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Xtandi 40mg soft capsules
Last Updated on eMC 17-May-2016 View changes | Astellas Pharma Ltd Contact details
- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions.
PosologyThe recommended dose is 160 mg enzalutamide (four 40 mg capsules) as a single oral daily dose.Medical castration with an LHRH analogue should be continued during treatment of patients not surgically castrated.If a patient misses taking Xtandi at the usual time, the prescribed dose should be taken as close as possible to the usual time. If a patient misses a dose for a whole day, treatment should be resumed the following day with the usual daily dose.If a patient experiences a ≥ Grade 3 toxicity or an intolerable adverse reaction, dosing should be withheld for one week or until symptoms improve to ≤ Grade 2, then resumed at the same or a reduced dose (120 mg or 80 mg) if warranted.Concomitant use with strong CYP2C8 inhibitorsThe concomitant use of strong CYP2C8 inhibitors should be avoided if possible. If patients must be co-administered a strong CYP2C8 inhibitor, the dose of enzalutamide should be reduced to 80 mg once daily. If co-administration of the strong CYP2C8 inhibitor is discontinued, the enzalutamide dose should be returned to the dose used prior to initiation of the strong CYP2C8 inhibitor (see section 4.5).
Older peopleNo dose adjustment is necessary for older people (see section 5.1 and 5.2).
Hepatic impairmentNo dose adjustment is necessary for patients with mild, moderate or severe hepatic impairment (Child-Pugh Class A, B or C, respectively). An increased drug half-life has however been observed in patients with severe hepatic impairment (see section 4.4 and 5.2).
Renal impairmentNo dose adjustment is necessary for patients with mild or moderate renal impairment (see section 5.2). Caution is advised in patients with severe renal impairment or end-stage renal disease (see section 4.4).Paediatric populationThere is no relevant use of enzalutamide in the paediatric population in the indication of treatment of adult men with metastatic castration-resistant prostate cancer.
Method of administrationXtandi is for oral use. The capsules should be swallowed whole with water, and can be taken with or without food.
Risk of seizureCaution should be used in administering Xtandi to patients with a history of seizures or other predisposing factors including, but not limited to, underlying brain injury, stroke, primary brain tumours or brain metastases, or alcoholism. In addition, the risk of seizure may be increased in patients receiving concomitant medicinal products that lower the seizure threshold.
Posterior reversible encephalopathy syndromeThere have been rare reports of posterior reversible encephalopathy syndrome (PRES) in patients receiving Xtandi (see section 4.8). PRES is a rare, reversible, neurological disorder which can present with rapidly evolving symptoms including seizure, headache, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably magnetic resonance imaging (MRI). Discontinuation of Xtandi in patients who develop PRES is recommended.
Concomitant use with other medicinal productsEnzalutamide is a potent enzyme inducer and may lead to loss of efficacy of many commonly used medicinal products (see examples in section 4.5). A review of concomitant medicinal products should therefore be conducted when initiating enzalutamide treatment. Concomitant use of enzalutamide with medicinal products that are sensitive substrates of many metabolising enzymes or transporters (see section 4.5) should generally be avoided if their therapeutic effect is of large importance to the patient, and if dose adjustments cannot easily be performed based on monitoring of efficacy or plasma concentrations.Co-administration with warfarin and coumarin-like anticoagulants should be avoided. If Xtandi is co-administered with an anticoagulant metabolised by CYP2C9 (such as warfarin or acenocoumarol), additional International Normalised Ratio (INR) monitoring should be conducted (see section 4.5).
Renal impairmentCaution is required in patients with severe renal impairment as enzalutamide has not been studied in this patient population.
Severe hepatic impairmentAn increased drug half-life has been observed in patients with severe hepatic impairment, possibly related to increased tissue distribution. The clinical relevance of this observation remains unknown. A prolonged time to reach steady state concentrations is however anticipated, and the time to maximum pharmacological effect as well as time for onset and decline of enzyme induction (see section 4.5) may be increased.
Recent cardiovascular diseaseThe phase 3 studies excluded patients with recent myocardial infarction (in the past 6 months) or unstable angina (in the past 3 months), New York Heart Association Class (NYHA) III or IV heart failure except if Left Ventricular Ejection Fraction (LVEF) ≥ 45%, bradycardia or uncontrolled hypertension. This should be taken into account if Xtandi is prescribed in these patients.
Androgen deprivation therapy may prolong the QT intervalIn patients with a history of or risk factors for QT prolongation and in patients receiving concomitant medicinal products that might prolong the QT interval (see section 4.5) physicians should assess the benefit risk ratio including the potential for Torsade de pointes prior to initiating Xtandi.
Use with chemotherapyThe safety and efficacy of concomitant use of Xtandi with cytotoxic chemotherapy has not been established. Co-administration of enzalutamide has no clinically relevant effect on the pharmacokinetics of intravenous docetaxel (see section 4.5); however, an increase in the occurrence of docetaxel-induced neutropenia cannot be excluded.
ExcipientsXtandi contains sorbitol (E420). Patients with rare hereditary problems of fructose intolerance should not take this medicinal product.
Hypersensitivity reactionsHypersensitivity reactions manifested by symptoms including, but not limited to, tongue oedema, lip oedema and pharyngeal oedema have been observed with enzalutamide (see section 4.8).
Potential for other medicinal products to affect enzalutamide exposures
CYP2C8 inhibitorsCYP2C8 plays an important role in the elimination of enzalutamide and in the formation of its active metabolite. Following oral administration of the strong CYP2C8 inhibitor gemfibrozil (600 mg twice daily) to healthy male subjects, the AUC of enzalutamide increased by 326% while Cmax of enzalutamide decreased by 18%. For the sum of unbound enzalutamide plus the unbound active metabolite, the AUC increased by 77% while Cmax decreased by 19%. Strong inhibitors (e.g. gemfibrozil) of CYP2C8 are to be avoided or used with caution during enzalutamide treatment. If patients must be co-administered a strong CYP2C8 inhibitor, the dose of enzalutamide should be reduced to 80 mg once daily (see section 4.2).
CYP3A4 inhibitorsCYP3A4 plays a minor role in the metabolism of enzalutamide. Following oral administration of the strong CYP3A4 inhibitor itraconazole (200 mg once daily) to healthy male subjects, the AUC of enzalutamide increased by 41% while Cmax was unchanged. For the sum of unbound enzalutamide plus the unbound active metabolite, the AUC increased by 27% while Cmax was again unchanged. No dose adjustment is necessary when Xtandi is co-administered with inhibitors of CYP3A4.
CYP2C8 and CYP3A4 inducersFollowing oral administration of the moderate CYP2C8 and strong CYP3A4 inducer rifampin (600 mg once daily) to healthy male subjects, the AUC of enzalutamide plus the active metabolite decreased by 37% while Cmax remained unchanged. No dose adjustment is necessary when Xtandi is co-administered with inducers of CYP2C8 or CYP3A4.
Potential for enzalutamide to affect exposures to other medicinal products
Enzyme inductionEnzalutamide is a potent enzyme inducer and increases the synthesis of many enzymes and transporters; therefore, interaction with many common medicinal products that are substrates of enzymes or transporters is expected. The reduction in plasma concentrations can be substantial, and lead to lost or reduced clinical effect. There is also a risk of increased formation of active metabolites. Enzymes that may be induced include CYP3A in the liver and gut, CYP2B6, CYP2C9, CYP2C19, and uridine 5'-diphospho-glucuronosyltransferase (UGTs - glucuronide conjugating enzymes). The transport protein P-gp may also be induced, and probably other transporters as well, e.g. multidrug resistance-associated protein 2 (MRP2), breast cancer resistance protein (BCRP) and the organic anion transporting polypeptide 1B1 (OATP1B1).In vivo studies have shown that enzalutamide is a strong inducer of CYP3A4 and a moderate inducer of CYP2C9 and CYP2C19. Co-administration of enzalutamide (160 mg once daily) with single oral doses of sensitive CYP substrates in prostate cancer patients resulted in an 86% decrease in the AUC of midazolam (CYP3A4 substrate), a 56% decrease in the AUC of S-warfarin (CYP2C9 substrate), and a 70% decrease in the AUC of omeprazole (CYP2C19 substrate). UGT1A1 may have been induced as well. In a clinical study in patients with metastatic CRPC, Xtandi (160 mg once daily) had no clinically relevant effect on the pharmacokinetics of intravenously administered docetaxel (75 mg/m2 by infusion every 3 weeks). The AUC of docetaxel decreased by 12% [geometric mean ratio (GMR) = 0.882 (90% CI: 0.767, 1.02)] while Cmax decreased by 4% [GMR = 0.963 (90% CI: 0.834, 1.11)]. Interactions with certain medicinal products that are eliminated through metabolism or active transport are expected. If their therapeutic effect is of large importance to the patient, and dose adjustments are not easily performed based on monitoring of efficacy or plasma concentrations, these medicinal products are to be avoided or used with caution. The risk for liver injury after paracetamol administration is suspected to be higher in patients concomitantly treated with enzyme inducers. Groups of medicinal products that can be affected include, but are not limited to:• Analgesics (e.g. fentanyl, tramadol)• Antibiotics (e.g. clarithromycin, doxycycline)• Anticancer agents (e.g. cabazitaxel)• Anticoagulants (e.g. acenocoumarol, warfarin)• Antiepileptics (e.g. carbamazepine, clonazepam, phenytoin, primidone, valproic acid)• Antipsychotics (e.g. haloperidol)• Betablockers (e.g. bisoprolol, propranolol)• Calcium channel blockers (e.g. diltiazem, felodipine, nicardipine, nifedipine, verapamil)• Cardiac glycosides (e.g. digoxin)• Corticosteroids (e.g. dexamethasone, prednisolone)• HIV antivirals (e.g. indinavir, ritonavir)• Hypnotics (e.g. diazepam, midazolam, zolpidem)• Statins metabolized by CYP3A4 (e.g. atorvastatin, simvastatin)• Thyroid agents (e.g. levothyroxine)The full induction potential of enzalutamide may not occur until approximately 1 month after the start of treatment, when steady-state plasma concentrations of enzalutamide are reached, although some induction effects may be apparent earlier. Patients taking medicinal products that are substrates of CYP2B6, CYP3A4, CYP2C9, CYP2C19, or UGT1A1 should be evaluated for possible loss of pharmacological effects (or increase in effects in cases where active metabolites are formed) during the first month of enzalutamide treatment, and dose adjustment should be considered as appropriate. In consideration of the long half-life of enzalutamide (5.8 days, see section 5.2), effects on enzymes may persist for one month or longer after stopping enzalutamide. A gradual dose reduction of the concomitant medicinal product may be necessary when stopping enzalutamide treatment.
CYP1A2 and CYP2C8 substratesEnzalutamide (160 mg once daily) did not cause a clinically relevant change in the AUC or Cmax of caffeine (CYP1A2 substrate) or pioglitazone (CYP2C8 substrate). The AUC of pioglitazone increased by 20% while Cmax decreased by 18%. The AUC and Cmax of caffeine decreased by 11% and 4% respectively. No dose adjustment is indicated when a CYP1A2 or CYP2C8 substrate is co-administered with Xtandi.
P-gp substratesIn vitro data indicate that enzalutamide may be an inhibitor of the efflux transporter P-gp. The effect of enzalutamide on P-gp substrates has not been evaluated in vivo; however, under conditions of clinical use, enzalutamide may be an inducer of P-gp via activation of the nuclear pregnane receptor (PXR). Medicinal products with a narrow therapeutic range that are substrates for P-gp (e.g. colchicine, dabigatran etexilate, digoxin) should be used with caution when administered concomitantly with Xtandi and may require dose adjustment to maintain optimal plasma concentrations.
BCRP, MRP2, OAT3 and OCT1 substratesBased on in vitro data, inhibition of BCRP and MRP2 (in the intestine), as well as organic anion transporter 3 (OAT3) and organic cation transporter 1 (OCT1) (systemically) cannot be excluded. Theoretically, induction of these transporters is also possible, and the net effect is presently unknown.
Medicinal products which prolong the QT intervalSince androgen deprivation treatment may prolong the QT interval, the concomitant use of Xtandi with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de pointes such as class IA (e.g. quinidine, disopyramide) or class III (e.g. amiodarone, sotalol, dofetilide, ibutilide) antiarrhythmic medicinal products, methadone, moxifloxacin, antipsychotics, etc. should be carefully evaluated (see section 4.4).
Effect of food on enzalutamide exposuresFood has no clinically significant effect on the extent of exposure to enzalutamide. In clinical trials, Xtandi was administered without regard to food.
Women of childbearing potentialThere are no human data on the use of Xtandi in pregnancy and this medicinal product is not for use in women of childbearing potential.
Contraception in males and femalesIt is not known whether enzalutamide or its metabolites are present in semen. A condom is required during and for 3 months after treatment with enzalutamide if the patient is engaged in sexual activity with a pregnant woman. If the patient engages in sexual intercourse with a woman of childbearing potential, a condom and another form of birth control must be used during and for 3 months after treatment. Studies in animals have shown reproductive toxicity (see section 5.3).
PregnancyEnzalutamide is not for use in women. Enzalutamide is contraindicated in women who are or may become pregnant (see sections 4.3 and 5.3).
Breast-feedingEnzalutamide is not for use in women.
FertilityAnimal studies showed that enzalutamide affected the reproductive system in male rats and dogs (see section 5.3).
Summary of the safety profileThe most common adverse reactions are asthenia/fatigue, hot flush, headache, and hypertension. Other important adverse reactions include falls, nonpathologic fractures, cognitive disorder, and neutropenia. Seizure occurred in 0.5% of enzalutamide-treated patients, 0.1% of placebo-treated patients, and 0.3% in bicalutamide-treated patients.Rare cases of posterior reversible encephalopathy syndrome have been reported in enzalutamide-treated patients (see section 4.4).
Tabulated summary of adverse reactionsAdverse reactions observed during clinical studies are listed below by frequency category. Frequency categories are defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
|Table 1: Adverse reactions identified in controlled clinical trials and post-marketing
|MedDRA System organ class
|Blood and lymphatic system disorders
|uncommon: leucopenia, neutropenia not known*: thrombocytopenia
|Immune system disorders
|not known*: tongue oedema, lip oedema, pharyngeal oedema
|General disorders
|very common: asthenia/fatigue
|Psychiatric disorders
|common: anxiety uncommon: visual hallucinations
|Nervous system disorders
|very common: headache common: memory impairment, amnesia, disturbance in attention, restless legs syndrome uncommon: cognitive disorder, seizure not known*: posterior reversible encephalopathy syndrome
|Cardiac disorders
|not known*: QT-prolongation (see sections 4.4 and 4.5)
|Reproductive system and breast disorder
|common: gynaecomastia
|Vascular disorders
|very common: hot flush, hypertension
|Gastrointestinal disorders
|not known*: nausea, vomiting, diarrhoea
|Skin and subcutaneous tissue disorders
|common: dry skin, pruritus not known*: rash
|Musculoskeletal and connective tissue disorders
|common: fractures** not known*: myalgia, muscle spasms, muscular weakness, back pain
|Injury, poisoning and procedural complications
|common: falls
Description of selected adverse reactions
SeizureIn controlled clinical studies, 10 patients (0.5%) experienced a seizure out of 2051 patients treated with a daily dose of 160 mg enzalutamide, whereas one patient (<0.1%) receiving placebo and one patient (0.3%) receiving bicalutamide experienced a seizure. Dose appears to be an important predictor of the risk of seizure, as reflected by preclinical data, and data from a dose-escalation study. In the controlled clinical studies, patients with prior seizure or risk factors for seizure were excluded.In the AFFIRM trial, six patients (0.8%) experienced a seizure out of 800 post-chemotherapy patients treated with a daily dose of 160 mg enzalutamide, whereas no seizures occurred in patients receiving placebo. Potentially contributing factors were present in several of these patients that may have independently increased their risk of seizure. In the PREVAIL trial, one patient (0.1%) out of 871 chemotherapy-naive patients treated with a daily dose of 160 mg enzalutamide, and one patient (0.1%) receiving placebo experienced a seizure. In bicalutamide-controlled trials, 3 patients (0.8%) out of 380 chemotherapy-naïve patients treated with enzalutamide and 1 patient (0.3%) out of 387 receiving bicalutamide experienced a seizure.The mechanism by which enzalutamide may lower the seizure threshold is not known, but could be related to data from in vitro studies showing that enzalutamide and its active metabolite bind to and can inhibit the activity of the GABA-gated chloride channel.
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
Mechanism of actionProstate cancer is known to be androgen sensitive and responds to inhibition of androgen receptor signalling. Despite low or even undetectable levels of serum androgen, androgen receptor signalling continues to promote disease progression. Stimulation of tumour cell growth via the androgen receptor requires nuclear localization and DNA binding. Enzalutamide is a potent androgen receptor signalling inhibitor that blocks several steps in the androgen receptor signalling pathway. Enzalutamide competitively inhibits binding of androgens to androgen receptors, inhibits nuclear translocation of activated receptors and inhibits the association of the activated androgen receptor with DNA even in the setting of androgen receptor overexpression and in prostate cancer cells resistant to anti-androgens. Enzalutamide treatment decreases the growth of prostate cancer cells and can induce cancer cell death and tumour regression. In preclinical studies enzalutamide lacks androgen receptor agonist activity.
Pharmacodynamic effectsIn a phase 3 clinical trial of patients who failed prior chemotherapy with docetaxel, 54% of patients treated with enzalutamide, versus 1.5% of patients who received placebo, had at least a 50% decline from baseline in PSA levels.
Clinical efficacy and safetyEfficacy of enzalutamide was established in two randomized placebo-controlled multicentre phase 3 clinical studies [CRPC2 (AFFIRM), MDV3100-03 (PREVAIL)] of patients with progressive metastatic prostate cancer who had failed androgen deprivation therapy [luteinising hormone-releasing hormone (LHRH) analogue or after bilateral orchiectomy]. The PREVAIL study enrolled chemotherapy-naive patients; whereas the AFFIRM study enrolled patients who had received prior docetaxel. All patients continued on a LHRH analogue or had prior bilateral orchiectomy. In the active treatment arm, Xtandi was administered orally at a dose of 160 mg daily. In both clinical trials, patients received placebo in the control arm and patients were allowed, but not required, to take prednisone (maximum daily dose allowed was 10 mg prednisone or equivalent).Changes in PSA serum concentration independently do not always predict clinical benefit. Therefore, in both studies it was recommended that patients be maintained on their study treatments until discontinuation criteria were met as specified below for each study.
MDV3100-03 (PREVAIL) study (chemotherapy-naive patients)A total of 1717 asymptomatic or mildly symptomatic chemotherapy-naive patients were randomized 1:1 to receive either enzalutamide orally at a dose of 160 mg once daily (N = 872) or placebo orally once daily (N = 845). Patients with visceral disease, patients with a history of mild to moderate heart failure (NYHA Class 1 or 2), and patients taking medications associated with lowering the seizure threshold were allowed. Patients with a previous history of seizure or a condition that might predispose to seizure and patients with moderate or severe pain from prostate cancer were excluded. Study treatment continued until disease progression (evidence of radiographic progression, a skeletal-related event, or clinical progression) and the initiation of either a cytotoxic chemotherapy or an investigational agent, or until unacceptable toxicity. Patient demographics and baseline disease characteristics were balanced between the treatment arms. The median age was 71 years (range 42-93) and the racial distribution was 77% Caucasian, 10% Asian, 2% Black and 11% other or unknown races. Sixty-eight percent (68%) of patients had an ECOG performance status score of 0 and 32% patients had ECOG performance status 1. Baseline pain assessment was 0-1 (asymptomatic) in 67% of patients and 2-3 (mildly symptomatic) in 32% of patients as defined by the Brief Pain Inventory Short Form (worst pain over past 24 hours on a scale of 0 to 10). Approximately 45% of patients had measurable soft tissue disease at study entry, and 12% of patients had visceral (lung and/or liver) metastases. Co-primary efficacy endpoints were overall survival and radiographic progression-free survival (rPFS). In addition to the co-primary endpoints, benefit was also assessed using time to initiation of cytotoxic chemotherapy, best overall soft tissue response, time to first skeletal-related event, PSA response (≥ 50% decrease from baseline), time to PSA progression, and time to FACT-P total score degradation. Radiographic progression was assessed with the use of sequential imaging studies as defined by Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria (for bone lesions) and/or Response Evaluation Criteria in Solid Tumors (RECIST v 1.1) criteria (for soft tissue lesions). Analysis of rPFS utilized centrally-reviewed radiographic assessment of progression.At the pre-specified interim analysis for overall survival when 540 deaths were observed, treatment with enzalutamide demonstrated a statistically significant improvement in overall survival compared to treatment with placebo with a 29.4% reduction in risk of death [HR = 0.706, (95% CI: 0.596; 0.837), p < 0.0001]. An updated survival analysis was conducted when 784 deaths were observed. Results from this analysis were consistent with those from the interim analysis (Table 2, Figure 1). At the updated analysis 52% of enzalutamide-treated and 81% of placebo-treated patients had received subsequent therapies for metastatic CRPC that may prolong overall survival. Table 2: Overall Survival of Patients Treated with Either Enzalutamide or Placebo in the PREVAIL Study (Intent-to-Treat Analysis)
|Enzalutamide (N = 872)
|Placebo (N = 845)
|Pre-specified interim analysis
|Number of deaths (%)
|241 (27.6%)
|299 (35.4%)
|Median survival, months (95% CI)
|< 0.0001
|Hazard ratio (95% CI)b
|0.71 (0.60, 0.84)
|Updated survival analysis
|Number of deaths (%)
|368 (42.2%)
|416 (49.2%)
|Median survival, months (95% CI)
|31.3 (28.8, 34.2)
|Hazard ratio (95% CI)b
|0.77 (0.67, 0.88)
Figure 1: Kaplan-Meier Overall Survival Curves Based on Updated Survival Analysis in the PREVAIL Study (Intent-to-Treat Analysis)
Figure 2: Updated Overall Survival Analysis by Subgroup: Hazard Ratio and 95% Confidence Interval in the PREVAIL Study (Intent-to-Treat Analysis)At the pre-specified rPFS analysis, a statistically significant improvement was demonstrated between the treatment groups with an 81.4% reduction in risk of radiographic progression or death [HR = 0.186 (95% CI: 0.149, 0.231), p < 0.0001]. One hundred and eighteen (14%) enzalutamide-treated patients and 321 (40%) of placebo-treated patients had an event. The median rPFS was not reached (95% CI: 13.8, not reached) in the enzalutamide-treated group and was 3.9 months (95% CI: 3.7, 5.4) in the placebo-treated group (Figure 3). Consistent rPFS benefit was observed across all pre-specified patient subgroups (e.g., age, baseline ECOG performance, baseline PSA and LDH, Gleason score at diagnosis, and visceral disease at screening). A pre-specified follow-up rPFS analysis based on the investigator assessment of radiographic progression demonstrated a statistically significant improvement between the treatment groups with a 69.3% reduction in risk of radiographic progression or death [HR = 0.307 (95% CI: 0.267, 0.353), p < 0.0001]. The median rPFS was 19.7 months in the enzalutamide group and 5.4 months in the placebo group.
Figure 3: Kaplan-Meier Curves of Radiographic Progression-Free Survival in the PREVAIL Study (Intent-to-Treat Analysis)In addition to the co-primary efficacy endpoints, statistically significant improvements were also demonstrated in the following prospectively defined endpoints.The median time to initiation of cytotoxic chemotherapy was 28.0 months for patients receiving enzalutamide and 10.8 months for patients receiving placebo (HR = 0.350, 95% CI: [0.303, 0.403], p<0.0001).The proportion of enzalutamide-treated patients with measurable disease at baseline who had an objective soft tissue response was 58.8% (95% CI: 53.8, 63.7) compared with 5.0% (95% CI: 3.0, 7.7) of patients receiving placebo. The absolute difference in objective soft tissue response between enzalutamide and placebo arms was 53.9% (95% CI: 48.5%, 59.1%, p < 0.0001). Complete responses were reported in 19.7% of enzalutamide-treated patients compared with 1.0% of placebo-treated patients, and partial responses were reported in 39.1% of enzalutamide-treated patients versus 3.9% of placebo-treated patients.Enzalutamide significantly decreased the risk of the first skeletal-related event by 28% [HR = 0.718 (95% CI: 0.610, 0.844) p-value < 0.0001]. A skeletal-related event was defined as radiation therapy or surgery to bone for prostate cancer, pathologic bone fracture, spinal cord compression, or change of antineoplastic therapy to treat bone pain. The analysis included 587 skeletal-related events, of which 389 events (66.3%) were radiation to bone, 79 events (13.5%) were spinal cord compression, 70 events (11.9%) were pathologic bone fracture, 45 events (7.6%) were change in antineoplastic therapy to treat bone pain, and 22 events (3.7%) were surgery to bone.Patients receiving enzalutamide demonstrated a significantly higher total PSA response rate (defined as a ≥ 50% reduction from baseline), compared with patients receiving placebo, 78.0% versus 3.5% (difference = 74.5%, p < 0.0001).The median time to PSA progression per PCWG2 criteria was 11.2 months for patients treated with enzalutamide and 2.8 months for patients who received placebo [HR = 0.169, (95% CI: 0.147, 0.195), p < 0.0001].Treatment with enzalutamide decreased the risk of FACT-P degradation by 37.5% compared with placebo (p < 0.001). The median time to degradation in FACT-P was 11.3 months in the enzalutamide group and 5.6 months in the placebo group.
9785-CL-0222 (TERRAIN) study (chemotherapy-naïve patients)The TERRAIN study enrolled 375 chemo- and antiandrogen-therapy naïve patients who were randomized to receive either enzalutamide at a dose of 160 mg once daily (N = 184) or bicalutamide at a dose of 50 mg once daily (N = 191). Median PFS was 15.7 months for patients on enzalutamide versus 5.8 months for patients on bicalutamide [HR = 0.44 (95% CI: 0.34, 0.57), p < 0.0001]. Progression-free survival was defined as objective evidence of radiographic disease progression by independent central review, skeletal-related events, initiation of new antineoplastic therapy or death by any cause, whichever occurred first. Consistent PFS benefit was observed across all pre-specified patient subgroups.
CRPC2 (AFFIRM) study (patients who previously received chemotherapy)The efficacy and safety of enzalutamide in patients with metastatic castration-resistant prostate cancer who had received docetaxel and were using a LHRH analogue or had undergone orchiectomy were assessed in a randomised, placebo-controlled, multicentre phase 3 clinical trial. A total of 1199 patients were randomised 2:1 to receive either enzalutamide orally at a dose of 160 mg once daily (N = 800) or placebo once daily (N = 399). Patients were allowed but not required to take prednisone (maximum daily dose allowed was 10 mg prednisone or equivalent). Patients randomised to either arm were to continue treatment until disease progression (defined as confirmed radiographic progression or the occurrence of a skeletal-related event) and initiation of new systemic antineoplastic treatment, unacceptable toxicity, or withdrawal.The following patient demographics and baseline disease characteristics were balanced between the treatment arms. The median age was 69 years (range 41-92) and the racial distribution was 93% Caucasian, 4% Black, 1% Asian, and 2% Other. The ECOG performance score was 0-1 in 91.5% of patients and 2 in 8.5% of patients; 28% had a mean Brief Pain Inventory score of ≥4 (mean of patient's reported worst pain over the previous 24 hours calculated for seven days prior to randomization). Most (91%) patients had metastases in bone and 23% had visceral lung and/or liver involvement. At study entry, 41% of randomized patients had PSA progression only, whereas 59% of patients had radiographic progression. Fifty-one percent (51%) of patients were on bisphosphonates at baseline.The AFFIRM study excluded patients with medical conditions that may predispose them to seizures (see section 4.8) and medicinal products known to decrease the seizure threshold, as well as clinically significant cardiovascular disease such as uncontrolled hypertension, recent history of myocardial infarction or unstable angina, New York Heart Association class III or IV heart failure (unless ejection fraction was ≥ 45%), clinically significant ventricular arrhythmias or AV block (without permanent pacemaker).The protocol pre-specified interim analysis after 520 deaths showed a statistically significant superiority in overall survival in patients treated with enzalutamide compared to placebo (Table 3 and Figures 4 and 5).Table 3: Overall Survival of Patients Treated with Either Enzalutamide or Placebo in the AFFIRM Study (Intent-to-Treat Analysis)
|Enzalutamide (N = 800)
|Placebo (N = 399)
|Deaths (%)
|308 (38.5%)
|212 (53.1%)
|Median survival (months) (95% CI)
|13.6 (11.3, 15.8)
|p valuea
|< 0.0001
|Hazard ratio (95% CI)b
|0.631 (0.529, 0.752)
Figure 4: Kaplan-Meier Overall Survival Curves in the AFFIRM Study (Intent-to-Treat Analysis)
Figure 5: Overall Survival by Subgroup in the AFFIRM Study Hazard Ratio and 95% Confidence IntervalECOG: Eastern Cooperative Oncology Group; BPI-SF: Brief Pain Inventory-Short Form; PSA: Prostate Specific AntigenIn addition to the observed improvement in overall survival, key secondary endpoints (PSA progression, radiographic progression-free survival, and time to first skeletal-related event) favoured enzalutamide and were statistically significant after adjusting for multiple testing.Radiographic progression-free survival as assessed by the investigator using RECIST v 1.1 for soft tissue and appearance of 2 or more bone lesions in bone scan was 8.3 months for patients treated with enzalutamide and 2.9 months for patients who received placebo (HR = 0.404, 95% CI: [0.350, 0.466]; p < 0.0001). The analysis involved 216 deaths without documented progression and 645 documented progression events, of which 303 (47%) were due to soft tissue progression, 268 (42%) were due to bone lesion progression and 74 (11%) were due to both soft tissue and bone lesions.Confirmed PSA decline of 50% or 90% were 54.0% and 24.8%, respectively, for patients treated with enzalutamide and 1.5% and 0.9%, respectively, for patients who received placebo (p < 0.0001). The median time to PSA progression was 8.3 months for patients treated with enzalutamide and 3.0 months for patients who received placebo (HR = 0.248, 95% CI: [0.204, 0.303]; p < 0.0001).The median time to first skeletal-related event was 16.7 months for patients treated with enzalutamide and 13.3 months for patients who received placebo (HR = 0.688, 95% CI: [0.566, 0.835]; p < 0.0001). A skeletal-related event was defined as radiation therapy or surgery to bone, pathologic bone fracture, spinal cord compression, or change of antineoplastic therapy to treat bone pain. The analysis involved 448 skeletal-related events, of which 277 events (62%) were radiation to bone, 95 events (21%) were spinal cord compression, 47 events (10%) were pathologic bone fracture, 36 events (8%) were change in antineoplastic therapy to treat bone pain and 7 events (2%) were surgery to bone.The efficacy of enzalutamide in patients who have previously received abiraterone acetate has not been studied.
Older peopleOf the 1671 patients in the phase 3 trials who received enzalutamide, 1261 patients (75%) were 65 years and over and 516 patients (31%) were 75 years and over. No overall differences in safety or effectiveness were observed between these older patients and younger patients.
Paediatric populationThe European Medicines Agency has waived the obligation to submit the results of studies with enzalutamide in all subsets of the paediatric population in prostate carcinoma (see section 4.2 for information on paediatric use).
AbsorptionMaximum plasma concentrations (Cmax) of enzalutamide in patients are observed 1 to 2 hours after administration. Based on a mass balance study in humans, oral absorption of enzalutamide is estimated to be at least 84.2%. Enzalutamide is not a substrate of the efflux transporters P-gp or BCRP. At steady state, the mean Cmax values for enzalutamide and its active metabolite are 16.6 μg/mL (23% coefficient of variation [CV]) and 12.7 μg/mL (30% CV), respectively.Food has no clinically significant effect on the extent of absorption. In clinical trials, Xtandi was administered without regard to food.
DistributionThe mean apparent volume of distribution (V/F) of enzalutamide in patients after a single oral dose is 110 L (29% CV). The volume of distribution of enzalutamide is greater than the volume of total body water, indicative of extensive extravascular distribution. Studies in rodents indicate that enzalutamide and its active metabolite can cross the blood brain barrier.Enzalutamide is 97% to 98% bound to plasma proteins, primarily albumin. The active metabolite is 95% bound to plasma proteins. There was no protein binding displacement between enzalutamide and other highly bound drugs (warfarin, ibuprofen and salicylic acid) in vitro.
BiotransformationEnzalutamide is extensively metabolized. There are two major metabolites in human plasma: N-desmethyl enzalutamide (active) and a carboxylic acid derivative (inactive). Enzalutamide is metabolized by CYP2C8 and to a lesser extent by CYP3A4/5 (see section 4.5), both of which play a role in the formation of the active metabolite. In vitro, N-desmethyl enzalutamide is metabolized to the carboxylic acid metabolite by carboxylesterase 1, which also plays a minor role in the metabolism of enzalutamide to the carboxylic acid metabolite. N-desmethyl enzalutamide was not metabolized by CYPs in vitro. Under conditions of clinical use, enzalutamide is a strong inducer of CYP3A4, a moderate inducer of CYP2C9 and CYP2C19, and has no clinically relevant effect on CYP2C8 (see section 4.5).
EliminationThe mean apparent clearance (CL/F) of enzalutamide in patients ranges from 0.520 and 0.564 L/h. Following oral administration of 14C-enzalutamide, 84.6% of the radioactivity is recovered by 77 days post dose: 71.0% is recovered in urine (primarily as the inactive metabolite, with trace amounts of enzalutamide and the active metabolite), and 13.6% is recovered in faeces (0.39% of dose as unchanged enzalutamide).In vitro data indicate that enzalutamide is not a substrate for OATP1B1, OATP1B3, or OCT1; and N-desmethyl enzalutamide is not a substrate for P-gp or BCRP.In vitro data indicate that enzalutamide and its major metabolites do not inhibit the following transporters at clinically relevant concentrations: OATP1B1, OATP1B3, OCT2, or OAT1.
LinearityNo major deviations from dose proportionality are observed over the dose range 40 to 160 mg. The steady-state Cmin values of enzalutamide and the active metabolite in individual patients remained constant during more than one year of chronic therapy, demonstrating time-linear pharmacokinetics once steady-state is achieved.
Renal impairmentNo formal renal impairment study for enzalutamide has been completed. Patients with serum creatinine > 177 μmol/L (2 mg/dL) were excluded from clinical trials. Based on a population pharmacokinetic analysis, no dose adjustment is necessary for patients with calculated creatinine clearance (CrCL) values ≥ 30 mL/min (estimated by the Cockcroft and Gault formula). Enzalutamide has not been evaluated in patients with severe renal impairment (CrCL < 30 mL/min) or end-stage renal disease, and caution is advised when treating these patients. It is unlikely that enzalutamide will be significantly removed by intermittent haemodialysis or continuous ambulatory peritoneal dialysis.
Hepatic impairmentHepatic impairment did not have a pronounced effect on the total exposure to enzalutamide or its active metabolite. Drug half-life was however doubled in patients with severe hepatic impairment compared with healthy controls (10.4 days compared to 4.7 days), possibly related to an increased tissue distribution.The pharmacokinetics of enzalutamide were examined in subjects with baseline mild (N = 6), moderate (N = 8) or severe (N=8) hepatic impairment (Child-Pugh Class A, B or C, respectively) and in 22 matched control subjects with normal hepatic function. Following a single oral 160 mg dose of enzalutamide, the AUC and Cmax for enzalutamide in subjects with mild impairment increased by 5% and 24%, respectively, the AUC and Cmax of enzalutamide in subjects with moderate impairment increased by 29% and decreased by 11%, respectively, and the AUC and Cmax of enzalutamide in subjects with severe impairment increased by 5% and decreased by 41%, respectively, compared to healthy control subjects. For the sum of unbound enzalutamide plus the unbound active metabolite, the AUC and Cmax in subjects with mild impairment increased by 14% and 19%, respectively, the AUC and Cmax in subjects with moderate impairment increased by 14% and decreased by 17%, respectively, and the AUC and Cmax in subjects with severe hepatic impairment increased by 34% and decreased by 27%, respectively, compared to healthy control subjects.
RaceMost patients in the clinical trials (> 84%) were Caucasian. Based on pharmacokinetic data from a study in Japanese patients with prostate cancer, there were no clinically relevant differences in exposure between Japanese and Caucasians. There are insufficient data to evaluate potential differences in the pharmacokinetics of enzalutamide in other races.
Older peopleNo clinically relevant effect of age on enzalutamide pharmacokinetics was seen in the population pharmacokinetic analysis.
Capsule contentsCaprylocaproyl macrogol-8 glycerides Butylhydroxyanisole (E320)Butylhydroxytoluene (E321)
Capsule shellGelatinSorbitol sorbitan solutionGlycerol Titanium dioxide (E171)Purified water
Printing inkIron oxide black (E172)Polyvinyl acetate phthalate
Astellas Pharma Ltd
2000 Hillswood Drive, Chertsey, Surrey, KT16 0RS, UK
+44 (0) 203 379 8820
+44 (0) 203 379 8700
0800 783 5018
+44 (0) 203 379 8721
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Added On: 2014-11-30 22:36:00 • Views: 777 • Duration: 01:21
Categories: Downblouse
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Description: Holly can be my secretary any day
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company Invoice - repost 2
This project received 34 bids from talented freelancers with an average bid price of $383 USD.Get free quotes for a project like this
Project Budget$250 - $750 USD
Total Bids34
Project Description
I need to create a company database to find customer base on phone numer, last name, vehicle [url removed, login to view] create and store work order information.
will provide empty invoice to create same style
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|Franklin NHL Championship Shooting Target 72" x 48"
Lowest Price Guarantee
view large
The Franklin NHL Championship Shooting Target will help elevate your shooting game to the next level so when it comes to it, you can score that OT game-winner that everyone dreams of. Constructed of 600 denier nylon, this heavy-duty shooting trainer can withstand both street and roller hockey pucks and balls so you can get endless use out of it. The shooter trainer has five holes so you can hone your sniping skills and is fastened with 2" Velcro straps for a secure fit. Full size goalie graphic on the front. Fits standard 4' x 6' hockey goals.
Goal not included.
- Model Number: 12190F4
- Recommended Use: Street and Roller Hockey


text:
With Instructables you can share what you make with the world, and tap into an ever-growing community of creative experts.
First, if your just doing this because you want to be cool, stop right now. If you don't, and you are new to the skateboarding world, read this. ...
Be yourself. Don't wear skate clothes all the time because you might be called a poser. Just wear a simple shirt with a logo, some jeans, and some ...
Skaters call guys "Dude" or "Bro". For girls, "Dudette" or "Bra". Get used to this.
Just one thing about your skateboard. You would rather have an expensive skate shop board than a cheap toy store one. And pick out some nice, comfortable pads. ...
Try your hardest at skating. Practice and practice until you master a trick. I would start out with a ollie, the basic movement to unlock a whole world ...
How to Start a Skate Teamby forktim
Skateboarding: Setup and Stylesby NinJa_RaiZer
How to be Like a Skaterby awesume
Join 2 million + to receive instant DIY inspiration in your inbox.
© 2016 Autodesk, Inc.


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"Celtic Thunder has never been a disappointment and this CD is no exception! There is something for everyone and every mood."
"Phil Coulter and Sharon Browne have yet to fail me! I have listen to Celtic Thunder since March of 2008 and still love them! Even more than when I first heard them"
"The product description of It's Entertainment is spot on. What you get here is an enthusiastic collection of songs from some of their own musical influences and favorite artists. You can tell that they've had a blast doing their own take on music that speaks to them"
"I am thrilled with Celtic Thunder's new release! Didn't think they could get much better.....yet, here you go!!!!! A definite must! Music SO tight...production superb.....photography excellent!"
"Their best singing to date! Wonderful melody, harmony, style and good fun! So happy to hear Neil Byrne sing in this CD. He's got the voice of an angel. More Neil in the future I hope!!!! "
"Celtic Thunder HAS done it again. These lads have always exceeded expectations and this is no exception. I couldn't possibly pick any musical favorites, as they are all great. Their exceptional blending of voices, their fun personalities and now choreography-who could ask for more!"
"Celtic Thunder's chameleon career hits another 5-star performance with It's Entertainment. This is Sharon Brown's and Phil Coulter's latest effort and what a hit it is! This is a little different from the other CD's Celtic Thunder produced, but it is on the way to becoming another hit!"
"I highly recommend this CD! You'll love it!!"
"Absolutely LOVE it!! Love the singing, the dancing, the interaction and the "old time" songs! Some brought back some great memories. Also loved the bonus part at the castle!"
"Just received my copy today....fantastic job with the whole show. I can not wait to see the live version when you tour. It was really great to see how much the guys have grown as performers and artists"
"Truly without a doubt " AMAZING""
"Very entertaining, very energetic, very "slick", very professional! GREAT JOB, GUYS!! I especially liked "The Story So Far""
"AMAZING I got both the CD and DVD and I love it. I was there at the taping and it brought back so many memories. Can not wait o see it on tour. The guys were out of this world as only they can be. The band was great. Sharon and Phil you did it again."
"received my DVD today...Got the CD earlier in the week. The name fits....IT'S ENTERTAINMENT at it's finest! Thanks CT."
"Celtic Thunder has outdone themselves again. I loved th CD and DVD. It really is ENTERTAINMENT!"
"Received my copy of "It's Entertainment" CD today. Fantastic music can't wait till the DVD gets here. By the way it's only Monday ( somehow I received my CD Early)."
"Just bought my copy of the "It's Entertainment" album. Really good stuff! Looking forward for "Storm" to come out!"
"Couldn't wait for my CDs and DVDS, so went out today and bought some more. CD is wonderful, listened to it all the way home. Am just getting ready to watch the DVD and am excited already. THANK YOU ALL FOR A JOB WELL DONE!!"
"I just received my copies of It's Entertainment. I am vey pleased with it, once again, YOU MADE MY DAY. You are my favorite group"
"I bought the cd and dvd of "It's Entertainment". I love it! Looking forward to the Storm and the fall tour. Thank you. Love.:))"
"BRILLIANT!!!! Absolutely Brilliant! Had preordered both the DVD and CD which arrived yesterday despite all our bad weather and haven't stopped watching and listening since! Sharon and Phil - completely outdid yourselves. Any fans who haven't bought it - run out now!!!!"
"LOVE LOVE LOVE the new CD/DVD. So amazing, already watched it about 10 times..and plenty more times to come."
"Got the DVD and CD yesterday. It's completely AMAZING!!!!!! You out did yourselves!"
"The new songs rocked as well, Damian McGinty,George Donaldson, Paul Byrom, Ketih Harkin. All of you have amazing voices. Damian your voice is just amazing! I could go on and on, I highly recommend it. I think it's the BEST ever! Everyone did a brilliant performance. "
"The absolutely best group of singers! Y'all's voices blend so well. I wouldn't be able to drive without one of your CD's going."


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Narrow Your Results
Center Ring
Lining Material
Made with heavy-duty webbing with thick, natural-colored synthetic fleece, the Dover Saddlery Premium Fleece Girth offers comfort and an attractive look. Center D-ring.
The Dover Saddlery Fancy-Stitched Hunter Girth in Wickett & Craig American leather has a fancy-stitched pattern on the overlay. A classically-styled hunter girth with triple elastic at both ends.
The Dover Saddlery Overlay Girth has fancy stitching for show ring style. This high-quality leather girth has triple elastic at both ends and long-wearing stainless steel roller buckles.
The Professional's Choice® VenTech™ Fleece Combo Girth promotes cooling airflow with a removable strip of VenTech material next to your horse's skin. Synthetic fleece adds to your horse's comfort. This unique girth has elastic at both ends, stainless steel roller buckles and a center D-ring.
Designed for your horse's comfort, the Toklat Contoured Dressage Girth is lined with synthetic, black fleece and shaped for optimal fit. Double elastic at both ends.
The Dover Saddlery Everyday Fleece Girth is Equifleece-lined for chafeless comfort against your horse. This girth has elastic on both ends and roller buckles to make adjusting easy.
Ideal for training, performance or competition, the Professional's Choice® SMX Girth is non-chafing, flexible and slip-resistant, making it ideal for horses with sensitive skin. The neoprene material is durable and can be washed with soap and water. A great buy!
Dover's Split End Girth has classic overlay style. Appropriate for both showing and schooling, this girth has one split end and triple elastic at the other for even adjustment. Stainless steel roller buckles won't rust.
Durable and affordable, the Ovation® Airfoam Chafeless Girth is made from easy care synthetic material and features stainless steel roller buckles. Elasticized inserts provide ease in adjustment and help alleviate pressure points as the horse moves. Won't chafe or pinch.
The competitively priced Dover Saddlery Everyday Stitched Girth moves easily from the practice ring to the show ring. This girth features classic overlay styling with fancy-stitch detail.
This Ovation® Gel Body Form Dressage Girth maintains a great look as it adds to your horse's comfort. Anatomically shaped and constructed with a gel insert in the middle.
Ovation® Dry-Tex® Equalizer Girth keeps your horse comfortable with great moisture-wicking technologies. Stainless steel roller buckles allow for easy tightening.


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Day 3 in Ekaterinburg
Trip Start Aug 04, 2008
28Trip End Ongoing
Map your own trip!
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Where I stayed
Ekateringburg Hostel
Then we went to the Ekaterinburg History Museum, not bad if a little brief.
Now Nat's sleeping, before we go on our 50 hour train journey, that leads into a 6 hour bus journey!!!!
Gordon & Nat


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When Blacks Get Their American Dream 'Burb On
The WSJ reports that, for the first time, 'black' cities like DC and Atlanta are losing their historic black populations to the suburbs. News, certainly. But why they gotta turn it into a big ol' drama?
The only difference between this and white flight is that blacks are running toward something (supposed peace and tranquility) and not away from something (coloreds). We'd a done it sooner but for the economic discrimination that kept us from affording to join those stupid commuters with their 'bowling alone' anomie. And, oh, y'all killing us for trying.
Now, we get our American Dream 'burb on—and we media types can't just report already dramatic news. It's gotta be a race war.
Here's the WSJ's sub hed:
For the First Time in Decades, Cities' Black Populations Lose Ground, Stirring Clashes Over Class, Culture and Even Ice Cream.
Heavens! Formerly black churches are courting newly gentrifying whites rather than, oh, I dunno, closing. White candidates have a shot at winning 'black' mayoralties and municipalities are flinging up jazz spots all over town, knowing that Negroes can't resist a hot sax anymore than Paris Hilton can resist a camera. Race war!
Why can't news about blacks just be that—news about blacks? White folks: Everything ain't about y'all all the time.


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Dr. David Weinberg MD
- Ophthalmology Concord, NH
Patient Reviews
Reviews reflect patients' level of satisfaction with the care they received from this provider. Dr. David Weinberg xhas an overall rating of 4.1.
Dr. David Weinberg, MD is a Doctor primarily located in Concord, NH. He has 33 years of experience. His specialties include Ophthalmology. Dr. Weinberg is affiliated with New London Hospital and Concord Hospital. He speaks English.
Patients rate and review their physicians based on criteria of care including bedside manner, doctor-patient face time, and degree of follow-up. Patients also provide their doctor with an overall ratings. Vitals analyzes these ratings annually, along with other quality measures, to identify and award the top physicians.
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Specialties & Expertise
Dr. David Weinberg has the following 12 areas of expertise, 1 specialty and 1 board certification.
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See the board certifications this doctor has received. Board certifications provide confidence that this doctor meets the nationally recognized standards for education, knowledge and experience.
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Health Guides
Contact Lens Care
A complete overview of what you need to know about your contact lenses.
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Dr. David Weinberg, MD is similar to these 3 Doctors near Concord, NH.
Dr. Paul Rychwalski
Dr. Peter Wasserman
Dr. Thomas Hand


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Sweepstakes App for Facebook
This project received 6 bids from talented freelancers with an average bid price of $160 USD.Get free quotes for a project like this
Project Budget$30 - $250 USD
Total Bids6
Project Description
My company is looking to develop Facebook Sweepstakes apps quarterly that we can integrate with our Facebook page.
Looking for the Apps to support the following:
-User submitted content (photos)
-registration (name, age, contact info)
-Winner will be selected on 'likes'
-options to share photos and sweepstakes
Skills Required
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Craig Sheffer Net Worth: Craig Sheffer is an American actor who has a net worth of $1 million. Craig Sheffer was born in York, Pennsylvania in April 1960. Sheffer competed in regional and state high school drama competitions at 15. At one point he slept under the marble staircase in the Grand central Terminal and sold newspapers. His first role came in the TV series One Life to Live in 1982. He played Mick in the TV series Teen Wolf from 1986 to 1987. His next major TV role came as Keith Scott on One Tree Hill from 2003 to 2012. Sheffer has starred in the films That Was Then… This Is Now, Fire with Fire, Some Kind of Wonderful, Baby Cakes, Nightbreed, A River Runs Through It, The Program, Fire in the Sky, Head Above Water, Bliss, Sleep With Me, Hellraiser: Inferno, The Mark, and Bad Ass. He has appeared in episodes of Married with Children, Psych, Criminal Minds, The Mentalist, CSI: Crime Scene Investigation, and Major Crimes. Sheffer also directed the straight to DVD movie American Crude in 2008. After filming Nightbreed Craig was diagnosed with cancer which went into remission.
Craig Sheffer Net Worth
Craig Sheffer
Date of Birth
Apr 23, 1960 (56 years old)
Actor, Voice Actor, Film Producer, Film Director
United States of America
6 ft 2 in (1.88 m)
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All net worths are calculated by applying a proprietary algorithm. The results are then fact checked and confirmed by a team of editors. We scan all publicly available data and resources and work diligently to ensure that our numbers are the most accurate and up to date net worth data you will find anywhere on the internet.


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- Home
- Gardening Supplies
- Raised Garden Beds
- Frame It All Stainless Steel Veggie Wall
- Home
- Gardening Supplies
- Gardening Accessories
- Frame It All Stainless Steel Veggie Wall
Product Description
Expandable Trellis System adapts to all Frame It All raised gardens or directly into the ground. Ideal for growing tomatoes, cucumbers, pole beans, squash and flowering vines. The increased air circulation allows plants to dry out quicker after watering, reducing plant diseases. Less exposure to soil pathogens, critters and bugs; grows healthier stronger plants.
- Greater access to sunlight-increasing photosynthesis
- Easier harvesting-little bending easier on back and knees
- Increases garden's surface area by 48 square feet!
- 6' upright stainless steel tubing
- 4' stainless steel cross pieces
- Strong nylon netting
- Weight 5.9 lbs.
- Raised bed not included
Includes 3 durable Stacking Stakes that anchor your Veggie Wall to the frame-it-all Raised Garden or directly in the ground. Sturdy construction is made from 6 ft, upright stainless steel tubing and 4 ft, stainless steel cross pieces, Strong nylon netting, 3 durable stacking stakes that anchor your veggie wall to our Frame-It-All Raised garden or directly into the ground. Add another Veggie Wall for an extra large 4 ft. x 8 ft. garden.


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I took it as he was making a joke about Mac vrs PC...as in, the "inappropriate" comment could be...(This is only an example).
"Gee, it works on my PC's maybe you should switch..."
Or some other Apple Vs. PC comment like you would see on their commercials as of late.
I would think he was just poking fun and that is why he didn't actually say it...


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Play Video
Strokker Geyser
Posted by ravagewing on Jul. 24, 2007
Hollywood's most glamorous night has come to a close- which means it's time...
Need some natural inspiration this monday? Here's our top 10!
1. What's the one role an actor passed on, that you wish they accepted? 2....
Posted by ravagewing on Jul. 24, 2007


text: TabsArticle Panel on Dietetic Products, Nutrition and Allergies EFSA Journal: EFSA Journal 2014;12(2):3581 [25 pp.]. doi: 10.2903/j.efsa.2014.3581 Panel Members: Carlo Agostoni, Roberto Berni Canani, Susan Fairweather-Tait, Marina Heinonen, Hannu Korhonen, Sébastien La Vieille, Rosangela Marchelli, Ambroise Martin, Androniki Naska, Monika Neuhäuser-Berthold, Grażyna Nowicka, Yolanda Sanz, Alfonso Siani, Anders Sjödin, Martin Stern, Sean (J.J.) Strain, Inge Tetens, Daniel Tomé, Dominique Turck and Hans Verhagen Acknowledgements: The Panel wishes to thank the members of the Working Group on Dietary Reference Values for vitamins: Monika Neuhäuser-Berthold, Grażyna Nowicka, Kristina Pentieva, Hildegard Przyrembel, Sean (J.J.) Strain, Inge Tetens, Daniel Tomé and Dominique Turck for the preparatory work on this scientific opinion. Contact: firstname.lastname@example.com Type: Opinion of the Scientific Committee/Scientific Panel On request from: European Commission Question Number: EFSA-Q-2011-01219 Adopted: 5 February 2014 Published in the EFSA Journal: 24 February 2014 Affiliation: European Food Safety Authority (EFSA), Parma, Italy Send Print Note: Read the article on the Wiley Online Library Abstract: Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies (NDA) derived Dietary Reference Values (DRVs) for pantothenic acid. Pantothenic acid is a water-soluble vitamin, which is a component of coenzyme A (CoA) and acyl-carrier proteins. Pantothenic acid is ubiquitous and deficiency is rare. There are no suitable biomarkers that can be used to derive the requirement for pantothenic acid. Data available on pantothenic acid intakes and health consequences are very limited and cannot be used to derive DRVs for pantothenic acid. As there is insufficient evidence available to derive an Average Requirement and a Population Reference Intake, an Adequate Intake (AI) is proposed. The setting of AIs is based on observed pantothenic acid intakes with a mixed diet and the apparent absence of signs of deficiency in the EU, suggesting that current intake levels are adequate. The AI for adults is set at 5 mg/day. The AI for adults also applies to pregnant women. For lactating women, an AI of 7 mg/day is proposed, to compensate for pantothenic acid losses through breast milk. For infants over six months, an AI of 3 mg/day is proposed by extrapolating from the pantothenic acid intake of exclusively breast-fed infants aged zero to six months, using allometric scaling and reference body weight for each age group, in order to account for the role of pantothenic acid in energy metabolism. The AI for children and adolescents is set at 4 and 5 mg/day, respectively, based on observed intakes in the EU. © European Food Safety Authority, 2014 Keywords: pantothenic acid, Dietary Reference Value, Adequate Intake Print on demand Number of Pages: 25


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The Horse Forum (http://www.horseforum.com/forumindex.php)
- Horse Pictures (/horse-pictures/)
- - I want your Mustangs! (http://www.horseforum.com/horse-pictures/i-want-your-mustangs-77880/)
I want your Mustangs!
5 Attachment(s)
If you saw my thread in the Breeds category, I'm thinking about getting a gentled Mustang for my next horse. I'd like to see some pictures of yours! Thanks!!
2 Attachment(s)
you probably saw mine already but here they are again. palamino is gelding. other is a mare
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text: Staying at the Adjoining Best Western Hotel, I booked a specific round table 5 days earlier to celebrate my 50th birthday with my 3 guests. I have used this restaurant probably 20 times on various trips to the area since 2008 and always had fantastic service and excellent cuisine. The warning signs appeared on arriving at the restaurant; the table... More


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Fay Miller recovering at the Royal Adelaide Hospital
Broadcast: 17/03/2006
Fay Miller, thank you very much for joining us.
It's a pleasure Melinda.
Well Fay, how are you feeling?
I'm feeling absolutely wonderfully glad to be alive Melinda,
Can you tell us about the accident, what happened that day?
There was some water on the road and the ,oment the car hit the water i was facing back towards Alice Springs, going side ways, off the side of the road it was happening very quickly, but with unbelivable noise, and rolled the car i think 3 or 4 times, and but fortunatey landed on its wheels, facing back towards Alice Springs.
What happened then?, how did you know, did you know how injured you were at the time?
I knew thet soemthing had snapped on my spine, i felt it, i felt it on my vertibrae, and i knoew as a former St Johns ambulence person trained in advanced care that i had a problem, but i can assure you that i started wriggling my toes, and i could feel them, wriggled my fingers and i could feel those, and i could actually move my head a little bit, but i chose not to do that, i chose to sit there very quietly and Mike was a great suport and he was fortunately not injured at all, and except naturally extremily shaken up, so he was sitting with me for the hour and a quater that it took before the ambulence personell were able to pll the car doors off and remove me.
We've heard that you had surgery on Wednesday, just a couple of days ago, whats the long time prognosis? How are yopu recovering?
Very well thanks Melinda, despite the fact that i have the neck the moment that looks like Mike Tyson, i think it is probabally bigger, the swelling i have not, i have to tell you i have not had a head ache, and i have been concious all the time, there has not been one time that i have not been concious since the begining of this incident, on Sunday, and so im very greatful for thet. i have a pin in my 6th vetibrae and that has now stabilised, and i can asure you that that feels fantastic, and was wearing i guess they call it a halo, on my head to try and bring the vertibrae back to line, but we got up to 40 pounds of weight on my head and at this stage it was pulling me over the end of the bed practically, so we knew we could not continue that so the choice was to have surjury and im very very plesed to say that that was sucessful.
We had heard just after the accident that, you injuries were potentially very dibilitating, that must have been a frightening experience?
Well i didn't hear that but of course Melinda i was the person that was actually bearing those injuries, and my eperiences told me that i was going to be okay, providing that i listened to and obeyed instructions, and i have been known in the past not to be very good at obeying instrucions, but i listened at all times and i made sure that i did exactly what the medical practitioners advised me to do, and i can not thank enought the ambulence officers in Alsice Springs the medical staff in Alice Springs, the Flying Doctors and of course this fantastic staff here at the spinal unit in Royal Adelaide Hospital, its been absolutely brillian.
Fay Miller What have doctors told you just briefly about when you might be back in the saddle, when you might be back at work?
I can be back at work as soon as this sweeling has gone down and as soon as i am able to maintain the brace and as soon as i am able to show them that i can do that with no discomfort and thats not too far away because the sweeling is going down each day.
Fay Miller, thank you very much for taking the time from your hospital bed for and we wish you all the best in your recovery and we look forward to seeing you back at Parliament House.
Thank you so much and believe me, I can't wait to be back Melinda.


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By Ray Fittipaldo Pittsburgh Post-Gazette
The Atlantic Coast Conference announced Pitt's home and road opponents for the 2013-14 men's basketball season.
The ACC will play employ an 18-game conference schedule with the addition of three new schools. The Panthers will play host to Duke, Maryland, Syracuse, Clemson, North Carolina State, Florida State, Wake Forest, Virginia and Virginia Tech.
The Panthers will travel to Miami, Georgia Tech, North Carolina, Boston College, Notre Dame, Maryland, Syracuse, Clemson and North Carolina State.mobilehome - breaking - pittsports
Ray Fittipaldo: firstname.lastname@example.com and Twitter @rayfitt1.
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Welcome to Myrtle Manor Trailer Park Skank-Off
Welcome to my first recap of "Trailer Park: Welcome to Myrtle Manor." Holy good Jesus what have I gotten myself into???
This show is in Season 2, and I didn't watch or recap Season 1, so I have tried to catch up this week. Wow. So if you didn't watch Season 1… here is a little recap of the characters (meant in more ways than one) and what went down in Season 1.
The show is set at a Trailer Park (duh) in Myrtle Beach, South Carolina, called Myrtle Manor. I've heard through the grapevine that it also called "Patrick's." Myrtle Manor is a park consisting of 120 trailers, and there are TONS of rules one has to follow as a resident of Myrtle Manor. They won't rent to people with bad rims or tats or dress seductively…or so they say, but so far it seems this is ONLY to whom they rent.
The owner of Myrtle Manor is Cecil Patrick. He's an older, no-nonsense gentleman who has put his daughter, Becky, in charge. His motto is "No Pay, No Stay." He's consistently grouchy, is constantly threatening to evict people and always tells Becky she is doing a crap job. He has owned the park for many, many years, but at the end of Season 1, he basically sold the park… but more on that later.
Becky, while sometimes tough, is also a pushover with a soft heart. Her father turned the management of the park over to her, but she keeps making a mess of things and he's constantly threatening to fire her. She tries to enforce the rules and holds a weekly Town Hall Meeting at the trailer park's hair salon- Tangulls- and every week it's "The Airing of the Grievances." And normally, the topics and issues are stuff that really shouldn't be between landlord and tenant.
Alyson is Becky's 20 year old daughter who took over management of the park for a short time in Season 1. Cecil turned it over to her when Becky had jacked something up particularly badly. The residents made her cry and boycotted her Town Hall meeting with picket signs, so Becky was put back in charge.
There is a narrator- "Jeana with a J" is her name. Jeana is Becky's Aunt (and Cecil's sister in law), although they have to be pretty close in age. Jeana just ended her 20 year marriage and is motorcycle chick. BTW- Rule #17 of Myrtle Manor is "Idle in / Idle out" no moped or motorcycle riding in the park. Jeana seems pretty normal.
The other residents are a bunch of characters… and they tend to drink a lot:
There's Jared who is a useless drifter. He rides a motorcycle. Becky has a soft spot for Jared and basically GAVE him a trailer to live in for free until he found a job. The problem is, Jared doesn't like to work, isn't motivated to find a job and when he gets a job he can't actually KEEP the job. He's, kind of, a musician, but in season 1 had stints as a Putt Putt maintenance man, dish washer, and male stripper. None of them lasted.
Then there are the Darlin' Dogs / Wiener Girls. Season 1 starts with Chelsey and Lindsey. They sell hot dogs on the beach, and don't sell very many of them. Probably because they can't cook. They smoke cigarettes constantly- even when preparing the hot dogs. They always seem to have enough money for cigs and beer.
They have a Hot Dog cart, but neither of them has a trailer hitch on their car in order to USE the cart to sell the hot dogs.
Midway through Season 1, they meet Amanda at a bar and ask her to move in with them and work at Darlin' Dogs with them. The main reason they hook up with her is because she has a trailer hitch on her Jeep. Amanda is a drunken red neck, but she is pretty likeable. Although it turned out to be a good move because Amanda is a hard worker (relatively speaking) and she can cook.
Amanda and Lindsey don't really get along and they end up having a fist fight and Lindsey leaves Darlin' Dogs and moves out… never to be heard from again.
Every lasting relationship begins with a Beer Bong
Jared and Chelsey hook up in Season 1 and end up getting married in the Season Finale… and they are actually STILL married a year later. They are both pretty dumb so… yeah, this should work out.
Tangulls is the Myrtle Manor hair salon- rumored to have been built just for the show. But it was condemned in Episode #2… so if it was built just for the show and condemned that quickly… you can imagine what a filthy sh*thole it is. Gina and Roy run Tangulls.
I don't think either of them actually lives in Myrtle Manor, but they are the gossip center of the park. Roy is an old Queen show loves to dress in drag. Roy worked in pageants and is a make-up artist. He has cheek implants and gets his lips injected… but his Wookie Tits are all his.
Roy and Gina also drink heavily.
This is, pretty much, every day with these two
There is also Taylor and Jessica who are dating, but they aren't in Season 2, so I won't even elaborate other than to say they are bat sh*t crazy. But Taylor's mom Anne is still around. Anne is a little bit nuts.
Typical decor in Anne's Trailer
She loves her cat that almost died in Season 1, she loves Flamingos and she likes to drink white wine. Anne is good friends with Marvin.
Not feeling very secure, are you?
Marvin is the head of the security at Myrtle Manor. He rarely makes sense and he has a gostache, which, is PRACTICALLY a Hitler 'stache. He has pink hubcaps also. He was the lead investigator in "PeeGate" Season 1. Marvin things Jared is a vampire.


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Civilization Committee
From Grand Theft Wiki
The CC (Civilization Committee) is GTA IV's version of the United Nations. The is located in Hatton Gardens on the shore of the Humboldt River. The CC is guarded by the LCPD and going through the gate (also known as trespassing) will result in a 4 star wanted level.


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Top Definition
Jared Meyers after his introduction to Erin Wenger. Characteristics: Liberal, accepting of all living cultures and their lifestyles, man of the Earth, very caring, good sense of style, dormant member of The Group
"Would you please stop talking? Let's have a logical, reasonable, reevaluation and discuss our differences." -Post-Jarin
by JNSD March 23, 2005
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Reconstituted jam band PHISH will perform at Blossom Music Center on Saturday, June 4.
The band's most recent studio album Joy was released in 2009 and was a Top 15 charting record.
Of course, their latest in-studio recording doesn't really matter to the legions of Phisheads.
Tickets for the concert will be $45 and $60 and go on sale at 11 a.m. Saturday, March 12.
To purschase tickets dial (that's right, I said "dial") (800)745-3000 or point your Intergoogle Machine to Livenation.com
So, mark your calendars.
In a shameless attempt to keep you here a little longer here's PHISH performing LOVING CUP from their 3D Movie


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This post is courtesy of BTBA judge, Scott Esposito. Scott Esposito blogs at Conversational Reading and you can find his tweets here.
I like the fact that the BTBA has a strong track record for picking not only the massive, monumental doorstoppers that tend to garner the lion's share of award attention but also the slim, sleek books that are often much richer and better-constructed. The best possible example is our first award, in which we gave the svelte Tranquility by Attila Bartis the nod over the imposing 2666 from, of course, Roberto Bolaño. 2011 saw us pick the slender The True Deceiver by Tove Jansson (beating out sizable finalists Hocus Bogus by Romain Gary, Agaat by Marlene Van Niekerk, and Georg Letham: Physician and Murderer by Ernst Weiss). But we've also gone for the bulky books: in 2013 we gave it to the sizable Satantango by Laszlo Krasznahorkai, and in 2012 is was Wiesław Myśliwski's epic Stone Upon Stone.
So, in that spirit, here's my discussion of some of the more sizable books that I both think are strong contenders for the award, and that I think should be left out.
Blinding by Mircea Cartarescu.
This is, quite simply, one of the most amazing books I've read this year. Cartarescu is one of the few authors I've read that could legitimately claim the legacy of Thomas Pynchon (now that Pynchon is writing parodies of himself). I'll have lots more to say about it in an upcoming review at The Kenyon Review, but for now, here are links to a review and interview at The Quarterly Conversation. Read it.
My Struggle: Book Two by Karl Ove Knausgaard
I have a feeling that when it's all said and done, this will be many people's favorite volume of the My Struggle sextet. It's subtitled "A Man In Love," and that's just what it is: the story of Knausgaard falling in love with the woman who is now his wife. There are so many passionate, ecstatic moments in here that anyone who has ever been in love will recognize, wrought extraordinarily well by Knausgaard. Plus, the book also has: his on and off feud with his crazy neighbor, who might be a prostitute; why he hates interviews; and the story of the incident in which he turned his face into a bloody mess with a razor blade.
Leg over Leg, Volume 1 and 2 by Ahmad Faris al-Shidyaq
This is billed as the Arabic world's answer to Tristram Shandy by Laurence Sterne. Apparently it begins with a lengthy list of synonyms for various parts of the male and female genitalia.
Seiobo There Below by Laszlo Krasznahorkai
If the Nobel committee would ever give their award to a writer like Krasznahorkai, this would be the book they would give it to him for. An inquiry into what humanity needs spirituality that is unlike anything I have ever read. Grand in scope, accomplishment, virtuosity. Grand, grand, grand. Read my review in Wednesday's Washington Post.
Where Tigers Are at Home by Jean-Marie Blas de Robles
Reviews have made this book sound extremely diverse and remarkably achieved. Could either be incredible or too big for its own good.
A Treatise on Shelling Beans by Wiesław Myśliwski
Okay, the title of this book is not awesome. But it is by the author of Stone Upon Stone, a book that seemingly everybody loves (I did enjoy it). And it is reputed to be even more of a masterpiece than that one.
City of Angels or, The Overcoat of Dr. Freud by Christa Wolf
An autobiographical look at '90s Los Angeles interspersed with memories of the Eastern Bloc where she re-discovers that she was actually a Stasi agent? Might just be crazy enough to work.
Maybe Not
In the Night of Time by Antonio Munoz Molina
Billed as the War and Peace of the Spanish Civil War. Muñoz Molina is certainly one of Spain's pre-eminent authors, but I've already read War and Peace.
Altai by Wu Ming
I'm tossing this on because "Wu Ming" is an awesome name and it's a pseudonym for a collective of Italian writers. How cool is that? Apparently not cool enough to make something more than middlebrow Dan Brown. The collective's previous book, Q, was a massive hit: I hope this book makes Verso boatloads of money so they can keep publishing Badiou and Ranciere.
Prose translators will likely disagree, but I believe translating poetry requires a significant level of talent, a commitment to the text, and near mania, all of which suggests that the undertaking is the greatest possible challenge. The task is to. . .
The biggest issues with books like The Subsidiary often have to do with their underpinnings—when we learn that Georges Perec wrote La Disparition without once using the letter E, we are impressed. Imagine such a task! It takes a high. . .
Following The Infatuations, Javier Marías's latest novel seems, like those that have preceded it, an experiment to test fiction's capacity to mesmerize with sombre-sexy atmospheres and ruminative elongated sentences stretched across windowless walls of paragraphs. Thus Bad Begins offers his. . .
Death by Water, Kenzaburo Oe's latest novel to be translated into English, practically begs you to read it as autobiography. Like The Changeling, as well as many other works not yet released in English, Death by Water is narrated in. . .
Jocelyne Saucier's Twenty-One Cardinals is about the type of unique, indestructible, and often tragic loyalty only found in families. For a brief but stunningly mesmerizing 169 pages, Twenty-One Cardinals invited me in to the haunting and intimate world of the. . .
We know so very little; so little that what we think to be knowledge is hardly worth reckoning with at all; instead we ought to settle for being pleasantly surprised if, on the edge of things, against all expectations, our. . .
Many of Virginie Despentes's books revolve around the same central idea: "To be born a woman [is] the worst fate in practically every society." But this message is nearly always packaged in easy-to-read books that fill you with the pleasure. . .
Ilja Leonard Pfeijffer's La Superba is appropriately titled after the Italian city of Genoa, where, after escaping the pressures of fame in his own country, the semi-autobiographical narrator finds himself cataloguing the experiences of its mesmerizing inhabitants with the intention. . .
It took reading 44 pages of Intervenir/Intervene before I began to get a sense of what Dolores Dorantes and Rodrigo Flores Sánchez were up to. Recurring throughout these 44 pages—throughout the entire book—are shovels, shovel smacks to the face, lobelias—aha!. . .
As presaged by its title, contradiction is the theme of Peter Stamm's novel, All Days Are Night. Gillian, a well-known television personality, remains unknowable to herself. And Hubert, a frustrated artist and Gillian's lover, creates art through the process of. . .


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Tag - Roadrunner
IBM Roadrunner supercomputer shuttered over power usage
The Los Alamos National Laboratory is shutting down its Roadrunner supercomputer, after deeming it too energy inefficient. Constructed by IBM in 2008, the five-year-old supercomputer was at one point the fastest in the world after achieving a speed exceeding one petaflop: one million billion calculations per second.
Emails from Comcast, RoadRunner going missing at Apple
Some emails sent to me.com or .mac addresses are going missing, according to complaints on Apple's support forums. In particular messages sent from Comcast but predominantly RoadRunner domains are either arriving as much as a day late, or disappearing entirely. The affected domains are also scattered across the country rather than located in a particular region. Unexpectedly, forwarding a message from one account to another may work without issues.
Palm's Enyo framework to allow tablets, high-end phone apps
HP and Palm's Joe Hayashi at the Palm Developer Day this Saturday provided some of the first details of the developer platform that will support a slew of new webOS devices next year. The Enyo framework will replace Mojo and is built to support different designs beyond the mix of touchscreen and physical keyboard, such as full-touch phones and tablets like the PalmPad. The JavaScript code underneath should run faster and will be more modular to help fix bugs and add new features sooner than before.
HP to launch webOS 2.0 Roadrunner HD phone early 2011
A Senior HP company exec has stated that its first webOS 2.0 phones will ship in early 2011. The result of HP�s acquisition of Palm, one of the first handsets likely to launch could be the rumored Roadrunner HD said to feature an iPhone 4 Retina display equaling 960x640 resolution.
HP/Palm Roadrunner device, webOS 2.0 show in app logs
WebOS developer Zhephree has found mention of a Palm RoadRunner device and mentions of webOS 2.0 in the operating system charts. He made this discovery in the logs on Metrix, and while this indicates that a device and/or webOS 2.0 is currently under development, it could be a ruse planted by a mischievous developer. That webOS 2.0 is currently under development is very likely, but this is the first mention of a RoadRunner device.
Cray supercomputer tops speed records at 1.75 petaflops
IBM's Roadrunner supercomputer has been dethroned from the TOP500 list in terms of computing performance by the Cray XT5 supercomputer, nicknamed Jaguar. The XT5 uses AMD Opteron cores and posted up a 1.75 petaflop/s speed in the Linpack test, outpacing the Roadrunner's 1 petaflop/s performance.
Now AAPL Stock: 137.08 ( + 0.42 )
Cirrus creates Lightning-headphone dev kit
Apple supplier Cirrus Logic has introduced a MFi-compliant new development kit for companies interested in using Cirrus' chips to create Lightning-based headphones, which -- regardless of whether rumors about Apple dropping the analog headphone jack in its iPhone this fall -- can offer advantages to music-loving iOS device users. The kit mentions some of the advantages of an all-digital headset or headphone connector, including higher-bitrate support, a more customizable experience, and support for power and data transfer into headphone hardware. Several companies already make Lightning headphones, and Apple has supported the concept since June 2014. http://bit.ly/29giiZj
Apple Store app offers Procreate Pocket
The Apple Store app for iPhone, which periodically rewards users with free app gifts, is now offering the iPhone "Pocket" version of drawing app Procreate for those who have the free Apple Store app until July 28. Users who have redeemed the offer by navigating to the "Stores" tab of the app and swiping past the "iPhone Upgrade Program" banner to the "Procreate" banner have noted that only the limited Pocket (iPhone) version of the app is available free, even if the Apple Store app is installed and the offer redeemed on an iPad. The Pocket version currently sells for $3 on the iOS App Store. [32.4MB]
Porsche adds CarPlay to 2017 Panamera
Porsche has added a fifth model of vehicle to its CarPlay-supported lineup, announcing that the 2017 Panamera -- which will arrive in the US in January -- will include Apple's infotainment technology, and be seen on a giant 12.3-inch touchscreen as part of an all-new Porsche Communication Management system. The luxury sedan starts at $99,900 for the 4S model, and scales up to the Panamera Turbo, which sells for $146,900. Other vehicles that currently support CarPlay include the 2016 911 and the 2017 models of Macan, 718 Boxster, and 718 Cayman. The company did not mention support for Google's corresponding Android Auto in its announcement. http://bit.ly/295ZQ94
Apple employees testing wheelchair features
New features included in the forthcoming watchOS 3 are being tested by Apple retail store employees, including a new activity-tracking feature that has been designed with wheelchair users in mind. The move is slightly unusual in that, while retail employees have previously been used to test pre-release versions of OS X and iOS, this marks the first time they've been included in the otherwise developer-only watchOS betas. The company is said to have gone to great lengths to modify the activity tracker for wheelchair users, including changing the "time to stand" notification to "time to roll" and including two wheelchair-centric workout apps. http://bit.ly/2955JDa
SanDisk reveals two 256GB microSDXC cards
SanDisk has introduced two 256GB microSDXC cards. Arriving in August for $150, the Ultra microSDXC UHS-I Premium Edition card offers transfer speeds of up to 95MB/s for reading data. The Extreme microSDXC UHS-I card can read at a fast 100MB/s and write at up to 90MB/s, and will be shipping sometime in the fourth quarter for $200. http://bit.ly/294Q1If
Apple's third-quarter results due July 26
Apple has advised it will be issuing its third-quarter results on July 26, with a conference call to answer investor and analyst queries about the earnings set to take place later that day. The stream of the call will go live at 2pm PT (5pm ET) via Apple's investor site, with the results themselves expected to be released roughly 30 minutes before the call commences. Apple's guidance for the quarter put revenue at between $41 billion and $43 billion. http://apple.co/1oi1Pbm
Twitter stickers slowly roll out to users
Twitter has introduced "stickers," allowing users to add extra graphical elements to their photos before uploading them to the micro-blogging service. A library of hundreds of accessories, props, and emoji will be available to use as stickers, which can be resized, rotated, and placed anywhere on the photograph. Images with stickers will also become searchable with viewers able to select a sticker to see how others use the same graphic in their own posts. Twitter advises stickers will be rolling out to users over the next few weeks, and will work on both the mobile apps and through the browser. http://bit.ly/29bbwUE


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Chefs and bartenders are increasingly turning to vinegar, even making their own, to add another level of flavor to their cocktails. San Francisco bartender Carlo Splendorini, of the Michael Mina Group of restaurants, enjoys this trend. He favors balsamic vinegar because he finds the warm flavors of these vinegars from Modena bring depth, nuance and a hint of sweetness to his cocktails. His Spring Sparkle is made with rum, Champagne and a vinegar-soaked sugar cube. Read more.
Full Story:zesterdaily.com


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- Sporty Bra with Back Straps
- This stylish sports bra works great on its own or paired with any of our stylish tops.
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- Fit is true to size
- Style Number: 1006
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Roane State Community College's Tennessee Small Business Development Center and the Oak Ridge Chamber of Commerce are offering a couple of free workshops for area business owners.
The March 14 workshop on government contracting will be from 9 a.m. to noon in the Oak Ridge Chamber of Commerce offices at 1400 Oak Ridge Turnpike.
A workshop on franchising will be from 11:30 a.m. to 1 p.m. March 15 in the Oak Ridge Chamber.
Contact Jutta Bangs at 865-483-2663 or firstname.lastname@example.com for details.
The coaches in District 4-AA recently got together to choose their all-district teams, and the news turned out good for a total of four players from Kingston as Haley Cornellison, Makayla Cordell, Robbie Szozda and Brandon Griffis all received all-district recognition.
Margaret Larson Evans purchased a piece of property in Paint Rock Farm Lake Estates for $100,000 in 2006.
"I did it because I used to have a horse out here and knew a bunch of people in the neighborhood," she said. "So to me it was worth $100,000 to retire here."
The Roane County Property Assessor's Office caused her to have second thoughts in 2010 when appraisers valued her land at $166,400.
• Kingston United Methodist Church's All 4 Kids sale will begin at 9 a.m. in the fellowship hall of Bethel Presbyterian Church at 203 S. Kentucky St., Kingston. The sale continues from 9 a.m. to noon Saturday.
• Riggs Chapel Baptist Church, Harriman, will have its first-ever Only Believe family rally beginning at 6 p.m. in the church at 623 Riggs Chapel Road. The church's youth drama team, with help from some of the adults, will perform skits and songs. Bruce Armes will be the guest speaker.
Kingston Elementary School's three-day annual science fair last month included participation by 325 students.
Each third-, fourth- and fifth-grader participating had to propose a scientific hypothesis, write an abstract, design an experiment to test the hypothesis, keep records and present the finding in a poster session before a panel of judges.
Kingston Rotary Club and community volunteers served on a panel of 19 judges for the three-day event.
Roane County's School-Wide Positive Behavior Support is a team-based, proactive approach to teaching and prevention that fosters a safe, effective learning environment and a positive social culture.
When implemented properly, the program augments student security and success as well as increases the potential for making school a positive experience.
In such an atmosphere, students are inspired to excel and feel excited about being in school.
• Rockwood Zoning Board and Regional Planning Commission will meet in regular monthly session at 6:30 p.m. in Rockwood City Hall.
• Roane County Commission's fire board will meet at 6 p.m. in the Qualls Commission Room of Roane County Courthouse, Kingston.
• Rockwood Recreation Board will meet in regular session at 6 p.m. in Rockwood Community Center.
Editor's note: The deadline for including items in Calendar is at least one week before the event. Items appear as a public service as space is available. Unless otherwise noted, all events and activities are open to the public.
Editor's note: The deadline for including items in Calendar is at least one week before the event. Items appear as a public service as space is available. Unless otherwise noted, all events and activities are open to the public.
• Bradbury United Methodist Church's Relay for Life team will have a bean and soup supper and auction beginning at 6 p.m. in the church at 3506 Buttermilk Road West, Kingston. All money raised will go to the American Cancer Society. Call the church office at 376-2990 for details.
Copyright © 2017
The Roane County News is your source for local news, sports, events, and information in Roane County and Kingston, Tennessee, and the surrounding area.


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News & Events
Graduate Certificate Program in African American Studies Approved!
The certificate program emphasizes how blackness intersects with other ethnic identities and how it is shaped by gender, sexuality, and economic inequity.
Allison Davis Lecture
Thursday, October 27, 4:00 PM
Barbara Ransby
Leon Forrest Lecture
Monday, April 24, 4:00 PM
Anna Deavere Smith


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Paul Ryan Gets Testy And Ends Interview
When asked about guns and taxes in an interview with ABC12 in Flint, Michigan. Campaign: "Eventually you're going to see a local reporter embarrass himself."
Update: Ryan spokesman Brendan Buck tells BuzzFeed: "The reporter knew he was already well over the allotted time for the interview when he decided to ask a weird question relating gun violence to tax cuts. Ryan responded as anyone would in such a strange situation. When you do nearly 200 interviews in a couple months, eventually you're going to see a local reporter embarrass himself."
The headline of this item has been changed.
- "Moonlight" won Best Picture at the Oscars, but they accidentally gave it to "La La Land" first 😳
- Philip Bilden, the businessman nominated by President Trump to be secretary of the Navy, has withdrawn himself from consideration.
- Actor Bill Paxton has died at 61. He starred in classics including "Twister" and "Titanic."
- The Nokia brick phone is making a comeback — it's been reimagined with a colored screen, but the game Snake hasn't gone anywhere 🐍📲