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FDA Approves Esbriet to Treat Idiopathic Pulmonary Fibrosis »
"The U.S. Food and Drug Administration today approved Esbriet (pirfenidone) for the treatment of idiopathic pulmonary fibrosis (IPF).
Idiopathic pulmonary fibrosis is a condition in which the lungs become progressively scarred o"...
Read the FDA Approves Esbriet to Treat Idiopathic Pulmonary Fibrosis article »
Mechanism Of Action
Tadalafil is an inhibitor of phosphodiesterase type 5 (PDE5), the enzyme responsible for the degradation of cyclic guanosine monophosphate (cGMP). Pulmonary arterial hypertension is associated with impaired release of nitric oxide by the vascular endothelium and consequent reduction of cGMP concentrations in the pulmonary vascular s mooth muscle. PDE5 is the predominant phosphodiesterase in the pulmonary vasculature. Inhibition of PDE5 by tadalafil increases the concentrations of cGMP resulting in relaxation of pulmonary vascular smooth muscle cells and vasodilation of the pulmonary vascular bed.
Studies in vitro have demonstrated that tadalafil is a selective inhibitor of PDE5. PDE5 is found in pulmonary vascular smooth muscle, visceral smooth muscle, corpus cavernosum, skeletal muscle, platelets, kidney, lung, cerebellum, and pancreas.
In vitro studies have shown that the effect of tadalafil is more potent on PDE5 than on other phosphodiesterases. These studies have shown that tadalafil is >10,000–fold more potent for PDE5 than for PDE1, PDE2, PDE4, and PDE7 enzymes, which are found in the heart, brain, blood vessels, liver, leukocytes, skeletal muscle, and other organs. Tadalafil is >10,000–fold more potent for PDE5 than for PDE3, an enzyme found in the heart and blood vessels. Additionally, tadalafil is 700.fold more potent for PDE5 than for PDE6, which is found in the retina and is responsible for phototransduction. Tadalafil is >9,000-fold more potent for PDE5 than for PDE8, PDE9, and PDE10. Tadalafil is 14–fold more potent for PDE5 than for PDE11A1 and 40–fold more potent for PDE5 than for PDE11A4, two of the four known forms of PDE11. PDE11 is an enzyme found in human prostate, testes, skeletal muscle and in other tissues. In vitro, tadalafil inhibits human recombinant PDE11A1 and, to a lesser degree, PDE11A4 activities at concentrations within the therapeutic range. The physiological role and clinical consequence of PDE11 inhibition in humans have not been defined.
Effects On Blood Pressure When Administered With Nitrates
In clinical pharmacology studies, tadalafil (5 to 20 mg) was shown to potentiate the hypotensive effect of nitrates. Do not use ADCIRCA in patients taking any form of nitrates [see CONTRAINDICATIONS].
A double–blind, placebo–controlled, crossover study in 150 male subjects at least 40 years of age (including subjects with diabetes mellitus and/or controlled hypertension) assessed the interaction between nitroglycerin and tadalafil. Subjects received daily doses of tadalafil 20 mg or matching placebo for 7 days and then were given a single dose of 0.4 mg sublingual nitroglycerin (NTG) at pre–specified timepoints following their last dose of tadalafil (2, 4, 8, 24, 48, 72, and 96 hours after tadalafil). A significant interaction between tadalafil and NTG was observed at each timepoint up to and including 24 hours. At 48 hours, by most hemodynamic measures, the interaction between tadalafil and NTG was not observed, although a few more tadalafil subjects compared to placebo experienced greater blood–pressure lowering effects at this timepoint. After 48 hours, the interaction was not detectable. [See CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS].
Effects On Blood Pressure
Tadalafil 20 mg administered to healthy male subjects produced no significant difference compared to placebo in supine systolic and diastolic blood pressure (difference in the mean maximal decrease of 1.6/0.8 mm Hg, respectively) and in standing systolic and diastolic blood pressure (difference in the mean maximal decrease of 0.2/4.6 mm Hg, respectively). In addition, there was no significant effect on heart rate.
Effects On Blood Pressure When Administered With Antihypertensives
A study assessed the interaction between amlodipine (5 mg daily) and tadalafil 10 mg. There was no effect of tadalafil on amlodipine blood levels and no effect of amlodipine on tadalafil blood levels. The mean reduction in supine systolic/diastolic blood pressure because of tadalafil 10 mg in subjects taking amlodipine was 3/2 mm Hg, compared to placebo. In a similar study using tadalafil 20 mg, there were no clinically significant differences between tadalafil and placebo in subjects taking amlodipine.
Angiotensin II receptor blockers (with and without other antihypertensives)
A study assessed the interaction between angiotensin II receptor blockers and tadalafil 20 mg. Subjects in the study were taking any marketed angiotensin II receptor blocker, either alone, as a component of a combination product, or as part of a multiple antihypertensive regimen. Following dosing, ambulatory measurements of blood pressure revealed differences between tadalafil and placebo of 8/4 mm Hg in systolic/diastolic blood pressure.
A study assessed the interaction between bendroflumethiazide (2.5 mg daily) and tadalafil 10 mg. Following dosing, the mean reduction in supine systolic/diastolic blood pressure because of tadalafil 10 mg in subjects taking bendroflumethiazide was 6/4 mm Hg, compared to placebo.
A study assessed the interaction between enalapril (10 to 20 mg daily) and tadalafil 10 mg. Following dosing, the mean reduction in supine systolic/diastolic blood pressure because of tadalafil 10 mg in subjects taking enalapril was 4/1 mm Hg, compared to placebo.
A study assessed the interaction between sustained.release metoprolol (25 to 200 mg daily) and tadalafil 10 mg. Following dosing, the mean reduction in supine systolic/diastolic blood pressure because of tadalafil 10 mg in subjects taking metoprolol was 5/3 mm Hg, compared to placebo.
Effects On Blood Pressure When Administered With Alcohol
Alcohol and PDE5 inhibitors, including tadalafil, are mild systemic vasodilators. The interaction of tadalafil with alcohol was evaluated in three clinical pharmacology studies. In two of these, alcohol was administered at a dose of 0.7 g/kg, which is equivalent to approximately 6 ounces of 80–proof vodka in an 80–kg male, and tadalafil was administered at a dose of 10 mg in one study and 20 mg in another. In both these studies, all patients imbibed the entire alcohol dose within 10 minutes of starting. In one of these two studies, blood alcohol levels of 0.08% were confirmed. In these two studies, more patients had clinically significant decreases in blood pressure on the combination of tadalafil and alcohol as compared to alcohol alone. Some subjects reported postural dizziness, and orthostatic hypotension was observed in some subjects. When tadalafil 20 mg was administered with a lower dose of alcohol (0.6 g/kg, which is equivalent to approximately 4 ounces of 80–proof vodka, administered in less than 10 minutes), orthostatic hypotension was not observed, dizziness occurred with similar frequency to alcohol alone, and the hypotensive effects of alcohol were not potentiated.
Tadalafil did not affect alcohol plasma concentrations and alcohol did not affect tadalafil plasma concentrations.
Effects On Blood Pressure When Administered With Alpha-Blockers
Alpha-blockers and PDE5 inhibitors, including tadalafil, are systemic vasodilators. In subjects receiving concomitant tadalafil (20 mg single dose) and doxazosin (8 mg daily), an alpha-1 adrenergic receptor blocker, there was an augmentation of the blood pressure–lowering effect of doxazosin. This effect was still present at 12 hours postdose and had generally disappeared at 24 hours. The number of subjects with potentially clinically significant standing –blood– pressure decreases was greater for the combination.
An additional study was performed with tadalafil (20 mg single dose) and doxazosin (4 and 8 mg daily) using ambulatory blood pressure monitoring. The augmentation appeared unrelated to dosing times and resulted in a greater number of outliers for the combination than had been observed in the previous study. Both of these studies had some symptomatology associated with these blood pressure changes.
A further study was carried out with doxazosin (up to 4 mg daily) added to tadalafil (5 mg daily) and there was again an augmentation of response. In this clinical pharmacology study there were symptoms associated with the decrease in blood pressure, including syncope.
An interaction study with tadalafil (20 mg single dose) and alfuzosin, also an alpha-1 adrenergic receptor blocker, showed no clinically significant effect on blood pressure.
In two clinical pharmacology studies in healthy volunteers, tadalafil (5 mg daily, and 10 mg and 20 mg single dose) had no clinically significant effect on blood pressure changes because of tamsulosin, a selective alpha-1a adrenergic receptor blocking agent.
Effects On Cardiac Electrophysiology
The effect of a single 100 mg dose of tadalafil (2.5 times the recommended dose) on the QT interval was evaluated at the time of peak tadalafil concentration in a randomized, double.blinded, placebo, and active.controlled (intravenous ibutilide) crossover study in 90 healthy males aged 18 to 53 years. The mean change in QTc (Fridericia QT correction) for tadalafil, relative to placebo, was 3.5 milliseconds (two–sided 90% CI=1.9, 5.1). The mean change in QTc (Individual QT correction) for tadalafil, relative to placebo, was 2.8 milliseconds (two–sided 90% CI=1.2, 4.4). In this study, the mean increase in heart rate associated with a 100 mg dose of tadalafil compared to placebo was 3.1 beats per minute.
Effects On Exercise Stress Testing
The effects of tadalafil on cardiac function, hemodynamics, and exercise tolerance were investigated in a single clinical pharmacology study. In this blinded crossover trial, 23 subjects with stable coronary artery disease and evidence of exercise–induced cardiac ischemia were enrolled. The primary endpoint was time to cardiac ischemia. The mean difference in total exercise time was 3 seconds (tadalafil 10 mg minus placebo), which represented no clinically meaningful difference. Further statistical analysis demonstrated that tadalafil was similar to placebo with respect to time to ischemia. Of note, in this study, in some subjects who received tadalafil followed by sublingual nitroglycerin in the post– exercise period, clinically significant reductions in blood pressure were observed, consistent with the augmentation by tadalafil of the blood–pressure–lowering effects of nitrates.
Effects On Vision
Single oral doses of PDE inhibitors have demonstrated transient dose-related impairment of color discrimination (blue/green), using the Farnsworth– Munsell 100–hue test, with peak effects near the time of peak plasma levels. This finding is consistent with the inhibition of PDE6, which is involved in phototransduction in the retina. In a study to assess the effects of a single dose of tadalafil 40 mg on vision (N=59), no effects were observed on visual acuity, intraocular pressure, or pupillometry. Across all clinical studies with tadalafil, reports of changes in color vision were rare (<0.1% of patients).
Effects On Sperm Characteristics
Three studies were conducted in men to assess the potential effect on sperm characteristics of tadalafil 10 mg (one 6-month study) and 20 mg (one 6-month and one 9-month study) administered daily. There were no adverse effects on sperm morphology or sperm motility in any of the three studies. In the study of 10 mg tadalafil for 6 months and the study of 20 mg tadalafil for 9 months, results showed a decrease in mean sperm concentrations relative to placebo, although these differences were not clinically meaningful. This effect was not seen in the study of 20 mg tadalafil taken for 6 months. In addition there was no adverse effect on mean concentrations of reproductive hormones, testosterone, luteinizing hormone or follicle stimulating hormone with either 10 or 20 mg of tadalafil compared to placebo.
Dose-Response Relationship
Dose-response relationships, between 20 mg and 40 mg, were not observed for 6-minute walk distance or pulmonary vascular resistance (PVR) in subjects with PAH in the placebo-controlled study. Median change from baseline in 6-minute walk distance was 32 meters and 35 meters at 16 weeks in subjects receiving 20 mg and 40 mg daily, respectively. Mean change from baseline PVR was -254 dynes*sec*cm-5 and -209 dynes*sec*cm-5 at 16 weeks in patients receiving 20 mg and 40 mg daily, respectively.
Over a dose range of 2.5 to 20 mg, tadalafil exposure (AUC) increases proportionally with dose in healthy subjects. In PAH patients administered between 20 and 40 mg of tadalafil, an approximately 1.5-fold greater AUC was observed indicating a less than proportional increase in exposure over the entire dose range of 2.5 to 40 mg. During tadalafil 20 and 40 mg once daily dosing, steady-state plasma concentrations were attained within 5 days, and exposure was approximately 1.3-fold higher than after a single dose.
After single oral-dose administration, the maximum observed plasma concentration (Cmax) of tadalafil is achieved between 2 and 8 hours (median time of 4 hours). Absolute bioavailability of tadalafil following oral dosing has not been determined.
The rate and extent of absorption of tadalafil are not influenced by food; thus ADCIRCA may be taken with or without food.
The mean apparent volume of distribution following oral administration is approximately 77 L, indicating that tadalafil is distributed into tissues. At therapeutic concentrations, 94% of tadalafil in plasma is bound to proteins.
Tadalafil is predominantly metabolized by CYP3A to a catechol metabolite. The catechol metabolite undergoes extensive methylation and glucuronidation to form the methylcatechol and methylcatechol glucuronide conjugate, respectively. The major circulating metabolite is the methylcatechol glucuronide. Methylcatechol concentrations are less than 10% of glucuronide concentrations. In vitro data suggests that metabolites are not expected to be pharmacologically active at observed metabolite concentrations.
Following 40 mg, the mean oral clearance for tadalafil is 3.4 L/hr and the mean terminal half-life is 15 hours in healthy subjects. In patients with pulmonary hypertension not receiving concomitant bosentan, the mean oral clearance for tadalafil is 1.6 L/hr, and the mean terminal half-life is 35 hours. Tadalafil is excreted predominantly as metabolites, mainly in the feces (approximately 61% of the dose) and to a lesser extent in the urine (approximately 36% of the dose).
Population Pharmacokinetics
In patients with pulmonary hypertension not receiving concomitant bosentan, the average tadalafil exposure at steady-state following 40 mg was 26% higher when compared to those of healthy volunteers. The results suggest a lower clearance of tadalafil in patients with pulmonary hypertension compared to healthy volunteers.
Geriatric Patients
In healthy male elderly subjects (65 years or over) after a 10 mg dose, a lower oral clearance of tadalafil, resulting in 25% higher exposure (AUC) with no effect on Cmax was observed relative to that in healthy subjects 19 to 45 years of age.
Renal Impairment
In clinical pharmacology studies using single-dose tadalafil (5 to 10 mg), tadalafil exposure (AUC) doubled in subjects with mild (creatinine clearance 51 to 80 mL/min) or moderate (creatinine clearance 31 to 50 mL/min) renal impairment. In subjects with end-stage renal disease on hemodialysis, there was a two-fold increase in Cmax and 2.7-to 4.1-fold increase in AUC following single-dose administration of 10 or 20 mg tadalafil, respectively. Exposure to total methylcatechol (unconjugated plus glucuronide) was 2-to 4-fold higher in subjects with renal impairment, compared to those with normal renal function. Hemodialysis (performed between 24 and 30 hours post-dose) contributed negligibly to tadalafil or metabolite elimination [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS].
Hepatic Impairment
In clinical pharmacology studies, tadalafil exposure (AUC) in subjects with mild or moderate hepatic impairment (Child-Pugh Class A or B) was comparable to exposure in healthy subjects when a dose of 10 mg was administered. There are no available data for doses higher than 10 mg of tadalafil in patients with hepatic impairment. Insufficient data are available for subjects with severe hepatic impairment (Child-Pugh Class C) [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS].
Patients With Diabetes Mellitus
In male patients with diabetes mellitus after a 10 mg tadalafil dose, exposure (AUC) was reduced approximately 19% and Cmax was 5% lower than that observed in healthy subjects. No dose adjustment is warranted.
Pharmacokinetic studies have included subjects from different ethnic groups, and no differences in the typical exposure to tadalafil have been identified. No dose adjustment is warranted.
In healthy female and male subjects following single and multiple-doses of tadalafil, no clinically relevant differences in exposure (AUC and Cmax) were observed. No dose adjustment is warranted.
Drug Interaction Studies
Tadalafil is a substrate of and predominantly metabolized by CYP3A. Drugs that inhibit CYP3A can increase tadalafil exposure.
Ritonavir (500 mg or 600 mg twice daily at steady state), an inhibitor of CYP3A, CYP2C9, CYP2C19, and CYP2D6, increased tadalafil 20–mg single-dose exposure (AUC) by 32% with a 30% reduction in Cmax, relative to the values for tadalafil 20 mg alone. Ritonavir (200 mg twice daily), increased tadalafil 20.mg single-dose exposure (AUC) by 124% with no change in Cmax, relative to the values for tadalafil 20 mg alone. Ritonavir inhibits and induces CYP3A, the enzyme involved in the metabolism of tadalafil, in a time-dependent manner. The results suggest the initial inhibitory effect of ritonavir on CYP3A may be mitigated by a more slowly evolving induction effect so that after about 1 week of ritonavir twice daily, the exposure of tadalafil is similar in the presence of and absence of ritonavir [see DOSAGE AND ADMINISTRATION , WARNINGS AND PRECAUTIONS , and DRUG INTERACTIONS]. Although specific interactions have not been studied, other HIV protease inhibitors would likely increase tadalafil exposure.
Other Cytochrome P450 Inhibitors
CYP3A (e.g., ketoconazole)
Ketoconazole (400 mg daily), a selective and potent inhibitor of CYP3A, increased tadalafil 20 mg single-dose exposure (AUC) by 312% and Cmax by 22%, relative to the values for tadalafil 20 mg alone.
Ketoconazole (200 mg daily) increased tadalafil 10.mg single-dose exposure (AUC) by 107% and Cmax by 15%, relative to the values for tadalafil 10 mg alone.
Although specific interactions have not been studied, other CYP3A inhibitors, such as erythromycin, itraconazole, and grapefruit juice, would likely increase tadalafil exposure.
Cytochrome P450 Inducers
CYP3A (e.g., rifampin, bosentan)
Rifampin (600 mg daily), a CYP3A inducer, reduced tadalafil 10 mg single. dose exposure (AUC) by 88% and Cmax by 46%, relative to the values for tadalafil 10 mg alone.
Bosentan (125 mg twice daily), a substrate of CYP2C9 and CYP3A and a moderate inducer of CYP3A, CYP2C9 and possibly CYP2C19, reduced tadalafil (40 mg once per day) systemic exposure by 42% and Cmax by 27% following multiple-dose co-administration.
Although specific interactions have not been studied, other CYP3A inducers, such as carbamazepine, phenytoin, and phenobarbital, would likely decrease tadalafil exposure.
Cytochrome P450 Substrates
Tadalafil is not expected to cause clinically significant inhibition or induction of the clearance of drugs metabolized by cytochrome P450 (CYP) isoforms.
CYP1A2 (e.g., theophylline)
Tadalafil (10 mg once per day) had no significant effect on the pharmacokinetics of theophylline. When tadalafil was administered to subjects taking theophylline, a small augmentation (3 beats per minute) of the increase in heart rate associated with theophylline was observed.
CYP2C9 (e.g., warfarin)
Tadalafil (10 mg and 20 mg once per day) had no significant effect on exposure (AUC) to S.warfarin or R.warfarin, nor did tadalafil affect changes in prothrombin time induced by warfarin.
CYP3A (e.g., midazolam, lovastatin or bosentan)
Tadalafil (10 mg and 20 mg once per day) had no significant effect on exposure (AUC) to midazolam or lovastatin. Tadalafil (40 mg once per day) had no clinically significant effect on exposure (AUC and Cmax) of bosentan, a substrate of CYP2C9 and CYP3A, or its metabolites.
Tadalafil (10 mg and 20 mg once per day) did not potentiate the increase in bleeding time caused by aspirin.
P-Glycoprotein (e.g., Digoxin)
Coadministration of tadalafil (40 mg once per day) for 10 days did not have a significant effect on the steady-state pharmacokinetics of digoxin (0.25 mg/day) in healthy subjects.
Combined Oral Contraceptives
At steady-state, tadalafil (40 mg once per day) increased ethinyl estradiol exposure (AUC) by 26% and Cmax by 70% relative to oral contraceptive administered with placebo. There was no significant effect of tadalafil on levonorgestrel.
Simultaneous administration of an antacid (magnesium hydroxide/aluminum hydroxide) and tadalafil (10 mg) reduced the apparent rate of absorption of tadalafil without altering exposure (AUC) to tadalafil.
H2 Antagonists (e.g., Nizatidine)
An increase in gastric pH resulting from administration of nizatidine had no significant effect on tadalafil (10 mg) pharmacokinetics.
Animal Toxicology And/Or Pharmacology
Animal studies showed vascular inflammation in tadalafil–treated mice, rats, and dogs. In mice and rats, lymphoid necrosis and hemorrhage were seen in the spleen, thymus, and mesenteric lymph nodes at unbound tadalafil exp osure of 1– to 17–fold the human exposure (AUCs) at the MRHD of 40 mg. In dogs, an increased incidence of disseminated arteritis was observed in 1– and 6-month studies at unbound tadalafil exposure of 0.5– to 38–fold the human exposure (AUC) at the MRHD of 40 mg. In a 12–month dog study, no disseminated arteritis was observed, but 2 dogs exhibited marked decreases in white blood cells (neutrophils) and moderate decreases in platelets with inflammatory signs at unbound tadalafil exposures of approximately 4– to 10–fold the human exposure at the MRHD of 40 mg. The abnormal blood–cell findings were reversible within 2 weeks upon removal of the drug.
Reproductive Toxicology Studies
Reproduction studies have been performed in rats and mice at exposures up to 17 times the MRHD of 40 mg and have revealed no evidence of impaired fertility or harm to the fetus because of tadalafil. In addition, there was no evidence of teratogenicity, embryotoxicity, or fetotoxicity when tadalafil was given to pregnant rats or mice at exposures up to 7 times the MRHD during the period of major organ development.
In a rat prenatal and postnatal development study at doses of 60, 200, and 1000 mg/kg, a reduction in postnatal survival of pups was observed. The no-observed-effect-level (NOEL) for maternal toxicity was 200 mg/kg/day and for developmental toxicity was 30 mg/kg/day. This gives approximately 8- and 5-fold exposure multiples, respectively, of the human AUC for the MRHD of 40 mg. Tadalafil and/or its metabolites cross the placenta, resulting in fetal exposure in rats.
Tadalafil and/or its metabolites were secreted into the milk in lactating rats at concentrations approximately 2.4– fold greater than found in the plasma.
Clinical Studies
ADCIRCA For Pulmonary Arterial Hypertension
A randomized, double-blind, 16 week placebo-controlled study was conducted in 405 patients with pulmonary arterial hypertension, defined as a resting mean pulmonary artery pressure (mPAP) ≥25 mm Hg, pulmonary capillary wedge pressure (PCWP) ≤15 mm Hg, and pulmonary vascular resistance (PVR) ≥3 Wood units via right heart catheterization. Allowed background therapy included bosentan (maintenance dosing up to 125 mg twice daily) and chronic anticoagulation. The use of prostacyclin or analogue, L.arginine, phosphodiesterase inhibitor, or other chronic PAH medications were not permitted.
Subjects were randomly assigned to 1 of 5 treatment groups (tadalafil 2.5, 10, 20, 40 mg, or placebo) in a 1:1:1:1:1 ratio. Subjects had to be at least 12 years of age and had a diagnosis of PAH that was idiopathic, heritable, related to connective tissue disease, anorexigen use, human immunodeficiency virus (HIV) infection, associated with an atrial-septal defect, or associated with surgical repair of a congenital systemic-to-pulmonary shunt of least 1 year in duration (for example, ventricular septal defect, patent ductus arteriosus). Patients with a history of left-sided heart disease, severe renal insufficiency, or pulmonary hypertension related to conditions other than specified in the inclusion criteria were not eligible for enrollment.
The mean age of all subjects was 54 years (range 14 - 90 years) with the majority of subjects being Caucasian (81%) and female (78%). PAH etiologies were predominantly idiopathic or heritable PAH (61%) and related to connective tissue disease (23%). More than half (53%) of the subjects in the study were receiving concomitant bosentan therapy. The majority of subjects had a World Health Organization (WHO) Functional Class III (65%) or II (32%). The mean baseline 6minute walk distance (6-MWD) was 343 meters. Of the 405 subjects, 341 completed the study.
The primary efficacy endpoint was the change from baseline at week 16 in 6-MWD (see Figure 1). In the ADCIRCA 40 mg treatment group, the placebo-adjusted mean change increase in 6-MWD was 33 meters (95% C.I. 15-50 meters; p=0.0004). The improvement in 6-MWD was apparent at 8 weeks of treatment and then maintained at week 12 and week 16.
Placebo-adjusted changes in 6-MWD at 16 weeks were evaluated in subgroups (see Figure 2). In patients taking only ADCIRCA 40 mg (i.e., without concomitant bosentan), the placebo-adjusted mean change in 6-MW D was 44 meters.
In patients taking ADCIRCA 40 mg and concomitant bosentan therapy, the placebo adjusted mean change in 6-MWD was 23 meters.
There was less clinical worsening (defined as death, lung transplantation, atrial septostomy, hospitalization because of worsening PAH, initiation of new PAH therapy [prostacyclin or analog, endothelin receptor antagonist, PDE5 inhibitor], or worsening WHO functional class) in the ADCIRCA 40 mg group compared to the placebo group and the groups that used lower doses of ADCIRCA.
Table 2: Number (percent) with Clinical Worseninga
|2.5 mg
|10 mg
|20 mg
|40 mg
|Total with clinical worsening
|13 (16)
|10 (12)
|7 (9)
|8 (10)
|4 (5)
|Hospitalization for worsening PAH
|New PAH therapy
|Worsening WHO class
|a Subjects may be counted in more than one category
The Kaplan-Meier plot of times to clinical worsening is shown below in Figure 3.
Long-Term Treatment Of Pulmonary Arterial Hypertension
Patients (N=357) from the placebo-controlled study entered a long-term extension study. Of these, 311 patients have been treated with tadalafil for at least 6 months and 182 for 1 year (median exposure 356 days; range 2 days to 415 days). The survival rate in the extension study was 96.5 per 100 patient years. Without a control group, these data must be interpreted cautiously.
Last reviewed on RxList: 5/22/2017
This monograph has been modified to include the generic and brand name in many instances.
Adcirca FDA Prescribing Information
Additional Adcirca Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Women's Health
Find out what women really need.


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German Shepherd Dog Forums (http://www.germanshepherds.com/forum/)
- General Information (http://www.germanshepherds.com/forum/general-information/)
- - Free pups with a $2,000 doghouse (http://www.germanshepherds.com/forum/general-information/424442-free-pups-%242-000-doghouse.html)
Free pups with a $2,000 doghouse
I occasionally scan Craigslist and this one is REALLY a winner. FREE MALINOIS PUPPIES.... Nice that he keeps his (as he calls it ) family protection German Shepherd on a chain in the backyard like a sled dog. I'm sure the malinois pups are all health checked and have super bloodlines... right! And only someone with a proven track record and waitlists for pups like Ivan Balabanov can sell malinois pups for $2,000. I rarely see malinois pups for sale up here (which is a good thing), but it's very sad to see this. Ad copied below...
"FREE MALINOIS PUPPIES... ...with the purchase of any dog house.
Alaska Made! Disabled Veteran built! Designed specifically for Alaska conditions!! Room for insulation underneath and slanted roof with large overhang for snow conditions!!
Solid dog houses built of 3/4" plywood, and mounted on a solid pallet. Painted with 5 year rated outdoor wood protectant. Roof has additional rubberized coating for durability.
Contact me for more details....
Price per house: $2000.00
In the event that we run out of free puppies, we will give away a dog obstacle course instead...it is really nice!"
That is really weird....
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Check out the GSD on a chain with the prong collar on its neck.
Maybe this dude is getting around the broker/breeder laws for puppies. He doesn't have to be under the department of agriculture or under any breeder-laws if he is "giving" away the puppies.
Here by this $120 crate, for $2500 and you get a purebred GSD puppy absolutely free.
I suppose there are ways around everything.
Isn't a malinois a little short coated for alaska's nasty weather, and that house looks way too big to keep that dog warm.
Ah well.
I just clicked the link and actually looked at the $2000 dog houses...wow...
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I think you would have to have that thing packed with cocaine and the little crack puppy for 2K.
Wow. Just. Wow.
Very odd indeed.
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Heck-uva a way to get around craigslist rules...... :crazy:
My 9 year old could build a better dog house
Just a typical BYB thinking they're cleverly avoiding Craigslist's ban on pet sales. Flag it as prohibited and it should be deleted. Not that it helps all the dogs involved :(
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(Rick Hickman / American Press)
Last Modified: Monday, March 25, 2013 11:44 AM
By Lance Traweek / American PressDiana Walker and husband Frank have been renovating their home at 623 Shell Beach Drive for the last 15 years.
"My favorite part has been raising my four children here," Diana Walker said. "I've enjoyed fixing it up, and we love entertaining and having people over."
The three-story home was built in 1927 in the Scottish Balmoral-Tudor style, which caters to leaded glass, brick-and-stucco exteriors and an elaborate slate roofs.
"I've always wanted to have an old home," she said. "We're not finished yet. We have a long way to go, but if I were an artist this home would be like my canvas."
On Sunday, the Walker house was one of five homes included in the 38th annual Palm Sunday Tour of Homes. This year's theme, "Windows on the Water," focused on homes along Shell Beach Drive, and hundreds came out for the tour put on by the Calcasieu Historical Preservation Society. The tour also included the residences of John and Sherrie Raggio, David and Anne Reinauer, Jim and Claudia Boyer and Wendell and Nancy Fontenot.
Janice Higginbotham of Lake Charles toured the homes with her daughter, cousin and a friend.
"It was a beautiful day, and we wanted to see the pretty homes," she said. "We drive down here, and I always wanted to see what they looked like inside because they're so beautiful from the outside."
Molly Reed of Lake Charles said she enjoyed the historic quality of the homes.
"The charming antiques and decor give me ideas for my home, as well," she said.
Martha Laborde toured the homes with aunt Helen Boyer and friend Lesley Leger.
"The architecture and the history of the homes is particularly fascinating," she said.
Toni Collins of Lake Charles said it was an exciting day for her.
"I learned a lot about the culture of people who live here in Lake Charles," Collins said.
Deidre Ardoin of Sulphur went with her mother-in-law and her sister. "I loved seeing the older homes and how they've been restored," she said.
Each home had docents placed throughout to explain various parts of the home.
"The docents were very knowledgeable about the homes," said Laura Lanza of Moss Bluff. "These are beautiful homes you see on a daily basis but you don't know what it looks like inside."


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What are the Benefits of Teaching with Yoga Dots?
- A fun way to get kids interested in yoga and movement
- Enable creative play, games, language arts, spatial relationships, math
- Support academic learning in an innovative, integrative way
- Promote creative problem solving
- Help kids to self regulate
- Develop critical thinking
- Increase concentration
- Support a fully functioning body, which stimulates a fully functioning brain!
- Fun and inviting – kid-friendly size, shape, and colors
- Environmentally friendly – no harmful phthaltes
- Safe for all ages and abilities
- Help to organize any space
- Soft and flexible – only 1/4″ thick
- Slip free preventing falls and injuries
- Can be used on hardwood floors
- Durable, machine washable
- Minimal storage needed
- Easy to transport
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On Children
Kahil Gibran
Your children are not your children. They are the sons and daughters of Life's longing for itself. They come through you but not from you, And though they are with you yet they belong not to you.
You may give them your love but not your thoughts, For they have their own thoughts. You may house their bodies but not their souls, for their souls dwell in the house of tomorrow, which you cannot visit, not even in your dreams. You may strive to be like them, but seek not to make them like you. For life goes not backward nor tarries with yesterday.
You are the bows from which your children as living arrows are sent forth. The archer sees the mark upon the path of the infinite, and He bends you with His might that His arrows may go swift and far. Let your bending in the archer's hand be for gladness: For even as He loves the arrow that flies, so He loves also the bow that is stable.


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Fri, 12/13/2013 - 01:29pm
Driggers PTA organized the WATCH D.O.G.S.® program on our Driggers campus this year. WATCH D.O.G.S.® are fathers, grandfathers, uncles, and other father-figures who volunteer for at least one day each year at an official WATCH D.O.G.S.® school. During the day, WATCH D.O.G.S.® may read and work on flash cards with students, play at recess, eat lunch with students, watch the school entrances and hallways, assist with traffic flow and any other assigned activities where they actively engage with not only their own students, but other students as well. Many school principals have reported that the mere presence of a WATCH D.O.G.® dramatically reduces reports of bullying. On the day of their participation, WATCH D.O.G.S.® are given a brief review of their involvement, and they wear an official
WATCH D.O.G.S.® t-shirt with a disposable 'Dog Tag' identifying them as WATCH D.O.G.S.®. More detailed information about this national program being implemented at Driggers can be found here.


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There is a golden rule to follow on planet Earth, certainly for the past two thousand years. If something bad happens, just find the nearest Jew to blame. The Pope has trouble with errant priests, blame it on the Jews! The deficit is high in America, blame it on the Jews! Your wife had an affair, blame it on the Jews! Turkish Prime Minister Recep Erdogan blames the Egyptian military coup on–who else? Them Jews!. Proof? The US condemned the remarks of Erdogn so what does the Erdogan administration conclude: "the US has hurried to respond to us before Israel."
Got it? Them Jews control America, they control protesting people in Turkey and it you check out the Chinese leadership you will find evidence of them Jews!


text: Winter Wildlife Festival presented by Virginia Beach Parks & Recreation with the Virginia Department of Game and Inland Fisheries January 20 - 22, 2017 | Princess Anne Recreation Center This is your chance to witness winter wildlife all around Virginia Beach; whether it's following fascinating bird activity, exploring the natural areas of our community or the musings of harbor seals near the Chesapeake Bay Bridge Tunnel. Learn what it takes to properly observe and identify wildlife in their natural settings. View 2016 festival photos | View the 2017 bird species list Registration Information Register Online Our new online registration system allows you to use your email address to login or create an account. Open the registration page, then check to see if you already have an account, by clicking 'Sign In' then "Forgot Your Password'. If you're new, you can click on 'Create an Account' to get started. Search Winter Wildlife Festival and sign up for the Main Registration first, then you'll be able to register for individual sessions. Register now Register by Mail or Walk In Complete the registration form and submit with payment via mail to: Special Events - Winter Wildlife Festival, 300 Edwin Drive, Virginia Beach, VA 23462. Or register in person at any Virginia Beach Recreation Center. Note: Most sessions have limited capacity. Online registration is recommended to secure your space early! You can join the waitlist for any full trips here: https://vbforms.seamlessdocs.com/f/fBPODj. Exhibit Hall Saturday, January 21 | 10:00 am - 4:00 pm Stop by Princess Anne Recreation Center for the 2017 Winter Wildlife Exhibit Hall to check out the vendors and environmental exhibitors, walk-up workshops, live animals and raffles! Children's activities will take place at the neighboring Princess Anne Library. Local food truck, Ferg's Missing Ingredient, will offer delicious eats from 11:00 am to 2:00 pm. Want to become an exhibitor? Download an exhibitor application Children's Activities at Princess Anne Library Stellaluna and Bat Friends Storytime | 10:30 – 11:30 a.m.Ages 3-8 | Enjoy moonlit tales of bats winging their way through stories and puppet plays as we celebrate with the Winter Wildlife Festival!No registration required. Our Wonderful Birds of Prey | 2 – 3:30 p.m. Grades K - 8 | Celebrate the amazing birds of prey in our region! Gather facts and make a craft as you learn about hawks, eagles and owls. Meet one of our feathered friends. No registration required Special thanks to our Festival Partners: Department of Game & Inland Fisheries | Back Bay National Wildlife Refuge | Lynnhaven River Now | Virginia Aquarium | Virginia Beach Audubon Society Club | Virginia Beach Public Library | Virginia State Parks Festival Excursions & Sessions Chesapeake Bay Bridge Tunnel & Fisherman's Island - FULL This trip is full, but you can join the waitlist. 18 & up | Spend the morning on the man-made islands of the Chesapeake Bay Bridge Tunnel looking for wintering water birds and seals. After a stop for lunch at Stingray's – an Eastern Shore local's favorite (lunch is not included in price) – we'll head to Fisherman's Island National Wildlife Refuge. This Virginia barrier island is classified as "a wetland of international importance," and due to the critical nature of its habitats for wildlife, it is only accessible during guided tours. Additional registration form required by Jan 6. Recommended for experienced birders. | $45, lunch is on your ownMeet at Bayville Farms Park, 4132 First Court Rd., for transportation to locationsFriday, January 20 | 8:00 am – 4:00 pm Birding Basics Workshop & Field Session 10 & up | Are you just starting to get into birds? Do you enjoy watching them in your backyard and wish you knew what they were? Then this class is for you! This workshop will introduce you to the pastime of birding and will cover all of the basics: how to identify birds, tips for finding birds, and the materials and equipment you need to get started. There will be an indoor presentation, followed by an outdoor nature walk to practice your new birding skills! A limited supply of binoculars will be available for loan during the class, but if you have your own, it is recommended to bring them. Recommended for new birders. | $5 for adults; free for youth ages 10-17Meet at Brock Environmental Center, 3663 Marlin Bay DriveFriday, January 20 | 9:00 am – 11:30 am NEW Explore the Bay Sea Adventure -Trip Cancelled 12 & up | Join the Virginia Aquarium in a special 4 hour encounter to explore the waters of the Chesapeake Bay and the man-made islands of the Chesapeake Bay Bridge Tunnel in search of migrating wildlife. This unique experience may offer eye-level views of whales, dolphins, porpoises, seals, and locally rare seabirds. Aquarium experts will provide in-depth information on species identification and natural history, as well insight on how we care for similar animals at the Aquarium. Wildlife enthusiasts and photographers will not want to miss the diversity that this unique habitat provides during the winter. Marine mammal sightings are not guaranteed. All experience levels welcome. | $30Meet at Virginia Aquarium Dock, 717 General Booth BoulevardFriday, January 20 | 9:00 am – 1:00 pm Festival Keynote: "The Narrow Edge – A Tiny Bird, an Ancient Crab and an Epic Journey" with Deborah CramerSponsored by Lynnhaven River NOW, Virginia Beach Audubon Society, the Virginia Beach Hotel Association, and the Virginia Beach Restaurant Association 12 & up | Deborah Cramer's eloquent book, "The Narrow Edge," is the recipient of the Rachel Carson Book Award and the National Academy of Sciences Best Book Award. Hear about her extraordinary odyssey accompanying tiny shorebirds along the length of two continents and explore how Virginia is critical to the story. More about Deborah | Free; registration requiredMeet at Joint Use Library, intersection of S. Rosemont and Faculty DriveFriday, January 20 | 7:00 pm – 8:30 pm Chesapeake Bay Boat Trip 16 & up | View the Chesapeake Bay Bridge Tunnel Islands "up close and personal"! This boat trip offers eye-level views of birds, harbor seals and other wildlife on and around the CBBT islands. This is an excellent opportunity to view sea ducks, shorebirds and seabirds. Recommended for experienced birders. | $40Meet at Dockside Marina, 3311 Shore DriveSaturday, January 21 | 8:00 am – 11:30 am Cape Henry Tour 8 & up | This trip highlights two destinations in the historic Cape Henry area of Virginia Beach; First Landing State Park and the Old Cape Henry Lighthouse located on Fort Story. These locations offer views of the Chesapeake Bay where shorebirds, wintering seabirds, and waterfowl can be plentiful. In addition to wildlife viewing this trip will include historical information on the first landing of the Virginia Company and the old Cape Henry Lighthouse. Participants 16 & older are required to bring a government-issued picture ID for access to Fort Story. All experience levels welcome. | $15Meet at Princess Anne Recreation Center for transportation to locationsSaturday, January 21 | 8:30 am – 11:30 am Pleasure House Point Birding 16 & up | This 188-acre site at Lynnhaven Inlet encompasses Maritime forest, beaches, marshes and mudflats and was recently added to the Virginia Birding Trails. These varied habitats support a wide array of birds and wildlife like songbirds, raptors, shorebirds and is home to many breeding diamondback terrapins. At one time this site was targeted for intense development, but a partnership between the City of Virginia Beach, the Chesapeake Bay Foundation and The Trust for Public Land made the preservation of this space possible. Recommended for experienced birders. | $5Meet at Pleasure House Point Natural Area, 3957 Marlin Bay Drive (please park along roadway)Saturday, January 21 | 8:30 am – 11:00 am NEW Waterfowl Walk - FULL 10 & up | Thousands of waterfowl visit the Back Bay every year to rest and feed during the winter migration. This one-mile walk will be led by local expert birders and focus on identification of the various ducks found at Back Bay National Wildlife Refuge. Binoculars and cameras are highly recommended. A spotting scope will be available, but participants may bring their own if desired. | $5Meet at Back Bay National Wildlife Refuge, 4005 Sandpiper RdSaturday, January 21 | 9:00 am – 11:00 am Intro to Nature Photography 16 & up | Award winning photographer, G. Michael Brown will inspire you with his superb nature images. Learn the basics of your digital camera and how to apply them in capturing the extraordinary natural subjects that inhabit our area. Basic concepts of image composition and proper lighting will be highlighted using bird, flower, and landscape digital images. All experience levels welcome. | $5This classroom session meets at Princess Anne Recreation CenterSaturday, January 21 | 10:30 am – 11:30 am NEW Fisherman's Island: A Wildlife, Nature, and History Walk - FULL This trip is full, but you can join the waitlist. 10 & up | Fisherman's Island has been a marine hospital (1890), an artillery site (1942), part of Back Bay (1973) and the Eastern Shore of Virginia (1984). Additionally, it is critical habitat for royal terns and brown pelicans. Join us as we walk along sandy trails thru maritime forest, swales, secondary dunes, and beach areas. Migratory birds and a variety of flora and fauna are also part of this walk. Don't miss out on the spectacular views this location offers of the Chesapeake Bay Bridge Tunnel! | $15Meet at Bayville Farms Park, 4132 First Court Rd., for transportation to locationsSaturday, January 21 | 8:00 am – 12:00 pm Back Bay/False Cape Terra-gator and Tram Tour - FULL This trip is full, but you can join the waitlist. All ages | Take a scenic tram ride through Back Bay National Wildlife Refuge and False Cape State Park to the site of the historic Wash Woods community in what is now False Cape State Park. Hike the 1-mile round-trip trail to the historical site, where a church steeple and cemetery remain. Ride back along the remote beach observing shorebirds and perhaps whales while riding in our unique beach transporter, the Terra-Gator. All experience levels welcome. | $15Meet at Princess Anne Recreation Center for transportation to locationSaturday, January 21 | 12:30 pm – 5:00 pm Urban Birding Tour 12 & up | Did you know that there are many "birdie" places right in the heart of the city? This trip will take you to some of Virginia Beach's prime urban bird spots where a surprising variety of birds can be seen. Some of the sites are so easy to bird, we may not have to leave the bus! This trip focuses on acquainting you with various places to go birding in Virginia Beach. Recommended for new or casual birders, but all experience levels welcome. A limited supply of binoculars will be available for loan during the class, but please bring your own if you have them. | $15Meet at Princess Anne Recreation Center for transportation to locationsSaturday, January 21 | 1:00 pm – 5:00 pm NEW Macro Photography 16 & up | Most of today's digital cameras offer settings that allow photographers to create close-up photographs. Professional photographer G. Michael Brown will explore the often unseen in nature's world through Macro or close up Photography. He'll share tips and techniques of how to capture the patterns, textures, and drama of insects, plants, and other subjects. The importance of composition will also be discussed. | $5This classroom session meets at Princess Anne Recreation CenterSaturday, January 21 | 1:00 pm – 2:00 pm Whales & Wildlife Sea Adventure All ages | Join the Virginia Aquarium & Marine Science Center, the longest running and most experienced whale watching entity in Virginia, in an immersive encounter with some of the ocean's most magnificent creatures. Specialized educators will share a program built upon the Aquarium's scientific research and almost three decades of experience connecting guests with the area's marine mammal visitors. Trips take place on a spacious and stable catamaran that boasts one of the most comfortable rides in Virginia Beach, and has been outfitted especially for conducting dolphin & whale watching trips. Experience spectacular views from the outdoor covered seating areas, or from cushioned seats inside a heated cabin. This ~2.5 hour adventure is an exploration in search of whales, dolphins, seals, and seabirds. Marine mammal sightings are not guaranteed. All experience levels welcome. | $23 for ages 12 & up; $18 for ages 3-11; free for children under age 3Meet at the Virginia Aquarium Dock, 717 General Booth Blvd.Saturday, January 21 | 2:00 pm – 4:30 pm First Landing Nature Walk 5 & up | Experience firsthand the amazing habitats that exist within First Landing State Park. Discover what makes the park's environment so unique that it has been made a national natural area. The 2 mile hike will take participants across swamp overlooks and through maritime forest in search of wildlife and natural phenomena found within the park. All experience levels welcome. | $5Meet at the First Landing State Park Trail Center, 2500 Shore DriveSaturday, January 21 | 2:00 pm – 4:00 pm Owl Prowls 10 & up | Choose from two locations! Explore the night time woods of West Neck Natural Area or Great Neck Park looking and listening for their nocturnal hunters. Great horned, barred and screech owls and other creatures of the night are all possibilities for these trips. All experience levels welcome. | $10Meet at West Neck Natural Area or Great Neck ParkSaturday, January 21 | 7:00 pm – 8:30 pm NEW Owls and S'mores 5 & up | Enjoy this traditional nighttime outdoor activity. Listen and look for nocturnal animals of First Landing State Park, especially the park's owl inhabitants. Then join park rangers around the campfire for special activities and of course a S'more! | $10Meet at First Landing State Park (2500 Shore Drive) at the large Chesapeake Bay Center sign in front of the main office buildingSaturday, January 21 | 7:00 pm – 8:30 pm Chesapeake Bay Bridge Tunnel 12 & up | The man-made islands of the Chesapeake Bay Bridge Tunnel provide rest stops for migrating and wintering birds. The islands can offer unusual or locally rare sightings. Northern gannet, brant, king eider, harlequin duck, little gull, great cormorant, purple sandpiper and rarities such as black-tailed gull make this one of the best winter birding sites in Virginia. The presence of the occasional harbor seals and wintering whales adds to the appeal of this unique site. All experience levels welcome. Additional registration form required by Jan 6. | $15Meet at Bayville Farms Park, 4132 First Court Rd., for transportation to locationSunday, January 22 | 8:00 am – 12:00 pm Mackay Island Birding - FULL This trip is full, but you can join the waitlist. 12 & up | Located in North Carolina, just one mile past the Virginia border, this National Wildlife Refuge offers a variety of habitats including freshwater and brackish marshes to upland and lowland eastern pine hardwood forests. Its location on the edge of Back Bay and the Currituck Sound, make this peninsula a fascinating place to view winter wildlife including large numbers of snow geese. Refuge volunteers will provide a guided tour of the main refuge. Recommended for experienced birders. | $15Meet at Princess Anne Recreation Center for transportation to locationSunday, January 22 | 8:00 am – 12:30 pm Princess Anne Wildlife Management Area Birding 12 & up | This trip will visit the Beasly Tract of Princess Anne Wildlife Management Area, a patchwork of marshes, weedy fields, narrow freshwater impoundments, and pine woodland. Likely bird sightings include raptors, sparrows, wintering songbirds, and other grassland/ shrubland birds. Snow geese and tundra swans are likely fly overs. (Please note: Due to on-going installation of a new pumping system at this site, the freshwater impoundments may be dry, so the high numbers of waterfowl and wading birds usually seen during the winter season will most likely not be present this year.) Comfortable waterproof shoes or rubber boots are recommended as trails may be wet. Recommended for experienced birders. | $15Meet at Princess Anne Recreation Center for transportation to locationSunday, January 22 | 8:00 am – 12:00 pm Back Bay/False Cape Birding 12 & up | Take a scenic ride through Back Bay National Wildlife Refuge on the "Blue Goose Express" observing wintering snow geese, swans and other wildlife. Journey to the heart of False Cape State Park for a chance to further observe and photograph the abundant wintering waterfowl. Scopes and cameras are allowed and encouraged. Recommended for experienced birders. Due to refuge policy, no stops will be made while traveling through Back Bay. | $15Meet at Princess Anne Recreation Center for transportation to locationSunday, January 22 | 8:00 am – 12:30 pm Seal Spotting Sea Adventure All ages | Seals are frequent visitors to this area when the water temperatures drop, although their favorite haul-out spots can make them difficult to see. During this trip, catch eye-level observations while educators from the Virginia Aquarium & Marine Science Center provide information about the species that frequent our waters. Possible sightings include harbor seals, gray seals, harp seals, and hooded seals. Learn about the most recent research conducted by the Virginia Aquarium's Stranding Response Team, and how we care for similar animals at the Aquarium. The 65-foot Atlantic Explorer provides spectacular views from the outdoor, covered seating areas as well as from the interior heated cabin. Marine mammal sightings are not guaranteed. All experience levels welcome. | $23 for ages 12 & up; $18 for ages 3-11; free for children under age 3Meet at the Virginia Aquarium Dock, 717 General Booth Blvd.Sunday, January 22 | 2:00 pm – 4:30 pm Walk-Up Workshops at Princess Anne Recreation CenterAll workshops are free and take place at Princess Anne Recreation Center. Pre-registration is preferred. Peregrine Falcons 10 & up | Join Reese Lukei, a volunteer for the U.S. Fish and Wildlife Service since 1974 and a licensed bird bander, as he discusses the description, behavior, nest sites, history, distribution, recovery and current status of the Peregrine Falcon (Falco peregrinus) in Virginia with a focus on the Tidewater and Eastern regions of Virginia. Saturday, January 21 | 10:30 am – 11:30 am Urban Predators 10 & up | Join DGIF Biologist Pete Aker as he discusses coyotes and bears, the largest predators in Virginia - both found in Virginia Beach! There will be additional information on bobcats, foxes, and mountain lions. Come learn which of these animals may live closer to you than you think, what they eat, and what to do if you spot one. Become informed on these intriguing species and how to keep them away from your home, while enjoying them respectfully. Saturday, January 21 | 12:00 pm – 1:00 pm Choosing Optics for Nature Observation 16 & up | Explore what goes into making a great binocular for birding and nature observation. Learn what the numbers mean, how to use various binoculars and why some may or may not be best suited to what you do. This session includes hands-on time with a number of ZEISS binoculars. Saturday, January 21 | 1:30 pm – 2:30 pm Birding for conservation: Virginia Breeding Bird Atlas Season 2 (VABBA2) 10 & up | Join DGIF Biologist Becky Gwynn, as she shares stories and results from the fantastic first season of the VA Breeding Bird Atlas. Learn why scientists and wildlife managers need the help of volunteers to gather essential information on bird distribution and breeding. The VA Breeding Bird Atlas Season 2 project is a fun way to make your own contribution towards preserving heritage while learning a lot about bird behavior and conservation.Saturday, January 21 | 3:00 pm – 4:00 pm Additional Festival Activities Sea Watch Station on the Boardwalk at Rudee Inlet All ages | Stop by the boardwalk at Rudee Inlet to see what birds are flying over the waves, feeding, or resting on the water. You are likely to see Surf & Black Scoters, Buffleheads, Northern Gannets, Double-crested Cormorants, and an assortment of gulls (Ring-billed, Herring, Lesser Black-backed, & Great Black-backed). Red-throated & Common Loons, Red-breasted Mergansers, Laughing Gulls, and Forster's Terns are also possible. And if you are really lucky, you might see a Common Eider, White-winged Scoter, Horned Grebe, or Bonaparte's Gull. Bring binoculars if you have them. If not, we'll have birding scopes set up. Dress warmly! | Free; no registration required Saturday, January 21 | 1:30 pm – 3:30 pm Flying WILD Teacher Workshop For formal & non-formal educators | Celebrate birds with Flying WILD, a conservation education guide featuring interdisciplinary hands-on classroom activities. Key concepts include migration, adaptation, the importance of habitat and bird conservation efforts. Designed originally for middle school teachers and students, the guide contains activities suitable for all grade levels. All participants will receive a copy of the Flying WILD Activity Guide and supplementary materials on Virginia birds. Additional registration form required (unless registering online) | $10Meet at First Landing State Park Trail Center, 2500 Shore DriveTuesday, January 24 | 6:00 pm – 9:00 pm Page Content2017 Photo Contest WinnersWildlife: PortraitOverall Category Winner: Michael ShroyerHonorable Mention: Timothy CurtisWildlife: ActionOverall Category Winner: Pam Monahan Honorable Mention: Preston OzmarFestival in ActionOverall Category Winner: Harry ShockHonorable Mention: Michael Shroyer YouthOverall Category Winner: Jonas M. Honorable Mention: Malaya P. People's ChoiceOverall Category Winner: Pam Monahan Do you have an eye for photography? Enter our photo contest!Show off your skills by capturing unique moments during the Winter Wildlife Festival and enter to win some great prizes. Contest is open to all registered participants. Submissions due by 5 pm on Thursday, January 26. One photo per category; submissions in multiple categories permitted. View full contest rulesPhoto submissions for the photo contest has now ended. 2017 Photo Categories Wildlife Portrait – must show wildlife during a festival excursion; animal(s) must be still. Excludes animal ambassadors in exhibit hall, children's activities and walk-up workshops. Winning photograph receives a pair of ZEISS TERRA ED Pocket Binoculars (8x25)! Action - must show wildlife during a festival excursion; animal(s) in motion, displaying a behavior, etc. Excludes animal ambassadors in exhibit hall, children's activities and walk-up workshops. Winning photograph receives a pair of ZEISS TERRA ED Pocket Binoculars (8x25)! Festival in Action – any picture taken during any festival activity of any subject; includes: exhibit hall, walk-up workshops, keynote, excursions, other festival participants, education animals, children's activities, etc.Winning photograph receives a L.L. Bean Backpack and 4-person kayak lesson courtesy of L.L. Bean! Youth - any subject, any festival location; must be under 16 to qualify. Winning photograph receives a 4-pack of tickets to the Virginia Aquarium and a festival partner prize pack! People's Choice – any subject, any festival location. Photographs entered in any of the above categories may also be entered in the People's Choice category. Winner will be chosen by followers of Virginia Beach Parks & Recreation on Facebook. Winner of this category receives a 4-pack of tickets to The Adventure Park at Virginia Aquarium! 2016 Photography Contest WinnersWe received some amazing photos capturing the Winter Wildlife Festival. Congratulations to all the winners!WildlifeAriel Johnson | Ibis on tree at Mackay Island Wildlife Refuge Wildlife - Honorable MentionWilliam Miller | Vocal Pelicans (grooming pelicans and cormorants on floating dock in Rudee Inlet) Festival in ActionPreston Ozmar | Participants on beach at Fisherman's Island People's ChoicePam Monahan | Tundra Swans on alert at Mackay Island Wildlife Refuge YouthCecilia P. (age 5) | Smokey Bear at Princess Anne Recreation Center 2016 Photo CategoriesWildlife – shows wildlife during a festival excursion; animal(s) may be still, in motion, displaying a behavior, etc. Winning photograph received a pair of ZEISS TERRA ED Pocket Binoculars (8x25)!Festival in Action – any picture taken during any festival activity of any subject; includes: exhibit hall, walk-up workshops, keynote, excursions, other festival participants, education animals, children's activities, etc. Winning photograph received a Winter Wildlife Festival prize pack!Youth - any subject, any festival location; must be under 16 to qualify. Winning photograph received a family 4-pack of tickets to the Virginia Aquarium and The Adventure Park!People's Choice – any subject, any festival location; one photo per photographer may be considered for this award in addition to the above categories. Pictures were posted on our Facebook page and winner was determined by most likes in specified time period. Winner of this category received a $100 Whole Foods Market gift card!View full contest rules. Contact InformationOutdoor & Environmental Programs(757) firstname.lastname@example.com Forms Registration Form Schedule at a Glance Chesapeake Bay Bridge Tunnel Release Form Flying WILD Registration Form Exhibitor Application Join on Facebook Photo Contest


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With an oversized designer-logo monogram, Yves Saint Laurent's metallic-black and gold tweed clutch is an elegant way to inject molten glamour to your look. Pair it with impeccable tailoring in rich jewel tones as an ode to the label's signature sophistication. Shown here with an Yves Saint Laurent jacket and top, Lanvin necklace, Jimmy Choo shoes and Michael Kors pants.
- Metallic-black and gold tweed clutch with a fold-over magnetic-fastening flap front. Yves Saint Laurent clutch has a designer-logo monogram at front, an internal pouch pocket, and is fully lined in black leather and satin. Designer color: Stone/Nero.
Product Code: 96099
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The Pope and Iraqi Prime Minister Nouri A-Maliki speak out, but the world's second most powerful Christian has nothing to say while Islamic jihadists force thousands of co-religionists from their homes.
Kurdish fighters have repelled ISIS rebels, but have seen anything like the bloody clashes and tit-for-tat murders in Sunni and Shiite communities further south
Embedded with rebels in Aleppo, James Harkin explains how the revolt against Syria's Assad dynasty became an apocalyptic struggle between Sunnis and Shiites
Ten years after the invasion of Iraq, the entire region stands on the brink of violent political upheaval
Lebanon's tourism minister threatens a lawsuit over the portrayal of Beirut as a nest of terrorists in the TV series Homeland. Unfortunately, the threat comes amid sectarian violence after the country's intelligence supremo is assassinated.
The attacks were the deadliest in Iraq since August 15, 2011 when 74 people were killed
An Iranian rapper living in Germany has a $100,000 bounty on his head after an Islamist website offered a reward for anyone who kills him over a song that satirizes the Islamic Republic and irreverently addresses Ali al-Hadi al-Naqi.
More than 20 bombs hit cities and towns across Iraq on Thursday, killing at least 36 and wounding more than 100, police and hospital sources said, raising fears of sectarian strife in a country keen to show it can now maintain security.
Four months after most U.S. troops left Iraq, the jihadists had to find a new reason to sustain their continued presence — enter Iran and the Shi'ite-led Iraqi regime.
Could the tiny Persian Gulf island state of Bahrain be the next U.S. diplomatic domino to fall in a rapidly changing Middle East? As riot police in Bahrain attacked hundreds of pro-democracy demonstrators Monday with tear gas, rubber bullets and concussion grenades, U.S. strategic interests in the...


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How To Confirm 100% Hatch Rate?
1,170pages onAdd New Page
this wiki
this wiki
I have been told by some people that If I get the Data from the same Digimon that I want to hatch , it is confirmed 100% Hatch Rate? I've found this with Togemon , but please I need confirmation on this!


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LISA NAPOLI: Just when it looked like air fares might take off again, United and American Airlines are doing a 180. They've backed away from raising business fares by $5 for one-way trips and $10 for roundtrips. Marketplace's Bob Moon reports, that may not necessarily be bad news for the airlines.
BOB MOON: So what if the fare increase didn't stick?
As industry expert Terry Trippler sees it, just the attempt by United, American and Delta to raise business fares suggests they're getting a firmer hand on the controls.
TERRY TRIPPLER: "The airlines have gained some pricing power. Started last Thanksgiving, and it has continued on and this recent attempt to increase fares shows that pricing power is still there."
That may seem counterintuitive, but Trippler sees the glass as half full, since this has all played out a little more than a week after heightened security concerns.
TRIPPLER:"Many of us would not have been surprised to see a big sale, or airfares drop. Instead the opposite occurred, means good news for the industry."
Indeed, with three of the major airlines so quick to nibble at the idea, Trippler says fares could yet rise.
TRIPPLER:"I would not be surprised to see an attempt made this coming weekend, or the weekend after."
Trippler says the airlines have been more successful than not in nudging fares up during the past year.
In Los Angeles, I'm Bob Moon for Marketplace.


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Spook (about the science of trying to determine an afterlife)
she wrote Stiff (about what happens to us when we die)
Bonk (about....sex)
"The Innocent Man" by Grisham. True story and a good read too. My favorite books of all times are the james herriot books- All Creatures great and Small, The lord god made them all, All things bright and beautiful and All things Wise and wonderful. Easy read, makes you laugh and cry and grin and all good human emotionsI also really enjoyed, Unduanted Courage, about lewis and Clark


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Los Angeles Dodgers Pool/Beach/Bath Towel
Angelenos love the beach and what better way to show that they are Thinking Blue all the time - even while catching some rays and surf - than with this Dodger beach towel.
I have seen this before, this is kinda cool!Tags: towels, chalk, beach towels, chalk outlines, dead bodyAdded 8 Years Ago from Amazon.com
Large large towels are a must when you are trying to prevent the neighbor's apartment below you from flooding also.Tags: neon, beach, towels, beach towels, Towels for TwoAdded 9 Years Ago from Amazon.com
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text: The transition for Michigan WR/QB Denard Robinson (5-10½, 196) hasn't been as easy as he hoped. For example, he had a false start today. But being able to take the yellow jersey off allowed him to run and show his ability to run with the ball in his hands. That has helped matters. With that yellow jersey on, it put him on an island and put him in situations where he wasn't comfortable. Moving forward it's important as to who is coaching him and with whom he is playing. If he goes back to Ann Arbor, Mich., and focuses on running a fast 40, that's not going to work. He needs to focus on running routes and catching the football. That's just one piece of the puzzle. Robinson will have his pro day, but teams that are interested in him are going to work him out separately on campus in Ann Arbor. If he shows improvement there, that will be a huge help. • Washington CB Desmond Trufant (5-11⅛, 190) doesn't have elite man-to-man coverage skills, but he has done a nice job on trail covers this week. He seems to be most comfortable in that type of coverage, and we've seen that on tape, too. On tape, he has been inconsistent with balls skills, but had a nice interception on Thursday. • Oregon RB Kenjon Barner (5-9¼, 188) was quick running routes and caught the ball well. He had a nice touchdown during the team period. He looked fluid and clean catching the ball. • You can see why UConn LB Sio Moore (6-foot-0¾, 242 pounds), who was a late addition and who looked good on Wednesday, is an intriguing prospect, especially in terms of him taking the next step when it comes to the combine. You can see Moore has strong east-west reach. The way he was running makes you think he will test well at the combine. In terms of the offseason process, he's capitalizing and he looks as if he can continue that momentum into Indianapolis. http://insider.espn.go.com/nfl/blog...878176/2013-nfl-draft-denard-robinson-do-list


text:
New York City's Mayor Michael Bloomberg just announced the launch of the Urban Technology Innovation Center which will help fast track sustainable building practices by connecting building owners looking to be more eco-friendly with companies developing cutting edge green technology. The partnership — which will be led by the City of New York, Columbia University, the Polytechnic Institute of New York University, and City University of New York — will help building owners go green at a lower cost while allowing sustainable innovators to test their products in the marketplace and gather data about their performance in the real world.
Mayor Bloomberg has lofty goals — that we wish every city had — for New York City's sustainable future and he's been on a roll lately introducing green initiatives. From the recent green roof initiative to helping to expand New York's car free zones to other parts of the city Bloomberg is putting some serious action into greening the Big Apple. Most of Bloomberg's plans of action, including this latest one, are covered under New York City's PlaNYC 2030 program. "We will never meet the ambitious carbon reduction goals in PlaNYC unless we reduce the emissions from New York's one million existing buildings," Mayor Bloomberg noted. "The NYC Urban Technology Innovation Center will capitalize on some of our City's greatest strengths, creating jobs and helping realize our vision of a greener, greater New York."
The Urban Technology Innovation Center will help New York — and hopefully other cities across the world — get to that greener future in three ways. First and foremost it will get green technology into the marketplace quickly to test its strengths. Second, it will create an information clearinghouse of all tested technology, its costs and its proven functionality. Third, it will host forums between the private sector and academic institutions about city-specific green building challenges in order to help spread the word about the newest, most innovative sustainable building practices.
+ The Urban Technology Innovation Center
Via R & D
Images by AngMoKio


text:
Fairfield Inn & Suites by Marriott Woodbridge
Select your stay dates to check availability at Fairfield Inn & Suites by Marriott Woodbridge
Fairfield Inn & Suites by Marriott Woodbridge
About the Hotel
Property Location
Located in Avenel, Fairfield Inn & Suites by Marriott Woodbridge is in the business district and close to Union County Performing Arts Center and Rahway River Park. This hotel is within close proximity of Wilson Park and Woodbridge Center.
Make yourself at home in one of the 90 air-conditioned rooms featuring microwaves. Complimentary wired and wireless Internet access keeps you connected, and cable programming provides entertainment. Bathrooms have complimentary toiletries and hair dryers. Conveniences include desks and complimentary newspapers, as well as phones with free local calls.
Take advantage of recreational opportunities offered, including a health club, an indoor pool, and a spa tub. Guests can catch a ride to nearby destinations on the complimentary area shuttle.
Grab a bite from a snack bar/deli serving guests of Fairfield Inn & Suites by Marriott Woodbridge. A complimentary continental breakfast is included.
Business, Other Amenities
Featured amenities include complimentary high-speed (wired) Internet access, a business center, and complimentary newspapers in the lobby. Event facilities at this hotel consist of conference space and a meeting room. A roundtrip airport shuttle is provided at no charge.
Hotel Facilities
- Coffee/tea in common areas
- Elevator/lift
- Free wired high-speed Internet
- Conference space
- Snack bar/deli
- Free newspapers in lobby
- Free airport transportation
- Safe-deposit box at front desk
- Spa tub
- Accessible bathroom
- Dry cleaning/laundry service
- One meeting room
- Indoor pool
- Free self parking
- Smoke-free property
- Roll-in shower
- Free WiFi
- Health club
- Free breakfast
- Total number of rooms - 90
- Business center
- Free area shuttle
Room Facilities
- Sofa bed
- Air conditioning
- Free local calls
- Coffee/tea maker
- Free toiletries
- Free WiFi
- Phone
- Television
- Free wired high-speed Internet
- Free newspaper
- In-room climate control (air conditioning)
- Cable TV service
- Daily housekeeping
- Iron/ironing board
- Hair dryer
- Desk
- Microwave
- Refrigerator (on request)
Hotel Policy
Know Before You Go
- Children 18 years old and younger stay free when occupying the parent or guardian's room, using existing bedding.


text:
"10 Biggest Car Failures".
Expand Messages
- Okay, here we go again with writer Daniel Bukszpan, another "car expert" who's trying hard to prove that he needs a job. This is what he wrote in www.CNBC.com:
The American people have had a long love affair with cars. Whether it's a teenager's new found independence or a grown man's show of status and power, cars represent much more to people than just a way to get from one place to another. Cars make a statement about their owners--or at least how their owners wish to be perceived.
That being the case, there are likely no car owners who want to be perceived as hideously ugly, poorly engineered, or hazardous to life and limb. For that reason and many others, a lot of cars become consigned to the dustbin of history, forever branded embarrassing failures.
Some are off-putting because of styling as enticing as a leisure suit. Some earned a reputation as a danger to the driver and everyone else on the road. The reasons for their failures are varied, and while some of the companies that manufactured them recovered, many didn't.
Which cars have been among the biggest failures in automotive history?
By Daniel Bukszpan
Posted 30 September 2011
Crosley Hotshot
The Crosley Hotshot was the work of Powel Crosley Jr., an Ohio industrialist who owned Crosley Broadcasting and the Cincinnati Reds. Despite this impressive resume, he was unsatisfied. Crosley longed to make cars, and in 1939 he founded Crosley Motors. Despite his success in several different businesses over the years, however, the car company never took off, and it became a black mark on Crosley's otherwise impressive career.
One of the company's biggest embarrassments was the 1950 Hotshot. A stylish enough car on the outside, its major design flaw was its engine. The car could only manage an average speed of 52 miles per hour , and instead of casting it in iron, it was welded together with tin. The welding failed on a regular basis, and heated the inside of the vehicle to an alarming degree. Crosley Motors closed its doors in 1952, but the Hotshot lives in infamy for a generation who saw a mangled specimen in the 1961 driver's education film "Mechanized Death."
(Later he said the '56 Dodge "failed" because it had a phonograph. Really.)
- I'd guess he wants to write for a Republican or Tea Party PAC.
A Home Away From Home
Phone: (812) 594-2374
Email: awayfromhome@...
Your message has been successfully submitted and would be delivered to recipients shortly.


text:
My name is Jeanna Koerner, and I am the Counselor at Green Valley Elementary. I have been a counselor for ten years-- three at Smithfield Middle School and the past eight years here at Green Valley.
Before becoming a Counselor, I taught and coached at Smithfield Middle School and Birdville High School. I am proud to say that I have been in BISD my entire life. I am a proud Smithfield Wildcat, Smithfield Raider and Richland Rebel! I can not imagine myself anywhere other than Birdville ISD!I have always known that I would work with children, but it took me a while to figure out my exact calling. I love the fact that I have been at all the different levels. I feel like I can better prepare our scholars and parents for what is to come and work along side them as they ask questions, set goals, and pursue those goals!
I must say that FAMILY is everything to me. I have an amazing husband, who is the Principal of North Oaks Middle School in BISD. We have two precious children, who also attend/attended Green Valley. Much of my time is spent carting kiddos around to practice and games as well as church activities. I enjoy reading, exercising, spending time with friends and family, and scrapbooking!
I honestly feel like I am right where I am meant to be. I am blessed to serve our Green Valley Gator families and I look forward to many years working with our amazing faculty, staff, scholars, families, and community.
Green Valley is truly the place to be! GO GATORS!


text:
Berklee Today
L.A. Newsbriefs
|Peter Gordon '78
Giving back by alumni can take many interesting forms. One of the more creative examples is scheduled for December 10 when Justis Kao '03 presents a Christmas Benefit Concert, entitled "If I Had One Wish" at the Richard & Karen Carpenter Performing Arts Center in Long Beach. Kao was recently nominated for the 2006 Los Angeles Music Awards in the Best Male Singer/Songwriter of the Year category. He already has a very strong following in the Los Angeles area and the concert is expected to attract a large audience.
Many of the performing musicians at the concert will be Berklee alumni, and the evening promises to be full of energy and celebration. Consisting of a full rhythm section, two grand pianos, five back-up singers and a string quartet, the ensemble will perform music that blends rock, pop, gospel, and funk.
Most significantly, Kao is donating all proceeds collected to the Berklee City Music Program, enabling musically talented inner-city Los Angeles teens to attend the Five-Week Summer Performance Program in Boston. It's a wonderful gift and I hope many will join us that evening. Visit www.carpenterarts.org and click on "tickets." For information on Kao, go to www.justiskao.com.
Recently local alumni have released a number of impressive CDs. Film composer Gernot Wolfgang '89 has recorded Common Ground, a collection of his chamber pieces. As one reviewer states, "the music is dancing, it has a logic and beauty all its own." For more, visit www.gernotwolfgang.com.
Former faculty member and drummer Jerry Kalaf '72 released Just Like Old Times. For this recording, Kalaf composed eight songs for his trio and a full string orchestra. The result is a warm blend of mainstream jazz, with excellent soloing and appealing orchestrations. The track "Monk and Mingus" is a standout. To learn more, visit www.jerrykalaf.com.
Award-winning composer Alf Clausen '66 has released a CD of big-band arrangements entitled Swing Can Really Hang You Up the Most, featuring a jazz orchestra comprising A-list L.A. studio musicians. Johnny Mandel describes the music as "superb in every way." Maria Schneider says, "this is just great writing." Alan and Marilyn Bergman note that "the arrangements sparkle with humor and wit and, most importantly, they swing." For information, visit www.alfclausen.com.
|Alf Clausen's CD jacket for: Swing Can Really Hang You Up the Most
Geoff Zanelli '96 recently won an Emmy for the score he wrote for Steven Spielberg's miniseries Into the West, a Dreamworks production that aired on TNT. He also scored David Duchovny's film House of D, and wrote additional music for Pirates of the Caribbean: Dead Man's Chest.
There were also several alumni Emmy nominees. Sound effects editor David Van Slyke '82 was once again recognized for his stellar work on CSI: Crime Scene Investigation. Daniel Colman '95 was nominated for outstanding sound effects editing in the nonfiction-programming category, for Two Days in October, aired by PBS on their American Experience history series. In the category of Outstanding Single-Camera Sound Mixing, Elmo Ponsdomenech '83 received a nomination for the "Youmud-Din" episode of Sleeper Cell. Composer Gigi Meroni '96 won a Daytime Emmy for his music featured in Off-Mikes, the ESPN animated show from ESPN radio's Mike and Mike in the Morning. Congratulations to all!
After finishing her second season on the Emmy Award-winning NBC daytime series Starting Over, composer Sharon Farber '97 spent the summer scoring two feature films. When Nietzsche Wept is a dramatic period piece starring Ben Cross and Armand Assante, and The Tribe is a horror/thriller starring Jewel Staite.
In the world of music supervision, Curt Sobel '78 and Gary Schreiner '79 have placed their songs in such films as Fun with Dick and Jane, Larry the Cable Guy, Eight Below, Mrs. Harris, Thank You for Smoking, and, most recently, My Super Ex-Girlfriend.
On the performance front, guitarist Fernando Hernandez '03 played with the legendary Frances Yip at the Palomar Starlight Theater in June. In Yip's 37-year recording career, she has released more than 80 albums, mostly of songs in English, Cantonese, and Mandarin.
Terry Wollman '80 has been touring in Keb' Mo's band playing guitar, mandolin, and keyboards. Recently, the group has been opening for Bonnie Raitt. Wollman also made on on-camera appearance playing guitar in an episode of Desperate Housewives. That's all for now. Stay in touch.
-Peter Gordon '78, Director,
Berklee Center in Los Angeles


text:
Just arrived the stunning New Sea Ray 250 SLX (European) is now available to view and offered for sale. Fitted with a single 6.2L MerCruiser (300hp) with a Bravo 3 sterndrive. This is a new model for 2016 season, styled on the orginal 250 SLX but with much, much more...
In this transaction Marina Marbella are acting as Brokers only. We are informed that the sale is not related to the owner's business, trade or profession. Whilst every care has been taken in their preparation, the correctness of these particulars is not guaranteed. The particulars are intended only as a guide and they do not constitute a term of any contract. A prospective buyer is stronly advised to check the particulars and where appropriate to have the vessel fully surveyed and inspected, sea trialed and opened up.
Unit 12, Universal Marina
Crableck Lane, Sarisbury Green
Southampton, Hampshire SO31 7ZN
United Kingdom


text:
Southern Company Boosts Dividend By 3.7%
Southern Company (SO) today said it increased its annual dividend by 7 cents per share to $1.96 per share, saying the 3.7 percent increase marks the 11th straight year that it's raised its common stock dividend. The Atlanta-based energy company also announced a regular quarterly dividend, including an increase of 1.75 cents per share on a quarterly basis, of 49 cents per share payable June 6 to shareholders of record as of May 7.
"Southern Company remains committed to providing ever-increasing value for our customers in the form of industry-leading reliability, affordable rates, personalized service and community involvement," said Thomas Fanning, chairman, president and CEO, in a statement. "That longstanding commitment has translated into a history of sustained value for our shareholders as well."


text:
How the trial rules work
Page Tools
The experimental rules for the opening Super Series one-day international against at Telstra Dome.
+ One replacement player (super sub) per side per match.
+ Can bowl or bat, but not if player he replaces has already been dismissed or bowled 10 overs.
+ Can replace any player at any stage, including when batting
+ Replaced batsmen retired, not out. No loss of wicket
+ Can bowl remaining overs allotted to replaced player.
+ Fielding restrictions compulsory for first 10 overs of innings
+ Fielding captain nominates two more blocks of 5 overs at any time.
+ Field umpires may consult third (TV) umpire on any decision, including:
- Ball pitching in line for LBW
- Ball clearing stumps on LBW (but not using Hawkeye)
- Ball hitting pad outside line in LBW
- Ball hitting bat first in LBW
- Ball hitting bat for catch
- Ball caught cleanly
- Fieldsman staying inside boundary
- Batsman caught off no-ball
+ TV umpire has final say on stumpings, runouts referred to him
+ Field umpires have final say on all other decisions.
Get The Age home delivered for as little as $2.70 a week*


text:
Well, I think I messed up. Last year I started playing with starter strips. I used them in the second deep in a two-hive body system. Most of the strips were used for honey storage. This year I had to rearrange things between hives and didn't pay too much attention on where I was placing the frames containing the comb built from the starter strips. About six weeks ago, I noticed that the queen was laying up these frames with a large percentage of drone brood and as a result, over the past few weeks the drone population has been dramatically increasing. Now today, the hive has a massive population of drones that are consuming all surplus honey. There are so many drones that it was impossible to find the queen. I did see uncapped worker brood, so I guess she is still present, but brood pattern was not great. I removed three frames from outside of the brood nest and placed new foundation in the center of the box.
My guess is that this starter strip built comb resulted in drone-sized cells, true? Shouldn't the queen do a better job at regulating the number of drones, or was this a complete rookie mistake? I would like to eliminate some of these drones using a shake down and an excluder, but if I can't find the queen itÂs going to be a problem.
Any suggestions?


text:
If you are considering employing our services, it might help for you to know the core beliefs of our work.
I do not know if you feel like we do, but it does seem as if quality of work and attention to detail are not what they used to be. High quality work takes time and attention. At the end of a work day, we like to go home secure in the knowledge that we did the best work that we could do, no cutting corners, no sacrificing quality.
Standards and protocols are what allow people to communicate. We feel that communication is very important, and that nothing should stand in the way. As such, we strongly support open standards in everything that we do. We refuse to use technologies that stand in the way of open standards, and use open-source software for our work almost exclusively.


text:
|Ronan Conroy <firstname.lastname@example.com>
|Re: st: boxplot
|Tue, 06 Aug 2002 11:38:38 +0100
on 6/8/02 11:14 AM, Olivia Keiser at email@example.com wrote: > Is it possible to omit the extreme values in the boxplot? > > I've found the option 'symbol(i)' where the outliers are not plotted but > the axis scale still remains large (and with yscale I can't make it smaller). > If I include the 'if', the graph looks nicer, but all the extreme values > are not included to calculate the boxplots. You could use an -if- condition to exclude them. Stata will not resize a graph so that it is smaller than the data space. However, one of the important points of a boxplot is precisely that it does show outliers. I would at least add a note that outliers at (specify values) not shown, as people will automatically think that if there are no outliers visible, then there aren't any. Ronan M Conroy (firstname.lastname@example.com) Lecturer in Biostatistics Royal College of Surgeons Dublin 2, Ireland +353 1 402 2431 (fax 2329) -------------------- And now, Mr President, how about the global alliance against climate change? * * For searches and help try: * http://www.stata.com/support/faqs/res/findit.html * http://www.stata.com/support/statalist/faq * http://www.ats.ucla.edu/stat/stata/
|© Copyright 1996–2017 StataCorp LLC | Terms of use | Privacy | Contact us | What's new | Site index


text:
In his office, arm casually draped over the side of his sofa, Hunt seems to have things under control. On the walls are a photo of him meeting Arnold Schwarzenegger, a Grayson Perry print and a politically correct chart documenting the emergence of ethnic minority female singers ('I inherited it from my predecessor it's erm by Sonia Boyce,' he explains). On his coffee table is a biography of the pop trio N-Dubz. 'Well, Tulisa is going to be gracing our screens, isn't she?' he declares, proud to be so up on The X Factor. 'That's the joy of this portfolio, actually, that it encompasses everything.' The Ministry of Fun, David Mellor christened it, but that doesn't mean it's all giggles at the DCMS these days.
When he arrived last year, with six years of experience as an MP and a £4 million fortune from Hotcourses, the education website he co-founded, Hunt allegedly informed civil servants that there were difficult times ahead. All would have to make sacrifices; indeed he himself may even have to travel to the opera by Tube. 'I've been impressed with the resilience of the cultural sector in challenging times,' he says.
The arts world has warmed more to his underling, Arts Minister Ed Vaizey, but at least Hunt's enthusiastic approach to cutting has endeared him to the Conservative leadership. It is not hard to see why he has been tipped as a future leader, even if, since Jim Naughtie made that famous gaffe on the Today programme, he's replaced James Blunt in the rhyming-slang lexicon.
He's pleased with the Olympics preparations so far - the Games are on budget, we are told - despite the fact that he missed out on tickets. He was looking forward to taking his Chinese wife Lucia to the table tennis (they have been married for two years and have a one-year-old son), but only managed to get badminton. Still, he maintains, the lottery was the correct way to manage demand. 'It's very hard to think of a fairer way. The reason that there are so many disappointed people is because two thirds of the tickets were £50 or less and a third of the tickets were at £20; if you price the tickets below the market level, what you get is huge demand.'
It is not the only time he waves the term 'market level', with the hint that we taxpayers ought to count ourselves lucky. As for the 106 miles of 'VIP' driving lanes that will be cordoned off for the 'Games Family', he eventually concedes, 'It's part of our agreement in hosting the Games that we have this Olympic Route Network and, you know, that's why we have to do it.' Which ought to make those £200 fines for non-VIPs caught using them easier to bear. 'You can't underestimate the scale of the Olympics,' he says. 'In the end, people understand that we will have to do things differently for those 60 days.'
The excitement of the Games may well drown out the concerns. But for the moment, there's a sneaking worry that London is being invaded for a sort of global corporate PR-fest. The construction of the 115m-tall ArcelorMittal Orbit tower at the behest of the multibillionaire Lakshmi Mittal feels emblematic - more to do with a rich man's ego than concern for East London. 'It's only half up. We have to wait until it's up to see how it grows on people,' he says. 'A lot of people criticised the Olympic logo when it was first published.' I think they still do, actually. 'Well,' he laughs, 'I didn't particularly like it at first but I warmed to it.'
What about Wenlock and Mandeville, those sinister CCTV-camera mascots? Even Hunt must admit they're a bit rubbish. 'Well, do you know what, we could have had a British pillar box or other predictable things.' We could have had something that feels British, something with an ounce of charm, surely? 'Those two things they are quite fun, and they grow on you and there's lots to um no, I think we'll I think the best that can be said is that you don't get bored of them' - his voice blooms with what sounds suspiciously like a suppressed laugh - 'on first look.'
He is on surer ground with the 12-week- long Cultural Olympiad, which will feature a Doctor Who-themed immersive theatre piece from Punchdrunk; a Damon Albarn-penned Elizabethan opera; and a National Gallery-Royal Ballet collaboration called Titian 2012. 'If you say: "What's going to make London 2012 different?" I think it's the strength of our cultural offering.'
But that's the advantage of Hunt's position: whenever something doesn't work, he can blame someone else; whenever it does, he can claim the credit. He seems quite at ease with his place in the world as he makes casual assertions as to the meaning of sport (it's about 'helping you to cope with disappointments'); art ('giving you insights into the present, understanding things and giving you different angles on things'); and politics ('usually an argument about the future'). It's only when I ask what happened to the idea that the Olympics would get us all participating in sport that the arm undrapes itself from the sofa. 'If I may say, you're taking a somewhat sceptical stance,' he says, reminding me that Labour found that bit hard, too. He tells me he recently attended the launch of a new inter-school games, 'which is part of an initiative that this government has launched to get Olympic-style sports competitions into every school.'
So it's all about competition rather than participation? 'Both! The point is that, yes, there'll be a lot more com-petitive sport, but there'll be a lot more opportunities for kids to play it.' When I refer to Education Secretary Michael Gove's proposed cuts to school sports funding, he tells me that's part of a new approach 'which is essentially bottom-up rather than a top-down.' So: here's a ball, get on with it? 'Well, he believes very much in competitive sport, and PE is remaining part of the curriculum, even in the period when other parts of the curriculum are being dramatically slowed down.'
Back in his school days at Charterhouse, Hunt was no elite sportsman - 'I had so little coordination that I was banished to the cross-country running team,' he says - and has had to get up to speed fast (he confused the US Open and the US Masters when congratulating golfer Rory McIlroy recently). He's learning to be a football referee and hopes to referee matches in his constituency of South West Surrey. The qualities of fairness and even-handedness should also serve him well as a minister, I say: which brings us neatly to the vexed issue of Rupert Murdoch's proposed takeover of BSkyB. After Business Secretary Vince Cable admitted to undercover reporters that he was 'waging war against Murdoch', the responsibility was handed over to the supposedly unbiased Hunt. 'Now why did I think you were coming to that?' he says. 'Yes, we're still waiting for the final analysis from Ofcom and the OFT.'
Does he regret taking it on? 'No. You go into politics to make difficult decisions.' I ask whether he thinks he was an appropriate choice for the task, but his press officer intercedes and we're back on to the Olympics. 'We have a massive sporting tradition in this country: eight of the world's top ten sports were either invented or codified here. I think we've got every chance of getting a clutch of gold medals,' he says. Another hour ticks past on the Olympics clock. ES
On the town
Where do you live?
Pimlico and Farnham, Surrey.
What's your favourite restaurant?
Aubergine in Chelsea.
What book are you currently reading?
Bounce by Matthew Syed.
What was the last play you saw?
Anya Reiss's new play The Acid Test at the Royal Court.
Which football team do you support?
Chelsea - which is a little bit of a cliché for a Conservative culture secretary!
If you had to represent Team GB, which sport would you choose?
Probably the 800 metres, but you dragged that out of me.
Who's the sexiest MP?
Not me. I don't know Ed Vaizey's sexier than I am.
Did everyone making fun of your name annoy you?
Not in the slightest. I'm sure that was one of the things they hurled at me at school.
- More about:
- Lakshmi Mittal
- N-Dubz
- Olympics
- Olympic Stadium
- Tulisa (Singer)
- X Factor


text:
Cam Angle Sensor Question - 95 engine in a 97
Posted by greddy_1700, Jun 25, 2009
Newbie Forum - Beginner DSM modification questions and discussions. Common, repetitive, and general discussions will get dumped here from other tech forums. Unless you're a Probationary member you shouldn't post threads here.
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