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I Wonder..
Can one man dominate a team sport?
By Josh Kirkendall@Josh_Kirkendall Jan 29, 2007, 12:47pm EST
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When it comes to focus and the ability to perform under the most intense pressure, there's no one better than Tiger Woods. There are few athletes that dominate their sport like Woods. Roger Federer is one. Lance Armstrong is another -- no matter how hard the sore losing French try to attach doping allegations on him.
Individual sports are the hardest to flourish in; much less dominate. Can you imagine hundreds of people standing at the edge of the green as you judge a nine foot putt that goes slightly right to left dramatically uphill to win a million dollars? Can you blind the hundreds watching yards away and the millions and millions watching around the world as you line up your shot? Would the concern of missing the shot and looking embarrassed outweigh the thought of actually making the shot?
Roger Federer doesn't concern himself with pressure. He dominates the field so much that no one is close to his zip code. In the "last three-plus years, Federer has collectively compiled a 254-15 record and 35 titles in 50 tournaments". That's nuts!
You have your Peyton Mannings, LaDainian Tomlinsons, Chad Johnsons, Brian Urlachers and Champ Baileys. What you don't have in the NFL, is a player that people would agree that's "dominated" the sport for any period of time.
I believe it contemplates a debate. Can domination, from a single player, happen in team based sports? Perhaps we're spoiled watching Federer and Woods in the prime of their careers. Both are generating "best _____" of all time in their respective sports. You can easily say that LaDainian Tomlinson is the best running back today, but most dominating player? Barry Bonds could have been as close to an example as anything during his peak of suspected love of unknown creams. Even so, his namesake and image has been scarred because of the very thing he thought would help him cheat the odds of aging. But Albert Pujols was a close second -- some considered better than the cheatin' Bonds -- therefore eliminating the actual "domination" discussion.
If you can make an argument for an active player in a team-based sport dominating like Tiger Woods or Roger Federer, go for it. I'm all ears. I just don't think you can claim that someone dominates a team-based sport still playing today. Yester-years? Michael Jordan. OK, yea, I can support that. He changed the game. He created mountains of new fans that only watched because Jordan was playing -- similar to watching golf because Tiger Woods is playing. The NHL Record book is titled: Wayne Gretzky's autobiography.
But is there anyone out there that dominates team-based sports playing today?
A slight sidenote: animals do NOT count. If we included horses, we'd have to include greyhounds and weiner-dog sprints.
Ben Roethlisberger takes the lead...
Tiger's streak is something to behold [ESPN]
Woods picks up seventh consecutive PGA Tour win [ESPN]
Tiger Makes it Seven In a Row [Waggle Room]
Who is the more dominant performer? [ESPN]


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Katja Küttner (née Kukkola) has received the jury's best actress award for her leading role in Arto Halonen's Princess at Tallinn Black Nights Film Festival PÖFF's EurAsia main competition series. Küttner received her prize on Friday, the 3rd of December, at the festival's award gala, where the jury stated: "It was easy to choose the best actress, as she made such a surreal character believable, convincing us that we were in presence of royalty." The competition at the festival was intense: for instance, Abbas Kiarostami's Copie Conforme, for which Juliette Binoche received the best female actress award at Cannes, left PÖFF without any prizes.
The EurAsia series is the main competition series at the Tallinn Black Nights Film Festival, and this year consisted mainly of award-winners and films that received their premieres in competition at various renowned film festivals, including Cannes, Berlin, Venice and Sundance. The 21 films featured in the competition also included Oscar-nominees and well-known directors' works, such as Danny Boyle's 127 Hours, Abbas Kiarostami's Copie Conforme, Mohamed Al-Daradji's Son of Babylon, Susanne Bier's In a Better World and Estonia's own competition entry, Veiko Õunpuu's The Temptation of St. Tony. The series focuses on European and Asian cinema, and is featured in the festival programme for the 7th time. The festival, with its numerous sideline events, is held 19.11.-5.12.2010, and is the biggest film event in the Baltic region. The International Federation of Film Producers Associations (FIAPF) places the festival on its list of significant international film competitions.
This year's Jury consisted of the American producer David Willis (Die Hard - With a Vengeance), Egyptian film star and UNICEF Goodwill Ambassador Khaled Abol Naga, Iranian actress Fatemeh Simin Motamed-Arya, programme director for Abu Dhabin and Rotterdam film festivals Intishal al Timimi, producer of the Estonian production company Allfilm Piret Tibbo-Hudgins and Hungarian filmmaker and academic Csaba Káel.
Princess, already a huge success in Finland with over 273 000 viewers, received its world premiere in August 2010 at Montréal's World Film Festival, an A-list competitive festival, in its competition series for feature length debut films. The Princess' story is also featured in a book, written by Ilkka Raitasuo and Terhi Siltala and published in August by Like Publishing Ltd. Since its release, the book has quickly become one of the best-selling non-fiction books in Finland. Partly due to the success of Princess, Arto Halonen has been awarded The Finnish National Mental Health Prize, the City of Helsinki Culture Prize for 2010, and the Civil Action Prize of the Finnish Federation for Social Welfare and Health (which has never before been awarded to a cultural representative as opposed to a political or social figure).


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is a scallop-shaped Kofun period burial mound located in what is now the Kashima neighborhood of the city of Ōta, Gunma Prefecture in the northern Kantō region of Japan. The site was designated a National Historic Site of Japan in 1927. It is the third largest scallop-shaped kofun (帆立貝形古墳) in Japan after the Otomeyama Kofun in Nara Prefecture (128.3 meters) and the Osabotsuka Kofun in Miyazaki Prefecture (175 meters)

Overview
The Nyotaizan Kofun is located on a small plateau south of the Kanayama hills. It is part of a group of tumuli which includes the Ōta Tenjinyama Kofun. Its main dimensions are:

Overall length: 106 meters
Posterior circle: 84 meter diameter by 7 meters high
Anterior width: 18 meters by 1 meter high

The tumulus is covered in fukiishi and is surrounded by a moat with a width varying from 11 to 19 meters. Numerous cylindrical haniwa have also been found. The burial chamber was accessed from above, and was pillaged in ancient times; however, the tumulus has not been excavated. From the style, it is estimated that this tumulus dates from the middle of the fifth century AD. It is slightly older than the neighboring Ōta Tenjinyama Kofun, but shares the same orientation, so the two tumuli must be related.

The tumulus is about a 20 minutes walk from Ōta Station on the Tōbu Isesaki Line.

See also
List of Historic Sites of Japan (Gunma)

References

External links

Ōta City official site

Kofun
History of Gunma Prefecture
Ōta, Gunma
Archaeological sites in Japan
Historic Sites of Japan

redpajama_set_name: RedPajamaWikipedia


JAKARTA: Indonesia has found the cockpit voice recorder from a Lion Air plane more than two months after the Boeing 737 MAX jet crashed into the sea near Jakarta, killing all 189 on board, an official said on Monday.
Naval Lieutenant Colonel Agung Nugroho told Reuters a weak signal from the recorder had been detected for several days and that it had been found buried in about 8m of mud in waters about 30m deep.
"We don't know what damage there is, it has obvious scratches on it," Nugroho said.
Haryo Satmiko, deputy head of Indonesia's National Transportation Safety Committee (NTSC), told AFP that the recorder was "broken into two pieces" but hoped it was "still useful" to investigators.
More human remains were also found near the voice recorder, he added, without giving details.
"We're thankful and grateful that they have found the CVR, but it's not enough," said Evi Samsul Komar, whose son and nephew were on the fatal flight.
"There are still many passengers unaccounted for."
The cockpit voice recorder is one of two so-called black boxes crucial for the investigation of a plane crash.
The other black box, the flight data recorder, was recovered three days after the crash.
The flight data recorder gathers information about the speed, altitude and direction of the plane with enough storage for 25 hours of data, while the cockpit voice recorder keeps track of pilots' conversations and other sounds in the cockpit.
"This will really help the investigation ... and could give some more answers on the cause" of the crash, said Jakarta-based aviation analyst Dudi Sudibyo.
Investigators brought in a navy ship for a renewed search effort on Jan 8 to find the cockpit voice recorder after the plane crashed into the Java Sea in October.
The crash was the world's first of a Boeing 737 MAX jet.
Separately, Colonel Johan Wahyudi told Metro TV the recorder had been retrieved and taken aboard the ship.
Contact with flight JT610 was lost 13 minutes after it took off on Oct 29 from the capital Jakarta heading north to the tin-mining town of Pangkal Pinang.
Investigators said Lion Air kept putting the plane back into service despite repeatedly failing to fix a problem with the airspeed indicator, including on its second-last flight from Bali to Jakarta.
Black box data showed the plane also had an airspeed indicator issue on multiple earlier flights.
The plane had also flown erratically during a flight the previous evening when it experienced a "technical problem", according to data from flight-tracking website FlightRadar24.
"The plane was no longer airworthy and it should not have kept flying," Nurcahyo Utomo, aviation head at the National Transport Safety Committee, told reporters.
Following the incident, Indonesian rescuers began retrieving body parts from the crash site. There were 178 adult passengers, one child, two infants, two pilots and six cabin crew on board.
Authorities eventually called off the grim task of identifying victims of the crash in November, with 125 passengers officially recognised after testing on human remains that filled some 200 body bags.


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Joe Donnelly continues bucking Democrats on military bills
Maureen Groppe
Sen. Joe Donnelly was faced Wednesday with voting for a military spending bill he helped write, or backing President Barack Obama's objections.
The Indiana Democrat voted for the bill.
"I'm disappointed to hear the president plans to veto the bill," Donnelly told Indiana reporters shortly before the Senate voted 70-27 to approve the annual bill setting military policy.
Although that's enough votes to override a veto, the House vote of 270 to 156 last week fell short of the two-thirds majority needed.
The White House opposes the bill because it designates some routine military spending as emergency war expenses to get around spending caps imposed by a 2011 budget deal.
Donnelly, a member of the Senate Armed Services Committee, said there were better ways to write the bill.
"But this is the way it was done and this is the only bill we have to vote on," he said. "And so I want to make sure we can move forward with the defense bill."
The bill includes language Donnelly pushed to improve mental health care for service members and their families.
The bill sets military policy, including spending parameters. But the funding itself comes in the annual spending bills that lawmakers were supposed to approve by the end of September.
After Congress failed to send the bills to the president, lawmakers passed a short-term funding measure last month to keep the government operating until Dec. 11.
Senate Democrats have been using the power of the filibuster to block votes on spending bills until Republicans agree to renegotiate budget caps put in place by the 2011 bipartisan agreement to raise the federal debt limit.
Donnelly was the only Senate Democrat to vote last week to call up for debate the annual spending bill for military construction and veterans' issues.
He was also the only Senate Democrat to vote in July to consider the military spending bill.
Donnelly said he understands the president's concern that "we have to adequately fund both defense and non-defense" programs, and is hopeful an agreement can be worked out to do that.
But in a time of increasingly complex global challenges, Donnelly said, "we need to set a clear policy with the Department of Defense to move forward and protect our national security and take care of our men and women in uniform."
Email Maureen Groppe at mgroppe@gannett.com. Follow her on Twitter: @mgroppe.

redpajama_set_name: RedPajamaCommonCrawl


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You are here: Home / Cancer Causes / New Study Says Air Pollution Kills 600,000 Children Each Year
New Study Says Air Pollution Kills 600,000 Children Each Year
By Ty Bollinger
1,217 Facebook Shares
A recent report by the World Health Organization (WHO) says that air pollution is responsible for killing an estimated 600,000 children each year. According to the report, 93% of children live in environments with air pollution that exceeds WHO guidelines. This amounts to nearly 1.8 billion children whose health and development are at risk each day.
While this is a growing and global problem, children are the most vulnerable among us. The report estimates that more than 25% of deaths in children under five are directly or indirectly related to environmental risks. Exposure and negative effects are particularly acute in low- and middle-income countries, especially African, South-East Asian, and Eastern Mediterranean nations. Something like 90% of deaths linked to air pollution occur in these countries.
Air pollution has been linked with many adverse effects such as stillbirth, respiratory disease, obesity, lowered IQ and stunted cognitive development, and cancer. The WHO study focused primarily on particulate matter in the single-digit micrometers, which include toxins like sulfate and black carbon. These dangerous toxins can lead to strokes, heart disease, pneumonia, and lung cancer. Children exposed to excessive toxins are also at greater risk for developing chronic disease as adults.
The study looked at both ambient and household air pollution. Household air pollution is caused primarily by polluting fuels for cooking and heating, smoking, and other household toxins. According to the study, poverty can compound the effects of air pollution due to limited access to information, treatment, and other health care resources. Dirty cooking fuels, like charcoal, are estimated to cause over 3.5 million premature deaths every year.
Ambient air quality is a more complex problem to tackle and will require participation from governments and corporations to reduce the toxic load on our environment. The best ways to combat ambient air pollution are lobbying politicians to prioritize environmental toxins and "voting with your dollars" by not supporting companies that prioritize profit while poisoning our resources.
Air pollution is now responsible for more deaths each year than tobacco, prompting the WHO to call air pollution "the new tobacco". Director general of the WHO, Dr. Tedros Adhanom Ghebreyesus, said "The world has turned the corner on tobacco. Now it must do the same for the 'new tobacco' – the toxic air that billions breathe every day. No one, rich or poor, can escape air pollution. It is a silent public health emergency."
In a statement to The Guardian, Dr. Ghebreyesus summarized the implications of the report:
Despite this epidemic of needless, preventable deaths and disability, a smog of complacency pervades the planet. This is a defining moment and we must scale up action to urgently respond to this challenge."
He goes on to say that "A clean and healthy environment is the single most important precondition for ensuring good health. By cleaning up the air we breathe, we can prevent or at least reduce some of the greatest health risks."
Unfortunately, while access to clean fuel and other household products is increasing, the report warns that "improvements are not even keeping pace with population growth in many parts of the world." Nine out of the world's ten most polluted cities can be found in India, one of the most populated countries on the planet. Much of this pollution is due to stubble burning, used by farmers to clear fields after harvest, and the increased use of oil lamps and fireworks during Diwali, a Hindu festival that takes place each fall. In a 2017 study published by the Energy Policy Institute at the University of Chicago estimates that residents of Delhi, India's capital city, could live up to 9 years longer if air pollution was reduced to within WHO standards.
Considering this study, detoxification should be front and center in protecting our health. Our bodies have powerful, built-in mechanisms for removing toxins. A cleanse or detox regimen simply helps these mechanisms function at their best. Cleaning chemicals, environmental pollution, pharmaceutical drugs, and processed foods all contribute to a massive burden on the body's natural cleansing systems. Keep your family safe and treat your body like the temple it is by reducing toxic chemicals in your home and supporting natural detoxification.
Toxic overload is one of the leading causes of cancer. The Truth About Detox can help activate your body's natural cancer-fighting system.
Air pollution and child health: prescribing clean air - Advance Copy
Air pollution and child health: prescribing clean air - Summary Report
Air pollution kills 600,000 children each year: WHO
More than 90% of world's children breathe toxic air, report says, as India prepares for most polluted season
More than 90% of the world's children breathe toxic air every day
WHO says air pollution kills 600,000 children every year
Air pollution is the 'new tobacco', warns WHO head
Nine out of 10 people breathing polluted air: WHO
How Junk Food Leads to Cancer: Part 2 (Video)
Have You Heard about the Nocebo Effect? (video)
About Ty Bollinger
Ty Bollinger is a happily married husband, the father of four wonderful children, devoted Christian, best-selling author, medical researcher, talk radio host, health freedom advocate, former competitive bodybuilder and also a certified public accountant.After losing several family members to cancer (including his mother and father), Ty refused to accept the notion that chemotherapy, radiation, and surgery were the most effective treatments available for cancer patients. He began a quest to learn all he possibly could about alternative cancer treatments and the medical industry. Ty has now made it his life mission to share the most remarkable discovery he made on his quest: the vast majority of all diseases (including cancer) can be easily prevented and even cured without drugs or surgery.Ty speaks frequently to health groups, at seminars, expos, conferences, churches, and is a regular guest on multiple radio shows and writes for numerous magazines and websites. Speaking from personal experience and extensive research, Ty has touched the hearts and changed the lives of thousands of people around the world.
Duke Study: How BPA Inhibits Breast Cancer Drugs
Help Our Children Build a Healthier Immune Response
Study May Spare Thousands of Breast Cancer Patients From Unnecessary Chemotherapy
The Landmark Johns Hopkins Sulforaphane Cancer Study Your Doctor Isn't Telling You About
I love what Ty and his wife do their passion to share knowledge comes through in their presentations.
Customer Success says
Hi Manuel,
Thank you so much for being with us! We appreciate you supporting our mission.
One thing people can do is stop using blowers for lawn maintenance!!! Think about all the chemicals etc that are present! That are now airborne!!!
Margit says
Great comment. Blowers do add big time to pollution. Rakes are good exercise.
Steve Heller says
Thank You Ty and Charlene and Team for the terrific work you are doing. You all are true blessings on this Earth helping to reduce suffering and guiding folks with the important information as to how to live full and happy lives.
God Bless You and Keep You,
Steve Heller
Judy lopez says
We are surely blessed to have You give i.e. such important information that we would never get or have known knowledge is power Thank You
CaptTurbo says
Ya … fireworks are causing it. Right.
Karen Baines says
Yes – they contribute to air pollution and can trigger heart attacks, asthma, and strokes.
smet annie says
wel bedankt voor je opzoekingswerk en het meedelen van belangrijke info aan het publiek Ik begrijp niet dat ze niet meer geneesheren opstaan en zich verzetten tegen die agressieve therapieën als chemo en bestraling. Maar de ergsten zijn toch onze politici, zij laten het gebruik van al die giftige stoffen toe.
Edith says
Sounds an awful lot like the toxins that vaccines contain and the subsequent autoimmune responses they induce. It looks like the WHO is trying to pull a fast one on the world population, because it couldn't possibly be related to the miracle vaccines. Love how it even says to "vote with your dollars" by not supporting companies that produce the pollution. It even seems as though "pollution" and "vaccines" are completely interchangeable in this article.
Jim Phelps says
The increase of Deuterium levels with aging, with too much sugar and Carbs is well associated with the end of life causality for every person on Earth. Which is an even bigger deal.
My question is kind of piggybacking off of the previous persons question, however, wouldn't any burning substance contribute to polluting to our air – including cigarettes, camp fires , any anything else that burns and smokes ? Also , what about vape clouds from vapors ? The people vaping produce large vape clouds , and I can't imagine that chemical cloud is healthy for our environment.
Peter R Johnson says
The majority of the PM <2.5 and gaseous toxins are from burning fossil fuels. The WHO estimates about 7 million people die annually, globally from air pollution. Vaping, camp fires and the like are insignificant.
Now we just need to figure out the exact people that are killing us and making us sick and put them behind bars.
Margaretha Toerney says
The WHO has a double standard according to all the info we have seen in the videos on cancer and I think this news is a tactical diversion from all else they do. Sad that the truth is belong suppressed from the world and lives are cut off too soon.
GuardDuck says
… not to mention extremely noisy leaf blowers -5- days week in uncontrollable HOAs (homeowner associations), redistributing toxic particles, pesticides & herbicides (Round-Up) into the air we are forced to breathe! We, too, appreciate the Bollinger's passionate knowledge!
jjoan prater says
the chemtrails and their chemical emisions of toxic poisons should be stopped. aluminum which burns and is responsibe for ca fires . it is sickening. all the secrets of what is going on in the world.
Maurice Lacy says
Kem Trales are the coughs of the deadly air pollution killing people dropped by the new world organization look it up
Paul M Faulkner says
Why can anybody make the foolish statement ie: Ya … fireworks are causing it. Right.
I am unfortunately all too often dismayed by what are really silly, negative responses to anything that evidentally does not fit their sacred opinion, whether inaccurate, truthful , or simply biased.
Come on folks, this is serious business and I assure you that when receiving a confirmed diagnosis of rampant Cancer, it is scary. Wear this hat next time you read/hear and learn and treat with realistic belief, especially from Ty Bollinger.
Wood burning in cities in the winter is responsible for 40% of all PM2.5 particle emissions. That's actually higher than city traffic. Wood burning stoves are the main culprits – many of them installed for 'ambience' others installed so that the owner can have 'free' fuel – burning anything for heat. This usually includes scrap wood that has been treated or painted giving off even more highly toxic fumes. The ones at greatest risk are infants, children and the elderly. Their immune systems are compromised or not fully developed. Wood smoke contains carcinogens like Benzo-a-Pyrene, Formaldehyde VOH's and PAH's. No matter how 'eco' friendly or modern the wood burner is it can not prevent these toxins entering the room or being emitted into the neighbourhood. Wood stove emissions can trigger strokes, asthma and heart attacks. Pollution is everywhere and it is taking it's toll on human health – from whatever source it comes. I'm glad to see that this message is getting across and organisations are starting to join up the dots.
jez b says
i think the biggest air pollutant is the daily spraying of chemical trails left by aircraft which contain Aluminium, barium, strontium,, man made viruses and germs being deliberately sprayed on us for at least the last 10 years that I would imagine would have a worse effect than cooking
with charcoal
Thanks for your comment Jez!
Joel Walbert says
SRM Aerosols (barium, strontium, aluminum nano-particles plus possibly others)
We live in the Pacific Northwest, 6 weeks of our normal beautiful summers, were left with poor poor air quality first time I ever had to get masks!! We are burning up around here, with it Boeing November, and the wild fires are out of control in California,, I get how this can cause lasting effects on so many!!💔
A BIG THANK YOU to both of you!!!!!
Faodail says
How about all the geoengineering? All the chemicals that are being sprayed in the air also has an adverse effect. Wish the WHO would look into that. Alumiun, Barium, plus many others. We are breathing it in and it has to be affecting our brains, etc. Thinking alzheimer's and the increase alzheimers in kids too.
Ty & Charlene, would love to see you look into geoengineering (aka chemtrails as some call it). They are spraying everywhere these days and more often while covering beautiful blues skies to reflect the sun?? How insane is that? Let nature be. We don't need more chemicals in the environment! No wonder Monsanto was patenting aluminum resistant seeds. They know something we don't. Like what geoengineering is going to be doing to our future crops and soil that are being sprayed with aluminum. All for has the world gone insane? All for profit. It's sad.
Yesi says
Name of the article 'New Study Says Air Pollution Kills 600,000 Children Each Year'.
Alfred Leuta says
Thank you so much for the Information, since watching and listening to your videos have learned so much.
That is great to hear! We are so glad that you are with us and learning lots.
Please keep up the good work, we all need to hear this.
Frank Kline says
If CO2 is warming the planet why are so many Americans buying large vehicles [SUVs and trucks] these days. It's like these people don't care. I guess it's because gas is too cheap these days. A lot if these large vehicle owners have children and grandchildren, who are going to be the most affected, so I guess the large vehicle owners don't care about their offspring.
sumru ramsey says
I don't know what more do people need to pay attention to this serious problem. When our children are dying there should be something that we can do.


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Dozens of Palestinians said injured in clashes with IDF
Palestinian media reports some 20 protesters hit by live fire in West Bank; Israel confirms two injured in riots
By TOI staff	29 November 2015, 8:39 pm Edit
Palestinian demonstrators hurl rocks at Israeli security forces during clashes in al-Bireh on the outskirts of Ramallah in the West Bank, on November 29, 2015. (AFP/Abbas Momani)
Dozens of Palestinians were injured in violent clashes with Israeli security troops in a series of riots in the West Bank Sunday afternoon, according to Palestinian reports.
In the northern West Bank city of Tulkarem, the Israel Defense Forces said security forces used Ruger sniper rifles to disperse rioters throwing rocks and Molotov cocktails at soldiers patrolling the nearby Nitzana checkpoint, and confirmed that at least one person was injured in the clashes, Israel Radio reported.
According to the Palestinian Red Crescent, eight students from the city's technical university were injured by live fire when IDF forces entered the campus. Medics said one man who was shot in the abdomen was in serious condition and dozens of others were treated for teargas inhalation, the Palestinian Ma'an News reported.
Red Crescent officials said a rubber-coated bullet fired by Israeli security forces struck one of their ambulances.
Elsewhere in the West Bank, Palestinian protesters hurled rocks and Molotov cocktails and rolled burning tires toward Israeli forces near al-Bireh, a town between Ramallah and the Israeli settlement of Beit El.
The IDF confirmed to AFP that one protester was shot and injured during the clashes.
"The force identified a rioter with a lit firebomb in hand," a military spokeswoman said. "The force fired at the rioter… and a hit was confirmed."
The extent of the man's injuries was not immediately known.
The Palestinian Ma'an news agency reported at least 12 Palestinians were injured by live fire in the al-Bireh clashes, including a man who was driving nearby and who was struck by a rubber-coated bullet fired by Israeli security forces.
The clashes come hours after a stabbing attack at an entrance to Jerusalem's Old City and another near a bus stop left two people wounded and an attacker killed.
Early on Sunday, a 38-year-old Palestinian stabbed an Israeli Border Police officer at Damascus Gate, lightly wounding him. The attacker, who was identified as Bassem Salah from the northern West Bank city of Nablus, was shot dead by officers at the scene.
Later in the morning, a Nepalese woman was lightly wounded in a stabbing attack near a bus stop in Jerusalem, after which the terrorist fled. A 17-year-old Palestinian suspect from Hebron was arrested at a construction site near the scene shortly after.
AFP contributed to this report.
West Bank protests
Palestinian Red Crescent Society
riot-dispersal
Beit El
Nitzana Border Crossing
Damascus Gate
stabbings
firebombing
stone throwing
Did the travel ban help? Why aren't vaccines working the same as with previous variants? Why don't antibody counts tell us if we're protected? Immunologist Dr. Yariv Wine answers
Christian adoption agency accused of discrimination after refusing Jewish couple


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Replacement Mattress Covers for Latex Memory Foam Air Beds Waterbeds Pillowtop zipper cover with organic cotton for california king waterbed mattress the mattress cover will help prevent punctures. ID IL IN IA KS. Color- mattress cover comes in off white. Y ou should use a quality mattress pad over the mattress cover which will help protect the cover.


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Tag Archives: Cicero
The Rhetor and the Knower: Wittgenstein and Achilles
Leave a comment Posted by Kevin von Duuglas-Ittu on May 15, 2008
The question of this post would be, if once verificationist epistemologies are found to be unsupportable, and speech use is acknowledged to be an act, has not the rhetor (the speaker) and the deed doer become the same thing? And does this not place all "meaning" in a horizon of power?
Homer writes of Phoenix, the tutor of Achilles, that he was to instruct Achilles so as to make him into a "speaker of speech" (a rhetor of mythos) and a "doer of deeds" (a praktēr of ergon). The greatness of Achilles is his eventual fusion of these two into a single form. The political and the performance in war are inter-dependently related.
Homer in the Iliad wrote:
[Peleus, your father] sent you out from Phthia to Agamemnon, a mere child, knowing nothing yet of evil war, nor of assembles in which men become preeminent. For this reason he sent me to instruct you in all these things, to be both a speaker of words and a doer of deeds (Iliad 9.338-444).
Cicero the great champion of rhetoric, decried that Greek philosophy of arguments from first principles had broken instruction into two entirely distinct realms, that of knowledge and that of persuasion. The tongue had been separated from the brain, the "knower" from those "with the capacity to speak" ("alii nos sapere, allii dicere docerent", Cicero De oratore 3.61). The result of which is a philosophical concern with the "res obscurae" and "non necessariae". Philosophy, in Cicero's view, had become preoccupied with its own products. The public and practical (pragmatic?) dimensions of knowing had atrophied.
Wittgenstein, a suitable Achillean character for a philosophical place like Cambridge, which can be our contemporary Troy, through his concept of "Language-games" and "meaning is use" breaks down this very rationalist Greek distinction. The rhetor and the gnostic are no longer divided. Speech is an act, one becomes a praktēr of mythos, and in language use one is a rhetor of ergon. The using of language is a kind of doing; knowing how to use words, how to "follow a rule" is the inscription of the realm of knowing itself, through the production of "meaning". Meaning as practice.
With the unsustainability of verificationist claims of epistemology, rhetoric, that is the effective use of words, becomes the horizon of knowing. Consider Aristotle's definition of Rhetoric in this respect.
Aristotle in Rhetoric wrote:
Rhetoric then may be defined as the faculty of discovering the possible means of persuasion in reference to any subject whatever. This is the function of no other of the arts, each of which is able to instruct and persuade in its own special subject; (translation J.H. Freese.)
Literal: Rhetoric thus is the capacity (dunamis) upon of each of the beheld (theōrēsai) to take in its own persuasiveness (pithanon), and not of each different thing (heteras) [this] is this skill's (technēs) work (ergon). For each of the other kinds, the underlying (hupokeimenon) of its own, it is instructive (didaskalykē) and persuasive (peistikē) of that sort. (1.2.1)
The literal translation brings about a certain richness.
Rhetorical "Faculty" is actually capacity, or power. A "Subject" is each thing beheld, seen, considered (from which we famously get the word "theory" ). The "Persuasion" of a perspective, it should be noted, is derived from Peithō, Persuasion a goddess attendant of Aphrodite.
Theorizing in the rhetorical sense, is beholding and taking upon oneself (endexomenon) the inherent persuasiveness in the thing considered, that is it is the capacity of capacities. It is interpreting in terms both of sense, and in the power to convince others in a social sphere. It requires a certain discernability that will be marked in terms of a power (dunamis), to join language games to each other, bringing about consent. Instead of epistemologies, there are capacities. It is notable that the capacities are performed in rhetoric through forming arguments (enthymemes) through the identification of topoi (that is literally places), which are ways of relating. The forms (topoi) of Aristotle argumentation it can be said correspond to the rules of Language-games (and in the end Lebensform) of Wittgenstein. The rhetor is gnostic.
[written May 14, 2006]
Philosophy, Wittgenstein	Achilles, Cicero, enthymemes, Epistemology, gnosis, Homer, power, Rhetor, Rhetoric, topoi, Verificationism, Wittgenstein
Cookery, Cuisine and the Truth: Plato's Gorgias
From Plato's Gorgias:
Polus: But what do you consider rhetoric to be? [462c]
Socrates: A thing which you say–in the treatise which I read of late–"made art."
Polus: What thing do you mean?
Socrates: I mean a certain habitude.
Polus: Then do you take rhetoric to be a habitude?
Socrates: I do, if you have no other suggestion.
Polus: Habitude of what?
Socrates: Of producing a kind of gratification and pleasure.
Polus: Then you take rhetoric to be something fine–an ability to gratify people?
Socrates: How now, Polus? Have you as yet heard me tell you [462d] what I say it is, that you ask what should follow that–whether I do not take it to be fine?
Polus: Why, did I not hear you call it a certain habitude?
Socrates: Then please–since you value "gratification"–be so good as gratify me in a small matter.
Polus: I will.
Socrates: Ask me now what art I take cookery to be.
Polus: Then I ask you, what art is cookery ? [462e]
Socrates: Then I reply, a certain habitude.
Polus: Of what? Tell me.
Socrates: Then I reply, of production of gratification and pleasure, Polus.
Polus: So cookery and rhetoric are the same thing?
Socrates: Not at all, only parts of the same practice.
Polus: What practice do you mean?
Socrates, in the Gorgias, compares rhetoric, that is the art of speaking, to cookery [opsopoiike ]. He distinguishes it from arts [techne ], calling it merely a practice [or habituation, empeirian ], or worse a routine [tribe ], and as cookery, it falls into being a subdivision of a larger devotion [epitedeuseos ], which is flattery [kolakeian ]. He contrasts cooking to medicine, and distinguishes that medicine is something that, unlike mere cooking, tells us the real nature of things [phusis ]. And he bases this distinction upon the idea that it is the soul commands the body:
For indeed, if the soul were not in command of the body, but the latter had charge of itself, and so cookery and medicine were not surveyed and distinguished by the soul, but the body itself were the judge, forming its own estimate of them by the gratification they gave it…everything would be jumbled together.
Now, a thinker like Nietzsche, (and in a way, one like Spinoza), would turn to the Latin word for wisdom, sapientia, and speak of how such a word is derived from the sense of experiencing, or literally tasting, and suggest that such a dichotomy between cooking and medicine is not so strict. Also, as the body/soul distinction begins to break down, does not the rhetoric/truth distinction also begin to break down? Is it not, in any particular monism one might have, that when we encounter a thought, we "taste" it, as if it were cooked up, and find ourself either repelled or attracted to it, almost instinctively. And is it not the case that through familiarizing ourselves with certain abstract "cuisines," we can acquire a taste for them, become able to digest with pleasure what in the past might have repelled us? And as we familiarize ourselves with these "practices," we even can become expert enough to cook some up ourselves, so that others who share our taste, in tasting them might like them?
And what of medicine itself. Would it not be more wise to consider medicine a sub-division, a derivative of cooking? Are not pharmaceuticals really very narrowly defined recipes of "cooked things," both in history (let's say from the processes of alchemy to those of chemistry), and in actual practice? Could this not be said of "truths," a series of cultural practices which "taste" has lead a community of thinkers to produce? And in the opposite direction, I have always found interesting the philosophical concept of "essence". How like in cooking, I am thinking of French Cuisine, does one try to reduce things to thier essential parts, boil it down to a concentrated form, whose digestion has a remarkable effect. Is it not a mistake to have taken Descartes' Cogito ergo sum to be something other than a French reduction, a boiling down of the bones and juice so as to make a sauce, designed to have appetitive affect (perhaps that Rosecrusian was himself confused).
Could it be that all this distillation and cooking has been meant to be nothing more than something experiential, a kind of cooking that aims for pleasure, (not the kind of "immoral" pleasure that rationality fights against), the kind of pleasure that comes with health and experience. There is a funny thing that happens when you study a philosophy in its detail, tasting all its distillations, all the recipes you have worked to become acquainted with: you begin to experience the world differently.
Perhaps Socrates got it wrong. The Body does do the discerning, and the result is not that all things are jumbled together. But rather that the body is wise, is tasting. And the result of this tasting, are things such as medicine, science and ethics (among so many other things, with which they are not jumbled). Is it not that with even the most abstract things we are still tasters, that work to refine and enhance our tasting capacities.
Cicero was of the opinion that Socrates in his division of rhetoric from philosophy did a great dis-service to both. It deprived rhetoricians of important things to say, and philosophy ways of saying them. It made philosohy otherworldly, meant to exist apart from the community of users ("tasters") that together made philosophy both possible and important. Achilles, by Homer, is described as being great in speech and deeds. He is both knowledgable in medicine, but also notably in preparing meals. Would it not be advisable to see clear, once again, the connection between cooking and thinking, and hence between thinking and community?
…What the word does is open one up to both the biological and cultural (historical) origins of discernment. Further, I think it demystifies judgments to a degree. We certainly don't know how "taste" works in any determinant experiential manner, but it is not mysterious. We accept the "foundationless" nature of taste without fearing that such a foundationlessness will fall into relativism. If we taste propositions, and either like them or not, we might not be so deluded into thinking it is due to something entirely ahistorical. And there is something potentializing in thinking about philosophies, or arguments as recipes. Or even essences as "reductions". This of course is not without precedence, for Plato in the Phaedrus, in telling the orgins of the written word, speaks speaks of writting as the "pharmakon" (which can mean either "poison" or "medicine"), properly the "potion". This is something that Derrida makes a great deal about, the inherent polysemy of words and meanings. Written texts are recipes that produce a multiplicity of effects.
[written September 5, 2006]
Philosophy, Spinoza	Cicero, Cooking, Gorgias, Nietzsche, Plato, Rhetoric, Truth


text:
package xfer

import (
	"sync"

	"github.com/docker/docker/pkg/progress"
	"golang.org/x/net/context"
)

// DoNotRetry is an error wrapper indicating that the error cannot be resolved
// with a retry.
type DoNotRetry struct {
	Err error
}

// Error returns the stringified representation of the encapsulated error.
func (e DoNotRetry) Error() string {
	return e.Err.Error()
}

// Watcher is returned by Watch and can be passed to Release to stop watching.
type Watcher struct {
	// signalChan is used to signal to the watcher goroutine that
	// new progress information is available, or that the transfer
	// has finished.
	signalChan chan struct{}
	// releaseChan signals to the watcher goroutine that the watcher
	// should be detached.
	releaseChan chan struct{}
	// running remains open as long as the watcher is watching the
	// transfer. It gets closed if the transfer finishes or the
	// watcher is detached.
	running chan struct{}
}

// Transfer represents an in-progress transfer.
type Transfer interface {
	Watch(progressOutput progress.Output) *Watcher
	Release(*Watcher)
	Context() context.Context
	Cancel()
	Done() <-chan struct{}
	Released() <-chan struct{}
	Broadcast(masterProgressChan <-chan progress.Progress)
}

type transfer struct {
	mu sync.Mutex

	ctx    context.Context
	cancel context.CancelFunc

	// watchers keeps track of the goroutines monitoring progress output,
	// indexed by the channels that release them.
	watchers map[chan struct{}]*Watcher

	// lastProgress is the most recently received progress event.
	lastProgress progress.Progress
	// hasLastProgress is true when lastProgress has been set.
	hasLastProgress bool

	// running remains open as long as the transfer is in progress.
	running chan struct{}
	// hasWatchers stays open until all watchers release the transfer.
	hasWatchers chan struct{}

	// broadcastDone is true if the master progress channel has closed.
	broadcastDone bool
	// broadcastSyncChan allows watchers to "ping" the broadcasting
	// goroutine to wait for it for deplete its input channel. This ensures
	// a detaching watcher won't miss an event that was sent before it
	// started detaching.
	broadcastSyncChan chan struct{}
}

// NewTransfer creates a new transfer.
func NewTransfer() Transfer {
	t := &transfer{
		watchers:          make(map[chan struct{}]*Watcher),
		running:           make(chan struct{}),
		hasWatchers:       make(chan struct{}),
		broadcastSyncChan: make(chan struct{}),
	}

	// This uses context.Background instead of a caller-supplied context
	// so that a transfer won't be cancelled automatically if the client
	// which requested it is ^C'd (there could be other viewers).
	t.ctx, t.cancel = context.WithCancel(context.Background())

	return t
}

// Broadcast copies the progress and error output to all viewers.
func (t *transfer) Broadcast(masterProgressChan <-chan progress.Progress) {
	for {
		var (
			p  progress.Progress
			ok bool
		)
		select {
		case p, ok = <-masterProgressChan:
		default:
			// We've depleted the channel, so now we can handle
			// reads on broadcastSyncChan to let detaching watchers
			// know we're caught up.
			select {
			case <-t.broadcastSyncChan:
				continue
			case p, ok = <-masterProgressChan:
			}
		}

		t.mu.Lock()
		if ok {
			t.lastProgress = p
			t.hasLastProgress = true
			for _, w := range t.watchers {
				select {
				case w.signalChan <- struct{}{}:
				default:
				}
			}

		} else {
			t.broadcastDone = true
		}
		t.mu.Unlock()
		if !ok {
			close(t.running)
			return
		}
	}
}

// Watch adds a watcher to the transfer. The supplied channel gets progress
// updates and is closed when the transfer finishes.
func (t *transfer) Watch(progressOutput progress.Output) *Watcher {
	t.mu.Lock()
	defer t.mu.Unlock()

	w := &Watcher{
		releaseChan: make(chan struct{}),
		signalChan:  make(chan struct{}),
		running:     make(chan struct{}),
	}

	if t.broadcastDone {
		close(w.running)
		return w
	}

	t.watchers[w.releaseChan] = w

	go func() {
		defer func() {
			close(w.running)
		}()
		done := false
		for {
			t.mu.Lock()
			hasLastProgress := t.hasLastProgress
			lastProgress := t.lastProgress
			t.mu.Unlock()

			// This might write the last progress item a
			// second time (since channel closure also gets
			// us here), but that's fine.
			if hasLastProgress {
				progressOutput.WriteProgress(lastProgress)
			}

			if done {
				return
			}

			select {
			case <-w.signalChan:
			case <-w.releaseChan:
				done = true
				// Since the watcher is going to detach, make
				// sure the broadcaster is caught up so we
				// don't miss anything.
				select {
				case t.broadcastSyncChan <- struct{}{}:
				case <-t.running:
				}
			case <-t.running:
				done = true
			}
		}
	}()

	return w
}

// Release is the inverse of Watch; indicating that the watcher no longer wants
// to be notified about the progress of the transfer. All calls to Watch must
// be paired with later calls to Release so that the lifecycle of the transfer
// is properly managed.
func (t *transfer) Release(watcher *Watcher) {
	t.mu.Lock()
	delete(t.watchers, watcher.releaseChan)

	if len(t.watchers) == 0 {
		close(t.hasWatchers)
		t.cancel()
	}
	t.mu.Unlock()

	close(watcher.releaseChan)
	// Block until the watcher goroutine completes
	<-watcher.running
}

// Done returns a channel which is closed if the transfer completes or is
// cancelled. Note that having 0 watchers causes a transfer to be cancelled.
func (t *transfer) Done() <-chan struct{} {
	// Note that this doesn't return t.ctx.Done() because that channel will
	// be closed the moment Cancel is called, and we need to return a
	// channel that blocks until a cancellation is actually acknowledged by
	// the transfer function.
	return t.running
}

// Released returns a channel which is closed once all watchers release the
// transfer.
func (t *transfer) Released() <-chan struct{} {
	return t.hasWatchers
}

// Context returns the context associated with the transfer.
func (t *transfer) Context() context.Context {
	return t.ctx
}

// Cancel cancels the context associated with the transfer.
func (t *transfer) Cancel() {
	t.cancel()
}

// DoFunc is a function called by the transfer manager to actually perform
// a transfer. It should be non-blocking. It should wait until the start channel
// is closed before transferring any data. If the function closes inactive, that
// signals to the transfer manager that the job is no longer actively moving
// data - for example, it may be waiting for a dependent transfer to finish.
// This prevents it from taking up a slot.
type DoFunc func(progressChan chan<- progress.Progress, start <-chan struct{}, inactive chan<- struct{}) Transfer

// TransferManager is used by LayerDownloadManager and LayerUploadManager to
// schedule and deduplicate transfers. It is up to the TransferManager
// implementation to make the scheduling and concurrency decisions.
type TransferManager interface {
	// Transfer checks if a transfer with the given key is in progress. If
	// so, it returns progress and error output from that transfer.
	// Otherwise, it will call xferFunc to initiate the transfer.
	Transfer(key string, xferFunc DoFunc, progressOutput progress.Output) (Transfer, *Watcher)
}

type transferManager struct {
	mu sync.Mutex

	concurrencyLimit int
	activeTransfers  int
	transfers        map[string]Transfer
	waitingTransfers []chan struct{}
}

// NewTransferManager returns a new TransferManager.
func NewTransferManager(concurrencyLimit int) TransferManager {
	return &transferManager{
		concurrencyLimit: concurrencyLimit,
		transfers:        make(map[string]Transfer),
	}
}

// Transfer checks if a transfer matching the given key is in progress. If not,
// it starts one by calling xferFunc. The caller supplies a channel which
// receives progress output from the transfer.
func (tm *transferManager) Transfer(key string, xferFunc DoFunc, progressOutput progress.Output) (Transfer, *Watcher) {
	tm.mu.Lock()
	defer tm.mu.Unlock()

	if xfer, present := tm.transfers[key]; present {
		// Transfer is already in progress.
		watcher := xfer.Watch(progressOutput)
		return xfer, watcher
	}

	start := make(chan struct{})
	inactive := make(chan struct{})

	if tm.activeTransfers < tm.concurrencyLimit {
		close(start)
		tm.activeTransfers++
	} else {
		tm.waitingTransfers = append(tm.waitingTransfers, start)
	}

	masterProgressChan := make(chan progress.Progress)
	xfer := xferFunc(masterProgressChan, start, inactive)
	watcher := xfer.Watch(progressOutput)
	go xfer.Broadcast(masterProgressChan)
	tm.transfers[key] = xfer

	// When the transfer is finished, remove from the map.
	go func() {
		for {
			select {
			case <-inactive:
				tm.mu.Lock()
				tm.inactivate(start)
				tm.mu.Unlock()
				inactive = nil
			case <-xfer.Done():
				tm.mu.Lock()
				if inactive != nil {
					tm.inactivate(start)
				}
				delete(tm.transfers, key)
				tm.mu.Unlock()
				return
			}
		}
	}()

	return xfer, watcher
}

func (tm *transferManager) inactivate(start chan struct{}) {
	// If the transfer was started, remove it from the activeTransfers
	// count.
	select {
	case <-start:
		// Start next transfer if any are waiting
		if len(tm.waitingTransfers) != 0 {
			close(tm.waitingTransfers[0])
			tm.waitingTransfers = tm.waitingTransfers[1:]
		} else {
			tm.activeTransfers--
		}
	default:
	}
}

redpajama_set_name: RedPajamaGithub


A freak windstorm during its opening weekend hurt the Delaware County Fair's bottom line, but couldn't keep it or its patrons down, fair officials declared last week.
The 2008 fair likely will be remembered as the first one which had to be evacuated, because of 75-mph winds.
The historic weather-induced closure on Sept. 14 also forced fair officials to delay the fair's opening until noon on Sept. 15, and left the fairgrounds without power until the following morning.
Although final revenue and attendance figures had yet to be tabulated as of last Wednesday, interim fair manager Phil Terry said the storm had a significant impact.
"Revenues were down because of Sunday and Monday," Terry said. "The gate was free on Monday, so we lost that entire day.
"We were very limited as far as racing on Monday, and were down over $100,000 in wagering on Monday. We also lost five races on Sunday, so we had to bring back four stake races (later in the week)."
Still, Terry dubbed the 2008 fair a success, and pointed to its rapid recovery from the storm as a key factor in reaching the conclusion.
"I think all things considered, it turned out very well," he said. "Once we got through the weather and electrical issues, we had good crowds.
"By 7:30 the night of the storm, we had almost every piece of significant damage recorded and things were being worked on. We were able to open back up because of that, and from that aspect, it was very pleasing."
Terry said the "amazing" work put in by fair board members and volunteers to clear the fairgrounds of fallen trees and other storm debris helped the fair to a rapid recovery.
He said Thursday's announced attendance of 50,700 for the Little Brown Jug harness race was a "very good crowd," and said attendance records likely were set on the fair's final two days.
"We had 600-and-some people more than we've ever had before on a final Friday, and about 1,100 more than we've ever had on a Saturday," he said.
Terry said fair traditions such as youth livestock exhibits, motor sports and harness racing events again proved to be popular, and the additions of a VIP tent on Jug Day and a closing fireworks display were well-received.
The community's efforts to help the fair resume after the storm also contributed to the 2008 fair's success, Terry said.
He added that the storm, its aftermath and the response it generated likely will make this year's fair one for the ages.
"I think it will be a memorable one for a long time," Terry said. "The way people responded when we had to stop the racing and evacuate the fairgrounds was just tremendous."


Abstract: Raloxifene hydrochloride, a highly effective drug for the treatment of invasive breast cancer and osteoporosis in post-menopausal women, shows poor oral bioavailability of 2%. The aim of this study was to develop, statistically optimize, and characterize raloxifene hydrochloride-loaded transfersomes for transdermal delivery, in order to overcome the poor bioavailability issue with the drug. A response surface methodology experimental design was applied for the optimization of transfersomes, using Box-Behnken experimental design. Phospholipon® 90G, sodium deoxycholate, and sonication time, each at three levels, were selected as independent variables, while entrapment efficiency, vesicle size, and transdermal flux were identified as dependent variables. The formulation was characterized by surface morphology and shape, particle size, and zeta potential. Ex vivo transdermal flux was determined using a Hanson diffusion cell assembly, with rat skin as a barrier medium. Transfersomes from the optimized formulation were found to have spherical, unilamellar structures, with a homogeneous distribution and low polydispersity index (0.08). They had a particle size of 134±9 nM, with an entrapment efficiency of 91.00%±4.90%, and transdermal flux of 6.5±1.1 µg/cm2/hour. Raloxifene hydrochloride-loaded transfersomes proved significantly superior in terms of amount of drug permeated and deposited in the skin, with enhancement ratios of 6.25±1.50 and 9.25±2.40, respectively, when compared with drug-loaded conventional liposomes, and an ethanolic phosphate buffer saline. Differential scanning calorimetry study revealed a greater change in skin structure, compared with a control sample, during the ex vivo drug diffusion study. Further, confocal laser scanning microscopy proved an enhanced permeation of coumarin-6-loaded transfersomes, to a depth of approximately160 µM, as compared with rigid liposomes. These ex vivo findings proved that a raloxifene hydrochloride-loaded transfersome formulation could be a superior alternative to oral delivery of the drug.
Osteoporosis, commonly known as a "silent disease", is a progressive medical condition, in which bone density slowly decreases with advancing age. As per report of a WHO Scientific Group, Geneva, World Health Organization, 2003 (WHO Technical Report Series, No. 921), osteoporosis-related fractures have been identified as a major health problem to the older population. With an aging population, the burden of osteoporosis is expected to continue to rise worldwide. With higher socioeconomic status and increasing urbanization in Asian countries, it is estimated that by 2050, more than 50% of the world's hip fractures will occur in Asia. According to a report, worldwide osteoporosis causes more than 8.9 million fractures annually, resulting in an osteoporotic fracture every 3 seconds.11 According to a 2007 WHO technical report, osteoporosis is estimated to affect 200 million women worldwide, mostly those older than 60.12 Thus, prevention of osteoporosis and its associated fractures will be important in controlling health costs in the future. Apart from the burden of osteoporosis, according to the latest report (12 December 2013, Press release No 223) from the International Agency for Research on Cancer (IARC), the specialized cancer agency of the World Health Organization, breast cancer is the most frequently-diagnosed cancer, and the most common cause of death among women. According to the American Cancer Society's report, around 232,340 new cases of invasive breast cancer in women were identified in the United States in 2013.13 Based upon a careful risk assessment, health care providers sometimes recommend therapy with one of several medications to reduce the chance of developing breast cancer, in women with increased risk.
Raloxifene hydrochloride, a second-generation selective estrogen receptor modulator, is used in the prevention and treatment of osteoporosis and invasive breast cancer in postmenopausal women. Being an estrogen agonist/antagonist, it mainly increases bone mineral density and decreases low-density lipoprotein cholesterol. It provides an antiestrogen effect on the breast, and reduces the risk of invasive breast cancer in postmenopausal women.14,15 Additionally, it serves as a substitute for long-term female hormone replacement therapy. It is mostly supplied as 60 mg tablets for daily dose. However, the major obstacle for oral delivery of raloxifene is its poor systemic exposure, with only 2% absolute bioavailability, because of its poor solubility in aqueous fluids and its extensive first-pass metabolism.16 Additionally, the commonly-reported adverse events associated with high and regular oral dosing of raloxifene hydrochloride are: hot flushes (flashes), leg cramps, and peripheral edema. Thromboembolic events and increased risk of fatal stroke are rarely-occurring events.16 So, there is huge scope to improve the bioavailability and avoid the commonly-occurring adverse events associated with oral medication, by delivering it through a transdermal route, as this might reduce dose without compromising therapeutic efficacy.
Thus, the aim of the present study was to develop and optimize a nanotransfersome formulation of raloxifene hydrochloride, by response surface methodology, in order to enhance percutaneous permeation and bypass the issue of poor oral bioavailability.
Raloxifene hydrochloride was purchased from Apollo Health Care Limited (People's Republic of China). Phospholipon® 90G (PC90G) was obtained as a generous gift sample from Lipiod GmbH, (Ludwigshafen, Germany). Sodium deoxycholate (SDC) (99.8%) and coumarin-6 were bought from Sigma-Aldrich (St Louis, MO, USA) and Thermo Fisher Scientific (Waltham, MA, USA), respectively. Chloroform, methanol, ethanol, and Triton® X-100 were received from Merck KGaA (Darmstadt, Germany). Acetonitrile, for high-performance liquid chromatography analysis, was obtained from Thermo Fisher Scientific. Polycarbonate membrane (Titan3™), of 0.45 μM and 0.22 μM size, was supplied by Thermo Fisher Scientific. All other reagents used in this study were of analytical grade. Ultrapure distilled water (Kulliyyah of Pharmacy, International Islamic University Malaysia, Pahang, Malaysia) was used throughout the experiment.
Raloxifene hydrochloride-loaded transfersomal vesicles (RTVs) were prepared using the conventional thin-layer rotary evaporation method, with slight modification in order to suit the existing instrumental facility.17 Briefly, PC90G, drug, and SDC were dissolved in a round-bottom flask with a mixture of chloroform and methanol (2:1, by volume). The organic solvent mixture was evaporated by rotary evaporator (Rotavapor® R-205; Buchi Labortechnik AG, Flawil, Switzerland) under reduced pressure at 40°C. The round-bottom flask was kept under vacuum overnight, to remove remaining solvent trace. The lipid film layer deposited onto the inner surface of the flask after solvent evaporation was allowed to hydrate for 1 hour in a saline phosphate buffer (PBS) (pH 6.5) at 41°C–44°C and 120 rpm. The suspended vesicles were furthered allowed to swell for 2–3 hours at room temperature, which resulted in large multilamellar vesicles. These were sonicated for 20–30 minutes using an ULTRASonic 28X (Neytech, Yucaipa, CA, USA), at 325 W power, to reduce their size further. These small vesicles were passed through 450 nM and 220 nM pore size polycarbonate membranes (Titan3™), to obtain final drug-loaded transfersomal vesicles, which were then stored under refrigeration (2°C–8°C) for further characterization. The drug-loaded liposomal formulation used as control for transdermal flux was prepared using the method described by Touitou et al.18 Similarly, coumarin-6 (0.03%, weight to volume) loaded transfersomes and liposomes were formulated to visualize drug permeation by confocal laser scanning microscopy.
A three-factor, three-level, Box-Behnken design (BBD) was applied, to optimize transfersome formulation, using response surface methodology (RSM). The amount of phospholipid (A), surfactant (B), and sonication time (C) were selected as independent variables, considering their overall effects on the formulation's stability and transdermal flux, as reported by many researchers.19–21 Accordingly, entrapment efficiency (EE) (Y1), vesicle size (Y2 ), and transdermal flux (Y3 ) were selected as dependent variables for the optimization process. After a significant number of preliminary studies, the amount of PC90G (A), SDC (B), and sonication time (C) were selected in the range of 100–300 mg, 15–55 mg, and 15–35 minutes, respectively, as independent variables for raloxifene hydrochloride loaded transfersomes formulation optimization by RSM (Table 1). Seventeen trial formulations of various factor combinations, including five center points, were prepared according to the BBD, as shown in Table 2. All other formulation and processing variables were kept constant throughout the study.
Notes: A, phospholipid (PC90G); B, surfactant (SDC); C, sonication time; Y1, entrapment efficiency; Y2, vesicles size; Y3, transdermal flux.
Abbreviations: SD, standard deviation; PDI, polydispersity index; PC90G, phospholipon® 90G; SDC, sodium deoxycholate; RTV, raloxifene hydrochloride-loaded transfersomal vesicle formulation.
where, Y is the measured response associated with each factor level combination; α0 is a constant value that represents the arithmetic average of all quantitative outcomes of 17 experimental trials; α1, α2, and α3 are linear coefficients computed from the observed experimental response values of Y; α12, α13, α23 are interaction coefficients between two factors; and α11, α22, α33 are their quadratic coefficients.22 Three-dimensional response surface graphs and two-dimensional contour plots were generated for individual response variables, in order to evaluate the effects of individual independent variables on response variables. The developed model was further validated, based on theoretical versus predicted values and their corresponding residual plot. Finally, the best formulation was selected using the point prediction method of the software, utilizing constrains of response values. The optimized formulation was further characterized by vesicular size, size distribution, shape, surface morphology, zeta potential, differential scanning calorimetry (DSC) study, and confocal laser scanning microscopy (CLSM) study.
Morphology of the vesicles was visualized by scanning electron microscopy (SEM). One drop of transfersomal preparation was spread onto a glass slide and was allowed to dry. Once dried, the specimen was gold-coated using a cool sputter coater (Leica EM SCD005, Leica Microsystems, Wetzlar, Germany), and viewed under a scanning electron microscope (EVO series, Carl Zeiss Microscopy) at an accelerating voltage of 10 KV.
The amount of raloxifene present in the transfersome formulation was determined by an HPLC method, as earlier reported by Trontelj et al with slight modification.24 Transfersome vesicles from 15 mL of formulation were separated by high-speed cold centrifugation. After that, the obtained vesicles were disrupted with 50 mL of 50% methanol, in order to release the entrapped drug into the solvent. The sample was then filtered through a 0.45 μM membrane filter, followed by 20-times dilution with mobile phase, and injection into the HPLC system (Agilent 1200 Compact LC; Agilent Technologies, Santa Clara, CA, USA), which was equipped with an ultraviolet detector. An Agilent Eclipse XDB-C18 column (150 mM ×4.6 mM; 5 μM particle size) (Agilent Technologies) was used for chromatographic separation. The mobile phase comprised of an isocratic mixture of acetonitrile and pH 3.0 buffer solution of orthophosphoric acid (33:67, by volume), delivered at a flow rate of 1 mL per minute. The buffer solution was prepared daily, filtered through a 0.45 μM membrane filter, and degassed before use. Analysis was carried out at 287 nM at 25°C. The injection volume was 10 μL, and the relative retention time of raloxifene was found to be 4.68±0.5 minutes. A six-point standard curve in the range of 0.125–5.0 μg/mL was prepared, taking the peak area of the drug versus the concentration (μg/mL), using a weighted linear least-squares regression (1/concentration2) as the mathematical model. The prepared standard curve was linear, and the equation was y =76.082×+8.466, with a correlation coefficient of 0.999.
where, A1 is the amount of drug added initially, A2 is the amount of drug determined in the supernatant, and A1−A2 is the amount of drug entrapped in the formulation.
Albino Wistar rats (80–120 gm) were obtained from the Faculty of Pharmacy, International Islamic University, Kuantan, Malaysia. Hair on the outer skin surface was removed with dissecting scissors, as close as possible to the skin, without harming the SC. The majority of subcutaneous tissue was removed with scissors. The adhering fatty layer and connective tissue layer were cleaned with isopropyl alcohol. The skin was washed with 0.9% sodium chloride solution, wrapped in aluminium foil, and stored in a deep freezer at −40°C, for a maximum of 1 month, for further use.
A Hanson diffusion cell assembly, with an effective permeation area of 1.5 cm2, receptor volume of 6 mL, and rat skin as a barrier medium, was utilized to measure in vitro drug release and its permeation from the transfersomal formulation. The receptor chamber was filled with a receptor medium composed of ethanol and PBS (40:60, by volume) (pH 7.4), maintained at 37°C±1°C, and stirred at 100 rpm. The skin sample was checked thoroughly, to ensure that it was free from any kind of defect that might influence the results of the study. On the day of the experiment, the skin sample was taken out from deep freeze and thawed at room temperature. Prior to the study, the skin sample was equilibrated for 30 minutes in 0.9% sodium chloride solution.
The skin sample was fixed over the diffusion cell so that the dermis side faced the receptor compartment, in contact with receptor medium, while the SC side faced the donor compartment, for formulation application. An amount of therapeutic transdermal daily dose was calculated and an amount of formulation equivalent to 1.2 mg of raloxifene hydrochloride was administered in the donor compartment. Samples of 200 μL were withdrawn from the receptor compartment, via the sample port, at 0.5, 1, 2, 4, and 6 hours. Immediately after sampling, the receptor compartment was compensated with an equal volume of fresh receptor medium, to maintain a sink condition throughout the study period. The permeation sample was analyzed by HPLC. A similar procedure was performed with the conventional liposome formulation, and with an ethanolic PBS of pure raloxifene hydrochloride. Once the permeation study was completed, the skin sample attached to the diffusion cell was removed and washed thoroughly in running tap water. The skin sample was cleaned, if required, with tissue paper, to remove any trace of the formulation attached to the skin. The skin was then cut into small pieces and sonicated with 10 mL of methanol for 30 minutes, to extract the drug retained in the skin. The formulation thus obtained was centrifuged for 10 minutes at 4,000 rpm. The supernatant liquid was separated, passed through a 0.45 μM nylon membrane filter, and analyzed using HPLC. The transdermal flux of tested formulations was calculated and further used to determine the enhancement ratio (ER), which is defined as the extent of enhancement of transdermal flux of the tested formulations, compared with that of the control formulation.
CLSM can be used to visualize improved skin delivery and skin structure. Furthermore, it allows the skin structure to be studied in three dimensions with very high accuracy.8 Three types of drug-loaded formulation (optimized transfersome formulation, conventional liposome, and ethanolic PBS solution), each of them tagged with coumarin-6 as a fluorescent marker, were used for a comparative study. Each sample was subjected to ex vivo study, nonocclusively, on a Hanson diffusion cell assembly (Hanson Research Corporation, Chatsworth, CA, USA) for 8 hours. At the end of the diffusion study, the skin samples were removed from the experimental setup and washed in running tap water, to remove any sample deposit. The skin samples – specifically the treatment area – were cut and sliced in sections of 5–10 μM thickness, and CLSM was used to optically scan through the z-axis of a confocal laser microscope (Leica TCS SPE, Leica Microsystems), using an argon beam at an excitation wavelength of 488 nM and emission wavelength of 502 nM. Relative fluorescence intensity of the probe in the skin samples was detected using Leica LAS AF advanced fluorescence software.
where, Td = therapeutic transdermal daily dose, F = bioavailability (as a percentage, after oral administration), and D0 = oral daily dose. Considering a 60 mg oral dose of raloxifene hydrochloride tablets, 2% oral bioavailability and 10%–15% transdermal absorption capacity of the applied dose, 15 mg of drug was loaded for all 17 formulations.
Preliminary trials were carried out (data not shown) to determine the probable ranges of the independent variables, which provide extreme effects on various dependent variables selected for this study. With respect to the formation of lipid vesicles, most of the available literature reported concentration ranges of phospholipid to surfactant in ratios of 75:25, 80:20, 85:15, 90:10, etc.17,18,20,24 However, the ratio of phospholipid and surfactant used in this study was optimized, based on the initial experiments and their observations (data not shown). PC90G concentrations less than 100 mg produced transfersomes with poor values of transdermal flux, whereas PC90G concentrations greater than 300 mg resulted in larger size vesicles, due to aggregation.20 In the case of the surfactant, it was observed that too low or too high a concentration of SDC was unsuitable for proper vesicle formation.19 In both cases, less than 15 mg or more than 55 mg of surfactant resulted in very low entrapment efficiency, as well as low transdermal flux. Vesicle size, which depends significantly on the sonication time, affects transdermal flux and skin deposition, as studied by Verma et al.21 In line with that report, we found that sonication time of less than 15 minutes was not sufficient for formation of transfersome vesicles with high concentration of phospholipid (about 300 mg) and the desired size was not achieved, due to aggregation of vesicles. Thirty-five minutes of sonication was too long; in one of the studies, a PC90G concentration of 100 mg and a surfactant concentration of 55 mg resulted in leaking of vesicles, with very low entrapment efficiency.
In order to optimize the raloxifene-loaded transfersome formulation, relationships among independent variables, such as PC90G (A), SDC (B), and sonication time (C), at three levels (−1, 0, +1), with dependent variables, such as entrapment efficiency (Y1), vesicles size (Y2), and transdermal flux (Y3), were evaluated by BBD, using Design Expert® software. The obtained response values of the individual trial formulations were fitted into the model matrix, in order to find the best-fitted model. After due consideration, the best model for all three dependent variables was found to be quadratic. Mathematical relationships generated using MLRA for the studied dependent variables are expressed in the following equations (6–8).
For estimation of the significance of the model, analysis of variance was performed using Design Expert® software (Table 4). Using a 5% significance level, a model is considered significant if the P-value (significance probability value) is less than 0.05.27 Most of the terms in Table 4, including the individual model, were found to be significant (P<0.05), except for a few terms (shown in bold). A positive coefficient represents a synergistic effect of the factor on the response, while a negative coefficient indicates an antagonistic effect. From the above equations (6–8), it is evident that independent variable A (first-order) and intercept have positive effects for all three responses. It is sugested that concentration of phospholipid (A) has a prominent effect on individual dependent variables. On the other hand, the other first-order main terms (B and C), interaction terms and, higher-order terms (except A2, in equation 6, B2 and BC, in equation 7, and A2 and C2, in equation 8) have negative effects on all of the dependent variables.
Figure 1 Response surface plots (A) and corresponding contour plots (B) which show effects of the independent variables on entrapment efficiency (Y1). Two variables are considered at a time, while the third one remains constant.
Abbreviations: SD, standard deviation; RTV, raloxifene hydrochloride-loaded transfersomal vesicle formulation.
Figure 2 Response surface plots (A) and corresponding contour plots (B), which show the effects of the independent variables on vesicle size (Y2) (nM). Two variables are considered at a time, while the third one remains constant.
The results of ex vivo skin permeation studies are shown in Table 2. RTV13, with a high concentration of PC90G and a medium concentration of SDC, showed maximum flux (ie, 6.5±1.1 μg/cm2/hour), whereas the minimum flux value was from RTV11 (1.5±0.4 μg/cm2/hour), with low concentration of PC90G and high concentration of SDC. The flux values for the liposomes and for the ethanolic PBS solution were 1.0±0.3 μg/cm2/hour and 0.7±0.4 μg/cm2/hour, respectively; the ER values shown by transfersomal formulation, compared against conventional liposomes and the ethanolic PBS solution, were 6.50 and 9.25, respectively. This enhancement ratio of transdermal flux in the transfersomal system is comparable to a previous finding of Mishra et al.20 A possible explanation for the better performance of the transfersome formulation, compared with conventional liposomes, may be the difference in their flexibility. Being more flexible in their nature, the transfersome vesicles can squeeze themselves through pores much smaller than their own diameters during permeation through the SC.34 The unique flexibility and deformability of the transfersome membrane are achieved by combining at least two lipophilic/amphiphilic components (phospholipid and biosurfactant) with sufficiently different packing characteristics into a single bilayer. Furthermore, these vesicles are highly stress-dependent and, as a result, they minimize the risk of complete vesicle rupture in the skin. Effects of the independent variables on transdermal flux are shown in three-dimensional response surface graphs and their corresponding contour plots (Figure 3). It was observed from these graphs and plots that after 6 hours of permeation studies, with rat skin as a barrier membrane, the transdermal flux from the RTV formulations initially increased with an increase of SDC concentration (from 15 mg to 35 mg), then decreased (Table 2). It is evident that too low or too high a concentration of SDC is unable to deliver the drug through viable skin. These findings are in agreement with the studies conducted by Cevc and Blume.9 In their study, transdermal flux was also found to be affected by the ratio of SDC to PC90G (determinant of drug entrapment efficiency).
Figure 3 Response surface plots (A) and corresponding contour plots (B) which show effects of the independent variables on transdermal flux (Y3) (μg/cm2/hour). Two variables are considered at a time, while the third one remains constant.
The theoretical values of Y1, Y2, and Y3, for all RTVs, were obtained by substituting their corresponding values of A, B, and C in the respective equations generated by Design Expert® software. Figure 4 quantitatively compares the resultant experimental values of the responses with those of predicted values. The theoretical (predicted) values and the observed values were in reasonably good agreement (data not shown). These results proved the validity of the RSM model developed.
Figure 4 Linear correlation plots (A–C) between actual and predicted values, and corresponding residual plots (D–F respectively), for all dependent variables.
Abbreviation: EE, entrapment efficiency; vs, versus.
The point prediction method of Design Expert® software was utilized to select the optimized formulation from 17 trial formulations, according to the BBD experimental design. This selection was based on the criteria of attaining maximum values of entrapment efficiency and transdermal flux, and a minimum value of vesicle size. After thorough evaluation by Design Expert® software, it was found that formulation RTV13, with the combination of 300 mg PC90G, 35 mg SDC, and 15 minutes sonication time, fulfilled the requisites of an optimum formulation. The optimized formulation showed 91.00%±4.90% entrapment efficiency, 134±9 nM vesicles size, and 6.5±1.1 μg/cm2/hour transdermal flux across rat skin.
The optimized transfersomal preparation (RTV13) was initially evaluated for shape and lamellarity using TEM (Figure 5A). Transfersomes were examined by negative staining with 0.1% phosphotungstic acid. The vesicles appeared as unilamellar and spherical in shape. The surface morphology and three-dimensional nature of the transfersomes were further visualized by SEM (Figure 5B).
Figure 5 TEM photomicrograph (A) and SEM image (B) of transfersome vesicles from optimized formulation (RTV13), following negative staining with 0.1% phosphotungstic acid.
Note: Magnification of (A) and (B) is 20 K and 2.24 K respectively.
Abbreviations: TEM, transmission electron microscopy; SEM, scanning electron microscopy; RTV, raloxifene hydrochloride-loaded transfersomal vesicle.
Vesicle size plays an important role in entrapment efficiency and transdermal permeation of RTVs, as shown in Figure 6. The vesicular size of the optimized formulation was found to be 134±9 nM. These drug-loaded, nano-size vesicles resulted in a better skin permeation profile (6.5±1.1 μg/cm2/hour). Subsequently for the formulation RTV16, vesicles' size was 180±12 nM and transdermal flux was found to be 2.9±0.4 μg/cm2/hour. A similar report on the importance of vesicular size towards the permeation of drug-loaded vesicles has been published by Verma et al.21 However, larger and smaller size vesicles, as observed in formulations RTV3 (191±11 nM) and RTV7 (113±6 nM), produced a similar transdermal flux. This contradiction may arise due to other influencing parameters, like vesicle charges, entrapment efficiency, PDI, etc. The vesicle charge of all trial formulations varied as the concentration of the phospholipid and anionic surfactant changed (Table 4). The values of the charges varied within a wide range of −16.1±3.5 mV to 7.7±2.1 mV. In addition to their nano-size ranges, a narrow and homogeneous size distribution of the optimized formulation (PDI =0.08) helped better drug permeation through the SC. In contrast, nano-size liposomes (226±20 nM) were found to produce minimum transdermal flux (1.0±0.3 μg/cm2/hour). As reported by Sinico et al charge is an important parameter that can affect the stability of a vesicular system, as well as skin–vesicle interaction.35 The charge of the optimized formulation was found to be −2.61±0.5 mV. Being negatively charged, transfersomal vesicles strongly improved skin permeation of the drug.
Figure 6 Effect of vesicle size on entrapment efficiency and transdermal flux of raloxifene-loaded transfersomal formulation.
Note: Bold type indicates not statistically significant, P>0.05.
Figure 7 Confocal laser scanning micrographs after application of 6-coumarin-loaded vesicular system. (A) RTV13, transfersomes of raloxifene hydrochloride, (B) liposomes of raloxifene hydrochloride, and (C) ethanolic PBS of raloxifene hydrochloride.
Abbreviations: RTV13, raloxifene hydrochloride-loaded transfersomal vesicle formulation 13; PBS, phosphate buffer saline.
The permeation-enhancing effect of transfersomes was further confirmed by DSC study of the transfersomal system, with treated and untreated skin. This study involved ex vivo permeation study of the optimized transfersomal formulation for 8 hours, and evaluation of its effects on SC structure, compared with untreated skin, based on thermal properties.36 Three expected transitions were observed in the untreated (control) SC sample, as shown in Figure 8: T1, at around 67°C, T2, at around 79°C, and T3, at around 105°C. The first two peaks (T1 and T2) were due to melting of the SC lipids; the third peak (T3) was due to denaturation of SC protein, as reported by Yamane et al.37 However, both T1 and T2 endotherms disappeared in the thermogram of the treated skin sample (Figure 8). It is expected that T1 melting or shifting happened, due to the lipid bilayer melting, T2 melting took place due to the melting of the lipids associated with keratin, or due to disruption of the polar head groups of the lipids.38 The T3 peak was shifted to a lower melting point (around 84°C), suggesting keratin denaturation and a possible intracellular permeation mechanism.
Figure 8 DSC thermogram of skin treated with the optimized transfersomal formulation (RTV13) (green), against the untreated skin, hydrated to 20%−25%, as control (blue).
Abbreviations: DSC, differential scanning calorimetry; RTV13, raloxifene hydrochloride-loaded transfersomal vesicle formulation 13; T, thermal transition temperature.
The result of the DSC investigation showed that problems associated with transdermal delivery of raloxifene hydrochloride could be overcome by incorporating it into transfersomes, the new "ultraflexible drug carrier". These lipid vesicles differ from conventional liposomes in their characteristic fluid membrane with high elasticity, which makes them special in responding to an external stress by rapid shape transformation. The elasticity of these vesicles is attributed to the simultaneous presence of different stabilizing (phospholipid) and destabilizing (surfactant) molecules and their tendency to redistribute in bilayers, which contributes to forming a flexible bilayer that can be deformed by itself.
Transfersome vesicles were studied as a possible vehicle for transdermal delivery of raloxifene hydrochloride. The optimized formulation resulted in an appropriate size, reasonable entrapment efficiency, and higher drug permeation capability, compared with conventional liposomes and an ethanolic PBS solution of the drug. CLSM further confirmed the potential of transfersomes, by showing a high fluorescent intensity of 6-coumarin-loaded formulation, compared with conventional liposomes and ethanolic PBS solution of the drug. The results of the DSC study further confirmed that skin treated with transfersomes was more fluidized, compared with untreated skin. Overall, these ex vivo findings indicate that the raloxifene hydrochloride-loaded transfersomal formulation has great potential to deliver the drug through the transdermal route. However, rat skin is very different from human skin. Therefore, the studies should be repeated on human cadaver skin to confirm ex vivo permeation efficacy of raloxifene hydrochloride formulated as transfersomal vesicles. Further investigations are also required on suitable in vivo models to establish the superiority of the developed tranfersomal formulation of raloxifene hydrochloride over existing oral medications of the drug.
This work was supported by the Fundamental Research Grant Scheme of the Ministry of Education, Malaysia (Grant number: 13-091-0332). The authors acknowledge the generous gift of phospholipon® 90G by Lipoid GmbH, Ludwigshafen, Germany.
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You and your pup now have a brand new place to spend some time together.
Dog Daze Cafe has officially opened in Upper Lawrencevile, and welcomes dogs of all breeds and sizes on their outdoor patio and deck area.
The cafe is part of the Big Easy Dog Daze boarding and dog daycare, and also features a full in-house veterinary hospital on site. The indoor/outdoor cafe space serves Cuban-style coffee drinks, like cortadito (espresso with a splash of steamed milk), cafecito (a Cuban coffee shot), and Cafe Bonbon (a specialty drink made with sweetened condensed milk, espresso, and milk foam or heavy whipping cream). You can also get hot chocolate, tea, and coffee from Grounds & Hounds, a Pittsburgh-based organic coffee company that donates 20% of all of their proceeds to animal rescue partners.
Fruit-based shakes called Batidos, made with fresh fruit like mangoes, papayas, and pineapples, and now on the menu, and Dog Daze Cafe will soon feature a food menu with Cuban pastries and empanadas.
The cafe is open from 6:00 a.m. to 2:00 p.m. on Mondays through Fridays.