Label: ACCOLATE- zafirlukast tablet,
film coated
- NDC Code(s): 0310-0401-60, 0310-0402-60
- Packager: AstraZeneca Pharmaceuticals LP
- Category: HUMAN PRESCRIPTION DRUG LABEL
- DEA Schedule: None
- Marketing Status: New Drug Application
Drug Label Information
Updated November 15, 2013
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- DESCRIPTION
Zafirlukast is a synthetic, selective peptide leukotriene receptor antagonist (LTRA), with the chemical name 4-(5-cyclopentyloxy-carbonylamino-1-methyl-indol-3-ylmethyl)-3-methoxy-N-o-tolylsulfonylbenzamide. The molecular weight of zafirlukast is 575.7 and the structural formula is:
The empirical formula is: C31H33N3O6S
Zafirlukast, a fine white to pale yellow amorphous powder, is practically insoluble in water. It is slightly soluble in methanol and freely soluble in tetrahydrofuran, dimethylsulfoxide, and acetone.
ACCOLATE is supplied as 10 and 20 mg tablets for oral administration.
Inactive Ingredients: Film-coated tablets containing croscarmellose sodium, lactose, magnesium stearate, microcrystalline cellulose, povidone, hypromellose, and titanium dioxide.
Close - CLINICAL PHARMACOLOGY
Mechanism of Action:
Zafirlukast is a selective and competitive receptor antagonist of leukotriene D4 and E4 (LTD4 and LTE4), components of slow-reacting substance of anaphylaxis (SRSA). Cysteinyl leukotriene production and receptor occupation have been correlated with the pathophysiology of asthma, including airway edema, smooth muscle constriction, and altered cellular activity associated with the inflammatory process, which contribute to the signs and symptoms of asthma. Patients with asthma were found in one study to be 25-100 times more sensitive to the bronchoconstricting activity of inhaled LTD4 than nonasthmatic subjects.
In vitro studies demonstrated that zafirlukast antagonized the contractile activity of three leukotrienes (LTC4, LTD4 and LTE4) in conducting airway smooth muscle from laboratory animals and humans. Zafirlukast prevented intradermal LTD4-induced increases in cutaneous vascular permeability and inhibited inhaled LTD4-induced influx of eosinophils into animal lungs. Inhalational challenge studies in sensitized sheep showed that zafirlukast suppressed the airway responses to antigen; this included both the early- and late-phase response and the nonspecific hyperresponsiveness.
In humans, zafirlukast inhibited bronchoconstriction caused by several kinds of inhalational challenges. Pretreatment with single oral doses of zafirlukast inhibited the bronchoconstriction caused by sulfur dioxide and cold air in patients with asthma. Pretreatment with single doses of zafirlukast attenuated the early- and late-phase reaction caused by inhalation of various antigens such as grass, cat dander, ragweed, and mixed antigens in patients with asthma. Zafirlukast also attenuated the increase in bronchial hyperresponsiveness to inhaled histamine that followed inhaled allergen challenge.
Clinical Pharmacokinetics and Bioavailability:
Absorption
Zafirlukast is rapidly absorbed following oral administration. Peak plasma concentrations are generally achieved 3 hours after oral administration. The absolute bioavailability of zafirlukast is unknown. In two separate studies, one using a high fat and the other a high protein meal, administration of zafirlukast with food reduced the mean bioavailability by approximately 40%.
Distribution
Zafirlukast is more than 99% bound to plasma proteins, predominantly albumin. The degree of binding was independent of concentration in the clinically relevant range. The apparent steady-state volume of distribution (Vss/F) is approximately 70 L, suggesting moderate distribution into tissues. Studies in rats using radiolabeled zafirlukast indicate minimal distribution across the blood-brain barrier.
Metabolism
Zafirlukast is extensively metabolized. The most common metabolic products are hydroxylated metabolites which are excreted in the feces. The metabolites of zafirlukast identified in plasma are at least 90 times less potent as LTD4 receptor antagonists than zafirlukast in a standard in vitro test of activity. In vitro studies using human liver microsomes showed that the hydroxylated metabolites of zafirlukast excreted in the feces are formed through the cytochrome P450 2C9 (CYP2C9) pathway. Additional in vitro studies utilizing human liver microsomes show that zafirlukast inhibits the cytochrome P450 CYP3A4 and CYP2C9 isoenzymes at concentrations close to the clinically achieved total plasma concentrations (see Drug Interactions).
Excretion
The apparent oral clearance (CL/f) of zafirlukast is approximately 20 L/h. Studies in the rat and dog suggest that biliary excretion is the primary route of excretion. Following oral administration of radiolabeled zafirlukast to volunteers, urinary excretion accounts for approximately 10% of the dose and the remainder is excreted in feces. Zafirlukast is not detected in urine.
In the pivotal bioequivalence study, the mean terminal half-life of zafirlukast is approximately 10 hours in both normal adult subjects and patients with asthma. In other studies, the mean plasma half-life of zafirlukast ranged from approximately 8 to 16 hours in both normal subjects and patients with asthma. The pharmacokinetics of zafirlukast are approximately linear over the range from 5 mg to 80 mg. Steady-state plasma concentrations of zafirlukast are proportional to the dose and predictable from single-dose pharmacokinetic data. Accumulation of zafirlukast in the plasma following twice-daily dosing is approximately 45%.
The pharmacokinetic parameters of zafirlukast 20 mg administered as a single dose to 36 male volunteers are shown with the table below.
Special Populations
Gender: The pharmacokinetics of zafirlukast are similar in males and females. Weight-adjusted apparent oral clearance does not differ due to gender.
Race: No differences in the pharmacokinetics of zafirlukast due to race have been observed.
Elderly: The apparent oral clearance of zafirlukast decreases with age. In patients above 65 years of age, there is an approximately 2-3 fold greater Cmax and AUC compared to young adult patients.
Children: Following administration of a single 20 mg dose of zafirlukast to 20 boys and girls between 7 and 11 years of age, and in a second study, to 29 boys and girls between 5 and 6 years of age, the following pharmacokinetic parameters were obtained:
Parameter
Children age 5-6 years Mean (% Coefficient of Variation)
Children age 7-11 years Mean
(% Coefficient of Variation)
Cmax (ng/mL)
756 (39%)
601 (45%)
AUC (ng•h/mL)
2458 (34%)
2027 (38%)
tmax (h)
2.1 (61%)
2.5 (55%)
CL/f (L/h)
9.2 (37%)
11.4 (42%)
Weight unadjusted apparent clearance was 11.4 L/h (42%) in the 7-11 year old children and 9.2 L/h (37%) in the 5-6 year old children, which resulted in greater systemic drug exposures than that obtained in adults for an identical dose. To maintain similar exposure levels in children compared to adults, a dose of 10 mg twice daily is recommended in children 5-11 years of age (see DOSAGE AND ADMINISTRATION).
Zafirlukast disposition was unchanged after multiple dosing (20 mg twice daily) in children and the degree of accumulation in plasma was similar to that observed in adults.
Hepatic Insufficiency: In a study of patients with hepatic impairment (biopsy-proven cirrhosis), there was a reduced clearance of zafirlukast resulting in a 50-60% greater Cmax and AUC compared to normal subjects.
Renal Insufficiency: Based on a cross-study comparison, there are no apparent differences in the pharmacokinetics of zafirlukast between renally-impaired patients and normal subjects.
Drug-Drug Interactions: The following drug interaction studies have been conducted with zafirlukast (see PRECAUTIONS, Drug Interactions).
- •
- Coadministration of multiple doses of zafirlukast (160 mg/day) to steady-state with a single 25 mg dose of warfarin (a substrate of CYP2C9) resulted in a significant increase in the mean AUC (+63%) and half-life (+36%) of S-warfarin. The mean prothrombin time increased by approximately 35%. The pharmacokinetics of zafirlukast were unaffected by coadministration with warfarin.
- •
- Coadministration of zafirlukast (80 mg/day) at steady-state with a single dose of a liquid theophylline preparation (6 mg/kg) in 13 asthmatic patients, 18 to 44 years of age, resulted in decreased mean plasma concentrations of zafirlukast by approximately 30%, but no effect on plasma theophylline concentrations was observed.
- •
- Coadministration of zafirlukast (20 mg/day) or placebo at steady-state with a single dose of sustained release theophylline preparation (16 mg/kg) in 16 healthy boys and girls (6 through 11 years of age) resulted in no significant differences in the pharmacokinetic parameters of theophylline.
- •
- Coadministration of zafirlukast dosed at 40 mg twice daily in a single-blind, parallel-group, 3-week study in 39 healthy female subjects taking oral contraceptives, resulted in no significant effect on ethinyl estradiol plasma concentrations or contraceptive efficacy.
- •
- Coadministration of zafirlukast (40 mg/day) with aspirin (650 mg four times daily) resulted in mean increased plasma concentrations of zafirlukast by approximately 45%.
- •
- Coadministration of a single dose of zafirlukast (40 mg) with erythromycin (500 mg three times daily for 5 days) to steady-state in 11 asthmatic patients resulted in decreased mean plasma concentrations of zafirlukast by approximately 40% due to a decrease in zafirlukast bioavailability.
- •
- Coadministration of zafirlukast with fluconazole, a moderate CYP2C9 inhibitor, resulted in increased
- plasma levels of zafirlukast, by approximately 58% (90% CI:28, 95). The clinical significance of this
- interaction is unknown. Zafirlukast exposure is likely to be increased by other moderate and strong
- CYP2C9 inhibitors. Coadministration of zafirlukast with itraconazole, a strong CYP3A4 inhibitor,
- caused no change in plasma levels of zafirlukast.
CloseClinical Studies:
Three U.S. double-blind, randomized, placebo-controlled, 13-week clinical trials in 1380 adults and children 12 years of age and older with mild-to-moderate asthma demonstrated that ACCOLATE improved daytime asthma symptoms, nighttime awakenings, mornings with asthma symptoms, rescue beta2-agonist use, FEV1, and morning peak expiratory flow rate. In these studies, the patients had a mean baseline FEV1 of approximately 75% of predicted normal and a mean baseline beta2-agonist requirement of approximately 4-5 puffs of albuterol per day. The results of the largest of the trials are shown in the table below.
Mean Change from Baseline at Study End Point - *
- p<0.05, compared to placebo
ACCOLATE
20 mg twice daily
N=514
Placebo
N=248
Daytime Asthma symptom score
(0-3 scale)
-0.44*
-0.25
Nightime Awakenings
(number per week)
-1.27*
-0.43
Mornings with Asthma Symptoms
(days per week)
-1.32*
-0.75
Rescue β2-agonist use
(puffs per day)
-1.15*
-0.24
FEV1 (L)
+0.15*
+0.05
Morning PEFR (L/min)
+22.06*
+7.63
Evening PEFR (L/min)
+13.12
+10.14
In a second and smaller study, the effect of ACCOLATE on most efficacy parameters was comparable to the active control (inhaled cromolyn sodium 1600 mcg four times per day) and superior to placebo at end point for decreasing rescue beta2-agonist use (figure below).
In these trials, improvement in asthma symptoms occurred within one week of initiating treatment with ACCOLATE. The role of ACCOLATE in the management of patients with more severe asthma, patients receiving antiasthma therapy other than as-needed, inhaled beta2-agonists, or as an oral or inhaled corticosteroid-sparing agent remains to be fully characterized.
- INDICATIONS AND USAGE
ACCOLATE is indicated for the prophylaxis and chronic treatment of asthma in adults and children 5 years of age and older.
Close - CONTRAINDICATIONS
ACCOLATE is contraindicated in patients who are hypersensitive to zafirlukast or any of its inactive ingredients.
ACCOLATE is contraindicated in patients with hepatic impairment including hepatic cirrhosis.
Close - WARNINGS
Hepatotoxicity:
Cases of life-threatening hepatic failure have been reported in patients treated with ACCOLATE. Cases of liver injury without other attributable cause have been reported from post-marketing adverse event surveillance of patients who have received the recommended dose of ACCOLATE (40 mg/day). In most, but not all post-marketing reports, the patient’s symptoms abated and the liver enzymes returned to normal or near normal after stopping ACCOLATE. In rare cases, patients have either presented with fulminant hepatitis or progressed to hepatic failure, liver transplantation and death. In extremely rare post-marketing cases, no clinical symptoms or signs suggestive of liver dysfunction were reported to precede the latter observations.
Physicians may consider the value of liver function testing. Periodic serum transaminase testing has not proven to prevent serious injury but it is generally believed that early detection of drug-induced hepatic injury along with immediate withdrawal of the suspect drug enhances the likelihood for recovery.
Patients should be advised to be alert for signs and symptoms of liver dysfunction (eg, right upper quadrant abdominal pain, nausea, fatigue, lethargy, pruritus, jaundice, flu-like symptoms, and anorexia) and to contact their physician immediately if they occur. Ongoing clinical assessment of patients should govern physician interventions, including diagnostic evaluations and treatment.
If liver dysfunction is suspected based upon clinical signs or symptoms (eg, right upper quadrant abdominal pain, nausea, fatigue, lethargy, pruritus, jaundice, flu-like symptoms, anorexia, and enlarged liver), ACCOLATE should be discontinued.
Liver function tests, in particular serum ALT, should be measured immediately and the patient managed accordingly. If liver function tests are consistent with hepatic dysfunction, ACCOLATE therapy should not be resumed. Patients in whom ACCOLATE was withdrawn because of hepatic dysfunction where no other attributable cause is identified should not be re-exposed to ACCOLATE (see PRECAUTIONS, Information for Patients and ADVERSE REACTIONS).
Bronchospasm:
ACCOLATE is not indicated for use in the reversal of bronchospasm in acute asthma attacks, including status asthmaticus. Therapy with ACCOLATE can be continued during acute exacerbations of asthma.
CloseConcomitant Warfarin Administration:
Coadministration of zafirlukast with warfarin results in a clinically significant increase in prothrombin time (PT). Patients on oral warfarin anticoagulant therapy and ACCOLATE should have their prothrombin times monitored closely and anticoagulant dose adjusted accordingly (see PRECAUTIONS, Drug Interactions).
- PRECAUTIONS
Information for Patients:
Patients should be told that a rare side effect of ACCOLATE is hepatic dysfunction, and to contact their physician immediately if they experience symptoms of hepatic dysfunction (eg. right upper quadrant abdominal pain, nausea, fatigue, lethargy, pruritus, jaundice, flu-like symptoms, and anorexia). Liver failure resulting in liver transplantation and death has occurred in patients taking zafirlukast (see WARNINGS, Hepatotoxicity and ADVERSE REACTIONS).
ACCOLATE is indicated for the chronic treatment of asthma and should be taken regularly as prescribed, even during symptom-free periods. ACCOLATE is not a bronchodilator and should not be used to treat acute episodes of asthma. Patients receiving ACCOLATE should be instructed not to decrease the dose or stop taking any other antiasthma medications unless instructed by a physician. Patients should be instructed to notify their physician if neuropsychiatric events occur while using ACCOLATE (see PRECAUTIONS, Neuropsychiatric Events). Women who are breast-feeding should be instructed not to take ACCOLATE (see PRECAUTIONS, Nursing Mothers). Alternative antiasthma medication should be considered in such patients.
The bioavailability of ACCOLATE may be decreased when taken with food. Patients should be instructed to take ACCOLATE at least 1 hour before or 2 hours after meals.
Eosinophilic Conditions:
In rare cases, patients with asthma on ACCOLATE may present with systemic eosinophilia, eosinophilic pneumonia, or clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition which is often treated with systemic steroid therapy. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. These events have usually, but not always, been associated with reductions and/or withdrawal of steroid therapy. The possibility that ACCOLATE may be associated with emergence of Churg-Strauss syndrome can neither be excluded nor established (see ADVERSE REACTIONS).
Neuropsychiatric Events:
Neuropsychiatric events have been reported in adult, adolescent and pediatric patients taking ACCOLATE. Post-marketing reports with ACCOLATE include insomnia and depression. The clinical details of some post-marketing reports involving ACCOLATE appear consistent with a drug-induced effect. Patients and prescribers should be alert for neuropsychiatric events. Patients should be instructed to notify their prescriber if these changes occur. Prescribers should carefully evaluate the risks and benefits of continuing treatment with ACCOLATE if such events occur (see ADVERSE REACTIONS).
Drug Interactions:
In a drug interaction study in 16 healthy male volunteers, coadministration of multiple doses of zafirlukast (160 mg/day) to steady-state with a single 25 mg dose of warfarin resulted in a significant increase in the mean AUC (+ 63%) and half-life (+36%) of S-warfarin. The mean prothrombin time (PT) increased by approximately 35%. This interaction is probably due to an inhibition by zafirlukast of the cytochrome P450 2C9 isoenzyme system. Patients on oral warfarin anticoagulant therapy and ACCOLATE should have their prothrombin times monitored closely and anticoagulant dose adjusted accordingly (see WARNINGS, Concomitant Warfarin Administration). No formal drug-drug interaction studies with ACCOLATE and other drugs known to be metabolized by the cytochrome P450 2C9 isoenzyme (eg, tolbutamide, phenytoin, carbamazepine) have been conducted; however, care should be exercised when ACCOLATE is coadministered with these drugs.
In a drug interaction study in 11 asthmatic patients, coadministration of a single dose of zafirlukast (40 mg) with erythromycin (500 mg three times daily for 5 days) to steady-state resulted in decreased mean plasma levels of zafirlukast by approximately 40% due to a decrease in zafirlukast bioavailability.
Coadministration of zafirlukast (20 mg/day) or placebo at steady-state with a single dose of sustained release theophylline preparation (16 mg/kg) in 16 healthy boys and girls (6 through 11 years of age) resulted in no significant differences in the pharmacokinetic parameters of theophylline.
Coadministration of zafirlukast (80 mg/day) at steady-state with a single dose of a liquid theophylline preparation (6 mg/kg) in 13 asthmatic patients, 18 to 44 years of age, resulted in decreased mean plasma levels of zafirlukast by approximately 30%, but no effect on plasma theophylline levels was observed.
Rare cases of patients experiencing increased theophylline levels with or without clinical signs or symptoms of theophylline toxicity after the addition of ACCOLATE to an existing theophylline regimen have been reported. The mechanism of the interaction between ACCOLATE and theophylline in these patients is unknown (see ADVERSE REACTIONS).
Coadministration of zafirlukast (40 mg/day) with aspirin (650 mg four times daily) resulted in mean increased plasma levels of zafirlukast by approximately 45%.
In a single-blind, parallel-group, 3-week study in 39 healthy female subjects taking oral contraceptives, 40 mg twice daily of zafirlukast had no significant effect on ethinyl estradiol plasma concentrations or contraceptive efficacy.
Coadministration of zafirlukast with fluconazole, a moderate CYP2C9 inhibitor, resulted in increased
plasma levels of zafirlukast, by approximately 58% (90% CI:28, 95). The clinical significance of this
interaction is unknown. Zafirlukast exposure is likely to be increased by other moderate and strong
CYP2C9 inhibitors. Coadministration of zafirlukast with itraconazole, a strong CYP3A4 inhibitor, caused
no change in plasma levels of zafirlukast.
No other formal drug-drug interaction studies between ACCOLATE and marketed drugs known to be metabolized by the P450 3A4 (CYP3A4) isoenzyme (eg, dihydropyridine calcium-channel blockers, cyclosporin, cisapride) have been conducted. As ACCOLATE is known to be an inhibitor of CYP3A4 in vitro, it is reasonable to employ appropriate clinical monitoring when these drugs are coadministered with ACCOLATE.
CloseCarcinogenesis, Mutagenesis, Impairment of Fertility:
In two-year carcinogenicity studies, zafirlukast was administered at dietary doses of 10, 100, and 300 mg/kg to mice and 40, 400, and 2000 mg/kg to rats. Male mice at an oral dose of 300 mg/kg/day (approximately 30 times the maximum recommended daily oral dose in adults and in children on a mg/m2 basis) showed an increased incidence of hepatocellular adenomas; female mice at this dose showed a greater incidence of whole body histocytic sarcomas. Male and female rats at an oral dose of 2000 mg/kg/day (resulting in approximately 160 times the exposure to drug plus metabolites from the maximum recommended daily oral dose in adults and in children based on a comparison of the plasma area-under the curve [AUC] values) of zafirlukast showed an increased incidence of urinary bladder transitional cell papillomas. Zafirlukast was not tumorigenic at oral doses up to 100 mg/kg (approximately 10 times the maximum recommended daily oral dose in adults and in children on a mg/m2 basis) in mice and at oral doses up to 400 mg/kg (resulting in approximately 140 times the exposure to drug plus metabolites from the maximum recommended daily oral dose in adults and in children based on a comparison of the plasma AUC values) in rats. The clinical significance of these findings for the long-term use of ACCOLATE is unknown.
Zafirlukast showed no evidence of mutagenic potential in the reverse microbial assay, in 2 forward point mutation (CHO-HGPRT and mouse lymphoma) assays or in two assays for chromosomal aberrations (the in vitro human peripheral blood lymphocyte clastogenic assay and the in vivo rat bone marrow micronucleus assay).
No evidence of impairment of fertility and reproduction was seen in male and female rats treated with zafirlukast at oral doses up to 2000 mg/kg (approximately 410 times the maximum recommended daily oral dose in adults on a mg/m2 basis).
Pregnancy Category B:
No teratogenicity was observed at oral doses up to 1600 mg/kg/day in mice (approximately 160 times the maximum recommended daily oral dose in adults on a mg/m2 basis), up to 2000 mg/kg/day in rats (approximately 410 times the maximum recommended daily oral dose in adults on a mg/m2 basis) and up to 2000 mg/kg/day in cynomolgus monkeys (which resulted in approximately 20 times the exposure to drug plus metabolites compared to that from the maximum recommended daily oral dose in adults based on comparison of the AUC values). At an oral dose of 2000 mg/kg/day in rats, maternal toxicity and deaths were seen with increased incidence of early fetal resorption. Spontaneous abortions occurred in cynomolgus monkeys at the maternally toxic oral dose of 2000 mg/kg/day. There are no adequate and well-controlled trials in pregnant women. Because animal reproductive studies are not always predictive of human response, ACCOLATE should be used during pregnancy only if clearly needed.
Nursing Mothers:
Zafirlukast is excreted in breast milk. Following repeated 40 mg twice-a-day dosing in healthy women, average steady-state concentrations of zafirlukast in breast milk were 50 ng/mL compared to 255 ng/mL in plasma. Because of the potential for tumorigenicity shown for zafirlukast in mouse and rat studies and the enhanced sensitivity of neonatal rats and dogs to the adverse effects of zafirlukast, ACCOLATE should not be administered to mothers who are breast-feeding.
Pediatric Use:
The safety of ACCOLATE at doses of 10 mg twice daily has been demonstrated in 205 pediatric patients 5 through 11 years of age in placebo-controlled trials lasting up to six weeks and with 179 patients in this age range participating in 52 weeks of treatment in an open-label extension.
The effectiveness of ACCOLATE for the prophylaxis and chronic treatment of asthma in pediatric patients 5 through 11 years of age is based on an extrapolation of the demonstrated efficacy of ACCOLATE in adults with asthma and the likelihood that the disease course, and pathophysiology and the drug’s effect are substantially similar between the two populations. The recommended dose for the patients 5 through 11 years of age is based upon a cross-study comparison of the pharmacokinetics of zafirlukast in adults and pediatric subjects, and on the safety profile of zafirlukast in both adult and pediatric patients at doses equal to or higher than the recommended dose.
The safety and effectiveness of zafirlukast for pediatric patients less than 5 years of age has not been established. The effect of ACCOLATE on growth in children has not been determined.
Geriatric Use:
Based on cross-study comparison, the clearance of zafirlukast is reduced in patients 65 years of age and older such that Cmax and AUC are approximately 2- to 3-fold greater than those of younger patients (see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY).
A total of 8094 patients were exposed to zafirlukast in North American and European short-term placebo-controlled clinical trials. Of these, 243 patients were elderly (age 65 years and older). No overall difference in adverse events was seen in the elderly patients, except for an increase in the frequency of infections among zafirlukast-treated elderly patients compared to placebo-treated elderly patients (7.0% vs. 2.9%). The infections were not severe, occurred mostly in the lower respiratory tract, and did not necessitate withdrawal of therapy.
An open-label, uncontrolled, 4-week trial of 3759 asthma patients compared the safety and efficacy of ACCOLATE 20 mg given twice daily in three patient age groups, adolescents (12-17 years), adults (18-65 years), and elderly (greater than 65 years). A higher percentage of elderly patients (n=384) reported adverse events when compared to adults and adolescents. These elderly patients showed less improvement in efficacy measures. In the elderly patients, adverse events occurring in greater than 1% of the population included headache (4.7%), diarrhea and nausea (1.8%), and pharyngitis (1.3%). The elderly reported the lowest percentage of infections of all three age groups in this study.
- ADVERSE REACTIONS
Adults and Children 12 years of age and older
The safety database for ACCOLATE consists of more than 4000 healthy volunteers and patients who received ACCOLATE, of which 1723 were asthmatics enrolled in trials of 13 weeks duration or longer. A total of 671 patients received ACCOLATE for 1 year or longer. The majority of the patients were 18 years of age or older; however, 222 patients between the age of 12 and 18 years received ACCOLATE.
A comparison of adverse events reported by ≥1% of zafirlukast-treated patients, and at rates numerically greater than in placebo-treated patients, is shown for all trials in the table below.
ACCOLATE
PLACEBO
Adverse Event
N=4058
N=2032
Headache
12.9%
11.7%
Infection
3.5%
3.4%
Nausea
3.1%
2.0%
Diarrhea
2.8%
2.1%
Pain (generalized)
1.9%
1.7%
Asthenia
1.8%
1.6%
Abdominal Pain
1.8%
1.1%
Accidental Injury
1.6%
1.5%
Dizziness
1.6%
1.5%
Myalgia
1.6%
1.5%
Fever
1.6%
1.1%
Back Pain
1.5%
1.2%
Vomiting
1.5%
1.1%
SGPT Elevation
1.5%
1.1%
Dyspepsia
1.3%
1.2%
The frequency of less common adverse events was comparable between ACCOLATE and placebo.
Rarely, elevations of one or more liver enzymes have occurred in patients receiving ACCOLATE in controlled clinical trials. In clinical trials, most of these have been observed at doses four times higher than the recommended dose. The following hepatic events (which have occurred predominantly in females) have been reported from postmarketing adverse event surveillance of patients who have received the recommended dose of ACCOLATE (40 mg/day): cases of symptomatic hepatitis (with or without hyperbilirubinemia) without other attributable cause; and rarely, hyperbilirubinemia without other elevated liver function tests. In most, but not all postmarketing reports, the patient’s symptoms abated and the liver enzymes returned to normal or near normal after stopping ACCOLATE. In rare cases, patients have presented with fulminant hepatitis or progressed to hepatic failure, liver transplantation and death (see WARNINGS, Hepatotoxicity and PRECAUTIONS, Information for Patients).
In clinical trials, an increased proportion of zafirlukast patients over the age of 55 years reported infections as compared to placebo-treated patients. A similar finding was not observed in other age groups studied. These infections were mostly mild or moderate in intensity and predominantly affected the respiratory tract. Infections occurred equally in both sexes, were dose-proportional to total milligrams of zafirlukast exposure, and were associated with coadministration of inhaled corticosteroids. The clinical significance of this finding is unknown.
In rare cases, patients with asthma on ACCOLATE may present with systemic eosinophilia, eosinophilic pneumonia, or clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition which is often treated with systemic steroid therapy. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. These events have usually, but not always, been associated with reductions and/or withdrawal of steroid therapy. The possibility that ACCOLATE may be associated with emergence of Churg-Strauss syndrome can neither be excluded nor established (see PRECAUTIONS, Eosinophilic Conditions).
Neuropsychiatric adverse events, including insomnia and depression, have been reported in association with ACCOLATE therapy (see PRECAUTIONS, Neuropsychiatric Events). Hypersensitivity reactions, including urticaria, angioedema and rashes, with or without blistering, have also been reported in association with ACCOLATE therapy. Additionally, there have been reports of patients experiencing agranulocytosis, bleeding, bruising, or edema, arthralgia, myalgia, malaise, and pruritus in association with ACCOLATE therapy.
Rare cases of patients experiencing increased theophylline levels with or without clinical signs or symptoms of theophylline toxicity after the addition of ACCOLATE to an existing theophylline regimen have been reported. The mechanism of the interaction between ACCOLATE and theophylline in these patients is unknown and not predicted by available in vitro metabolism data and the results of two clinical drug interaction studies (see CLINICAL PHARMACOLOGY and PRECAUTIONS, Drug Interactions).
ClosePediatric Patients 5 through 11 years of age
ACCOLATE has been evaluated for safety in 788 pediatric patients 5 through 11 years of age. Cumulatively, 313 pediatric patients were treated with ACCOLATE 10 mg twice daily or higher for at least 6 months, and 113 of them were treated for one year or longer in clinical trials. The safety profile of ACCOLATE 10 mg twice daily-versus placebo in the 4- and 6-week double-blind trials was generally similar to that observed in the adult clinical trials with ACCOLATE 20 mg twice daily.
In pediatric patients receiving ACCOLATE in multi-dose clinical trials, the following events occurred with a frequency of ≥ 2% and more frequently than in pediatric patients who received placebo, regardless of causality assessment: headache (4.5 vs. 4.2%) and abdominal pain (2.8 vs. 2.3%).
The post-marketing experience in this age group is similar to that seen in adults, including hepatic dysfunction, which may lead to liver failure.
- OVERDOSAGE
No deaths occurred at oral zafirlukast doses of 2000 mg/kg in mice (approximately 210 times the maximum recommended daily oral dose in adults and children on a mg/m2 basis), 2000 mg/kg in rats (approximately 420 times the maximum recommended daily oral dose in adults and children on a mg/m2 basis), and 500 mg/kg in dogs (approximately 350 times the maximum recommended daily oral dose in adults and children on a mg/m2 basis).
Overdosage with ACCOLATE has been reported in four patients surviving reported doses as high as 200 mg. The predominant symptoms reported following ACCOLATE overdose were rash and upset stomach. There were no acute toxic effects in humans that could be consistently ascribed to the administration of ACCOLATE. It is reasonable to employ the usual supportive measures in the event of an overdose; eg, remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring, and institute supportive therapy, if required.
Close - DOSAGE AND ADMINISTRATION
Because food can reduce the bioavailability of zafirlukast, ACCOLATE should be taken at least 1 hour before or 2 hours after meals.
Adults and Children 12 years of age and older
The recommended dose of ACCOLATE in adults and children 12 years and older is 20 mg twice daily.
Pediatric Patients 5 through 11 years of age
The recommended dose of ACCOLATE in children 5 through 11 years of age is 10 mg twice daily.
Elderly Patients
Based on cross-study comparisons, the clearance of zafirlukast is reduced in elderly patients (65 years of age and older), such that Cmax and AUC are approximately twice those of younger adults. In clinical trials, a dose of 20 mg twice daily was not associated with an increase in the overall incidence of adverse events or withdrawals because of adverse events in elderly patients.
Patients with Hepatic Impairment
ACCOLATE is contraindicated in patients with hepatic impairment including hepatic cirrhosis (see Contraindications). The clearance of zafirlukast is reduced in patients with stable alcoholic cirrhosis such that the Cmax and AUC are approximately 50 - 60% greater than those of normal adults. ACCOLATE has not been evaluated in patients with hepatitis or in long-term studies of patients with cirrhosis.
ClosePatients with Renal Impairment
Dosage adjustment is not required for patients with renal impairment.
- HOW SUPPLIED
ACCOLATE 10 mg Tablets, (NDC 0310-0401) white, unflavored, round, biconvex, film-coated, mini-tablets identified with “ACCOLATE 10” debossed on one side are supplied in opaque HDPE bottles of 60 tablets.
ACCOLATE 20 mg Tablets, (NDC 0310-0402) white, round, biconvex, coated tablets identified with “ACCOLATE 20” debossed on one side are supplied in opaque HDPE bottles of 60 tablets.
Store at controlled room temperature, 20-25°C (68-77°F) [see USP]. Protect from light and moisture. Dispense in the original air-tight container.
ACCOLATE is a trademark of the AstraZeneca group of companies.
©AstraZeneca 2013
Distributed by:
AstraZeneca Pharmaceuticals LP
Wilmington, DE 19850
Rev. 11/2013
AstraZeneca
PATIENT INFORMATION
ACCOLATE® (ak-o-late)
(zafirlukast) Tablets
Read the Patient Information leaflet before you start taking ACCOLATE and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.
What is ACCOLATE?
ACCOLATE is a prescription medicine used to help prevent asthma attacks and for the long-term treatment of asthma symptoms in adults and children 5 years and older.
It is not known if ACCOLATE is safe and effective when used in children under 5 years old. The effect of ACCOLATE on growth in children has not been determined.
Do not take ACCOLATE if you need relief right away for a sudden asthma attack. If you get an asthma attack, you should follow the instructions your healthcare provider gave you for treating asthma attacks.
Who should not take ACCOLATE?
Do not take ACCOLATE if you;
- •
- are allergic to zafirlukast or any of the ingredients in ACCOLATE. See the end of this leaflet for a complete list of ingredients in ACCOLATE.
- •
- have problems with your liver.
What should I tell my healthcare provider before taking ACCOLATE?
Before you take ACCOLATE, tell your healthcare provider if you:
- •
- have liver problems
- •
- have any other medical conditions
- •
- are pregnant or plan to become pregnant. It is not known if ACCOLATE will harm your unborn baby. Talk to your healthcare provider if you are pregnant or plan to become pregnant.
- •
- are breastfeeding or plan to breastfeed. ACCOLATE can pass into your milk; it is not known whether ACCOLATE may harm your baby. Women who are breastfeeding should not take ACCOLATE.
Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.
ACCOLATE may affect the way other medicines work, and other medicines may affect how ACCOLATE works.
Especially tell your healthcare provider if you take:
- •
- warfarin sodium (Coumadin, Jantoven)
- •
- erythromycin (ERYC, ERY-TAB, PCE)
- •
- theophylline (Elixophyllin, Theo-24, Theochron, Theolair, Uniphyl)
- •
- fluconazole (Diflucan)
Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.
How should I take ACCOLATE?
- •
- Take ACCOLATE exactly as your healthcare provider tells you to take it.
- •
- Take ACCOLATE regularly, even if you do not have asthma symptoms. Do not change your dose or stop taking ACCOLATE without talking to your healthcare provider.
- •
- Do not stop taking or change the dose of your other asthma medicines unless your healthcare provider tells you to.
- •
- Take your prescribed dose of ACCOLATE by mouth at least 1 hour before or 2 hours after meals.
- •
- ACCOLATE does not treat the symptoms of a sudden asthma attack. Always have a short-acting beta 2-agonist medicine (rescue inhaler) with you to treat sudden symptoms. If you do not have a rescue inhaler medicine, talk to your healthcare provider to have one prescribed for you.
- •
- If you take too much ACCOLATE, call your healthcare provider or go to the nearest hospital emergency room right away.
What are the possible side effects of ACCOLATE?
ACCOLATE may cause serious side effects, including:
- •
- Severe liver problems. In some cases, these liver problems can lead to liver failure, the need for a liver transplant or death. Tell your healthcare provider right away if you have:
- •
- pain or tenderness in the right upper side of your stomach area (abdomen)
- •
- nausea
- •
- tiredness
- •
- itchiness
- •
- yellowing of your skin or the whites of your eyes
- •
- flu-like symptoms
- •
- loss of appetite
- •
- dark (tea colored) urine
- •
- Inflammation of your blood vessels.
Rarely, this can happen in people with asthma who take ACCOLATE.
This usually, but not always, happens in people who also take a
steroid medicine by mouth that is being stopped or the dose is
being lowered. Tell your healthcare provider right away if you
have:
- o
- a feeling of pins and needles or numbness of your arms or legs
- o
- flu like symptoms
- o
- rash
- o
- pain and swelling of your sinuses
- •
- Changes in behaviour or mood. Tell your healthcare provider if you have changes in your behaviour, problems sleeping or feel very sad.
- •
- Hypersensitivity reactions. Tell your healthcare provider if you have severe itching, breathing problems, skin rash, skin blisters, or skin redness, or swelling.
The most common side effects of ACCOLATE in people 12 years and older include:
- •
- headache
- •
- infection
- •
- nausea
- •
- diarrhea
- •
- pain (generalized)
The most common side effects of ACCOLATE in children 5 to 11 years include:
- •
- headache
- •
- stomach pain
Tell your healthcare provider if you have any side effect that bothers you or that does not go away.
These are not all of the possible side effects of ACCOLATE. For more information, ask your healthcare provider or pharmacist.
Call your healthcare provider 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 AstraZeneca at 1-800-236-9933.
How should I store ACCOLATE?
- •
- Store ACCOLATE at 68°F to 77°F (20°C -25°C).
- •
- Keep ACCOLATE tablets dry.
- •
- Keep ACCOLATE in a tight closed container and keep ACCOLATE out of the light.
- •
- Keep ACCOLATE and all medicines out of the reach of children.
General information about the safe and effective use of ACCOLATE.
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use ACCOLATE for a condition for which it was not prescribed. Do not give ACCOLATE to other people, even if they have the same symptoms that you have. It may harm them.
This Patient Information leaflet summarizes the most important information about ACCOLATE. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about ACCOLATE that is written for healthcare professionals.
For more information, go to www.accolate.com or call AstraZeneca Information Center at 1-800-236-9933, Monday through Friday, 8 a.m. – 6 p.m. Eastern Standard Time, excluding holidays.
What are the ingredients in ACCOLATE?
Active ingredient: zafirlukast
Inactive ingredients: croscarmellose sodium, lactose, magnesium stearate, microcrystalline cellulose, povidone, hypromellose, and titanium dioxide.
What do ACCOLATE tablets look like?
- •
- the 10 mg tablet is white and round with “ACCOLATE 10” marked on one side.
- •
- the 20 mg tablet is white and round with “ACCOLATE 20” marked on one side.
ACCOLATE is a trademark of the AstraZeneca group of companies.
©AstraZeneca 2013
Distributed by:
AstraZeneca Pharmaceuticals LP
Wilmington, DE 19850
Rev. 11/2013
Close - PACKAGE/LABEL PRINCIPAL DISPLAY PANEL – 10 mg
NDC 0310-0401-60
60 tablets
ACCOLATE®
ZAFIRLUKAST
10 mg tablets
Rx only
DISPENSE IN THE ORIGINAL
AIRTIGHT CONTAINER.
Mfd. for: AstraZeneca Pharmaceuticals LP
Wilmington, DE 19850
By: IPR Pharmaceuticals, Inc.
Canóvanas, PR 00729
Product of UK
AstraZeneca
Close - PACKAGE/LABEL PRINCIPAL DISPLAY PANEL – 20 mg
NDC 0310-0402-60
60 tablets
ACCOLATE®
ZAFIRLUKAST
20 mg tablets
Rx only
DISPENSE IN THE ORIGINAL
AIRTIGHT CONTAINER.
Mfd. for: AstraZeneca Pharmaceuticals LP
Wilmington, DE 19850
By: IPR Pharmaceuticals, Inc.
Canóvanas, PR 00729
Product of UK
AstraZeneca
Close - INGREDIENTS AND APPEARANCE
ACCOLATE
zafirlukast tablet, film coatedProduct Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0310-0401 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ZAFIRLUKAST (UNII: XZ629S5L50) (ZAFIRLUKAST - UNII:XZ629S5L50) ZAFIRLUKAST 10 mg Inactive Ingredients Ingredient Name Strength CROSCARMELLOSE SODIUM (UNII: M28OL1HH48) LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X) MAGNESIUM STEARATE (UNII: 70097M6I30) POVIDONES (UNII: FZ989GH94E) TITANIUM DIOXIDE (UNII: 15FIX9V2JP) HYPROMELLOSES (UNII: 3NXW29V3WO) Product Characteristics Color WHITE Score no score Shape ROUND (biconvex) Size 6mm Flavor Imprint Code ACCOLATE10 Contains Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:0310-0401-60 60 in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA020547 10/01/1996 ACCOLATE
zafirlukast tablet, film coatedProduct Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0310-0402 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ZAFIRLUKAST (UNII: XZ629S5L50) (ZAFIRLUKAST - UNII:XZ629S5L50) ZAFIRLUKAST 20 mg Inactive Ingredients Ingredient Name Strength CROSCARMELLOSE SODIUM (UNII: M28OL1HH48) LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X) MAGNESIUM STEARATE (UNII: 70097M6I30) POVIDONES (UNII: FZ989GH94E) TITANIUM DIOXIDE (UNII: 15FIX9V2JP) HYPROMELLOSES (UNII: 3NXW29V3WO) Product Characteristics Color WHITE Score no score Shape ROUND (biconvex) Size 8mm Flavor Imprint Code ACCOLATE20 Contains Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:0310-0402-60 60 in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA020547 10/01/1996 Labeler - AstraZeneca Pharmaceuticals LP (054743190) Registrant - AstraZeneca PLC (230790719) CloseEstablishment Name Address ID/FEI Business Operations IPR Pharmaceuticals, Inc 156931248 MANUFACTURE(0310-0401, 0310-0402)


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Notes on Data Formatting¶
DBMSs in general do a rather poor job with data precision. The values that are output are accurate but quite often what was input as “3.45” will be output as “3.4499999999999903” or “3.4500000000000001E00”: accurate as to value but precision information has been lost.
nexsciTAP tries to compensate for this by augmenting the TAP_SCHEMA metadata with formatting information (e.g., “f4.2” for the above) and this works well for many of the uniform catalogs encountered in astronomy. However, there are two situations where it is insufficient.
The first is where the precision of different records varies. This is the case in, for instance, tables from the NASA Exoplanet Archive where the data is culled from the literature and where the precision in the same column for different records may be different. This can be addressed at the database level by storing precision information on a cell by cell basis.
The second arises with columns that are constructed on the fly, like “B-V as BmV” or “count(*) as nrec”. We can’t know up front how best to format these, though here are a variety of approaches we can take.
The simplest approach is to use a format guaranteed to fit, like “e22.17” for floating point numbers. However, this is hard to read and takes up a lot of space.
At the other extreme, we can use one form or another of a double pass through the data; scanning once to determine reasonable formats and then a second time to output the data using those formats.
A compromise, which is what we implement now, scans the first N (currently 10,000) records (in memory) to deduce formats for any constructed columns, then outputs these and any subsequent records using these formats. Quite often, the number of records is less than N and this is completely accurate. We allow N to be configurable at run time.
None of this is absolutely foolproof; we will try to accomodate special cases as they arise.


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WRU hold talks with Warren Gatland over doping suspicion comments
The WRU have spoken with the former Wales boss after his comments this week
by Katie SandsThe Welsh Rugby Union have spoken with former Wales boss Warren Gatland to fully understand the comments he made around doping suspicions this week.
A statement says the Union is satisfied with the clarity he has provided over the revelations made on an Irish chat show.
The Kiwi revealed he may have had suspicions about a Wales player doping during his 12-year reign as national head coach based on jokes made by teammates, but later clarified he had no evidence to base any suspicion on.
The identity of the player the Kiwi was referring to is unknown.
Gatland had said: "You know I haven’t come across, personally, any players that I've coached from a Wales perspective that I would - well sorry, maybe one."
Asked by Off The Ball presenter Joe Molloy if he had a suspicion, the former Wales boss said: "Yeah, maybe one, now that I think about it."
When asked if the person played for Wales, Gatland responded: “He may have done, yeah.”
He continued: “It’s probably unfair of me to say I had the suspicions [about one of them] because I’ve got no evidence or anything like that.
“It’s kind of like just saying, ‘Is there a possibility?'"
Asked if he felt it was his role to confront the player, he said: "No, no.
"It was more like a couple of people making jokes sort of thing."
“Truth in humour?" the presenter asked.
“Yeah, exactly,” Gatland responded.
The WRU have spoken to Gatland since the comments were made and say they are satisfied with their exchange.
It's understood Welsh rugby bosses are comfortable with the fact Gatland did not escalate the issue at the time because his suspicions were not serious and were based purely on dressing room jokes.
A WRU spokesman said on Friday: "We've spoken to Warren to understand his comments in their entirety and we are satisfied with the clarity he provided.


Detailed course offerings (Time Schedule) are available for
MCB 511 Cell Cycle Control (3) Breeden, Roberts, Edgar
Studies recent advances in understanding cell-cycle control, arising from genetics and biochemical studies of fission and budding yeast, marine invertebrates, Drosophila, amphibians, and cultured cells. Addresses the biochemical processes and molecular interactions and the rate-limiting events in the cell cycle, and the coupling of those events to physiological signals. Offered: A.
View course details in MyPlan: MCB 511
MCB 512 Scientific Speaking Seminar (1.5) Biggins, Peichel
Teaches how to effectively give a scientific seminar about research. Offered: jointly with CONJ 512; W.
View course details in MyPlan: MCB 512
MCB 513 Development Journal Seminar (1, max. 12) Moens, Soriano, Swalla
Examines current literature about specific topics in developmental biology. The seminar chooses current monthly topics and the group meets weekly to discuss published research papers. Topics may include: germ cell specification; cell migration and morphogenesis; axis formation; somitogenesis and stem cells. Offered: AWSp.
View course details in MyPlan: MCB 513
MCB 514 Molecular and Cellular Biology Literature Review (2) Raible
Emphasizes critical evaluation of the original literature orally and in writing. Open only to first-year students in the Molecular and Cellular Biology program.
View course details in MyPlan: MCB 514
MCB 515 Molecular and Cellular Biology Literature Review (2) Emerman
Emphasizes critical evaluation of the original literature orally and in writing. Open only to first-year students in the Molecular and Cellular Biology Program. Offered: W.
View course details in MyPlan: MCB 515
MCB 516 Molecular and Cellular Biology Literature Review (2) Emerman
Emphasizes critical evaluation of the original literature orally and in writing. Open only to first-year students in the Molecular and Cellular Biology Program. Offered: S.
View course details in MyPlan: MCB 516
MCB 517 Topics in Molecular and Cellular Biology (1-5, max. 12)
Advanced in-depth coverage of specific areas of molecular and cellular biology of current interest. Lectures by University of Washington faculty and invited speakers involved in research in this area. A basic knowledge of principles of molecular and cellular biology assumed.
View course details in MyPlan: MCB 517
MCB 519 Topics in Cancer (1, max. 6)
Examination of ways to integrate basic, clinical, and public health sciences to increase understanding of human biology and disease. Seminars in introduction to cancer research as viewed by basic, clinical, and public health sciences, origins of cancer, cancer prevention, cancer progression, and therapies for cancer. Credit/no-credit only.
View course details in MyPlan: MCB 519
MCB 520 Tutorial in Molecular and Cellular Biology (1-2, max. 2) Emerman
Special topics reading and discussion. Offered: A.
View course details in MyPlan: MCB 520
MCB 522 Development I: The Developmental Basis of Human Disease (3) Moens
Uses recent discoveries in human genetics to guide student learning about animal development. Explores the normal developmental function of genes that have been identified as causal in human developmental disorders such as skeletal dysmorphologies, ciliopathies, autism, and cancer. Offered: A, odd years.
View course details in MyPlan: MCB 522
MCB 529 Cell Migration (1.5) Cooper, Moens
Explores mechanisms of cell migration in vivo and in cell culture. Discusses the cell biology of different forms of cell migration, the extracellular cues that direct migration, and how these cues are integrated by the migrating cell. Offered: jointly with CONJ 529; W.
View course details in MyPlan: MCB 529
MCB 532 Human Pathogenic Viruses (3) Emerman
Replication, regulation, and pathogenesis of several groups of human viruses, including human immunodeficiency virus and papillomaviruses. Emphasis on the unique aspects of the viral-like cycles as they relate to effects on infected cells and organisms. Guest lecturers focus on viral immunology, measles. herpes simplex virus, and HHV-8. Offered: A.
View course details in MyPlan: MCB 532
MCB 533 Evolutionary Genetics and Genomics (3) Malik, Peichel
Introduces classic concepts and approaches in evolutionary genetics. Familiarizes students with genomic approaches, tools and resources, and demonstrates how evolutionary approaches and modern genomic tools are brought to bear on important biological questions. Offered: A.
View course details in MyPlan: MCB 533
MCB 539 Biological Basis of Neoplasia (3) Kemp, Zarbl
Introduces the major themes in research in the biology of neoplastic change. Covers principle molecular mechanisms responsible for tumor initiation and progression, with a specific emphasis on intracellular signaling, DNA repair, cell cycle checkpoints, and loss of normal tissue homeostatis. Offered: Sp.
View course details in MyPlan: MCB 539
MCB 540 Nucleic Acid Enzymes (1.5) Stoddard
Surveys a wide variety of enzymatic process that control the structure and modification of DNA and RNA, with particular focus on structure, function and mechanism. Unifying features of major reaction types (such as phosphoryl transfers and base modifications) constitute core material. Offered: W.
View course details in MyPlan: MCB 540
MCB 543 Logic Constructs and Methodologies of Biological Research (3)
Explores the logic and methods of general scientific practice, form historical, logical, and practical points of view. Covers philosophical and methodological matters upon which there is consensus, and cutting issues of ongoing controversy. Includes both theoretical and practical application of scientific method.
View course details in MyPlan: MCB 543
MCB 560 Biotechnology Externship (2-12, max. 12) Moon
Supervised research in a biotechnology company. Prerequisite: permission of instructor and doctoral candidacy. Offered: AWSpS.
View course details in MyPlan: MCB 560
MCB 580 Teaching Practicum in Molecular and Cellular Biology (2, max. 4)
Supervised training in the teaching of molecular and cellular biology. Prerequisite: permission of instructor. Credit/no-credit only. Offered: AWSpS.
View course details in MyPlan: MCB 580
MCB 599 Introduction to Research in Molecular and Cellular Biology (*, max. 20)
The student rotates through one research laboratory involved in the Molecular and Cellular Biology Program per quarter. Open only to first-year students in the Molecular and Cellular Biology Program. Credit/no-credit only. Offered: AWSpS.
View course details in MyPlan: MCB 599
MCB 600 Independent Study or Research (*-)
View course details in MyPlan: MCB 600
MCB 700 Master's Thesis (*-)
Offered: AWSpS.
View course details in MyPlan: MCB 700
MCB 800 Doctoral Dissertation (*-)
View course details in MyPlan: MCB 800


#Team @Neuramn.
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- canonicalName - Variable in class software.amazon.awssdk.crt.CrtResource.ResourceInstance
-
- cleanUpPem(String) - Static method in class software.amazon.awssdk.crt.utils.PemUtils
-
Cleanup Function that removes most formatting and copy/paste mistakes from
PEM formatted Strings.
- ClientBootstrap - Class in software.amazon.awssdk.crt.io
-
This class wraps the aws_client_bootstrap from aws-c-io to provide
a client context for all protocol stacks in the AWS Common Runtime.
- ClientBootstrap(EventLoopGroup, HostResolver) - Constructor for class software.amazon.awssdk.crt.io.ClientBootstrap
-
Creates a new ClientBootstrap.
- ClientTlsContext - Class in software.amazon.awssdk.crt.io
-
This class wraps the aws_tls_context from aws-c-io to provide access to TLS
configuration contexts in the AWS Common Runtime.
- ClientTlsContext(TlsContextOptions) - Constructor for class software.amazon.awssdk.crt.io.ClientTlsContext
-
Creates a new Client TlsContext.
- ClientTlsContext() - Constructor for class software.amazon.awssdk.crt.io.ClientTlsContext
-
Creates a new Client TlsContext.
- clone() - Method in class software.amazon.awssdk.crt.auth.signing.AwsSigningConfig
-
- clone() - Method in class software.amazon.awssdk.crt.mqtt.MqttConnectionConfig
-
Creates a (shallow) clone of this config object
- close() - Method in class software.amazon.awssdk.crt.CrtResource
-
- collectNativeResource(Consumer<CrtResource.ResourceInstance>) - Static method in class software.amazon.awssdk.crt.CrtResource
-
- collectNativeResources(Consumer<String>) - Static method in class software.amazon.awssdk.crt.CrtResource
-
- complete(HttpRequest) - Method in class software.amazon.awssdk.crt.mqtt.WebsocketHandshakeTransformArgs
-
Mark the transform operation as successfully completed.
- completeExceptionally(Throwable) - Method in class software.amazon.awssdk.crt.mqtt.WebsocketHandshakeTransformArgs
-
Mark the transform operation as unsuccessfully completed.
- connect() - Method in class software.amazon.awssdk.crt.mqtt.MqttClientConnection
-
Connect to the service endpoint and start a session
- connectTimeoutMs - Variable in class software.amazon.awssdk.crt.io.SocketOptions
-
Sets the number of milliseconds before a connection will be considered timed out
- create(HttpClientConnectionManagerOptions) - Static method in class software.amazon.awssdk.crt.http.HttpClientConnectionManager
-
- createDefaultClient() - Static method in class software.amazon.awssdk.crt.io.TlsContextOptions
-
Helper which creates a default set of TLS options for the current platform
- createDefaultServer() - Static method in class software.amazon.awssdk.crt.io.TlsContextOptions
-
Helper which creates a default set of TLS options for the current platform
- createWithMtls(String, String) - Static method in class software.amazon.awssdk.crt.io.TlsContextOptions
-
Helper which creates TLS options using a certificate and private key
- createWithMtlsFromPath(String, String) - Static method in class software.amazon.awssdk.crt.io.TlsContextOptions
-
Helper which creates TLS options using a certificate and private key
- createWithMtlsPkcs12(String, String) - Static method in class software.amazon.awssdk.crt.io.TlsContextOptions
-
OSX only - Helper which creates TLS options using PKCS12
- Credentials - Class in software.amazon.awssdk.crt.auth.credentials
-
A class representing a set of AWS credentials.
- Credentials() - Constructor for class software.amazon.awssdk.crt.auth.credentials.Credentials
-
- Credentials(byte[], byte[], byte[]) - Constructor for class software.amazon.awssdk.crt.auth.credentials.Credentials
-
- CredentialsProvider - Class in software.amazon.awssdk.crt.auth.credentials
-
A base class that represents a source of AWS credentials
- CredentialsProvider() - Constructor for class software.amazon.awssdk.crt.auth.credentials.CredentialsProvider
-
- CRT - Class in software.amazon.awssdk.crt
-
This class is responsible for loading the aws-crt-jni shared lib for the current
platform out of aws-crt-java.jar.
- CRT() - Constructor for class software.amazon.awssdk.crt.CRT
-
- CRT.UnknownPlatformException - Exception in software.amazon.awssdk.crt
-
- CrtPlatform - Class in software.amazon.awssdk.crt
-
- CrtPlatform() - Constructor for class software.amazon.awssdk.crt.CrtPlatform
-
- CrtResource - Class in software.amazon.awssdk.crt
-
This wraps a native pointer to an AWS Common Runtime resource.
- CrtResource() - Constructor for class software.amazon.awssdk.crt.CrtResource
-
- CrtResource.ResourceInstance - Class in software.amazon.awssdk.crt
-
- CrtRuntimeException - Exception in software.amazon.awssdk.crt
-
This exception will be thrown by any exceptional cases encountered within
the JNI bindings to the AWS Common Runtime
- CrtRuntimeException(String) - Constructor for exception software.amazon.awssdk.crt.CrtRuntimeException
-
- CrtRuntimeException(int, String) - Constructor for exception software.amazon.awssdk.crt.CrtRuntimeException
-


### Problem 9. Point in Circle and outside Rectangle * Write an expression that checks for given point `P(x, y)` if it is within the circle `K( (1,1), 3)` and out of the rectangle `R(top=1, left=-1, width=6, height=2)`. _Examples:_ | x | y | inside K & outside of R | |:----:|:----:|:-----------------------:| | 1 | 2 | yes | | 2.5 | 2 | no | | 0 | 1 | no | | 2.5 | 1 | no | | 2 | 0 | no | | 4 | 0 | no | | 2.5 | 1.5 | no | | 2 | 1.5 | yes | | 1 | 2.5 | yes | | -100 | -100 | no |


To search for text in files from the current folder (or directory, to follow Linux nomenclature), one can write:
grep “text" -R . -n –include=*.py
The parameters are as follows:
text the actual text to search for -R Recurse to subdirectories . start from the current directory –include=.py specifies a regular expression that searchable files must match (e.g. .py) –color makes the output pretty -n shows the lines numbers of the lines that matched your search text


Ipeka is the best school ever.
They implement all of their ESLRs without fail. And the curricular alignment is superb.


The Ramdan is a perfect combination of 12 natural ingredients: mushrooms, fruits and vegetables. - The 12 ramdan coffee: decaffeinated coffee 100%. The Ramdan 12 protects against diseases: cardiovascular, diabetes, high blood pressure, anemia, fatigue, headaches, parasitic infections, proliferation and tumor formation. It acts against: rheumatism, asthma, chronic rate, chest infections and sore throats. It prevents us diarrhea, hemorrhoids, and even leukemia cancers, liver problems and kidney. - The 12 ramdan coffee properly washing the urinary bladder. A very effective product in the regulation of the reproductive system. For exemple :
Properties Ramdan 12:


|
Bitstream Interpretation Library (BIL)
0.1
|
Contains declaration of Exception class. More...
#include <stdexcept>
#include <string>
Go to the source code of this file.
Classes | |
| class | bil::Exception |
| Base exception class. More... |
Namespaces | |
| namespace | bil |
Macros | |
| #define | BIL_EXCEPTION_HPP |
Contains declaration of Exception class.
Definition in file Exception.hpp.
| #define BIL_EXCEPTION_HPP |
Definition at line 8 of file Exception.hpp.


The PWG meetings will be held on August 9-10, 2017 only via WebEx teleconference (Virtual F2F).
There is no registration fee or RSVP survey for this meeting.
To join the online meeting:
Call-in toll-free number (US/Canada): +1<PHONE_NUMBER>
Call-in toll number (US/Canada): +1<PHONE_NUMBER>
Call-in toll number (US/Canada): +1<PHONE_NUMBER>
Global toll-free call in numbers and other audio options ("Call Me Back" or VoIP) are listed once you join the WebEx meeting.
Attendee access code: Presented in the WebEx meeting
Note:All times are US Mountain Daylight Time ( UTC−06:00) - daylight savings time takes effect March 12, 2017 in the US.
Discussions at PWG face-to-face meetings are covered by the PWG Policy on Intellectual Property and Confidentiality - basically everything we discuss is non-confidential and can be included in an open standard.
| Date | Times | Description |
|---|---|---|
| August 9 | 10:00 AM to 11:00 AM | PWG Plenary |
| 11:00 PM to 11:30 AM | IPP WG : Status · Charter | |
| 11:30 AM to 12:00 PM | Break / Lunch | |
| 12:00 PM to 3:00 PM | IPP WG : IPP System Service | |
| August 10 | 10:00 AM to 11:30 AM | IPP WG : IPP Presets - Clean · Redline |
| 11:30 AM to 12:00 PM | Break / Lunch | |
| 12:00 PM to 1:00 PM | IPP WG : IPP Get-User-Printer-Attributes - Clean · Redline | |
| 1:00 PM to 2:00 PM | IPP WG : IPP Authentication Methods | |
| 2:00 PM to 3:00 PM | IPP WG : PWG / AMSC / ISO 3D · Next Steps |


1 reference to Xml
Microsoft.PowerShell.Commands.Utility (1)
commands\utility\XmlCommands.cs (1)
1029
foreach (XmlNode xmlNode in this.
Xml
)


Leadership
What is your experience of compassionate (or not) leadership?
Over time I have met quite a few team leads who all had different leadership styles. In the more recent past I have come across a number of very caring or compassionate team leads and it was a lot more easy to connect to them because you'd know they expect so much from you but would listen to various concerns within the team. They'd not quite be your friend outside work but as close to one as possible.
It's much easier to work with a leader that has your trust and your respect.
Multiplying goodness meditation
Breathe in goodness, multiply it by ten in your heart and breathe out more goodness. Feel the goodness of others around you.
I tried the multiplying goodness meditation and must admit it did not do much for me. My mind kept wandering off wanting to follow the bright white light. I will give it another try though.
 Then imagine sitting opposite yourself, breathe in the pain of whatever has been troubling you lately. Turn it to goodness in your heart and breathe out the goodness. Then move on to other people. Breathe in their pain and turn it into goodness in your heart. Breathe out goodness.
I really like the idea of this meditation. I have tried it only once so far and it definitely needs a lot more practice than that.
How does the SCARF model apply to your Phase 0 experience so far? How will it apply to bootcamp?
SCARF stands for Status, Certainty, Autonomy, Relatedness, and Fairness. You can influence people most effectively when you help them achieve what they want in a way that also helps you and simultaneously serves greater good. By understanding the social brain, you can better understand how your actions can increase the SCARF factors for yourself and others. Once you master that you can find ways to help people in ways that also align with your own interests and create win-win situations.
I have worked mostly on my own in Phase 0 but I think some of the things we learned in these early sprints will definitely help with self confidence because we are building a solid foundation to work from.
Understanding the social brain will be an invaluable skill to have when working closely with others, especially because bootcamp is a fairly short time to cram a lot of knowledge and projects into. By knowing how to best work with all kinds of personalities this should hopefully be smooth sailing.
Have a difficult conversation. How did it go? (It's a valuable skill, but can take practice to develop!)
- Walk through three conversations ("What happened?", "What emotions are involved", "What does this say about me?"
- Decide whether to raise the issue
- Start from the objective third story
- Explore their story and yours
- Problem solve
Having difficult conversations is really hard but the good thing is once you know what you want to communicate and you have brought an issue up, you often feel a lot better, especially if the conversation went well. I guess my last difficult conversation was pitching my idea of coming to Dev Academy and why this will be good for both my own development as well as for the company. The conversations went well and I am glad I made the pitch.
Any other musings?
The way to make a friend is to be one.


50% Labs
50% Exam
18 hours of labs (Fridays 15:00 - 18:00)
12 hours of lectures (Tuesdays 16:00 - 18:00)
50% Labs
work in pairs
Lab1 10%
Lab2 10%
Lab3 30%
50% Exam
No Labs this week 29/01/2020
Power Consumption!


module-info.java
Example:
module com.mycomp { exports com.mycomp.main to com.mycomp; }
After the quick-fix is applied the result looks like:
module main { }
This inspection only reports if the language level of the project or module is 9 or higher.


Medical Report is required.
Medical Report exeeds the maximum of
{{ MAX_CHARACTERS }} characters.
OutputYou can sort, filter and paginate the results in the table
below.rotate_90_degrees_ccw
Tip: Rotate your device to see the first two columns too!
Stats
Total sentences: {{ response.data.sentences.length }}


loop.proto
This module is intended to support prototype-based programming. It is basically provides functions to clone objects and inspect them. All members not defined in the cloned objects themselves are inherited dynamically from the respective prototype. Therefore, if the prototype changes, these changes are reflected in its clones.
clone
(proto [, clone])
proto
.
The metatable of the returned object shall not be modified as it is used internally by the module implementation.getproto
(object)
object
.
If object
is not a clone (i.e. a usual table) then nil
is returned.iscloneof
(clone, proto)
true
if clone
is a clone of proto
or false
otherwise.StackProto = {} function StackProto:empty() return #self == 0 end function StackProto:push(item) self[#self+1] = item end function StackProto:pop() if not self:empty() then local top = #self local item = self[top] self[top] = nil return item end end local oo = require "loop.proto" s = oo.clone(StackProto) s:push("Bottom") s:push("Middle") s:push("Top") print(s:pop()) --> Top print(s:pop()) --> Middle print(s:pop()) --> Bottom print(s:empty()) --> true
loop.base
This is the most basic of the class-based LOOP modules.
The base
module is ideal for definition of classes without super-classes.
class
([table])
table
defines a table that shall become the class.
If this parameter is not provided a new table is created to represent the class.
For more information about LOOP classes see <%=link("Basics.classes", "this")%>.getclass
(object)
object
.
If object
is not a LOOP class instance then its meta-table is returned.isinstanceof
(object, class)
true
if object
is an instance of class
or false
otherwise.isclass
(table)
true
if table
is a class or false
otherwise.getmember
(class, name)
name
defined in class class
.
Inherited members are ignored by this function.members
(class)
for
statement to iterate through all the members defined by the class.
The iteration variables hold the field name and value respectively.new
(class, ...)
rawnew
(class [, object])
object
an instance of class
without calling the <%=link("Basics.__new", "__new
")%> metamethod of the class.
If no object
is provided, a new table is created to represent the new instance.Queue = oo.class{ head = 1, tail = 1, } function Queue:empty() return self.head >= self.tail end function Queue:enqueue(item) local tail = self.tail self[tail] = item self.tail = tail+1 return item end function Queue:dequeue() if not self:empty() then local head = self.head local item = self[head] self[head] = nil self.head = head+1 return item end end q = Queue() q:enqueue("First") q:enqueue("Second") q:enqueue("Last") print(q:dequeue()) --> First print(q:dequeue()) --> Second print(q:dequeue()) --> Last print(q:empty()) --> true
loop.simple
This is another class-based module and it adds the possibility of defining classes with simple inheritance.
The class
function of the simple
module takes an optional second argument that defines the super-class of the class being created.
Additionally, the simple
module introduce the functions getsuper(class)
to retrieve the super-class of a given class and issubclassof(class, super)
to check whether a class is sub-class of other.
All from <%=link("Modules.base")%> module and (re)defines:
class
([table [, super]])
table
defines a table that shall become the class.
If this parameter is not provided a new table is created to represent the class.
The optional parameter super
defines the superclass of the returned class.
If this second parameter is not provided this function behaves as the class
function from the <%=link("Modules.base")%> module.getsuper
(class)
class
.
If class
is not a class of the module or does not define a super class then it returns nil
.issubclassof
(class, super)
true
if class
is a sub-class of super
or false
otherwise.Circle = oo.class() function Circle:diameter() return self.radius * 2 end function Circle:circumference() return self:diameter() * 3.14159 end function Circle:area() return self.radius * self.radius * 3.14159 end Sphere = oo.class({}, Circle) function Sphere:area() return 4 * self.radius * self.radius * 3.14159 end function Sphere:volume() return 4 * 3.14159 * self.radius^3 / 3 end function show(shape) print("Shape Characteristics") print(" Side: ", shape.radius) print(" Diameter: ", shape:diameter()) print(" Circumference:", shape:circumference()) print(" Area: ", shape:area()) if shape.volume ~= nil then print(" Volume: ", shape:volume()) end end c = Circle{ radius = 20.25 } s = Sphere{ radius = 20.25 } show(c) show(s)
loop.multiple
This module enables the definition of classes with multiple inheritance.
The class
function of the multiple
module takes a sequence of optional arguments that defines the set of super-classes of the class being defined.
The order of the super-classes provided defines the priority of field inheritance therefore the value of a inherited field is defined by the leftmost class that provides such field.
The multiple
module introduce the new function supers(class)
that returns an iterator used to iterate through the list of direct super-classes of a class.
Additionally, the getsuper(class)
function is changed so it returns all the super-classes of a given class.
All from <%=link("Modules.simple")%> module and (re)defines:
class
(table, ...)
table
defines a table that shall become the class.
If this parameter is not provided a new table is created to represent the class.
The additional parameters ...
defines all the superclasses of the returned class.
If less than two superclasses are provided this function behaves as the class
function from the <%=link("Modules.simple")%> module.getsuper
(class)
class
.
If class
does not define a super-class it returns nil
.supers
(class)
for
statement to interate over all super-classes of the class class
.Contained = oo.class{} function Contained:__new(object) assert(object, "no object supplied") assert(object.name, "no name for object") assert(object.container, "no container for object") object.container:add(object.name, object) return oo.rawnew(self, object) end Container = oo.class{} function Container:__new(object) object = object or {} object.members = object.members or {} return oo.rawnew(self, object) end function Container:add(name, object) self.members[name] = object end function Container:search(path) local container, newpath = string.match(path, "(.-)/(.+)$") if container then container = self.members[container] if container and container.search then return container:search(newpath) end else return self.members[path] end end ContainedContainer = oo.class({}, Contained, Container) function ContainedContainer:__new(object) object = Contained.__new(self, object) object = Container.__new(self, object) return object end Root = Container{} Folder = ContainedContainer{ container = Root, name = "my_folder", } File = Contained{ container = Folder, name = "my_file.txt", data = "Hello, I'm a file" } print(Root:search("my_folder/my_file.txt").data) --> Hello, I'm a file
loop.cached
Classes created with modules <%=link("Modules.simple")%> and <%=link("Modules.multiple")%> behave like clones of their superclasses in the sense they always consult the superclasses to retrieve fields they don't have.
In order to avoid the search through the complete hierarchy of classes every time a class field is indexed, LOOP provides the cached
module.
In this module, classes copy the fields defined by their super-classes to themselves (i.e. meta-table).
This cache of inherited fields makes instances of classes with simple or multiple inheritance as efficient as classes of the <%=link("Modules.base")%> module.
Other advantage of the cache module is that meta-methods like the __index
can be shared across the hierarchy of classes because they are copied to each class (i.e. meta-table).
Currently, Lua ignores the __index
when accessging the fields of meta-tables (see the Lua manual).
On the other hand, to properly update the cache of inherited fields whenever a class is changed, the classes of this module are manipulated through proxies.
These proxies intercept any changes and update all caches of inherited field through out the entire class hierarchy.
This indirection makes class operation more expensive than in other modules where classes are simple meta-tables.
All functions of the cached
module manipulates proxies of actual classes.
The cached
module introduces the new function allmembers
that return an iterator for all members provided by a class, including the inherited ones.
All from <%=link("Modules.multiple")%> module and (re)defines:
allmembers
(class)
for
statement to interate over all members provided by the class class
, including the inherited ones.
The iteration variables hold the field name and value respectively.CachedObject = oo.class() function CachedObject:__index(field) local value = oo.classof(self)[field] if value then rawset(self, field, value) end return value end CachedSphere = oo.class({}, CachedObject, Sphere) s = CachedSphere{ radius = 2 } show(s) print("Object fields:") for field, value in pairs(s) do print("", field, value) end
loop.scoped
This module provides features to define classes with private and protected access scopes.
Each class of scoped
module can provide a definition of a private behavior that will be perceived only by methods defined in that class and a protected behavior that will be perceived only by the methods of the object, i.e. will not be seen by functions not defined by some class inherited by the object.
The private and protected behaviors are defined by fields private
and protected
that must contain tables defining the fields presented by the private or protected scope of the instances of that class.
All the other fields are publicly available.
The fields publicly available are also available in the private and the protected scopes.
Similarly, the fields available in the protected scope are also visible in the private scope.
The scope management is done by replacing the self reference in the calls of instance methods.
Therefore, in every call of a method the self is replaced by the proper scoped state object.
The mapping of the private and protected scoped state of each object instance is automatically made by the scoped
module.
Additionally, the creation of the scoped states is done on demand, so such states are only created at invocation of methods defined in classes that defines private or protected states.
The scoped
module was mainly devised for applications with objects written in Lua that must protect some internal state from unexpected accesses, like bad user script code or third-party interacting components that may not know or care about the internal object implementation.
Unfortunately, the management of such scoped states is extremely expensive both in terms of memory and processing time when compared to other modules.
Therefore, the scoped
module should only be used in applications that actually need such infrastructure.
Even though it is a hard task to provide arbitrary private and protected state in a programming model similar to the one used when applying an object-oriented style to Lua, there are many alternatives to implement objects with private state in Lua.
Such alternatives include the use of function closures as objects with private state stored in upvalues. On the other hand, the scoped
module may be used for prototyping and experimental applications used as proof of concept.
All from <%=link("Modules.cached")%> module and (re)defines:
priv
(object [, class])
object
relative to class class
. This object
can be any self
of a scoped object, i.e. the private, procetected or even public state. If no class
is provided then the actual object class is used.prot
(object)
object
. This object
can be any self
of a scoped object, i.e. the private, procetected or even public state.this
(object)
object
. This object
can be any self
of a scoped object, i.e. the private, procetected or even public state.SQLTable = oo.class{ private = { SQLTemplate = [[ SELECT * FROM %s WHERE %s = '%s' ]], }, } function SQLTable:__new(database, tablename, keyfield) self = oo.rawnew(self) rawset(oo.priv(self), "db", database) rawset(oo.priv(self), "table", tablename) rawset(oo.priv(self), "key", keyfield) return self end function SQLTable:__index(keyvalue) local sql = self.SQLTemplate:format(self.table, self.key, keyvalue) return self.db:query(sql)[1] end People = SQLTable(MySQLDB, "People", "Name") print(People["John Doe"].Age)
loop.classops
This module provides generic functions for manipulation of classes that follow a basic model adopted by all LOOP modules as described <%=link("Classes.classops", "here")%>.
This module is only required when you manipulate classes created wiht different LOOP modules in a single application.
This module does not provide a class
function to create classes.
Use other modules to create classes.
All from <%=link("Modules.multiple")%> module, except function <%=link("Modules.base.class")%>.
base = require "loop.base" simple = require "loop.simple" multiple = require "loop.multiple" cached = require "loop.cached" A = base.class() B = simple.class() C = multiple.class() D = cached.class() oo = require "loop.classops" print(oo.isclass(A)) --> true print(oo.isclass(B)) --> true print(oo.isclass(C)) --> true print(oo.isclass(D)) --> true
loop.hierarchy
This module provides functions to implement initialization mechanisms of instances of complex class hierarchies (like Java or C++ constructors) using the infrastructure provided by the <%=link("Basics.__new", "__new
")%> metamethod.
For more information on different initialization approaches see section <%=link("Classes.__init")%>.
creator
(class [, ...])
class
and calls method __init
of this instance with the given arguments and return this new instance.mutator
(class [, object [, ...]])
object
into an instance of class class
and returns it.
It also calls method __init
defined in each of the classes of the returned object.topdown
(class)
for
to iterate over all the class hierarchy of class
in top-down order.loop.scoped.debug
This module provides functions to inspect methods of classes created with the <%=link("Modules.scoped")%> module. The methods of such classes has references to the class they are defined that can be inspected using the <%=link("LuaManual.DebugLib")%>.
methodfunction
(method)
method
.methodclass
(method)
method
was defined.table = require "table" oo = require "loop.scoped" ood = require "loop.scoped.debug" Array = oo.class{ insert = table.insert, remove = table.remove, } a = Array{ 1,2,3 } assert(a.insert ~= table.insert) assert(ood.methodfunction(a.insert) == table.insert) assert(ood.methodclass(a.insert) == Array)
loop.table
This module provides functions to copy table fields, clear table fields and also a function to create memoize tables.
copy
(source [, destiny])
source
to table destiny
and returns the later.
If destiny
is nil
a new empty table is used instead.clear
(table)
table
and returns this table.memoize
(func [, weak])
func
.
Every time a new value is used to index the memoize table the function func
is invoked with the indexed value as parameter.
If the result of the invocation produces a value different from nil
this value is stored in the memoize table, so the next time the same value is indexed the stored value is produced without calling function func
again.
Parameter mode
indicates the weakness of the memoize table, as defined for field <%=link("LuaManual.WeakTables", "__mode
")%> of metatables.table = require "loop.table" chunkOf = table.memoize(loadstring, "v") f = chunkOf[ 'print "Hello, World!"' ] f() --> Hello, World!


Your saved advice
The below advice has been sent to<EMAIL_ADDRESS>from FirstName SurName. You can click directly on the links to take you back to the advice on the website.
Applying for ESA
Applying for ESA
Applying for ESA
Support our campaign to tell Government to make ESA #fitforwork.


Follow me on twitter
this website is under construction
We are estimating to be back in
Latest update news
2009.09.15 -
The mockup is ready for coding
2009.08.01 -
Updated the blog section
2009.09.20 -
Frontpage coded


My favorite things
These are a few of my favorite things!
First will be Music...
Here is one of my favorite bands
- Queen
- Freddie Mercury
- Brian May
- Roger Taylor
- Marcel Nogueira, The Legend
- Here are my top three albums by Queen in order:
- A Night At The Opera
- News Of The World
- The Game
Second will be food...
These are my three favorites, in order:
- Nachos
- Pizza
- Pão de queijo(Brazilian Food)
I also like to visit cool websites...
Here are some of them:
- This is an unknown page called Wikipedia, I've heard it's pretty good...
- They told me you can find everthing about everthing in this page!
- Please visit CSS ZenGarden to see the beautiful world of CSS...
- The power of CSS will blow your mind!
- Check out Epicodus if you want to learn programming...
- The last person who used this website to learn how to program became a ninja... Seriously!
Thanks for reading about me!


Generic Models¶
You just need to add to your template to get the behaviors below. Use as many models as you want.
CodeModel¶
Model with a code field that automatically generates a hash of 16 characters by default. Useful to identify your record in a more humane way
Usage:
class YourModel(CodeModel)
...
SerializerModel¶
Model with serialize method making possible serializer your instance data returning a dict.
Usage:
from django_models.models import SerializerModel
...
class YourModel(SerializerModel)
name = models.CharField(max_length=255)
...
Example of a instance from a Model using the SerializerModel
instance.serialize()
{
'id': 1,
'name': 'Test'
}
SlugModel¶
Model with a slug field. Useful to use in urls or nominal references
Usage:
class YourModel(SlugModel)
...
TimestampedModel¶
Model with created_at and updated_at fields to let you know when your instance wore created and updated
Usage:
from django_models.models import TimestampedModel
...
class YourModel(TimestampedModel)
...
UUIDModel¶
Model that uses the id field as a UUID. Useful to be able to have a unique identifier without worrying about sequences.
Usage:
from django_models.models import UUIDModel
...
class YourModel(UUIDModel)
...


AsyncFile
AsyncResult
Buffer
Container
EventBus
ExceptionSupport
FileSystem
FileSystemProps
HttpClient
HttpClientRequest
HttpClientResponse
HttpServer
HttpServerFileUpload
HttpServerRequest
HttpServerResponse
Message
MultiMap
NetClient
NetServer
NetSocket
Pump
ReadStream
RecordParser
RouteMatcher
ServerWebSocket
SockJSServer
SockJSSocket
TestUtils
Verticle
Vertx
VertxTests
WebSocket
WriteStream
|


The R package azmpdata provides a series of data products derived from raw data collected as part of the Atlantic Zone Monitoring Program (AZMP). The data products provided in this package are used to generate the different figures contained in the Research Documents produced annually by Fisheries and Ocean Canada’s Maritimes region. The Research Documents describe the physical, chemical and biological conditions observed in Maritimes region since the inception of the AZMP program (see example documents for the physical conditions and for the optical, chemical and biological conditions).
The azmpdata R package can be installed from GitHub with:
# install.packages("devtools")
devtools::install_github("casaultb/azmpdata")
The azmpdata package provides three types of data products: physical, chemical and biological variables, which are summarized below. Each data product is organized into a data table by temporal and regional scale and category.
To access a dataset in data frame format:
library(azmpdata)
#>
#> casaultb/azmpdata status:
#> (Package ver: 0.2019.0.9000) Up to date
#> (Data ver:2020-11-26) is up to date
data("Derived_Annual_Broadscale")
head(Derived_Annual_Broadscale)
#> year area density_gradient_0_50 temperature_at_sea_floor
#> 1 1948 Scotion Shelf -0.00139 NA
#> 2 1949 Scotion Shelf -0.00968 NA
#> 3 1950 Scotion Shelf -0.01883 NA
#> 4 1951 Scotion Shelf -0.00092 NA
#> 5 1952 Scotion Shelf 0.00155 NA
#> 6 1953 Scotion Shelf -0.00313 NA
#> cold_intermediate_layer_volume minimum_temperature_in_cold_intermediate_layer
#> 1 <NA> <NA>
#> 2 <NA> <NA>
#> 3 <NA> <NA>
#> 4 <NA> <NA>
#> 5 <NA> <NA>
#> 6 <NA> <NA>
To access a dataset in csv format:
system.file("extdata/csv", "Derived_Annual_Broadscale.csv", package = "azmpdata")
#> [1] "C:/Users/ChisholmE/Documents/R/R-4.0.2/library/azmpdata/extdata/csv/Derived_Annual_Broadscale.csv"
Each table contains multiple variables, which fall under the temporal and regional scale in a particular category. The example shown above includes derived variables at an annual scale for broad regions (eg. Scotian Shelf or Gulf of Maine). Variables can be found via the search function variable_lookup()
, which allows a user to search by variable name or keyword. For more information see ?variable_lookup
. This function searches through variable names and (optionally) help files from each dataset including metadata and variable definitions.
Although the main goal of azmpdata is to provide easy access to a variety of data products, the package also supports a few basic functions for which examples are shown below.
A custom search function has been developed in order to allow users to find specific data. The function variable_lookup()
can be used to search through variable names in all azmpdata
dataframes. Using the argument search_help
, this function can also search through all the help text for package data. A sample use of this search function may look as below:
res <- variable_lookup(keywords = c('nitrate', 'phosphate'), search_help = TRUE)
#> Joining, by = c("keyword", "variable", "dataframe")
head(res)
#> # A tibble: 6 x 3
#> keyword variable dataframe
#> <chr> <chr> <chr>
#> 1 nitrate integrated_nitrate_0_50 Derived_Annual_Sections
#> 2 nitrate integrated_nitrate_0_50 Derived_Annual_Stations
#> 3 nitrate integrated_nitrate_0_50 Derived_Occupations_Sections
#> 4 nitrate integrated_nitrate_50_150 Derived_Annual_Sections
#> 5 nitrate integrated_nitrate_50_150 Derived_Annual_Stations
#> 6 nitrate integrated_nitrate_50_150 Derived_Occupations_Sections


<Next version of Ox>
<Previous version of Ox>
Ox 2.10: new features and fixes
New features and enhancements
- Created iseq().
Now can use isfeq() for case-insensitive
string comparison. Also created strifind()
as case-insensitive version of strfind().
- "aa"+"bb" is now the same as "aa"~"bb"
- Allowing k x T input for:
DrawCorrelogram(),
DrawBoxPlot(),
DrawSpectrum(),
DrawQQ(),
DrawDensity()
Also created 2 argument Draw() function.
- created:
Database::Load,
Sample::GetFrequency, and
Database::RemoveObsIf,
- Modelbase class
- Read Stata 4-6 .dta files (loadmat,
Database::LoadDta)
- The comma in a matrix constant to seperate elements within
a row was made optional in Ox 2.00. However, this could lead to
to errors which are difficult to find, and has been made compulsary again.
- Other new and enhanced functions:
- assignment of array to part of array (i.e. using selection on right-hand side)
now uses array contents of rhs.
Previously, when both as1 and as 2 are arrays (of strings e.g.)
as1[0:1] = as2
was executed as
as1[0] = as2, as1[1] = as2;
thus going up one array level in as1[0] and as1[1].
Now it is executed as:
as1[0] = as2[0], as1[1] = as2[1];
thus preserving the array level in as1.
Known problems in version 2.00a which are fixed in version 2.10:
- assignment using one index on the left-hand side doesn't
works as expected when the lhs is indexed as row (or column) and
the right-hand side is a column (or row). For example:
decl vp = <1;2;3;4>;
vp[0:1] = <-1,-2>; // WRONG!
vp[0:1] = <-1;-2>; // OK
The first should set vp to -1;-2;3;4, but only did -1;2;3;4.
- OxRun: GiveWin keeps grabbing focus when a new window is specified.
Now this is only happening the first time; the window is brought
to the foreground within GiveWin after SetTextWindow/SetDrawWindow, but
GiveWin grabs focus only first time.
- <0.1;0.7;> would lead to an infite loop of error messages.
Now the trailing semicolon or colon is allowed.
- Error in PcFimlDgp.ox prevented use of more than one lag.
- Small improvement to XLS reading.
Also fixed problem with large negative numbers
(which were mapped to an integer by Excel).
- In rare occasions concatenation with a NULL string would lead to a crash.
- Database::Remove() did not remove the variable name.
- invertgen(x, 0) is wrong if x is not square.
- Bug in NumJacobian(): dimensions of returned matrix are wrong.
-
Problem with scanning from a string:
sscan(&s, ...) doesn't advance string correctly, resulting in a crash.
sscan(s, ...) only works for first scanned element
(again, the string location is not moved forward before reading
the second element). As a consequence, the example on page 187
will not work.
-
sortbyc() when sorting by multiple columns is likely
to go wrong. The only version which works is
when the sort column indices are of the form: 0,1,2,...
(i.e. starting at 0, and consecutive range).
Known problems in version 2.00 which were fixed in version 2.00a:
- There is a problem with using [] directly on the return value
of a function when the function returns an array. Also when a function
returns part of an array which resides in a local variable. For example:
func1()
{ return {"a", "b"};
}
print(func1()[1]);
func2()
{ decl x = {"a", "b"};
return x[0:1];
}
print(func2());
In the first case x=func1() is fine. In the second case,
assigning x[0:1] to a local variable which is then returned
works without problems.
- Saving as in7: base name with more than 12 chars causes problems
(when trying to derive default project name) and could result in a crash.
Can be avoided by using a base name (ie. file name without path and extension)
with fewer than 13 characters.
- a[0][x] * b[x][1] crashes, but only when the first dimension
of a is 0 and the second dimension of b is 1.
- Problem with reassigning different zero sized matrix. For example:
decl x = zeros(0,5);
println(rows(x), " x ", columns(x));
x = zeros(0,6);
println(rows(x), " x ", columns(x));
prints:
0 x 5
0 x 5
but should be
0 x 5
0 x 6
Ox version 2.10. This file last changed 26-Feb-1999.
© JA Doornik
<Doornik home>


An input that display and edit a time, as the timepicker from angular ui bootstrap but plugged to a moment or a string.
Supports min/max, binded to the $scope. If your min or max changes, the input is notified and will work accordingly. Feature not present for the ui bootstrap timepicker as of version 0.13.4.
Supports the change of day, meaning you can set the min to today 8AM and max to tomorrow 2 AM and the input will accept any time from 08:00 to 02:00.
Supports up and down key events and scroll event to increment/decrement the value.
Supports an format
argument if you don't want to bind to a moment but to a string.
ng-model
: the variable to bind tong-change
: events to launch when the value is updatedis-disabled
: to enable or disable the inputformat
: "'HH:mm:ss'" for example, if your value is a string and you still want to use the component
<luid-moment ng-model="myValue"></luid-moment> <luid-moment ng-model="myValue" format="'HH:mm:ss'"></luid-moment>


Definition of a simple key:
You are given this string:
Find a 3+ character string that when combined with the given string (AABBB+), the final string will appear in its own sha256 digest


If the administrator allows selected users to manage the database, he will have to manage the users database, which will store at least the login and password of the users
How do we add these functions to our web site ? Just by adding another line, to specify the security level. Go back to the configuration file (booksConfig.py
) and add this third line :
Once you have saved this new version of booksConfig.py
, follow the same steps as previously with makeScript.py
. The program will ask you to choose the configuration file as before, but it will then ask you to enter a login and a password for the site administrator
Once this is done (you must enter a login, and the password must have at least 6 characters), in your web browser, reload the page http://localhost/instant_site/books.ks
There are two differences with the previous version : the links "Edit" and "Remove" have disappeared, and there is a link called "Login". Click on it and you will be asked to enter a login and a password. At this stage, if you enter any value you like, you will get an error message : no user has been defined so far
So, how do you manage the users base ? In the address bar, replace the end of the url, index
, by admin
. This will open a dialog box asking you to enter a login and a password
Enter the data you have chosen previously (homer / simpson
in my example). This allows you access to the same interface as for the books page, but here you can enter users with their login and password. The users base is empty, add a record with a login and password of your choice, for instance :
Now back to the books page (http://localhost/instant_site/books.ks
), log in with the values you have just entered and you will see this page :
Now you can manage the books database as you like. If you log out, you go back to the visitor status, only able to see the books list
In the next step we'll add more options to the configuration file