner with brands in our spaces, our goal is to help you find that doll or that toy car or that book that will punctuate your memories of this very special time. So we'd love for you to join us in welcoming Manhattan Toy Company into our space. And, as with all the experiences that we create at Nook, we hope you'll make a memory.
photos by Erin Fabio Photography
#MTCxNook
#inspirationsatplay
#playatnook
About Nook
At Nook, we believe there's no time more important than this one: from the disorienting highs and lows of baby's first year, the rapid-fire succession of toddler and preschool milestones, to your growth as a parent balancing family needs with your own. So we set out to elevate the standard for "family-friendly" by bringing world-class design and artistry, quality and intention to spaces where young families play, learn, and celebrate.
Founders' Stories
Maria Vogelei
"I was frustrated with the play space options available to my daughter and me. They all seemed to speak in outdated generalizations: pinks, blues, and brightly colored plastic toys crammed in loud, chaotic spaces. I often found myself standing against a wall, counting down the minutes that would justify the cost of admission. Having struggled for years to start a family, I didn't want to be sidelined for my daughters' experience of play. This time is so precious and fleeting and important not only to my kids' development, but also to my growth as a woman and a mom—so I set out to create a brand that elevates family-friendly and reflects back to families, through high-end design, just how important this time is." Maria holds an MBA from Georgetown University. She is a mother of three.
Seo Yun (Sy) Yang
"Becoming a parent for the first time, I felt really disoriented. I thought I was a creator of life and family, but so many institutions made me feel like as a mom, I was there to simply do a 'job'. I wanted to create a space that recognized the reality of having young kids, but also saw me as a modern woman — a space where parents are people, too. I didn't 'press pause' on my life to have a family and raise my kids. My family life is my life and I wanted to create an experience and a community that truly celebrates and makes meaningful space for family." Sy holds an AB from Harvard University and law degrees from Columbia and McGill. She is a mother of three.
Ben Mickus
"From a very young age, I was always surrounded by creativity. Both of my parents were constantly putting me in situations which stimulated my curiosity and my desire to learn, by drawing, building, and experimenting in every possible medium. I am quite certain it was this creative stimulation that led me to architecture and design. Now, as a practicing architect and parent myself, I am keenly interested creating stimulating, multi-sensory experiences where kids can not only learn and grow, but find joy and excitement in the process. The mission of bringing thoughtful design to play holds tremendous potential, where parents and their children can participate together in a custom-designed environment, meant to serve as a catalyst for imagination. Ben holds a B.Arch from Cal Poly and an M.Arch from UCLA. He is a father of two.
#playlearncelebrate