text:
Project MOST is best known by the community and grateful parents for leading after-school programs during the school year. But this summer, thanks to a grant from the Levitt Foundation, Project MOST teamed up with the Seedlings Project at the Springs School's greenhouse and garden and offered a four-week camp for children, regardless of socioeconomic background, with a strong focus on nature.
Summer camps on the South Fork can range from a few hundred dollars a week to well into the thousands. But the Project MOST/Springs Seedlings educational summer program, which ends tomorrow, offered its lineup free to families with annual salaries of under $40,000, and $60 a week for those whose paychecks were more than that. The 8:30 a.m. to 1 p.m. day has seen the 40-plus children, mostly from the John M. Marshall elementary school and the Springs School, kayaking in Accobanac Harbor, visiting the shellfish hatchery on Napeague, and helping out the folks at the East End Cooperative Organic Farm on Long Lane.
The Levitt Foundation's goal is to combine education and nature, which it does by bestowing grants on programs that help to make children better "stewards of nature." Since 1949, the New York City organization has been doling out grant money to groups that help young people in the five boroughs and on Long Island learn to value the environment in which they live.
The foundation granted $51,000 to Project MOST's pilot summer program, to help kids learn about the environment "in a hands-on way, and make sure low-income children could access the program and have a productive summer," according to Tim Bryden, the program's executive director.
The Project MOST summer program has been focused around the Springs Seedlings greenhouse, featuring partnerships with the Group for the East End and the East Hampton Town Shellfish Hatchery.
On the Accabonac kayak exploration, children learned about undeveloped coastal wetlands, from the shore and the water. Thirty-two students, along with Martha Stotsky and Rebecca Morgan Taylor, the teachers, and Kayak Warriors, a boat-rental company, paddled out to observe plants and animals that are alive and well thanks to the stewardship of the waterway.
Barley Dunne, the executive director of the East Hampton shellfish hatchery, briefed the kids on current marine biology research. The kids went clamming, and were able to see firsthand how sulphur dioxide was depleting oxygen from the waters, killing the shellfish.
Children also did photo-essays with help from Ellen Watson, a professional local photographer, and wrote journals about what they saw, heard, and felt. They studied nutrition in a hands-on way, making community lunches like chilled cantaloupe soup, bean and green salads from the greenhouse, and fresh strawberry shortcake.
"Gardening and making a healthy lunch are a big part of the program," said Mr. Bryden.
The program ended last night with a family dinner, prepared by the campers, at which the children presented what they had learned this summer to their parents, community members, and teachers. It also included a photo display and a tour of the Springs Seedlings garden.
The program was a success, Mr. Bryden said, and he hopes it will continue, and expand.
"There is no question that the students will say as a result of the summer experience that they think more about the environment, better understand farming and fresh food, and enjoyed the new experiences such as kayaking in Acabonac Harbor and photographing nature," Mr. Bryden said, adding, "Paula Guerra, a student, said to me that she feels she has helped to make the world more beautiful this summer."


text:
look (a little/bit) off
look (a little/bit) off
1. To look sickly, unwell, or out of sorts, either physically or mentally. You're looking a little off, Jim. Are you feeling all right? That dog on the corner looks a bit off. I think we should walk another way home.
2. To appear somewhat strange, incorrect, inaccurate, or substandard. A: "The rest of your portrait is coming along really well, but the hands look a bit off." B: "I know, hands are just so hard to draw!" The gameplay is great, but the graphics on the characters' faces are off.
3. Of food, to appear spoiled or rotten. These chicken breasts look a little bit off—I think we should throw them in the garbage.

subset: commoncrawl


text: File this under "You're Old." Cindy Crawford's daughter Kaia has begun modeling for Versace, the same fashion house that Cindy acted as muse for throughout the 1990's. To be fair, it's Young Versace that Kaia is modeling for and she is only 10-years-old, though you wouldn't know that from the way people are talking about her. Human sweet potato Donatella Versace says, "Like her mother, Kaia has a very special gift. The camera really really loves her." Yes, the camera and the 15 years of age added by wardrobe and photoshop can't get enough of the kid.


text:
Gravitionally Lensed Light Caused by Ancient Massive Galaxy Cluster
An odd arc of light has led to one of the newest cosmology discoveries to come from the Hubble telescope: a massive, ancient galaxy cluster.
The arc of light comes from a fairly normal galaxy, but it's been warped in a process called gravitational lensing. Lensing occurs when an object is massive enough to distort the light rays traveling near it.
In this case, astronomers observed the light coming from behind a massive galaxy cluster more than 10 billion light-years away, and between the lensed galaxy and us. Lensing has never been seen that was caused by such a distant cluster. The researchers report their findings in the Astrophysical Journal. [Anthony H. Gonzalez et al., "IDCS J1426.5+3508: Cosmological implications of a massive, strong lensing cluster at Z = 1.75"]
In general, galaxy clusters are smaller the older they are, so finding such a massive galaxy cluster was improbable to begin with. This one is five to 10 times larger than other clusters of similar vintage, dating back to when the universe was only a quarter of its present age.
Further study may determine if concentrations of galaxies of this age and brightness are greater than previously thought, or whether this finding was just lucky. In other words, future research will shed more light.
—Evelyn Lamb
[The above text is a transcript of this podcast.]


text:
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text:
An appeals court has ruled that a Mobile County woman can't adopt her female partner's child because of Alabama's law that defines marriage as being between a man and woman.
The Alabama Court of Civil Appeals ruled Friday that the woman can't adopt her partner's child, even though the couple said they were married in California.
The unanimous opinion, written by Presiding Judge Bill Thompson, said one member of the couple cannot adopt the other's child.
The opinion said marriages between same-sex couples are not recognized in Alabama even if they were conducted in another state.
A supporter of Alabama's law banning same sex marriage, Republican Sen. Gerald Allen of Tuscaloosa, said he believes this is the first time a court has upheld the 2009 Alabama Marriage Protection Act.
(Copyright 2012 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.)


text:
bystolic (nebivolol) tablet
[Forest Pharmaceuticals Inc.]
2.5 mg, 5 mg and 10 mg
Rx only
The chemical name for the active ingredient in BYSTOLIC (nebivolol) tablets is (1RS,1'RS)-1,1'-[(2RS,2'SR)-bis(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)]- 2,2'-iminodiethanol hydrochloride. Nebivolol is a racemate composed of d-Nebivolol and l-Nebivolol with the stereochemical designations of [SRRR]-nebivolol and [RSSS]-nebivolol, respectively. Nebivolol's molecular formula is (C22H25F2NO4•HCl) with the following structural formula:
Nebivolol hydrochloride is a white to almost white powder that is soluble in methanol, dimethylsulfoxide, and N,N-dimethylformamide, sparingly soluble in ethanol, propylene glycol, and polyethylene glycol, and very slightly soluble in hexane, dichloromethane, and methylbenzene.
BYSTOLIC as tablets for oral administration contains nebivolol hydrochloride equivalent to 2.5, 5, and 10 mg of nebivolol base. In addition, BYSTOLIC contains the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, D&C Red #27 Lake, FD&C Blue #2 Lake, FD&C Yellow #6 Lake, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, pregelatinized starch, polysorbate 80, and sodium lauryl sulfate.
Nebivolol is a β-adrenergic receptor blocking agent. In extensive metabolizers (most of the population) and at doses less than or equal to 10 mg, nebivolol is preferentially β1 selective. In poor metabolizers and at higher doses, nebivolol inhibits both β1 and β2 - adrenergic receptors. Nebivolol lacks intrinsic sympathomimetic and membrane stabilizing activity at therapeutically relevant concentrations. At clinically relevant doses, BYSTOLIC does not demonstrate α1-adrenergic receptor blockade activity. Various metabolites, including glucuronides, contribute to β-blocking activity.
The mechanism of action of the antihypertensive response of BYSTOLIC has not been definitively established. Possible factors that may be involved include: (1) decreased heart rate, (2) decreased myocardial contractility, (3) diminution of tonic sympathetic outflow to the periphery from cerebral vasomotor centers, (4) suppression of renin activity and (5) vasodilation and decreased peripheral vascular resistance.
Nebivolol is metabolized by a number of routes, including glucuronidation and hydroxylation by CYP2D6. The active isomer (d-nebivolol) has an effective half-life of about 12 hours in CYP2D6 extensive metabolizers (most people), and 19 hours in poor metabolizers and exposure to d-nebivolol is substantially increased in poor metabolizers. This has less importance than usual, however, because the metabolites, including the hydroxyl metabolite and glucuronides (the predominant circulating metabolites), contribute to β-blocking activity.
Plasma levels of d–nebivolol increase in proportion to dose in EMs and PMs for doses up to 20mg. Exposure to l-nebivolol is higher than to d-nebivolol but l-nebivolol contributes little to the drug's activity as d-nebivolol's beta receptor affinity is > 1000-fold higher than l-nebivolol. For the same dose, PMs attain a 5-fold higher Cmax and 10-fold higher AUC of d-nebivolol than do EMs. d-Nebivolol accumulates about 1.5-fold with repeated once-daily dosing in EMs.
Absorption of BYSTOLIC is similar to an oral solution. The absolute bioavailability has not been determined.
Mean peak plasma nebivolol concentrations occur approximately 1.5 to 4 hours post-dosing in EMs and PMs.
Food does not alter the pharmacokinetics of nebivolol. Under fed conditions, nebivolol glucuronides are slightly reduced. BYSTOLIC may be administered without regard to meals.
The in vitro human plasma protein binding of nebivolol is approximately 98%, mostly to albumin, and is independent of nebivolol concentrations.
Nebivolol is predominantly metabolized via direct glucuronidation of parent and to a lesser extent via N-dealkylation and oxidation via cytochrome P450 2D6. Its stereospecific metabolites contribute to the pharmacologic activity (see Drug Interactions).
After a single oral administration of 14C-nebivolol, 38% of the dose was recovered in urine and 44% in feces for EMs and 67% in urine and 13% in feces for PMs. Essentially all nebivolol was excreted as multiple oxidative metabolites or their corresponding glucuronide conjugates.
Drugs that inhibit CYP2D6 can be expected to increase plasma levels of nebivolol. When BYSTOLIC is co-administered with an inhibitor or an inducer of this enzyme, patients should be closely monitored and the nebivolol dose adjusted according to blood pressure response. In vitro studies have demonstrated that at therapeutically relevant concentrations, d- and l-nebivolol do not inhibit any cytochrome P450 pathways.
Digoxin: Concomitant administration of BYSTOLIC (10 mg once daily) and digoxin (0.25 mg once daily) for 10 days in 14 healthy adult individuals resulted in no significant changes in the pharmacokinetics of digoxin or nebivolol (see PRECAUTION, Drug Interactions).
Warfarin: Administration of BYSTOLIC (10 mg once daily for 10 days) led to no significant changes in the pharmacokinetics of nebivolol or R- or S-warfarin following a single 10 mg dose of warfarin. Similarly, nebivolol has no significant effects on the anticoagulant activity of warfarin, as assessed by Prothrombin time and INR profiles from 0 to 144 hours after a single 10 mg warfarin dose in 12 healthy adult volunteers.
Diuretics: No pharmacokinetic interactions were observed in healthy adults between nebivolol (10 mg daily for 10 days) and furosemide (40 mg single dose), hydrochlorothiazide (25 mg once daily for 10 days), or spironolactone (25 mg once daily for 10 days).
Ramipril: Concomitant administration of BYSTOLIC (10 mg once daily) and ramipril (5 mg once daily) for 10 days in 15 healthy adult volunteers produced no pharmacokinetic interactions.
Losartan: Concomitant administration of BYSTOLIC (10 mg single dose) and losartan (50 mg single dose) in 20 healthy adult volunteers did not result in pharmacokinetic interactions.
Fluoxetine: Fluoxetine, a CYP2D6 inhibitor, administered at 20 mg per day for 21 days prior to a single 10 mg dose of nebivolol to 10 healthy adults, led to an 8-fold increase in the AUC and 3-fold increase in Cmax for d-nebivolol (see PRECAUTIONS, Drug Interactions).
Histamine-2 Receptor Antagonists: The pharmacokinetics of nebivolol (5 mg single dose) were not affected by the co-administration of ranitidine (150 mg twice daily). Cimetidine (400 mg twice daily) causes a 23% increase in the plasma levels of d-nebivolol.
Charcoal: The pharmacokinetics of nebivolol (10 mg single dose) were not affected by repeated co-administration (4, 8, 12, 16, 22, 28, 36, and 48 hours after nebivolol administration) of activated charcoal (Actidose-Aqua®).
Sildenafil: The co-administration of nebivolol and sildenafil decreased AUC and Cmax of sildenafil by 21 and 23% respectively. The effect on the Cmax and AUC for d -nebivolol was also small (< 20%). The effect on vital signs (e.g., pulse and blood pressure) was approximately the sum of the effects of sildenafil and nebivolol.
Other Concomitant Medications: Utilizing population pharmacokinetic analyses, derived from hypertensive patients, the following drugs were observed not to have an effect on the pharmacokinetics of nebivolol: acetaminophen, acetylsalicylic acid, atorvastatin, esomeprazole, ibuprofen, levothyroxine sodium, metformin, sildenafil, simvastatin, or tocopherol.
Protein Binding: No meaningful changes in the extent of in vitro binding of nebivolol to human plasma proteins were noted in the presence of high concentrations of diazepam, digoxin, diphenylhydantoin, enalapril, hydrochlorothiazide, imipramine, indomethacin, propranolol, sulfamethazine, tolbutamide, or warfarin. Additionally, nebivolol did not significantly alter the protein binding of the following drugs: diazepam, digoxin, diphenylhydantoin, hydrochlorothiazide, imipramine, or warfarin at their therapeutic concentrations.
Renal Disease: The apparent clearance of nebivolol was unchanged following a single 5 mg dose of BYSTOLIC in patients with mild renal impairment (ClCr 50 to 80 mL/min, n=7), and it was reduced negligibly in patients with moderate (ClCr 30 to 50 mL/min, n=9), but by 53% in patients with severe renal impairment (ClCr <30 mL/min, n=5). The dose of BYSTOLIC should be adjusted in patients with severe renal impairment. BYSTOLIC should be used with caution in patients receiving dialysis, since no formal studies have been conducted in this population (see DOSAGE AND ADMINISTRATION).
Hepatic Disease: d-Nebivolol peak plasma concentration increased 3-fold, exposure (AUC) increased 10-fold, and the apparent clearance decreased by 86% in patients with moderate hepatic impairment (Child-Pugh Class B). The starting dose should be reduced in patients with moderate hepatic impairment. No formal studies have been performed in patients with severe hepatic impairment and nebivolol should be contraindicated for these patients (see DOSAGE AND ADMINISTRATION).
The antihypertensive effectiveness of BYSTOLIC as monotherapy has been demonstrated in three randomized, double-blind, multi-center, placebo-controlled trials at doses ranging from 1.25 to 40 mg for 12 weeks (Studies 1, 2, and 3). A fourth placebo-controlled trial demonstrated additional antihypertensive effects of BYSTOLIC at doses ranging from 5 to 20 mg when administered concomitantly with up to two other antihypertensive agents (ACE inhibitors, angiotensin II receptor antagonists, and thiazide diuretics) in patients with inadequate blood pressure control.
The three monotherapy trials included a total of 2016 patients (1811 BYSTOLIC, 205 placebo) with mild to moderate hypertension who had baseline diastolic blood pressures (DBP) of 95 to 109 mmHg. Patients received either BYSTOLIC or placebo once daily for twelve weeks. Two of these monotherapy trials (Studies 1 and 2) studied 1716 patients in the general hypertensive population with a mean age of 54 years, 55% males, 26% non-Caucasians, 7% diabetics and 6% genotyped as PMs. The third monotherapy trial (Study 3) studied 300 Black patients with a mean age of 51 years, 45% males, 14% diabetics, and 3% as PMs.
Placebo-subtracted blood pressure reductions by dose for each study are presented in Table 1. Most studies showed increasing response to doses above 5 mg.
* p<0.05 based on pair-wise comparison vs placebo
¶ Study enrolled only African Americans.
^ Study on top of one or two other antihypertensive medications.
|Nebivolol dose (mg)
|Study 1
|Study 2
|Study 3¶
|Study 4^
Study 4 enrolled 669 patients with a mean age of 54 years, 55% males, 54% Caucasians, 29% Blacks, 15% Hispanics, 1% Asians, 14% diabetics, and 5% PMs. BYSTOLIC, 5 mg to 20 mg, administered once daily concomitantly with stable doses of up to two other antihypertensive agents (ACE inhibitors, angiotensin II receptor antagonists, and thiazide diuretics) resulted in significant additional antihypertensive effects over placebo compared to baseline blood pressure.
Effectiveness was similar in subgroups analyzed by age and sex. Effectiveness was established in Blacks, but as monotherapy the magnitude of effect was somewhat less than in Caucasians.
The blood pressure lowering effect of BYSTOLIC was seen within two weeks of treatment and was maintained over the 24-hour dosing interval.
BYSTOLIC is indicated for the treatment of hypertension. BYSTOLIC may be used alone or in combination with other antihypertensive agents.
BYSTOLIC is contraindicated in patients with severe bradycardia, heart block greater than first degree, cardiogenic shock, decompensated cardiac failure, sick sinus syndrome (unless a permanent pacemaker is in place), or severe hepatic impairment (Child-Pugh >B), and in patients who are hypersensitive to any component of this product.
Patients with coronary artery disease treated with BYSTOLIC should be advised against abrupt discontinuation of therapy. Severe exacerbation of angina and the occurrence of myocardial infarction and ventricular arrhythmias have been reported in patients with coronary artery disease following the abrupt discontinuation of therapy with β-blockers. Myocardial infarction and ventricular arrhythmias may occur with or without preceding exacerbation of the angina pectoris. Even patients without overt coronary artery disease should be cautioned against interruption or abrupt discontinuation of therapy. As with other β-blockers, when discontinuation of BYSTOLIC is planned, patients should be carefully observed and advised to minimize physical activity. BYSTOLIC should be tapered over 1 to 2 weeks when possible. If the angina worsens or acute coronary insufficiency develops, it is recommended that BYSTOLIC be promptly reinstituted, at least temporarily.
Sympathetic stimulation is a vital component supporting circulatory function in the setting of congestive heart failure, and β-blockade may result in further depression of myocardial contractility and precipitate more severe failure. In patients who have compensated congestive heart failure, BYSTOLIC should be administered cautiously. If heart failure worsens, discontinuation of BYSTOLIC should be considered.
BYSTOLIC was not studied in patients with angina pectoris or who had a recent MI.
In general, patients with bronchospastic diseases should not receive β-blockers.
If BYSTOLIC is to be continued perioperatively, patients should be closely monitored when anesthetic agents which depress myocardial function, such as ether, cyclopropane, and trichloroethylene, are used. If β-blocking therapy is withdrawn prior to major surgery, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures.
The β-blocking effects of BYSTOLIC can be reversed by β-agonists, e.g., dobutamine or isoproterenol. However, such patients may be subject to protracted severe hypotension. Additionally, difficulty in restarting and maintaining the heartbeat has been reported with β-blockers.
β-blockers may mask some of the manifestations of hypoglycemia, particularly tachycardia. Nonselective β-blockers may potentiate insulin-induced hypoglycemia and delay recovery of serum glucose levels. It is not known whether nebivolol has these effects. Patients subject to spontaneous hypoglycemia, or diabetic patients receiving insulin or oral hypoglycemic agents, should be advised about these possibilities and nebivolol should be used with caution.
β-blockers may mask clinical signs of hyperthyroidism, such as tachycardia. Abrupt withdrawal of β-blockers may be followed by an exacerbation of the symptoms of hyperthyroidism or may precipitate a thyroid storm.
β-blockers can precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease. Caution should be exercised in these patients.
Because of significant negative inotropic and chronotropic effects in patients treated with β-blockers and calcium channel blockers of the verapamil and diltiazem type, caution should be used in patients treated concomitantly with these agents and ECG and blood pressure should be monitored.
Nebivolol exposure increases with inhibition of CYP2D6 (see Drug Interactions). The dose of BYSTOLIC may need to be reduced.
BYSTOLIC should be used with caution in patients with severe renal impairment because of decreased renal clearance. BYSTOLIC has not been studied in patients receiving dialysis.
BYSTOLIC should be used with caution in patients with moderate hepatic impairment because of decreased metabolism. Since BYSTOLIC has not been studied in patients with severe hepatic impairment, BYSTOLIC is contraindicated in this population (see CLINICAL PHARMACOLOGY, Special Populations and DOSAGE AND ADMINISTRATION).
While taking β-blockers, patients with a history of severe anaphylactic reactions to a variety of allergens may be more reactive to repeated challenge either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reactions.
In patients with known or suspected pheochromocytoma, an alpha-blocker should be initiated prior to the use of any β-blocker.
Patients should be advised to take BYSTOLIC regularly and continuously, as directed. BYSTOLIC can be taken with or without food. If a dose is missed, the patient should take the next scheduled dose only (without doubling it). Patients should not interrupt or discontinue BYSTOLIC without consulting the physician.
Patients should know how they react to this medicine before they operate automobiles, use machinery, or engage in other tasks requiring alertness.
Patients should be advised to consult a physician if any difficulty in breathing occurs, or if they develop signs or symptoms of worsening congestive heart failure such as weight gain or increasing shortness of breath, or excessive bradycardia.
Patients subject to spontaneous hypoglycemia, or diabetic patients receiving insulin or oral hypoglycemic agents, should be cautioned that β-blockers may mask some of the manifestations of hypoglycemia, particularly tachycardia. Nebivolol should be used with caution in these patients.
BYSTOLIC should be used with care when myocardial depressants or inhibitors of AV conduction, such as certain calcium antagonists (particularly of the phenylalkylamine [verapamil] and benzothiazepine [diltiazem] classes), or antiarrhythmic agents, such as disopyramide, are used concurrently. Both digitalis glycosides and β-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.
BYSTOLIC should not be combined with other β-blockers. Patients receiving catecholamine-depleting drugs, such as reserpine or guanethidine, should be closely monitored, because the added β-blocking action of BYSTOLIC may produce excessive reduction of sympathetic activity. In patients who are receiving BYSTOLIC and clonidine, BYSTOLIC should be discontinued for several days before the gradual tapering of clonidine.
CYP2D6 Inhibitors: Use caution when BYSTOLIC is co-administered with CYP2D6 inhibitors (quinidine, propafenone, fluoxetine, paroxetine, etc.) (see CLINICAL PHARMACOLOGY, Drug Interactions).
In a two-year study of nebivolol in mice, a statistically significant increase in the incidence of testicular Leydig cell hyperplasia and adenomas was observed at 40 mg/kg/day (5 times the maximally recommended human dose of 40 mg on a mg/m2 basis). Similar findings were not reported in mice administered doses equal to approximately 0.3 or 1.2 times the maximum recommended human dose. No evidence of a tumorigenic effect was observed in a 24-month study in Wistar rats receiving doses of nebivolol 2.5, 10 and 40 mg/kg/day (equivalent to 0.6, 2.4, and 10 times the maximally recommended human dose). Co-administration of dihydrotestosterone reduced blood LH levels and prevented the Leydig cell hyperplasia, consistent with an indirect LH-mediated effect of nebivolol in mice and not thought to be clinically relevant in man.
A randomized, double-blind, placebo- and active-controlled, parallel-group study in healthy male volunteers was conducted to determine the effects of nebivolol on adrenal function, luteinizing hormone, and testosterone levels. This study demonstrated that 6 weeks of daily dosing with 10 mg of nebivolol had no significant effect on ACTH-stimulated mean serum cortisol AUC0-120 min, serum LH, or serum total testosterone.
Effects on spermatogenesis were seen in male rats and mice at ≥40 mg/kg/day (10 and 5 times the MRHD, respectively). For rats the effects on spermatogenesis were not reversed and may have worsened during a four week recovery period. The effects of nebivolol on sperm in mice, however, were partially reversible.
Mutagenesis: Nebivolol was not genotoxic when tested in a battery of assays (Ames, in vitro mouse lymphoma TK+/-, in vitro human peripheral lymphocyte chromosome aberration, in vivo Drosophila melanogaster sex-linked recessive lethal, and in vivo mouse bone marrow micronucleus tests).
Decreased pup body weights occurred at 1.25 and 2.5 mg/kg in rats, when exposed during the perinatal period (late gestation, parturition and lactation). At 5 mg/kg and higher doses (1.2 times the MRHD), prolonged gestation, dystocia and reduced maternal care were produced with corresponding increases in late fetal deaths and stillbirths and decreased birth weight, live litter size and pup survival. Insufficient numbers of pups survived at 5 mg/kg to evaluate the offspring for reproductive performance.
In studies in which pregnant rats were given nebivolol during organogenesis, reduced fetal body weights were observed at maternally toxic doses of 20 and 40 mg/kg/day (5 and 10 times the MRHD), and small reversible delays in sternal and thoracic ossification associated with the reduced fetal body weights and a small increase in resorption occurred at 40 mg/kg/day (10 times the MRHD). No adverse effects on embryo-fetal viability, sex, weight or morphology were observed in studies in which nebivolol was given to pregnant rabbits at doses as high as 20 mg/kg/day (10 times the MRHD).
Nebivolol caused prolonged gestation and dystocia at doses ≥5 mg/kg in rats (1.2 times the MRHD). These effects were associated with increased fetal deaths and stillborn pups, and decreased birth weight, live litter size and pup survival rate, events that occurred only when nebivolol was given during the perinatal period (late gestation, parturition and lactation).
No studies of nebivolol were conducted in pregnant women. BYSTOLIC should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Studies in rats have shown that nebivolol or its metabolites cross the placental barrier and are excreted in breast milk. It is not known whether this drug is excreted in human milk.
Because of the potential for β-blockers to produce serious adverse reactions in nursing infants, especially bradycardia, BYSTOLIC is not recommended during nursing.
Of the 2800 patients in the U.S. sponsored placebo-controlled clinical hypertension studies, 478 patients were 65 years of age or older. No overall differences in efficacy or in the incidence of adverse events were observed between older and younger patients.
Safety and effectiveness in pediatric patients have not been established. Pediatric studies in ages newborn to 18 years old have not been conducted because of incomplete characterization of developmental toxicity and possible adverse effects on long-term fertility (see Carcinogenesis, Mutagenesis and Impairment of Infertility).
The data described below reflect worldwide clinical trial exposure to BYSTOLIC in 6545 patients, including 5038 patients treated for hypertension and the remaining 1507 subjects treated for other cardiovascular diseases. Doses ranged from 0.5 mg to 40 mg. Patients received BYSTOLIC for up to 24 months, with over 1900 patients treated for at least 6 months, and approximately 1300 patients for more than one year. In placebo-controlled clinical trials comparing BYSTOLIC with placebo, discontinuation of therapy due to adverse events was reported in 2.8% of patients treated with nebivolol and 2.2% of patients given placebo. The most common adverse events that led to discontinuation of BYSTOLIC were headache (0.4%), nausea (0.2%) and bradycardia (0.2%).
Table 2 lists treatment-emergent signs and symptoms that were reported in three 12-week, placebo-controlled monotherapy trials involving 1597 hypertensive patients treated with either 5 mg, 10 mg or 20-40 mg of BYSTOLIC and 205 patients given placebo and for which the rate of occurrence was at least 1% of patients treated with nebivolol and greater than the rate for those treated with placebo in at least one dose group.
(n = 205)
5 mg
(n = 459)
10 mg
(n = 461)
20-40 mg
(n = 677)
|Chest pain
|Peripheral edema
Listed below are other reported adverse events with an incidence of at least 1% in the more than 5300 patients treated with BYSTOLIC in controlled or open-label trials, whether or not attributed to treatment, except for those already appearing in Table 2, terms too general to be informative, minor symptoms, or events unlikely to be attributable to drug because they are common in the population. These adverse events were in most cases observed at a similar frequency in placebo-treated patients in the controlled studies.
Body as a whole: asthenia.
Gastrointestinal System Disorders: abdominal pain
Metabolic and Nutritional Disorders: hypercholesterolemia and hyperuricemia
Nervous System Disorders: paraesthesia
In controlled monotherapy trials, BYSTOLIC was associated with an increase in BUN, uric acid, triglycerides and a decrease in HDL cholesterol and platelet count.
The following adverse events have been identified from spontaneous reports of BYSTOLIC received worldwide and have not been listed elsewhere. These adverse events have been chosen for inclusion due to a combination of seriousness, frequency of reporting or potential causal connection to BYSTOLIC. Events common in the population have generally been omitted. Because these events were reported voluntarily from a population of uncertain size, it is not possible to estimate their frequency or establish a causal relationship to BYSTOLIC exposure: abnormal hepatic function (including increased AST, ALT and bilirubin), acute pulmonary edema, acute renal failure, atrioventricular block (both second and third degree), bronchospasm, erectile dysfunction, hypersensitivity (including urticaria, allergic vasculitis and rare reports of angioedema), myocardial infarction, pruritus, psoriasis, Raynaud's phenomenon, peripheral ischemia/claudication, somnolence, syncope, thrombocytopenia, various rashes and skin disorders, vertigo, and vomiting.
In clinical trials and worldwide postmarketing experience there were reports of BYSTOLIC overdose. The most common signs and symptoms associated with BYSTOLIC overdosage are bradycardia and hypotension. Other important adverse events reported with BYSTOLIC overdose include cardiac failure, dizziness, hypoglycemia, fatigue and vomiting. Other adverse events associated with β-blocker overdose include bronchospasm and heart block.
The largest known ingestion of BYSTOLIC worldwide involved a patient who ingested up to 500 mg of BYSTOLIC along with several 100 mg tablets of acetylsalicylic acid in a suicide attempt. The patient experienced hyperhydrosis, pallor, depressed level of consciousness, hypokinesia, hypotension, sinus bradycardia, hypoglycemia, hypokalemia, respiratory failure and vomiting. The patient recovered.
Due to extensive drug binding to plasma proteins, hemodialysis is not expected to enhance nebivolol clearance.
If overdose occurs, BYSTOLIC should be stopped and general supportive and specific symptomatic treatment should be provided. Based on expected pharmacologic actions and recommendations for other β-blockers, the following general measures should be considered when clinically warranted:
Bradycardia: Administer IV atropine. If the response is inadequate, isoproterenol or another agent with positive chronotropic properties may be given cautiously. Under some circumstances, transthoracic or transvenous pacemaker placement may be necessary.
Hypotension: Administer IV fluids and vasopressors. Intravenous glucagon may be useful.
Heart Block (second or third degree): Patients should be carefully monitored and treated with isoproterenol infusion. Under some circumstances, transthoracic or transvenous pacemaker placement may be necessary.
Congestive Heart Failure: Initiate therapy with digitalis glycoside and diuretics. In certain cases, consideration should be given to the use of inotropic and vasodilating agents.
Bronchospasm: Administer bronchodilator therapy such as a short acting inhaled β2-agonist and/or aminophylline.
Hypoglycemia: Administer IV glucose. Repeated doses of IV glucose or possibly glucagon may be required.
In the event of intoxication where there are symptoms of shock, treatment must be continued for a sufficiently long period consistent with the 12-19 hour effective half-life of BYSTOLIC. Supportive measures should continue until clinical stability is achieved.
Call the National Poison Control Center (800-222-1222) for the most current information on β-blocker overdose treatment.
The dose of BYSTOLIC should be individualized to the needs of the patient. For most patients, the recommended starting dose is 5 mg once daily, with or without food, as monotherapy or in combination with other agents. For patients requiring further reduction in blood pressure, the dose can be increased at 2-week intervals up to 40 mg. A more frequent dosing regimen is unlikely to be beneficial.
In patients with severe renal impairment (ClCr less than 30 mL/min) the recommended initial dose is 2.5 mg once daily; upward titration should be performed cautiously if needed. BYSTOLIC has not been studied in patients receiving dialysis (see CLINICAL PHARMACOLOGY, Special Populations).
In patients with moderate hepatic impairment, the recommended initial dose is 2.5 mg once daily; upward titration should be performed cautiously if needed. BYSTOLIC has not been studied in patients with severe hepatic impairment and therefore it is not recommended in that population (see PRECAUTIONS and CLINICAL PHARMACOLOGY, Special Populations).
It is not necessary to adjust the dose in the elderly (see above and PRECAUTIONS, Geriatric Use).
(see CLINICAL PHARMACOLOGY, Pharmacokinetics)
No dose adjustments are necessary for patients who are CYP2D6 poor metabolizers. The clinical effect and safety profile observed in poor metabolizers were similar to those of extensive metabolizers.
BYSTOLIC is available as tablets for oral administration containing nebivolol hydrochloride equivalent to 2.5, 5, and 10 mg of nebivolol.
BYSTOLIC tablets are triangular-shaped, biconvex, unscored, differentiated by color and are engraved with "FL" on one side and the number of mg (2 ½ , 5, or 10) on the other side. BYSTOLIC tablets are supplied in the following strengths and package configurations:
|Tablet Color
|2.5 mg
|Bottle of 30
|Light Blue
|Bottle of 100
|5 mg
|Bottle of 30
|Bottle of 100
|10 x 10 Unit Dose
|10 mg
|Bottle of 30
|Pinkish -Purple
|Bottle of 100
|10 x 10 Unit Dose
Store at 20° to 25°C (68° to 77°F). [See USP for Controlled Room Temperature.]
Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.
Forest Pharmaceuticals Inc.
Subsidiary of Forest Laboratories
St. Louis, MO 63045, USA
Licensed from Mylan Laboratories, Inc.
Under License from Janssen
Pharmaceutica N.V., Beerse, Belgium
Actidose-Aqua® is a registered trademark of Paddock Laboratories, Inc.
Rev. 12/07
© 2007 Forest Laboratories, Inc.
|Bystolic (nebivolol)
|Bystolic (nebivolol)
|Bystolic (nebivolol)
Data are from FDA and U.S. National Library of Medicine.


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Catching Up With Pathogenesis and Cure Research From CROI 2014
May 16, 2014
In addition to studies covered in prior posts (a possible second pediatric cure case, Sangamo's gene therapy and limitations of latency-reversing agents), CROI 2014 featured a smorgasbord of presentations related to pathogenesis and cure research. Webcasts of all conference sessions are online, and many posters are now available in PDF format. Brief summaries of some notable studies are appended below, with links to webcasts and posters included where possible. Abstracts for posters that are unavailable as PDFs can be found in the final program and abstract book.
HIV Rebound in the Boston Patients
Timothy Henrich provided details on the two individuals in Boston who experienced a delayed return of HIV replication after a period during which it had been hoped they might be cured (this sobering news was covered on the blog last December). Henrich's presentation is available via webcast. Although they were monitored frequently after interrupting antiretroviral therapy (ART), viral load reached very high levels in both cases, and this was accompanied by symptoms of acute infection. The likely explanation is that their immune systems, having been newly generated by the stem cell transplants they had received to treat cancer, had not previously encountered HIV. Consistent with this possibility, HIV-specific cellular immune responses were undetectable prior to the viral load rebound but appeared afterward. At a community workshop on cure research immediately prior to CROI, Henrich noted that the size of the HIV reservoir had been reduced at least 3 logs in these individuals and was estimated to be very small at the time of the ART interruption; 290-2900 cells in one case, 40-730 cells in the other. The results suggest the bar is set very high for approaches that aim to cure HIV infection by shrinking the latent reservoir.
Treatment of Hyperacute HIV Infection
A large crowd congregated at a poster presentation (397LB) by Hiroyu Hatano from UCSF describing extremely early ART treatment in an individual who acquired HIV infection just prior to enrolling in a pre-exposure prophylaxis (PrEP) demonstration project. The infection occurred during a short 13-day window between a final screening visit and the day Truvada PrEP was first administered. When viral load results from the sample taken at Truvada initiation became available after seven days and showed a reading of 220 copies, the individual was switched to a conventional ART regimen. The viral load seven days later was 120 copies and there was a single measurement of cell-associated HIV RNA at a level of 4.7 copies per million CD4 T cells ~32 days after infection, but all subsequent tests for HIV RNA, DNA and replication-competent virus have been negative. The results raise the possibility that ART given at such an early stage of infection may have led to an adult equivalent of the Mississippi baby case. However, the experience of the Boston patients offers a cautionary tale about the interpretation of negative virological assay results. A treatment interruption will be considered after 12 months of ART.
Three Cured Mice
Qingsheng Li displayed an interesting poster immediately adjacent to Hatano's, but it didn't receive quite as much attention. Li's work attempted to recapitulate the Mississippi baby outcome in the humanized mouse model, by administering ART six hours after the animals were infected with HIV. ART was maintained for two weeks and then interrupted. HIV RNA and DNA remained undetectable after interruption, even when CD8 T cells were depleted, leading the researchers to conclude that a cure had been achieved. The initial experiment (reported in the conference abstract book) involved three ART-treated mice and three controls, but the poster included data on additional groups that received ART at later timepoints after infection (12 hours and 18 hours). In these animals, HIV rebounded after ART interruption. Unfortunately the poster is not yet available on the CROI website (there is a link, but it goes to the abstract book).
HIV Integration, Latency and CD4 T-Cell Survival
At least two published studies (Josefsson et al and Imamich et al) have documented that the homeostatic proliferation of memory CD4 T cells containing integrated HIV provirus can increase the amount of HIV DNA in the body. These studies tracked copies of grossly defective virus genomes that could only multiply as a result of the proliferation of the host CD4 T cell. Homeostatic proliferation is a normal immunological mechanism that sustains memory T cells, and causes them to expand in the setting of T-cell deficiency. The role of this process in maintaining the latent HIV reservoir was first described many years ago, based in part on the finding that lower CD4 T-cell counts are associated with an increased rate of CD4 T-cell proliferation and higher levels of HIV proviral DNA (although these levels remain extremely low compared to the overall size of the memory CD4 T-cell pool). Several presentations at CROI documented the phenomenon in a different way, by demonstrating the proliferation of HIV proviruses integrated at precisely the same location in the CD4 T-cell genome. Additionally, it was reported by Thor Wagner that HIV proviruses frequently integrate at very similar sites in certain CD4 T-cell genes associated with the cell cycle and differentiation, leading to the suggestion that HIV integration into these genes may somehow be promoting the growth and longevity of latently infected CD4 T cells. Wagner highlighted the fact that some of the genes into which HIV appears to preferentially integrate have been identified as having roles in cancers, and this point was echoed in a poster from Stephen Hughes laboratory at the National Cancer Institute. However, some cited examples such as Bach2 are also involved in CD4 T-cell differentiation (this is not mentioned in either CROI presentation), so it would be logical that genes such as this would be active in the CD4 T cells HIV infects, and the virus is already known to preferentially integrate into active genes. Additional research is needed to clarify whether there is anything sinister about these integration sites, or if they just reflect the locations HIV is most likely to have access to in the cells it is infecting. Based on the current evidence, it seems possible that these genes could simply be those that are active and available to HIV in CD4 T cells that are differentiating into a long-lived phenotype.
In an article about the research by Jon Cohen in Science, Wagner's colleague Lisa Frenkel goes so far as to suggest that there may be a link with cancers that occur in HIV-positive people, but to me this is a wildly speculative stretch given that most of these cancers have been shown to be associated with immunodeficiency (in both HIV-positive and HIV-negative people) and inflammation. The article also could be misread as suggesting that long-term HIV treatment causes higher cancer rates, when what the literature reports is that some HIV-positive people on ART still have an elevated risk of some non-AIDS defining cancers (NADCs) compared to HIV-negative people (age is the strongest, most consistent risk factor). A review on the subject from 2012 states: "the higher risk of NADCs is primarily among males, with HIV-infected women having no higher rates of NADCs compared with the overall population." A sex-biased cancer-promoting effect of HIV integration and latency does not appear very plausible, and T-cell cancers remain rare in HIV-positive people. In sum, pending further data, I would advocate extreme skepticism about Frenkel's suggestion that there may be a connection between HIV latency and the development of cancer. Links to CROI presentations on the topic are below.
Thor Wagner, Proliferation of Cells With HIV Integrated Into Regulatory Genes Is a Mechanism of Persistence
Mary Kearney, Massive Expansion of HIV Infected Cells With Identical Proviruses in Patients On Suppressive ART
Stephen Hughes, The Role of HIV Integration Sites in Extensive Clonal Expansion of Infected Cells in Patients
Eli Boritz, Central Memory and Effector Memory CD4 T Cells From HIV Controllers Harbor Distinct HIV Strains
Slim Success With Gut-Targeting Anti-Activation Strategies
Among the posters at CROI were results from four different clinical trials of therapies that aimed to ameliorate immune activation by targeting the microbial translocation pathway (the leakage of bacterial products from the gut into the systemic circulation). Sevelamer (a treatment for high blood levels of phosphorus that can bind bacterial lipopolysaccharide) and meselamine (a therapy that reduces mucosal inflammation in inflammatory bowel disease) had no effect on markers of microbial translocation or inflammation. The antibiotic rifaximin was associated with very small reductions in some markers of immune activation and inflammation. The probiotic supplement Biola was reported to significantly reduce the levels of the D-dimer by about one third over eight weeks in a small study (12 probiotic recipients, seven placebo recipients and six controls) and there were trends toward reduced CRP and IL-6. Markers of microbial translocation did not change. These results await confirmation in a larger trial with a longer duration of follow up.
This article was provided by Treatment Action Group. It is a part of the publication Michael Palm HIV Basic Science, Vaccines & Cure Project.
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"There is something dreamlike about the points that provide a view of the other side, but they belong not so much to the dreamtime as to dream work. The nomads enter the dreamtime not by setting off on some extraordinary, dangerous voyage, but through their everyday, ambulatory movement." -Cesar Aira, "Ghosts"
I have been thinking about Maren Miller's exhibition, Long Gone, for the last few weeks. When I begin to write about it, I pause, get lost in thought and forget about writing. Until this week, I had not yet found the framework with which to formalize my intuitive reactions.
What I saw: Across the street from The Hills Esthetic Center, stands a Juvenile Detention Center; Hills does not have a doorbell. A friendly face let me in after I called the prescribed telephone number. On my way up the stairs, several young men passed on their way out. For an old werehouse it was surprisingly warm inside. The steel stairs had been recently painted red. On the second floor, I walked through a wide hallway, went into one of many doors on the right and entered a welcoming living space. In the subsequent kitchen, a content-looking cat greeted me. It was polite—not overly friendly; it seemed to enjoy its hostly duties. The ceilings were at least 16 feet overhead and comparable windows bathed the room in light. There was a second room inside of this kitchen. Inside that second room hung Maren Miller's exhibit, Long Gone.
Miller builds architectural spaces with simple lines. I wanted to see if I might do the same with words.
Above one wall, the wall that the gallery shares with the kitchen, a mirror hung parallel to the floor. That way people in the kitchen could look into the exhibition space and people in the space could look into the kitchen. When I looked up, I was comforted by the domestic action of pots and pans on the other side of our common wall. They gave me more confidence in the clean, white room and periodically my eyes returned to the mirror, for a small, grounding break.
The show: Primarily red and blue and black and white. There is a sense of humor in the work and motifs refract through different pieces in an almost narrative arc: a labyrinth on a wood panel is akin to a snake-like canvas line, which is similar to a stream of paint that spills on a table that stands on a floor which, again, is reminiscent of the labyrinth. A chair covered in a tarp seat cover is the only three-dimensional presence other than myself. The chair beneath the tarp is intuited rather than seen and such considerations lean a little on the experience of my own physical presence. Behind the chair, a picture of a window is covered by a pictorial curtain. In another hanging canvas piece, a picture of what looks like text (blocky, reminiscent again of the labyrinth language) is cut off by what could be a curtain, or another very fat snake, or another stream of dripping paint. At the end of the room stands one real window. That window is also curtained by a patterned, unstretched canvas.
Each work in the show withholds something. It is covered by another piece of itself, asking to be uncovered or—in the most plain case of the labyrinth—solved. The motifs themselves are both banal and archetypal—the labyrinth, the snake, the window. Used in the everyday as they are in myth. Nevertheless, unlike their fabled counterparts, Miller's representations are insolvable; they cannot be uncovered and thus deny the traditional hero his or her epic fulfillment.
The painter is also in the index of archetypes, but Miller's paintings are not about a heroic painter.
The paintings are not stretched. Instead they hang on limp canvases, abstract, like cartoons of paintings. Other works on panels—the table with the floorboards, and the blue and white labyrinth—are not paintings at all, save for a gessoed background. These boast the illusion of paintings, for on closer inspection, the picture plane is defined by meticulously cut out (possibly electrical) tape. The surface of that tape lays flat, like a second layer of ink in a screen print. Here again, the surface is plastic and impenetrable.
Ghosts: A few days ago a friend quotes a section in Cesar Aira's book, Ghosts. The book takes place in South America, in the middle of a growing industrial city; it centers on a family living in a high-rise construction site. Everything smells like cement. Halfway through the middle of the book the main character, a 13 year old girl, takes a nap. At this point the whole family is asleep–enjoying a siesta before the evening, when the family will have a party on the roof. Up until this point, the action of the book takes place on a vertical plane as characters laboriously climb up and down half-built stairs. With this collective nap, the author introduces a horizontal axis, describing other human communities and the way their various architectural habitats reflect respective social priorities. In light of that digression, the book's monolithic skyscraper becomes one of many possible futures. In order to draw that conclusion, however—in order to shift from a vertical axis to a horizontal one, Aira uses dreams as vehicle of shift.
"There are societies in which the unbuilt dominates almost entirely: for example, among the Australian Aborigines. Instead of building, the Australians concentrate on thinking and dreaming the landscape in which they live, until by multiplying their stories they transform it into a complete and significant 'construction.' The process is not as exotic as it seems. It happens every day in the western world: it's the same as the 'mental city,' Joyce's Dublin, for instance….The visible landscape is an effect of causes that are to be found in the dreamtime. For example, the snake that dragged itself over this plain creating these undulations, etc. etc. These curious Aborigines make sure their eyes are closed while events take place, which allows them to see places as records of events. But what they see is a kind of dream, and they wake into a reverie, since the real story (the snake, not the hills) happened while they were asleep."
In waking, we see the affect of that gesture. In looking at Miller's work, I see a congress of decisions that took place before me. I cannot penetrate the surface she creates, because I was not present in the process of its creation. Further, the dimension I interpret is a product of my literacy—acquired over years and generations. Obviously this painted space is illusionistic, but its representation has repercussions in the way one regards other schemes of order. It is useful to recognize the myopic trajectory of history and progress—whether that history is about cities and human habitat, or painting or anything in between. Nevetheless Miller's work is not relativistic. These objects are sure of themselves and concrete. It is my relationship to them that shifts.
I looked at the mirror and saw the pots and pans and the cat was standing on a counter; its tail flicked.
Maren Miller's work points to the dream state, during which objects are made. Her work creates the affect of space and depth, but in fact remain a surface. We see the affect and intuited depth of her gestures, yet the desire look "beneath," to capture an intimate relationship (or "truth") of the work, will remain unsated. She entertains Painting, as a genre, and in my analogy the Painting Genre is like the skyscraper. Massive, towering, lofty. Miller takes a dream in that building, while dreaming a snake with paint on its back undulates over a white wall. Something else stamps architectural lines onto a flat surface, creating dimension in a previously dimensionless space. As I stood there I looked again at the panel with the table and the red paint. The floorboards depicted in the "painting" mirrored those on the floor under my feet. I turned towards the literal curtain behind me, thinking about the repetitions of mark-making, how that repetition reinforces a world-view. The premises of architecture and art are inherited and built upon.
It was nevertheless with some relief that I pulled back the curtain and saw a street outside. A car drove slowly past the window.
If you want to read another something about Maren Miller and her show at Hills, check out this interview with The Post Family.
Caroline Picard
Latest posts by Caroline Picard (see all)
- Corresponding Between Found and Made: An Interview with Jessica Stockholder - October 5, 2016
- Plant Humans of the Future: An Interview with Saya Woolfalk - August 30, 2016
- Reading with My Whole Body: An Interview with Essi Kausalainen - August 29, 2016


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Struggling with debt? You'll love today's story. Not only did WIM from the Paychecks & Balances podcast fight against debt and finally win, but he and Rich both share stories about getting back on the horse and fighting again to solve your money problems.
Of course, that's not all. We read many of the hilarious submissions in our funny numbers game. OG will pick the final four. On our Quotacy hotline call we answer a question about Roth contributions and withdrawals. Of course we have headlines, Doug's trivia, and more!
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Solve This (? + ? + ?=30)
If 1111=R, 2222=T, 3333=E, 4444=N Then 5555=?
Guess the Hindi Muhawara from the following whatsapp Emoticons?
Sweet, Medicine, Film, Girl, City, Car, Place, Doggy all are name same, guess which word it is?
Guess me who am I, I am the first on earth, the second in heaven...
Four Question, One Answer: One River Name, One Flower Name, One Film Name, One Actress Name?
A girl is blind, deaf, dumb and uneducated too. A boy loves her. How would he propose without touching her?
Which Indian cricketer is known as "Brown Bradman"?
What is the role of the "third-party" directory available in the "osf" folder in Batoi OSF?
What is Edge computing ?
2018 © Queryhome


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LOS ANGELES, March 24 (UPI) -- Kristen Stewart, Johnny Depp, Justin Bieber, and Katy Perry all won top awards at the 26th annual Nickelodeon's Kids' Choice Awards in Los Angeles.
The event took place Saturday at the University of Southern California's Galen Center in Los Angeles.
Josh Duhamel hosted the awards ceremony where kids honored their favorite actors, actresses, movies, musicians and more.
"Nothing was off-limits for first-time Kids' Choice Awards host Josh Duhamel, from ziplining across the arena to donning a milkshake costume and SpongeBob's square pants. This year's host took funny to an entirely new level," Nickelodeon programming executive Russell Hicks said in a release.
Stewart was named Favorite Movie Actress for her part in "The Twilight Saga: Breaking Dawn -- Part 2" and Depp was named Favorite Movie Actor for "Dark Shadows."
"The Hunger Games" took home the orange blimp for Favorite Movie.
Bieber won the Favorite Male Singer award and Perry won the Favorite Female Singer prize.
One Direction took home the award for Favorite Song for their hit "What Makes You Beautiful."


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Nissan Motor Co. Ltd. made a lot of noise at its global headquarters today about one of the most popular athletes of the 2012 Summer Games in London.
The Japanese automaker inked a deal with Jamaican sprinter Usain Bolt, who not only extends his brand ambassador deal with Nissan's hot GT-R sports car, but he gets the outrageous title of global title "Director of Excitement" at the company.
WOW! Fun stuff.
Nissan flew Bolt in for the hoopla and posted s lots of videos (in Japanese) of his arrival at the airport, leaving the airport in the GT-R and the more formal events with corporate brass in Yokohama. Said Bolt : "Racing is my inspiration, and I want to help Nissan become an even more exciting brand for everyone."
The carmaker said it will develop a special, limited-edition GT-R although no specifics were given. Nissan presented Bolt with a unique, gold GT-R, which will be auctioned online to benefit his Usain Bolt Foundation.
Details of that auction are due later this month and will benefit children and young adults in Jamaica.
Not usually a fan of celebrity tie-ins, but this one works since the GT-R is such a niche model. Nissan sold just 968 of them in the US in the first 9 months of 2012.
The links are almost too obvious, really. Bolt has a slew of Olympic gold medals & his special version of the car is gold. Bolt is called the fastest man in the world and the GT-R is crazy fast. The 2013 model churns out 545 horses, while still meeting ultra-low emission vehicle (ULEV) standards.
Nissan first hooked up with Bolt early this year. Within months, Bolt, a GT-R owner since 2009, was appearing in airport ads for the car and online videos like this one for Nissan, themed "What if you had no competition"
Smart move, Nissan.
MAKING TRACKS: General Motors Chairman-CEO CEO Dan Akerson tapped Robert Ferguson to the new position of vice president to lead Cadillac's growth and development globally. Ferguson, 53, joined GM in 2010 and was VP for global public policy. He'll now be responsible for Cadillac marketing, brand management and advertising around the world.
I'm sure Ferguson is a very smart and decent man. But the fact of the matter is Cadillac needs and deserves a proven player to lead it forward. There's no time for learning curves here. That boat has sailed and Cadillac is already late.
Follow me, Jean Halliday, on LinkedIn, Facebook, Reddit and Forbes.com
And on Twitter: @jhal2001


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With more crowdsourced intelligence on "Operation Ababil" published in the recent weeks, it's time to revisit the campaign's core strategy for harnessing enough bandwidth to successfully take down major U.S financial institutions.
As you can remember, in Part One of the OSINT analysis for "Operation Ababil" I emphasized on the crowdsourcing campaign launched by Izz ad-Din al-Qassam a.k.a Qassam Cyber Fighters, which led to the successful DDoS attack against these institutions. It appears that this is just one of the many stages of the campaign.
According to security researchers from Proxelic, the attackers also relied on a PHP based DDoS attack script known as "itsoknoproblembro" that was installed on servers susceptible to exploitation through the Bluestork Joomla template. By combining crowdsourced bandwidth and bandwidth from the compromised servers, the attackers managed to successfully achieve their objectives.
The DDoS script in question,"itsoknoproblembro", has been publicly available as a download for months before the attacks started, indicating that it was not on purposely coded to be used in the campaign against major U.S financial institutions.
Detection rate: PHP_DDoS.html - MD5: 9ebab9f37f2b17529ccbcdf9209891be - detected by 9 out of 44 antivirus scanners as PHP/Obfuscated.F; Heuristic.BehavesLike.JS.Suspicious.A
Next to Prolexic's claims, th3j35t3r also published an analysis of the situation that's primarily relying on wishful thinking and social engineering, claiming that Anonymous supplied the operators of "Operation Ababil" with DDoS bandwidth by using a service called Multiboot.me - 184.108.40.206; 18.104.22.168, AS13335.
Sample screenshots of the Multiboom.me's GUI:
With "Operation Ababil" continuing to fuel political tensions between the U.S and Iran, which is blamed for organizing the launching these attacks, it's worth emphasizing on the basics of 'false-flag' cyber operations, and "aggregate-and-forget" type of botnets.
When was the first time you heard of Izz ad-Din al-Qassam a.k.a Qassam Cyber Fighters? Appreciate my rhetoric - right after they started their crowdsourcing campaign. With the group lacking any significant digital fingerprint prior to these attacks, virtually anyone can localize their objectives with a little twist of politics and propaganda, and easily set the foundations for what is now perceived as an Iranian cyber operation.
Moreover, their bandwidth acquisition techniques clearly indicate that the attackers are aware of the dynamics of modern cyber operations in general, and by doing so, chose to acquire bandwidth without outsourcing their needs to ubiquitous and sophisticated Russian DDoS on demand services, which could have led to the easy identification of the service in question, next to the cybercriminals behind it.
Updates will be posted as soon as new intel becomes available.
This post has been reproduced from Dancho Danchev's blog. Follow him on Twitter.


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ASTA Solutions needed a new web page design and created a contest on 99designs.
A winner was selected from 34 designs submitted by 10 freelance designers.
ASTA Solutions
ASTA Solutions (ASTA) is an Australian based company that was established in 1999. ASTA's primary business objectives are to be:
• A creditable IT services partner to public and privately owned companies providing business consulting, managed I.T services and software development
• An independent service provider
• Professional in everything we do
• Considered by our customers as a business partner
Our organisational structure allows us to be:
• Flexible
• Customer focused
• Pragmatic - focused on value and affordability
• Reliable - available when required
• Always delivering on promises
• Innovative in recommending technology based solutions
• Skilled and appropriately trained in everything we do
Our propriety business management system allows us to be:
• Transparent in everything we do.
• Scalable in our growth.
• Accurate in delivering our services.
• Focused on providing business solutions.
ASTA considers itself as an IT consulting firm providing IT solutions to SMB's. The majority of our visitors are managers of SMBs seeking information on the services we offer.
Work Required
ASTA requires a website design comprising of:
• A home page
• A subpage
The designs should be in PSD format with layers organized into categories for easy editing. In addition any font types used should be included as part of the deliverable.
The objective of this project is to change the look and feel of ASTA's existing website (http://www.astasolutions.com.au). At present the site looks dull, out dated and simply boring. We want to revitalize this to reflect changing web design trends to be more bold, vibrant and engaging. It should be simple with large visible buttons and text yet professional and business oriented.
Please read the attached document for rough idea of what is expected.


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LOS ANGELES – Two men were wounded today in an intra-gang dispute in Boyle Heights and one victim drove them both to White Memorial Hospital where police were called and an investigation begun, a sergeant said.
The shooting occurred around 1 a.m. at Soto and Houston streets, said Sgt. Herb Chang of the Los Angeles Police Department's Rampart Station.
The victim who was driven to the hospital was wounded in the chest and hand, Chang said. He was transferred to County USC Medical Center because he needed more intensive treatment, the sergeant said.
The victim who drove to White Memorial suffered a gunshot wound to the arm, and stayed at that hospital, Chang said. Investigators were waiting to see whether the more seriously wounded man's condition would stabilize, he said.


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Tim McGraw Talks 'Busy Year' Ahead With Wife, Kids, Music and Movies
Tim McGraw's year is already off to a whirlwind start with a new record deal, the Brothers of the Sun tour with Kenny Chesney and a new single ('Truck Yeah') that impacted country radio on July 3. But that's not where things stop for the singer.
"It's a pretty busy time in the McGraw household," McGraw tells Taste of Country with a grin. "It's a busy summer [already]. My middle daughter goes into high school next year, so I'll have two daughters in high school. We're getting ready for that. My youngest goes into 5th grade [next year]. I have a couple of movie projects in the works, the tour, the new album, hopefully coming out in the fall some time, and my wife's finishing up an album! It's been a busy year!"
As far as the big screen goes, McGraw says there are a couple of irons in the fire... it's just a matter of finding the right one with the right timing that allows for him to be a committed husband to Faith Hill and a reliable dad to their three daughters.
"For me, I go through projects and try to find something that I like, and I try to find something that fits within a time frame that I'm available," McGraw explains. "I only have two or three months out of the year that I even have a chance to do anything like that, around music and family. [But I] first off have to find something that I like, then to find something that fits within that time frame, and thirdly find something where all those things fit that they actually want me for, because I'm certainly not in a position where they're going to move a movie around for me!"
One good thing that McGraw doesn't have to worry about much is finding and recording new music. The singer already has 20 new songs in the can for his next album and first on Big Machine Records, two of them being 'Truck Yeah' and 'Mexicoma,' both of which he has been playing in his live shows.


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Oct 7, 2009
Hello Dr. Bob,
Well done on all the great work you've done into HIV / AIDS, I really I appreciate what you do for everyone.
I recently had sex with one prostitute (using condom) and two hours later I have sex with my girlfriend (again with condom). What if I had some vaginal fluids from the prostitute in my pubic hair or lower shaft of the penis and infects my girlfriend? If I touched those vaginal fluids and then touched the outside of the condom while putting it on? I know HIV cannot transmit outside the body when its dry. However Im almost sure it would be still wet, as the position of the penis would press it to the pubic area and prevent air to dry it completely.
Thank you very much Dr. Bob. Donation will be coming your way ASAP!
Response from Dr. Frascino
WOW! You "wham bam thank you ma'am-ed" a naughty lady from Shady Lane and then two hours later nailed your main squeeze? Either you must be one horned-up love machine or you are of Italian descent. Either way your fears of infecting your girlfriend are completely unwarranted. HIV does not live long outside the body (even in your moist, warm, tighty whites!). So relax Max. You might be a bit of a cad for sleeping around, but you played safe and there is no significant HIV-transmission risk from your activities, OK?
Thank you for your donation to The Robert James Frascino AIDS Foundation (www.concertedeffort.org). It's warmly appreciated.
Be well. Stay safe.
Dr. Bob
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Exploring the New World of Travel Apps
Mar 1, 2013 5:00 AM PT
When Richard Rygg, the cofounder of HipGeo, sailed with his family last year through the islands of French Polynesia, he used his company's app to document the experience. The result is a multimedia blog complete with a GPS track of his adventure, and a collection of dozens of geo-tagged photos of sunsets, beaches and bays.
Sharing Tracks
HipGeo is part of a new generation of travel apps that allow for geotagged micro-blogging, and they are changing the way people travel, document, and share their adventures.
"HipGeo is all about capturing the whole story of any trip you take, and then sharing it with whomever you want," said Rygg. "We have deep integration with Facebook, so that anything you capture can automatically be posted there. You can also send it via email or share it on the HipGeo site."
A similar app, LiveTrekker, was launched last December. Like HipGeo, it uses GPS -- which works even out of cell range -- to create tracks and geotag photos, videos, text, and audio. Some of its unique features include the ability to do live tracking; upload media from cameras and devices other than a smartphone and insert them into a saved track; and search trips using keywords, coordinates, or dates.
"The core of LiveTrekker is being able to capture and relive your trip," Jean-Marc DeBaud, CEO and co-founder of LiveTrekker, told TechNewsWorld. "You can share with anyone in real time, and we capture travels with a level of detail that is unparalleled."
The idea for LiveTrekker, says DeBaud, came when he was traveling extensively in Asia and wished he had a way to give his wife an in-depth glimpse into his daily adventures.
"My wife and I were always talking on the phone, and we thought it would be nice to share what we're really doing," said DeBaud. "When you share this way, your conversations in the hotel in the evening are much more in context. It's very cool."
Tracking apps like these are useful not just for individual travelers, but also for businesses and others who want to share journeys.
"There's no doubt that sharing is fun, and it's great to show off the exciting places that you've visited to your friends," TrackMyTour's Chris Meyer told TechNewsWorld. "There are also more practical reasons that people are starting to share their travels, though. Recently, we've started to see businesses using the app for marketing. There have been bands that want to share things with their fans while they're on tour, and many charitable activities have wanted to keep sponsors up-to-date with the progress of the participants."
Getting Organized and Getting There
Travel apps are also giving travelers new ways to organize and share their itineraries. TripIt, for instance, consolidates airplane, hotel, rental car, and other travel information into one easy-to-read itinerary that can be shared with friends, family, or co-workers.
"When you're traveling, you make all your plans, and you end up with a lot of emails in your inbox," Edith Harbaugh, director of product with TripIt, told TechNewsWorld. "What TripIt does is organize your travel into a beautiful itinerary."
TripIt recognizes the confirmation email formats of dozens of travel companies and instantly pulls out key data, dates, and times from emails forwarded to its system. Travelers can then access these itineraries directly through the app, doing away with the need to carry paper printouts of all those emails.
"You have everything together, so it's really easy to see gaps or mistakes," explained Harbaugh. "It's made travel easier."
"The key message behind Scout is that it's a personal navigator," Mark Scalf, director of mobile products with Telenav, told TechNewsWorld. "It's helping you go about your daily life. Whether it's avoiding traffic, finding a place to eat, or just staying connected with friends, Scout is taking those things that people do on a daily basis and do it on a very simple way that's personalized."
As with other apps in this highly-networked world of travel and adventure, it allows for sharing.
"Users can pull up a place and share it with their friends," said Scalf. "We have simple ways for users to discover things to do, and encourage them to get out and explore their local surroundings."


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Roger Sutton has been the editor in chief of The Horn Book, Inc, since 1996. He was previously editor of The Bulletin of the Center for Children's Books and a children's and young adult librarian. He received his M.A. in library science from the University of Chicago in 1982 and a B.A. from Pitzer College in 1978. Follow him on Twitter: @RogerReads.
And THE CROSSOVER by Kwame Alexander
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The SpotJobs Job Seeker: Benefits
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Enes Kanter tweets he's OK after being detained at Romanian airport
Enes Kanter tweeted that he is OK after he was detained at an airport in Romania because the Turkish government canceled his passport.
The Thunder player said Saturday morning in a Twitter video that he has been detained at the airport by police for hours.
"The reason behind it is just, of course, my political views," said Kanter, who turned 25 Saturday. "The guy who did it is Recep Tayyip Erdogan, the president of Turkey. He's a bad, bad man. He's a dictator.
"And he's the Hitler of our century."
Erdogan visited the White House earlier this week. During the president's visit, protesters outside the Turkish Embassy were beat up by bodyguards, according to Washington, D.C., metropolitan police.
Shortly before 3 p.m., Kanter tweeted that he is OK and that he will discuss what happened Sunday during a news conference in New York.
"All good baby! Gonna give press conference tomorrow in NY. Got lots of things to say with lots of crazy stories. Be ready!!! Ohhh Yeeahhh," Kanter tweeted.
Thunder officials have told ESPN that they are working with the league office and gathering information through appropriate channels.


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Friday Traffic Updates and Construction Delays
Northwest Arkansas:
Fayetteville- Armstrong Ave. – Stone Bridge Road will see delays in construction zones while crews widen State Highway 16 from two lanes to four lanes with sidewalks and bike lanes. Traffic signals will be installed at three intersections. Should be complete by early 2015.
I-49– Slowdowns expected in Washington County as crews work to widen the Johnson Mill Blvd. overpass and access ramps on Interstate 49. This project is expected to be completed later this year.
Hwy. 112- Spur will see delays. It's being widened from two to four lanes.
Fayetteville- HWY 112 (Razorback Rd) is under construction for widening from MLK to Nettleship.
Hwy. 16– near Porter Rd. will see delays. The project plans to widen portions of I-49 to six lanes.
Hwy. 265- ALL lanes closed between Don Tyson Pkwy. and Joyce Blvd. from July 7-30th.
Hwy. 265- Delays are expected while crews widen portions of Hwy. 265 from E. Joyce Blvd in Fayetteville to the Hwy. 412 exit in Springdale. This project is expected to be completed in mid-2015.
Fayetteville– Van Asche Dr and Ball Ave between Jupiter Ave and Gregg Ave will be closed June 13-August 15th. Van Asche Dr will also be closed from McGuire St to Garland Ave until early September.
Fayetteville- The south side of Lafayette and the west side of Mock Ave will be closed, detours will be marked. The project will run June 23rd-August 4th.
Fayetteville- S. Washington Ave between South St. and E 4th St will be closed until July 9th.
Springdale- Lane closures expected for the next three weeks between Exit 69 in Johnson and Exit 72 in Springdale. Construction will continue on the Don Tyson Parkway Interchange. Traffic will be down to one lane each night, from 8 p.m. to 3 a.m. Mon. – Fri. The project aims to build an interchange between I-540 and Don Tyson.
Springdale- The intersection of 48th St. and Johnson Mill Blvd. will be closed from 9 am to 3 pm July 1st and 2nd. East and West bound traffic will still be allowed, but northbound traffic will be rerouted.
Hwy. 264– Delays are expected near the Wagon Wheel exit of Interstate 49 due to an ongoing Hwy. improvement project. The purpose of this project is to widen 2.5 miles of Interstate 49 to three lanes in Benton County.
Prairie Grove- Portions of the Hwy. 62 bypass will see delays while crews work on construct east and west connections. This project will be completed in Mid-2014.
Bella Vista Bypass- Delays are expected on Hwy. 72 due to a highway land widening project. This construction is expected to conclude in early 2016.
Centerton- Delays are expected near Greenhouse Road on Hwy. 102B while crews widen nearly two miles of the highway.
Huntsville– One passing of lane Hwy. 412 in Carroll County is under construction. Expect delays.
Avoca-North Garfield- U.S. Hwy 62 is being widened to five lanes. The project is expected to be finished by early 2015.
West Fork – Crews are working to overlay a 2-mile stretch of U.S. Hwy 71.
River Valley:
Hwy. 71-Hwy. 22- Delays are expected on this 5.8 mile stretch while crews work to pave Hwy. 71 near Fort Chaffee south of Van Buren in Sebastian County. This project will be completed in mid-2014.
Hwy. 71– Lane closures from Elmwood Cutoff to Howard Hill Rd. Expect delays in the area through the end of July.
Hwy. 22– Crews will be overlaying more than 2 miles of Highway 22 at Fort Chaffee.
Seeing slowdowns? Let us know, just tweet: #5traffic


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"DAVID MIERS is reported to be in the top 10 cage fighters in Gosford. He has some serious dish washing skills and thinks that Elizabeth Bennet is hot. Although he thinks that his wife Rowena is hotter. David works in youth ministry for a great church. Likes to: speak in third person, watch and play soccer, eat food and surf the web. He has never watched Star Wars."
"But far be it from me to boast except in the cross of our Lord Jesus Christ, by which the world has been crucified to me, and I to the world. Galatians 6:14 (esv)"
Oh hang on, that's not right... top
actually.... The Chinese New Year starts... in 5 days.
111 days to go? Man, thats aaaages! top


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A secretary dream cum true. Great set - superb beauty. I´m a sucker for glasses.
Office Flasher
Office Flasher
Dallas Dixon has a regular job and models part-time. But there is a lot more to Dallas than just that fact. She's been married for 10 years and her husband is fine and dandy with her fucking guys. He doesn't want to fuck other men's wives or other women he could meet. He enjoys seeing his wife get fucked in her SCORE Group videos and DVDs. Dallas likes it too. So they have this open marriage that allowed Dallas to do all these things in our studio without guilt. She even talks about her background on video in a SCORELAND Blog video. But even if Dallas couldn't do XXX with strangers because of a personal situation, we'd want her in the studio anyway because of those great tits, made for spraying with fucking hot cum! And no, she doesn't flash her headlights and her nice pussy at her office!
Featuring: Dallas Dixon
Date: March 31st, 2010
Duration: 58
Member Comments
7 years ago
7 years ago
Dallas Dixon is way hot. She makes my cock rock hard. What a hottie who is so gorgeous. Love ya honey!
7 years ago
I think Dallas Dixon is my favorite model here. She does indeed have that secretary next door look, all presented in an overwhelmingly voluptuous and well proportioned package.
8 years ago
Love love LOVE that belly!
8 years ago
she looks like the big titty secretary next door, i love that!
9 years ago
Should have kept the glasses on for the entire shoot.


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Paying one-pointed attention to your word is the essence of meditation. John Main always stressed: 'Just say your word.' That is all that is needed. But as you well know the mind just keeps on going off on its day dreams, keeps on worrying or planning. Hence the importance of our word, our aid to help us focus one-pointedly.
There is an Indian story that illustrates the usefulness of aids to focussing: Elephants are not as peaceful, wise and well behaved as often portrayed. If uncontrolled they will walk any which way, knocking over things on their path. Whenever possible their mischievous trunk will pick up what it can – bananas, mangoes, anything tempting on all the roadside stalls.
Those who train elephants, the mahouts, are very aware of this fact and when they have to take an elephant through the crowded streets in a religious or marriage procession, they have two ways of controlling the elephant's behaviour. First they dress him in a special way with decorations and a seat on his back, making him feel important. This encourages the elephant to walk in a careful and measured way. Secondly they give his mischievous trunk a stick to hold on to and the elephant proudly holds on to this and is not tempted in any way to pick up tasty morsels.
Our mind is really like this elephant: if like the mahout we tell our mind that we are doing something very important and we give it something to hold on to like a mantra, we make the seemingly impossible possible. If we accept the wayward nature of our mind and develop strategies to deal with it rather than getting irritated and cross, it too is not so tempted to follow its own inclinations and fancies and is less inclined to wander off.
Attention and prayer are inextricably linked: "When attention seeks prayer it finds it. For it there is anything that marches in the train of attention it is prayer, and so it must be cultivated." (Evagrius)
In the Gospel of Mark (13:33-37) Jesus tells us: "Be alert, be wakeful. You do not know when the moment comes. " We don't know at what stage of our meditation the Spirit will take over and lead us into the stream of love between Christ and the Creator. But we won't be aware of her promptings, if we are still caught in our own thoughts rather than repeating our prayer word in loving trust without any expectations: 'Your Father knows what your needs are before you ask him.'
The beauty of children's unconditional love and trust and their wonderful ability to be totally absorbed in whatever they are doing is an attitude we need to recover. "I tell you this: unless you turn around and become like children, you will never enter the Kingdom of Heaven." (Matt 18:1-4) A total absorption in our word is needed to bring us into the Divine Presence.
For further help with setting up and leading groups, please look at the 'Christian Meditation Groups' Website in English, Spanish and French, based on the book 'A Pearl of Great Price' by Laurence Freeman


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Nicolita at Mercedes Benz Fashion Week Swim 2013The fantastic Nicolita runway show owes its thanks to the collaborative effort between the brand, Christina Milian, and Brilliance makeup. Cuban roots inspired the swimwear line with a sexy, curve-conscious style based on vintage glamour. Their signature qualities feature "Cuban style bottoms" and "no pinch" elastic. Christiana Milian joined forces with Nicolita to showcase a creative display of retro swimsuits with a twist. Topping off the looks was the Brilliance makeup line, notably known for age-defying skin care, expert tools, and perfect finish mineral makeup. Down the runway, models wore high-waisted briefs in sailor motifs colored in yellow-gold, true blues, bright white and cool teal. Toggles and hanging embellishments were prominent, decorating rouched bottoms and one-piece suits. Along the vintage line, collection pieces were decorated in big bows, floral patterns and Nicolita's signature charms. A runway favorite was a fold-over bottom, turning a high-waisted suit or cover-up into a sexy low-waist. Cute skirts, off-the-shoulder blouses and t-strapped mono-kinis with sparkling hemlines completed the list of innovative silhouettes. Chains, pearls and flowing chiffon topped off metallic gold suits, for a fantastic finish. For all things Nicolita and to view the entire Havana Nights collection with Christina Milian, visit the official website.
Photo Credits: Cameus Chicoye Author: Megan Lynn Lewis


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About Andrew
I used to love Ubisoft games. In fact many of them still are really good games but from the time they started this protection and messing with users I just had enough.
I don't think this is over by a long shot. I think they will find a way to piss off the users even more.
I honestly don't trust them and they have a long long way to go before I even consider buying or even pirating a game from them.
I have other game companies to invest my money in who will treat me with some level of respect. As for the apology it won't matter either way if they do or do not. They have to earn a lot of people trust back before they can come back from this
This whole topic is pretty much been talked about and ignored but **AA people in general.
Most of the comments I have read have covered pretty much everything I would mention but the one driving point I want to point out. This problem happens when you try to put rules from one system onto the rules of a completely different system. What I mean is when you put the rules of the Analog world onto the digital world.
Digital goods are infinite, from now till the end of time there will be copies. While Analog/Physical goods are not and need to be produced. We can't possibly expect both systems to be ruled by the same laws, its not practical.
Its like if I asked you to add 10 and 11, you may point out its 21 but suppose I tell you it is binary you would actually get 101.
The industry needs to think closely about what is changing in our world and adapt. As this site and many others point out there are so many opportunities if you keep your eyes open and look for them.
The Disc Version is not STEAM, it links to STEAM but it is in noway STEAM. The point he is trying to make is that the ease of buying from STEAM should not necessarily be stopped cause of the region you are in, the people who made the game are getting your money either way. What is the difference if they bought it through STEAM or through a local game store?
I was baffled myself.
On another note congrats Mike. I been here for the last few years (not when you started). Ironically I found this blog through the google homepage when they first started doing that. I been an avid reader since.
Congrats again.
Even where I live (Trinidad and Tobago) we don't have laminated Driver's licenses anymore...
I hope someone calls the Senator on this crap. It amazes me how little they seem to use simple common sense to make decisions.
As for Apple's response I really am not surprised. They are always quick to pull apps even on silly reasons as this one.
"To the naked eye, you can see the substantial harm being caused (check out recorded music sales, even as recorded music consumption is at an all time high). You have to be wilfully blind or intending to profit from piracy to deny what appears on the surface to be true."
Proof needed here for your first sentence.
You also can't pigeon hole people into one of two choices like that. All the article is trying to point out is that research needs to be done before laws get implemented. I agree it is not a speedy process but then why is the process so long in the first place?
I don't think any legislation is baseless to begin with, it must come from somewhere.
The point that the article is trying to bring up is that its kind of silly to make legislation without doing the proper research first.
If you had to do an assignment on the types of pianos you wouldn't research 5 pianos then say you have researched it all. Same principle here if you ask me, do your ground work as best you can before you come up with crappy legislation that has to be fixed over and over.
I actually think this is a bold, wild, interesting and entertaining theory.
I am not bashing you btw but your right if they had some sort of explanation like what you theorized then it would make them look less foolish.
My opinion is the government has no reasonable explanation and that it is a lot of fabrication but I hope and pray that I am proven wrong.
But ootb where is the proof of all this that you are talking about. The main argument of this story is the fact that due process wasn't even followed. That alone, no matter what the site may/not be doing is scary as hell. The fact that they fabricated evidence is just as bad.
As much as you want to say this is about piracy its so much bigger than piracy and that is what you have to realize.
File sharing, depending on what is file shared is not illegal as far as I see. I really wish they would stop demonising the method of transfer.
I happen to think alot of these methods to transfer files are pretty cool and have real world applications. Ask anyone about Torrents or P2P and their first answer will be its illegal.
"give away and pray"
I've lost count how many times Mike says this is not what he suggests. But keep on going OOTB. Maybe one day you'll quote him correctly and stop deionizing everyone on the site.
On a side note you seem not to understand how Youtube works do ya?
I don't think anyone saying he has lost anything. But as many others have pointed out, non-commercial vs commercial and it was under contract.
As far as I know, no pirate makes money off the things they sell and have no contract to deal with. This does not mean I condone piracy and Mike has said time and time again he does not condone piracy and I am pretty sure most people on this site don't condone it. You are so quick to jump and call everyone a pirate. Personally I find that offensive but thats just my view.
In this story we have a case where a company who regularly come down harsh on people for copyright infringement and they are caught infringing on copyright on a massive scale. I think everyone should be accountable for what they do and that includes the big companies. We can't afford to keep on using a different measuring stick when it comes to a large coorperation.
Another thing too is if a coorperation can't obey the rules how do we expect them to even do the same when stronger laws come into place?
Its actually dropping quite quickly...its down to like a star now.
I don't know if people get the whole "Streisand Effect" and more people are learning the hard way. I don't have anything against this dentist but if this is how you treat your customers then good luck getting customers.
I never suggested they don't have people on the other side who don't think. Its not even about Mike's side either.
However a lot of people who are in support of SOPA generally are saying the same thing and to use your term seem like "SOPA-BOTS".
All I want is generally a good discussion. If it turns out that they are convincing enough or in the worse case scenario if I am wrong I will admit it and hopefully would have learned something new from the entire discussion.
Bob generally doesn't respond to logical thinking. This is in no means an insult to Bob but its just a trend.
In the end you can't have a discussion with these people who are so set in their ways and can't think independently. As the saying goes you can lead a horse to water but you can't make them drink.
Again...i wish they had a 4th button for "confused"
I really want to report this post but I just find it so confusing that I wonder if they should have a 4th button called "confused".
Its definitely interesting to see different view points on piracy. On one hand we have people like Ubisoft who believe lets crack down and increase our protection but then others who believe lets see how we can compete with piracy and bring a better platform so users actually want to play.
I don't live in the United States, I live outside and one of my major issues I always have is getting my hands on games at a reasonable price and time. I remember a few years back when a few friends of mine from the United States were trying to get me to get Left 4 Dead and it was really late so stores where I am won't be open that late so I would have to wait till the next day. Then one of them commented why don't I just use Steam and get it. Low and behold I downloaded Steam and in seconds I had purchased Steam (at a discount too if I remember correctly) and I was downloading it. About 2 hours after that I was playing Left 4 dead with my friends.
A lot of people are always concerned about the United States this and that but what you have to realize is that they have others out there who buy games too. I am an avid gamer and Steam for me was like a Godsend with its ease and it worked for me.
Ubisoft has had good games over the years but their lack of respect for me as a gamer was disconcerting and I haven't played anything from them since Assassin's Creed. I have other companies that I would rather give my money to and even to pirate the game isn't even worth my time.
I know it was never brought up in the article but whenever people talk of piracy they say its a lost sale but isn't me not buying your game or even purchasing your game a lost sale as well?
I think Ubisoft has to be careful what they say and even how they say it. Having good games is one thing but if you continue to piss off your gaming community it won't end well at all.
Are you seriously implying that there are only a few TSA agents working or that the % of passengers with this is that high? Its kind of why they have multiple staff and if anything move the person to the side until the call is made.
My overall point is, these people have a medical card that is supposed to let the authorities know what is what. The fact that they ignore them makes me wonder if they should be there in the first place.
To that I say these cards have the detailed information about doctor and number. If you are unsure use the card and call the doctor and get the information you want.