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Saturday, April 14, 2001
Definitions for bevy
- A group; an assembly or collection.
- A flock of birds, especially quails or larks; also, a herd of roes.
Get the Word of the Day Email
Citations for bevy
In an instant, a bevy of perfumed and coiffed poodles would begin a raucous race from her bedroom to the bottom of the stairs.
Shortt is a more attractive man, and was followed about by bevies of adoring damsels.
Origin of bevy
late Middle English
Bevy comes from Middle English bevey. It perhaps originally signified a drinking company, possibly deriving from Old French beivre, "to drink," from Latin bibere.

subset: commoncrawl


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Free Educational Hearing Seminars in Arizona
My Hearing Centers offers free hearing seminars right here in the Valley of the Sun. At our seminar, you'll learn about hearing loss, the latest hearing aid technology, tinnitus solutions and more.
Our goal is to provide people with all of the information they need to make an educated decision about their hearing health. This event is not intended to sell anything, and is strictly educational in nature. We look forward to answering any questions you might have!


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Here's what I remember reading, watching, etc. in March.
The Night Circus by Erin Morgenstern
Wicked After Midnight by Delilah S. Dawson
Short Fiction:
"Anyway: Angie" by Daniel José Older (Tor.com)
"Ghost Days" by Ken Liu (LightSpeed)
"The Moon" from Grimms' Fairy Tales
"The Crumbs on the Table" from Grimms' Fairy Tales
"The Grave Mound" from Grimms' Fairy Tales
"Death's Messengers" from Grimm's Fairy Tales
Inclusive Reviewing: A Discussion by Samuel R. Delany, L. Timmel Duchamp, Fabio Fernandes, Andrea Hairston, Alex Dally MacFarlane, Sofia Samatar, and Aishwarya Subramanian (Strange Horizons)
Escaping Ethnocentricity by Samuel R. Delany (Strange Horizons)
The Hunger Games (2012)
The Hunger Games: Catching Fire (2013)


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List of Open source software for home use – Part 1
At home, i have been using some of the Open Source Software for my daily productivity.
They are
Mozilla Firefox, the browser
Pidgin, the messenger
Azureus vuze, the bittorrent client
GIMP, the photoshop alternative
Open Office.org, Office productivity
There are tons of software available which we will see one by one in coming blog posts. meanwhile I will discuss some of the most widely and commonly used by me. you can suggest me on what type of software you wanted to write about here which could help others increase their productivity
Mozilla Firefox
As we all have been using Internet Explorer that bundled with Windows OS for the long time. Alternative to it, there are lots of browser available in the internet such as Mozilla Firefox, Mozilla, Opera, Apple Safari etc. Mozilla Firefox is the one that derived from Mozilla project which is huge as a software bundle that contains e-mail applications, browser etc. People find it hard to use it. Hence Mozilla foundation decided to release light weight version of Mozilla and hence Mozilla Firefox born. At present, you can download the latest version of Mozilla Firefox 3.x from Mozilla.com. some of the features are
Tabbed Browsing
Browser Add-ons
many more..
Pidgin, the messenger
There are already lots of messengers for each of the chat providers like Yahoo, MSN, AIM, Google Talk etc. the problem with these is that you have to download them each and then install it and configure it. Instead you can use the Pidgin which has the ability to talk to Yahoo, MSN, AIM, Google Talk and IRC too. Good na… But at present, it doesn't support VOIP. VOIP means the ability to talk to your beloved with no phone cost and this is free because it happens over Internet.
to be continued….


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Genya Rotenberg
Born: August 1, 1930
Lodz, Poland
Genya and her brother, Nahum, were raised by Jewish parents in Lodz, Poland's second-largest city and an industrial center. Before the war, one-third of Lodz's inhabitants were Jewish. Genya's parents placed emphasis on their children's education.
1933-39: In 1939, when I was 9, the Germans occupied Lodz. After that, it was forbidden for "Jews, Gypsies and dogs" to be in public places. Since Jews weren't allowed to go to school, my parents arranged to tutor me secretly at home, but I couldn't keep my mind on my books. One day, the Germans took my grandfather outside and ordered him to do exercises. He couldn't do them, so the Germans took a match and burned off his beard.
1940-45: We fled to Warsaw. Later, I escaped through the ghetto's sewage pipes to a family who hid me. But they were abusive, so I returned to my parents. In 1941 my father was sent to a labor camp for men. Since Mother had disappeared, I dressed as a boy and went with him. In the camp, while the men worked, I'd hide in the bed, holding my breath as officers searched for stragglers. Under the covers, I'd break up my bread ration into meals. I hid this way for weeks until women were brought to the camp.
In 1946, when she was 16, Genya immigrated to Palestine with a group of orphans from the Bergen-Belsen concentration camp. Her father joined her a year later.


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TV On My Terms: Welcome to Must-Flee TVJeffrey Kirkpatrick at . Comments
To riff on a popular Seth Meyers/SNL segment: Really, NBC?
What is going on over there these days? Your new mid-season schedule has elicited more jokes, ire, shock and ridicule from fans and critics in the last few hours than I can recall in some time. I don't get your decision making at all.
Do you really expect Whitney to get better ratings on Wednesday nights when it's obvious the only reason it's been doing decently - by your standards, only - is because it follows The Office? I'm certainly no fan of Whitney, but if something is working, why change it? So rather than hang on to some semblance of desperately-needed momentum, you instead opt to christen the Wednesday 8 p.m. hour "Must-Flee TV" by pairing Whitney with her drunker, sluttier cousin, Chelsea?
To make matters worse, you are removing Community from your schedule altogether to make room for 30 Rock's return?!? Evidently, you are completely unaware of the power of the Communies. They're as crazy as Dan Harmon. They'll cut you.
Do you actually think 30 Rock will fare any better at 8 p.m. than Community has? Really?!? It's essentially the same type of uber-smart/ultra-wacko comedy that 98% of America just doesn't get, yet somehow you expect miraculous results? Why replace one of your most critically acclaimed shows when you have a better chance of getting Chelsea Handler to switch to gin than of getting a hit in that time slot?! Really!
Why are you suddenly popping Geritol and keeping Harry's Law on the schedule when Prime Suspect is at least getting mostly positive reviews and has a slightly better shot of attracting the younger demographic to which you network execs would sell your mothers, not to mention your own souls?
And now suddenly you're riffing off your little brother Bravo by bringing us the Elle Macpherson-hosted reality competition Fashion Star in the hopes that somehow you'll attract a larger average of the American audience? I'm sorry... are you new to our country?
Your only bright light on the entire grid is the vocal competition The Voice, and I think that's mostly because people expect that if they watch long enough Adam Levine will eventually get so excited he'll drop trou. Or Christina Aguilera will eat him. Whichever comes first.
The only thing I learn from your mid-season schedule is that you have no clear direction. You might as well invite in second graders to play "Pin The Tail On The Peacock" with the schedule. They could certainly do no worse. In fact, I think someone needs to let a couple of them loose in the pen with you, and tell them to play live action Angry Birds - because clearly you are not getting the picture.
In the last six weeks, you have made a staggering twenty-five (25!?) script purchases and/or pilot orders and, to be frank, they generally sound like losers. Snoop Dogg in a family comedy? Really!? What is the matter with you NBC? Have you no pride in your content? I may have just answered my own question.
If I may suggest: look to your freewheeling kid sister, USA Network. She knows how to make shows that people want to watch. And she doesn't just offer herself up to every snazzy car that cruises by, either. She takes her time and nurtures shows that fit her vision and in which she has confidence. Imitate her example! Maybe you can be home to the next Suits!
Check out some of the other cable competitors who have made names for themselves developing quality content, such as FX and AMC. A little grit never hurt anybody. Dig deep and bust out some humanity-centric stories around flawed, but identifiable, characters. And, for goodness sake, stop playing it safe and don't be afraid to push the envelope. We'll respect you for it, and you won't be forced to take that morning after walk of shame anymore.
I know you can do this, NBC. Your plumage has been prestigious in the past. It can be again. I want this for you. But mostly for me because I'm sick of the sound of your three-chime tone. It reminds me of a death knell, and I don't like it.
Jeffrey Kirkpatrick is a TV Fanatic Staff Writer. Follow him on Twitter.


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Blackmail is the basis of this crime drama based on a novel by Edgar Wallace. The trouble begins when the leader of a ring of blackmailers becomes an amateur sleuth to outfox Scotland Yard. He spends a lot of time in the Yard getting to know the higher ups. When not schmoozing with the cops, the crook is plotting blackmail schemes. Despite their efforts the Yard has many problems figuring out the leader of the ring.
Add this movie to your queue to receive more information about
The Crimson Circle and we will let you know when it becomes available.


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Seeds of Hope from the Silver Screen
When the lights dim and curtains part, something magical happens. Raptured into stories of joy, sorrow, triumph and disappointment,movies can change us. I remember watching the English Patient many years ago. When the credits rolled up, my legs wouldn't move. I was paralysed by the sheer poetry of the tale. The irony of love - a power that gave life to one man plunges another to his death - gripped me for a long time after.
Movies are often frowned upon for the crass materialism, libertine sexuality, and hedonism they manipulate into our minds. We rightly reject them. Yet not throwing the baby out with the water, I believe many good movies can be watched redemptively. Listening at once to the story, to ourselves and to God - we may leave enlightened and strengthened in our journey of faith.
Listening to the story
While we don't have to swallow all that is fed to us, I find movies enriching when I'm thoughtfully receptive rather than censoriously judgmental. Movies, like the world we live in, reflect the full spectrum of evils of our fallenness. We can hardly expect movies to champion 'good Christian values' ala Sunday School!
In one of my favorites, Gladiator, Maximus (Russel Crowe) is Marcus Aurelius' trusted general who later defies his murderous and tyrant son. His wife and child brutally slain, himself a wounded fugitive, he becomes a slave-warrior in Rome's Coliseum fighting for his life and freedom. Blow by blow, duel after duel, he emerges through the dust as 'Maximus the Beloved'- shadowing even the new Caesar's popularity. The fallen general remains a courageous but compassionate man throughout - albeit as a slave behind bars.
Finally, in the ultimate duel between Emperor and Gladiator, he is sent into the ring already viciously bled. In a clash nearly Messianic in proportion, he vanquishes the evil emperor with his own royal dagger and then breathes his last after crying, 'Free my men! There was a dream that was Rome that must be realized! It is the wish of Marcus Aurelius.'
As he lay lifeless in the dust, the words were spoken: 'Is Rome worth one good man's life? He believed it once; make us believe in it again.'
Movies awaken us to our captive state by highlighting our human condition. They also compel us to cry out, and sometimes give voice to our primeval yearning for God's beauty, truth and goodness. The Eden we have been banished from has not left our breasts. The Pauline trinity of faith, hope and love is so central to many stories precisely because we are image-bearers of God homesick for a better reality.
Good stories draw us to Calvary for our freedom and catapult our imagination to the new heaven and earth.
Listening to ourselves
We are emotional beings. Movies can penetrate our guarded consciousness and help us 'feel aloud' those repressed feelings we keep from breaking through. Seeing ourselves in the characters of a movie helps us explore our unfulfilled emotions, and reclaim our total experience of humanity - rational, physical, emotional and spiritual.
In Contact, Jodie Foster is Dr. Araway, a hardcore physicist whose premise for life is rejecting the scientifically unknowable and pursuing truth through the empirical. But through her persecuted search for extra-terrestrial life, she finally decodes the 'message from the sky' and is internationally backed to make an inter-stellar trip to meet it! Yet upon her return, with no proof in hand, the world mocks her unsubstantiable claims. In that moment she discovers the faith that had brought her thus far was also all that she needed.
Faith was self-justifying. She had no answers for her interrogators, but she needed none. In times of darkness, I find Dr. Araway's journey analogous to my own - fraught with doubt at every turn, sometimes faced with mocking and opposition from those closest to you. The road forward seems to get narrower and lonelier with every step. In times like these, our God-given ability to believe is all we have to put one foot ahead of the other.
With open heart
Awakenings - a heart-wrenching screenplay of Oliver Sacks' book by the same title - defined me in a way nothing else could have. It appeared in that time of my life where, as a pre-university student, I struggled to chalk the best grades for a future I couldn't decide on! Robin Williams plays Dr. Malcolm Sayer, the experimental neurologist who unsuspectingly ends up devoting his life to victims of post-encephalitic coma. In a chance discovery of the then wonder drug L-DOPA, he brings a whole ward of
statues back to life! They have a short but exciting lease at recapturing theirlost decades. They learnt from their patients to celebrate life and to nurture it even in the comatose. But alas, they are doomed to slip, through tormenting tics and fits, into a prison of catatonia again: living zombies, locked within frozen, empty stares.
I wept bitterly. I was choked by the anguish of victim and family. But I was moved most of all by the impassioned life of Dr. Sayer and his staff.
Working through the tragedy, he declares: 'We can hide behind the veil of science,.. but.. reality is we don't know what went wrong anymore than we know what went right. What we do know is as the chemical window closed, another awakening took place. The human spirit is more powerful than any drug and that is what needs to be nourished.' Unbeknownst to me, a vocation was being defined: to embroil myself passionately in lives, walk alongside the afflicted, share in their struggle to keep alive their God-breathed identity. Almost a decade now into my career as a physician, I need to watch Awakenings again - lest I forget the calling to be scientist, healer and friend.
Movies, like all things around us are burning bushes to-be. They can inspire us to travel further in our journeys and reach higher through our dreams. But we need the eyes to see. We need to grow mindful hearts to hear. Cultivate an openness to receive. Like the soil in Jesus' parable of the sower, how we till our hearts determine how well seeds of new growth take root. So, with popcorn in one hand and ticket stub in the other, movies continue to be a companion for life - images that sometimes point us to the Way, the Truth and the Life in ways we least expect.
This article was written for the Kairos magazine - Understanding Truth Through Christian Eyes. Thanks to Siew Li who pushed me to write it, and Alvin Ung who lent his editorial kung-fu to it.


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"Sola Mia Papa" - The Fruit of the Reformation
Here is an excellent review of the historical and scriptural evidence for the papacy and its location in Rome, Italy. Since the reformation, people have attempted to downplay the role of the papacy and the geographical city of Rome as the locus centrali of Christendom. Why? Because if there is no proof that Rome was the original location and seat of the "thing" called a papacy, you can then attempt to dismantle the belief that Christ instituted a physical, visible Church that happened to develop its locus in the center of the ancient world and remain there for 2000 years. (give or take a few decades when the papacy moved to Avignon)
If there is no location for a papacy, then, maybe there was no papacy, and without a papacy..... one can become their own pope to fill the vacuum, which is essentially the ultimate consequence of the reformation. The ultimate fruit of Luther's new construct "Sola scriptura" was the support and development of the doctrine of "Sola Mi Papa" which roughly translates into "I am my own pope."
Yes, I realize it's a bit an oversimplification, but at the end of the day or even at the end of 500 years, this is what you get when you separate the Church from the Scriptures. "Every plowboy can become his own pope" was a common saying in the days after 1517.


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It is a Bleach arcade style fighting game. It has 9 characters from the anime and 6 stages you can battle it out on. Fight in bleach arena and combat with bleach anime characters. Fight against another person at the same keyboard as each of you choose your character and fight. Choose hero and stage scenario and start thrashing the CPU or a human opponent in this cool samurai ninja street figher game, tutorial included.
WASD = Move
F = Block
G = Attack
H = Special


text:
Buy Item $12.99 Retail:
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In StockStock No: WW4025647
Enesco Corporation / 2015 / Gift
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Designed by Karen Hahn in soft touch pastels, for her Foundations Collection of bestselling inspirational figurines. Each is exquisitely detailed, embellished, and trimmed to look lovely from every angle. 5
|Format: Gift
Vendor: Enesco Corporation
|Publication Date: 2015


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Happy Thursday everyone!
I hope you have all had a great week...and I hope you enjoyed the Zombilicious blog hop yesterday if you missed it stop by Terra's blog....now onto today's creation
due to all the fuss about the Skull Appreciation Day coming up (June 4) I was looking threw my stamps for what I have for skulls and found so many Smeared Ink ones that would work! So I busted out my As Death stamp set to play around a bit and begin my skull adventure...and here is what I came up with...it really got me in the skully mood....like I needed it ;)
For my background paper I painted it purple then smeared a black ink pad all over it. I colored my image with colored pencils then used some paint thinner to blend my colors (new technique I found) I stamped and cut out my favorite quote for this set, and lastly I made some super cool paper buttons (using parts of another as death stamp) another technique I picked up today...this one came from Creepy Glowbugg's blog...just punched 5 circles, stamped one, glued and stacked them poked holes and put liquid glass on top.
and there I have my super cool card! now onto create more skull things :) be sure to stop by the forum and join us for skull appreciation Day


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1. It's the end of Spring break. It's a mixed bad. I didn't get to sleep in everyday. In fact, I hardly slept in any days. I did enjoy the stress free mornings of not having to rush everyone around. What a drag. What I won't miss...everything MINE CRAFT. If you don't have a kid between 7 and 12 consider yourself lucky.
2. Captain America: The Winter Soldier...still trying to figure out when we are going to see this movie. So excited about it.
3. The Pirate Fairy. Yes, I totally bought it because Tom Hiddleston is James Hook. However, the movie is adorable. It has all kinds of Peter Pan references and I laughed so much. And just so you know Hook is a COD FISH! He's a meanie butt! I reccommend this movie to anyone.
4. "Life is what happens when your busy making other plans." Do you know who said that? Put your thinking caps on. I love this expression especially because it completely sums up Spring break for us. *
5. I have lost 14 pounds exactly. I am moving more and eating less. That is the big secret. Sorry. When I hit 5pounds, I bought myself a bracelet. Since I went past ten pounds I bought myself lotion and a smelly candle. When I offically lose 15 pounds I plan to buy a tiara! Why not! I am worthy of one.
This is a dress I tried on at Penney's. It is two sizes too big. However because my ribs and chest are...ahem...it didn't fit right. Looks cute tho. I need a Busty Girl Store. Is there one of those?
My lotion and candle
This is when Ryan was finally feeling better. He's still coughing, but otherwise himself.
This one is a throw back...it's ME! I think I was 4. This is my HOTROD!
Another throwback...this is from Jan...it was after Christmas. Showing off our weather. Sorry. Not sorry.
I am linking up with Emmy today for Friday Five!
*John Lennon is the one who said, "Life is what happens when you're busy making other plans."


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An itchy scalp is a common problem that can cause discomfort and embarrassment. A chronically itchy scalp can cause frustration as well. There are several possible causes of itchy scalp ranging from dandruff to the shampoo a person uses. If itching began recently, it may be necessary to check for conditions such as lice or use of a new hair care product, as these may cause itching.
Dandruff is the most common cause of itchy scalp. Dandruff, also known as seborrhea, occurs due to an overproduction of skin cells in the scalp. Most people are familiar with the white flakes of dandruff that fall from the scalp like snowflakes. Dandruff is simply dead skin cells but it can be quite irritating for those who have it in its severe form.
People often believe that only those with a dry scalp suffer from dandruff, but this is not true. People who have an oily scalp suffer from dandruff as well. In fact, their dandruff may be worse due to the heavy build up of oil which can cause the dandruff to adhere to the scalp rather than falling loose.
Dandruff Shampoos
There are several medicated brands of shampoos on the market specifically created for the treatment of dandruff. Although some people claim to have success with dandruff shampoos, others have not. If the dandruff is severe, doesn't improve or worsens with the use of a medicated shampoo, it may be wise to seek the advice of a dermatologist.
Proper Shampooing
The problem may not be the shampoo but the method of shampooing. If all of the shampoo is not rinsed out thoroughly, it can leave a residue that causes the scalp to itch, which only increases the problem rather than alleviating it.
Styling Products
Daily use of styling products such as hair spray or gel can cause the scalp to itch. Such products leave a residue and unless you shampoo daily, the residue will build up as you continue to use the product. It is best to use styling products in moderation.
Brushing can help to loosen and remove dead skin cells. Brushing also helps to keep the scalp and hair in top condition by thoroughly distributing the scalp's natural oils. You don't have to brush 100 strokes every time, but brush often for a healthy scalp and hair.


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- freely available
- re-usable
Int. J. Environ. Res. Public Health 2014, 11(11), 11325-11347; doi:10.3390/ijerph111111325
Abstract: The use of electronic cigarettes (e-cigs) continues to increase worldwide in parallel with accumulating information on their potential toxicity and safety. In this study, an in vitro battery of established assays was used to examine the cytotoxicity, mutagenicity, genotoxicity and inflammatory responses of certain commercial e-cigs and compared to tobacco burning cigarettes, smokeless tobacco (SLT) products and a nicotine replacement therapy (NRT) product. The toxicity evaluation was performed on e-liquids and pad-collected aerosols of e-cigs, pad-collected smoke condensates of tobacco cigarettes and extracts of SLT and NRT products. In all assays, exposures with e-cig liquids and collected aerosols, at the doses tested, showed no significant activity when compared to tobacco burning cigarettes. Results for the e-cigs, with and without nicotine in two evaluated flavor variants, were very similar in all assays, indicating that the presence of nicotine and flavors, at the levels tested, did not induce any cytotoxic, genotoxic or inflammatory effects. The present findings indicate that neither the e-cig liquids and collected aerosols, nor the extracts of the SLT and NRT products produce any meaningful toxic effects in four widely-applied in vitro test systems, in which the conventional cigarette smoke preparations, at comparable exposures, are markedly cytotoxic and genotoxic.
1. Introduction
The typical commercial electronic cigarette (e-cig) is comprised of three major components: a rechargeable or disposable battery, a heating element that generates an inhalable aerosol, and an associated switch or puff-activated circuitry. The circuitry serves to produce the aerosol only during the active puffing cycle, essentially eliminating sidestream emissions from the device during usage. The typical commercial e-cig also contains a liquid solution containing aerosol-forming excipients such as glycerol and/or propylene glycol, flavoring materials and, optionally, nicotine. This solution is usually delivered from a small reservoir by capillary wicking to the heating zone to affect the generation of an aerosol that superficially resembles cigarette smoke in appearance. A great variety of e-cig sizes, configurations, liquid formulations and designs are emerging on a continual basis in this rapidly-developing worldwide marketplace in response to users' evolving personal preferences.
As such, the popularity and sales volume of e-cigs continue to increase worldwide [1,2], and there is a need for a fuller scientific understanding of the potential benefits or risks that e-cigs may have, both to individual users as well as the general smoking and nonsmoking populations. A contemporary framework for assessing the relative risks and benefits to both individuals and populations must necessarily include the characterization of any potential toxicological hazard inherent to a product, and a consideration of those properties against those of other available alternative products. The individual risks to smokers and the harm to populations resulting from conventional cigarette smoking are very well understood and extensively documented [3]; however, the use of alternative products, such as electronic cigarettes, holds potential as an effective approach to advancing the public health amongst adult smokers in the near term [4,5,6].
It is well understood that tobacco cigarettes produce a multitude of harmful and toxic constituents that together induce deleterious health effects including chronic obstructive pulmonary disease (COPD), cardiovascular disease (CVD) and cancer [3]. Conversely, e-cigs do not burn tobacco and do not deliver harmful constituents in the numbers or in nearly the quantities that are found in the smoke of conventional tobacco cigarettes [7]. A recent review reporting on chemical, toxicological (mostly cytotoxicity studies on established cell lines) and clinical studies clearly indicates that e-cig liquids and aerosols contain far less and fewer chemicals, induce significantly less cytotoxicity or adverse effects, and result in considerably reduced cardiovascular and respiratory functional effects than are reported for tobacco cigarettes [8]. In prior investigations of aqueous extract of e-cig aerosols in mammalian fibroblast cells [9] and myocardial cells [10], some moderate cytotoxicity was observed for certain flavoring compounds found in the tested products. However, all such studies, to date, have reported the tested e-cig liquids and aerosols to be markedly less toxic than extracts prepared from the smoke of conventional cigarettes.
This study utilized an in vitro battery of established assays to examine the cytotoxicity (Neutral Red Uptake; NRU), mutagenicity (reverse bacterial mutagenicity test; Ames), genotoxicity (micronucleus formation; MN) and inflammatory effect (cytokine IL-8 release: IL-8) in cells exposed to preparations of various tobacco cigarettes, smokeless tobacco (SLT), nicotine replacement therapy (NRT) products, and commercial electronic cigarettes. Pre-incubation and in-media exposure methods were adopted for e-liquids, aqueous extracts of SLT, NRT products, and pad-collected aerosols from e-cigs as well as pad-collected smoke from tobacco cigarettes.
To date, no systematic toxicity studies have been reported that directly compared e-cig with SLT, NRT, and tobacco cigarettes. Therefore, the present comprehensive multi-endpoint study of a variety of tobacco and nicotine delivery products that have been previously assigned different positions on a risk continuum [11,12] was designed to address the following:
Toxicity of e-cig liquids;
Toxicity of SLT products;
Toxicity of a NRT lozenge product;
Toxicity of pad-collected particulate matter from freshly-generated smoke and aerosols from tobacco cigarettes and e-cigs, respectively.
2. Materials and Methods
2.1. Chemicals and Methods
All chemicals were purchased from Sigma-Aldrich (St. Louis, MO, USA) unless otherwise stated. Recommendations from Cooperation Centre for Scientific Research Relative to Tobacco (CORESTA) were followed for the selection of toxicological assays used in this study [13].
2.2. Product Characterization
Commercial blu e-cigs containing glycerol-based e-liquids, with and without nicotine and two market leader flavors (Classic Tobacco and Magnificent Menthol), were used in this study. For comparative purposes, tobacco burning cigarettes (Kentucky Reference 3R4F, 1R5F and Marlboro Gold), SLT products (Marlboro Snus, Copenhagen Snuff) and a NRT product (Nicorette Lozenge) were also tested. The products used in the study, their general specifications and the level of nicotine measured in test samples are detailed in Table 1.
2.3. E-Liquid Extraction
The e-liquids were extracted from the wicking material located inside the cartomizer for both rechargeable and disposable e-cigs under aseptic conditions. The mouth-end plug of e-cigs was removed and the polyester wicking material was removed with sterilized stainless steel forceps. The wet wicking material was then placed in a sterile 20 mL plastic syringe tipped with a sterile 0.45 µm pore size syringe filter. The e-liquids from the wet wicking material were extracted by pushing the syringe plunger and collected in a sterilized test tube. About 1.0 mL of e-liquid was extracted from each e-cig. Subsequently, the e-liquids were diluted and delivered to the respective test systems.
|Product Class
|Lot #
|Product Label Nicotine (mg)
|Nicotine Measured in Samples (mg/mL)
|Tobacco Cigarettes
|Kentucky Reference Cigarettes
|2.08 *
|1.27 ± 0.10
|Marlboro Gold, 72 mm
|Marlboro Gold
|1.96 ± 0.08
|Electronic Cigarettes (e-cig)
|Control e-cig
|0 ± 0
|blu™ e-cigs Classic Tobacco No Nicotine (Rechargeable)
|blu CT-Ø
|0 ± 0
|blu™ e-cigs Classic Tobacco High Nicotine (Cigalike)
|blu CT-High
|17.93 ± 0.34
|blu™ e-cigs Magnificent Menthol No Nicotine (Rechargeable)
|blu MM-Ø
|0 ± 0
|blu™ e-cigs Magnificent Menthol High Nicotine (Cigalike)
|blu MM-High
|20.43 ± 0.41
|Smokeless Tobacco (SLT)
|Marlboro® Snus
|0.42 ± 0.14
|Copenhagen® Snuff
|0.46 ± 0.03
|Nicotine Replacement Therapy (NRT)
|Nicorette® Lozenge
|0.10 ± 0.03
* Only one sample value.
2.4. Pad-Collected Aerosols for Tobacco Cigarettes and E-Cigs
All tobacco cigarettes were conditioned at 60% relative humidity at 24°C for at least 18 h prior to machine smoking. E-Cig batteries were charged immediately prior to use (rechargeable only). The e-liquid from the control e-cig contained a glycerol/water mixture, without flavors or nicotine, similar to the tested commercial products.
It has been suggested that realistic tobacco cigarette smoking, as well as the e-cig vaping profile, are more intense than the ISO machine smoking profile (35 mL puff volume, 2 s draw, 60 s puff interval). In the absence of a standardized vaping profile for e-cigs and our intention to compare e-cig toxicity with conventional cigarette toxicity, this study employed the Canadian Intense (CI) puffing conditions. Both tobacco and e-cigs were smoked on a VITROCELL® VC10 smoking robot (VITROCELL Systems, Waldkirch, Germany) under the CI puffing conditions: 55 mL puff volume, 2 s draw, 30 s puff interval, and 100% blocked air dilution in the case of tobacco cigarettes [14]. Wet Total Particulate Matter (WTPM) and e-cig aerosols were collected on Cambridge glass fiber filter pads, which capture in excess of 99% of cigarette smoke particulate matter. The filters were extracted into either dimethylsulfoxide (DMSO) for tobacco smoke or phosphate buffered saline (PBS) for e-cig aerosols, both to a final concentration of 40 mg/mL (w/v) and stored at −80 °C prior to analysis.
2.5. Aqueous Extract of Smokeless Tobacco (SLT) and Nicotine Replacement Therapy (NRT) Products
Aqueous extracts from commercially available products obtained at retail outlets were prepared based on previously reported methods [15]. Products were suspended in PBS at 80 mg/mL (Dulbecco's PBS, #14040, +MgCl2 +CaCl2, Gibco, Grand Island, NY, USA). The suspension was incubated at 37 °C for 21–24 h, shaking at 150 rpm on a shaker incubator. The final suspension was then centrifuged at 12,000 g for 10 min to remove particulates, filter sterilized, aliquoted and stored at −80 °C prior to analysis.
2.6. Nicotine Measurement
The level of nicotine in e-liquids and pad-collected smoke and aerosols was quantified using Gas Chromatography-Flame Ionization Detection (GC-FID) instrumentation with a six point calibration utilizing a nicotine standard concentration range [16]. The method precision "variability" was 0.3%–0.7%, method accuracy was 97.4%–98.6%, method LOD was 0.0524 mg/g and method LOQ was 0.1040 mg/g.
2.7. Cell Culture
Human lung epithelial carcinoma cells A549 (ATCC# CCL-185) were plated in 96-well plates in 200 μL per well of complete medium (Ham's F-12K medium with 10% heat-inactivated fetal bovine serum (FBS), 2 mM L-glutamine and 0.01 mg/mL gentamicin) at a seeding density of 75,000 cells/mL and allowed to attach and grow overnight at 37 °C in an atmosphere of 5% CO2 prior to exposures.
Chinese hamster ovary cells CHO-K1 (ATCC# CCL-61) were seeded in 96-well plates at 2500 cells/well in complete growth medium (Ham's F-12K medium with 10% FBS and 0.01 mg/mL gentamicin) and allowed to attach and grow overnight (37 °C, 5% CO2) prior to exposures.
2.8. Cell Treatment
Cells were treated for approximately 24 h with increasing levels of e-liquids, aqueous extracts, WTPM or pad-collected e-cig aerosols in fresh complete cell media prior to any toxicological evaluations. The cellular treatment dose range used for e-cigs (e-liquids and pad-collected aerosols) was 0–20 mg/mL and for tobacco cigarettes 0–0.5 mg/mL. The doses utilized for tobacco burning cigarette samples were based on dose range finding experiments that demonstrated high cytotoxicity occurring at or above 0.5 mg/mL. Solubility limitations of e-liquids were observed at doses beyond 20 mg/mL; therefore, doses above 20 mg/mL were not utilized in this study. The cellular treatment dose range used for SLT and NRT samples was 0–27 mg/mL, which incorporated the dose range previously utilized for smokeless tobacco products [15]. The toxicological responses were normalized with their respective vehicle controls, either DMSO for tobacco burning cigarettes or culture medium for all other samples.
2.9. Cytotoxicity and IL-8 Assay
Following cellular treatment with samples, a 200 µL aliquot of the exposure medium was taken from each well and processed for IL-8 analysis, and the cells adhered to the wells were processed for the cytotoxicity assay.
Cytotoxicity was measured in A549 cells by the NRU method [17,18]. In brief, the cell treatment medium was replaced with 1.5% (v/v) neutral red dye in fresh serum-free complete medium and incubated for 2.5 h. The plates were then washed and the cell-incorporated neutral red dye was released and quantified by measuring absorbance at 540 nm on an Infinite M200 Pro spectrophotometer (TECAN, Morrisville, NC, USA). The EC50 for NRU (mg/mL) was calculated and compared using GraphPad Prism v. 5.02 (two tailed; for comparisons, statistical significance @ p < 0.05).
The release of cytokine IL-8 was quantified [19] in cellular medium with an ELISA detection kit (Abazyme, Inc., MA, USA) by measuring absorbance at 450 on an Infinite M200 Pro spectrophotometer (TECAN). Results for the IL-8 release are reported as % vehicle control and compared using GraphPad Prism v. 5.02 (two tailed; for comparisons, statistical significance @ p < 0.05).
2.10. Bacterial Mutagenesis Assay
Ames reverse bacterial mutagenicity assays were conducted with the pre-incubation modification [20,21] in strains TA98 and TA100 with S9 activation. Aroclor-induced Sprague-Dawley rat liver S9 post-mitochondrial supernatant (Moltox, Inc., Boone, NC, USA), in 0.154 M KCl, was used for the S9-cocktail (0.1 M phosphate buffer, pH 7.4; 8 mM MgCl2, 33 mM KCl, 5 mM glucose-6-phosphate (G-6-P), 4 mM nicotinamide adenine diphosphate (NADP), 5% (v/v) S9-fraction).
The e-cig and SLT/NRT sample dose ranges utilized for the Ames reverse bacterial mutagenicity assay were 0–48 mg/mL and 0–3.2 mg/mL, respectively, due to the sample solubility and sample volume limits of the Ames exposure system. This SLT/NRT dose range is similar to the dose range previously reported for smokeless tobacco product extracts tested in the Ames assay [15]. The control sample for e-cig liquids, e-cig pad-collected aerosols, SLTs and NRT was PBS and the control sample for WTPM from tobacco burning cigarettes was DMSO.
Exposures of Salmonella tester strains were performed as follows: 100 μL of an overnight culture, 500 μL of the S9-mix, plus 25 µL sample were combined in a sterile tube, capped and shaken at 250 rpm for 20 min at 37 °C prior to the addition of 2.5 mL of histidine/biotin top agar and plated onto minimal glucose agar plates. Revertant colonies were counted after 48 hours of incubation at 37 °C. All exposures were conducted in triplicate in a minimum of two independent experiments. All colonies were counted with an automated colony counter, Synbiosis ProtoCOL3 (Frederick, MD, USA). Activity reported as revertants per mg was calculated from the linear portion of the dose response curve and compared using GraphPad Prism v. 5.02 (slope analysis, two tailed; for comparisons, statistical significance @ p < 0.05).
2.11. Micronucleus Assay
The in vitro MN assay was performed in CHO-K1cells as previously described [22], utilizing the MN HitKit-K11-0001-1 (Thermo Fisher Scientific, Pittsburgh, PA, USA). Cells were exposed to samples in the absence of S9 for 20 ± 2 h followed by treatment with the cytokinesis blocking agent, cytochalasin B. Cell viability was determined by the cytokinesis-block proliferation index (CBPI). MN frequency (%MN) was determined on a Cellomics® ArrayScan® VTi (Pittsburg, PA, USA) using the Micronucleus Bioapplication, V.4 software. Activity is reported as % Control and compared using GraphPad Prism v. 5.02 (two tailed; for comparisons, statistical significance @ p < 0.05).
3. Results and Discussion
This in vitro comparative toxicological study was designed to evaluate e-liquids extracted from commercial e-cig products and pad-collected aerosols and smoke delivered by laboratory machine smoking of e-cigs and combustible tobacco cigarettes. Although several in vitro tests are routinely used and accepted by regulatory authorities, there are inherent limitations which affect the usefulness of the assays to predict toxicity potential of a substance in vivo, and especially in humans. Given that no single in vitro test can fully replicate in vivo test results, a battery of in vitro tests with a high concordance to in vivo models has the potential to establish a weight-of-evidence approach for evaluating the biological impact associated with e-cigs. In addition, the in vitro toxicological analysis of appropriate comparative product types further provides context for results that otherwise may be misleading or lack relevancy to the determination of biological activity.
A battery of toxicological endpoints that have been amply demonstrated to appropriately characterize the responses to cigarette smoke preparations was selected to provide points of reference in terms of the cytotoxicity, mutagenicity, genotoxicity, and inflammatory responses elicited by the tested e-cigs.
Genotoxicity (Ames and MN formation) testing is an important part of the hazard assessment of a chemical for regulatory purposes and has been demonstrated to have very high concordance with rodent carcinogenicity or in vivo genotoxicity when tested together [23]. Additionally, inadequate resolution of inflammation and uncontrolled inflammatory reactions can evoke a state of chronic inflammation, which is a common etiologic factor for various human respiratory lesions, including cancer [24,25].
A list of all products evaluated in this study is detailed in Table 1. This study utilized the CI smoking profile to smoke both e-cigs as well as tobacco cigarettes. As a basis for comparative analysis, this study evaluated the toxicological impact of traditional tobacco products, commercial Marlboro Gold and two Kentucky reference cigarettes, four blu e-cigs, Copenhagen Snuff, Marlboro Snus, and Nicorette Lozenge. In addition to comparing products in different classes (tobacco cigarette, e-cig, SLT and NRT), the toxicological impact of nicotine using e-cigs with and without nicotine was also investigated.
3.1. E-Liquids, Smokeless Tobaccos (SLTs) and Nicotine Replacement Therapy (NRT): Cytotoxicity
The toxicological response of e-liquids and aqueous extracts of SLT and NRT products was evaluated in A549 cells and is shown in Figure 1A–E. No cytotoxicity was observed for any of the e-liquids, as well as for all SLT and NRT products tested up to their respective highest sample doses (Figure 1A).
Similarly, Bahl et al. reported little or no cytotoxicity for most of the 35 commercial refill liquids for e-cigs previously tested in human lung fibroblast cells [26]. This study utilized two blu e-cig market leading flavors, classic tobacco and magnificent menthol. To compare the dose levels, the maximum e-liquid dose utilized by Bahl et al. [26] was 12.6 mg/mL, equivalent to the highest dose of 1% (v/v), assuming a 100 µL MTT assay volume and an e-liquid density of about 1.22 g/mL. Additionally, Bahl et al. [26] also reported toxicity to adjacent wells at 10% (v/v) e-liquid dilutions, equivalent to approximately 126 mg/mL; however, the present study did not reveal any vapor toxicity from e-liquids at doses as high as 27 mg/mL to adjacent wells. The observed cytotoxicity in adjacent wells [26] may be a result of higher e-liquid concentrations used by Bahl et al. or the volatility of specific e-liquid ingredients or flavors released while incubating at 37 ºC, or the possibility of differential susceptibility of the lung fibroblasts used by Bahl et al. and the A549 cells used in this study.
At the lower doses of e-liquids utilized in this study, an increase in cell viability was observed (Figure 1A) which was also evident with cells treated with lower doses of pure nicotine (Figure 2A). This increase in cellular viability was primarily associated with higher cellular proliferation and cellular protection mediated by the low level of nicotine exposure [27]. Therefore, there may be an association between the lower nicotine present in e-cig liquids and increased cellular viability, thus cellular protection.
3.2. E-Liquids, Smokeless Tobaccos (SLTs) and Nicotine Replacement Therapy (NRT): Mutagenicity
The Ames test, also known as the bacterial reverse mutation assay, is widely used for the determination of a compound's ability to induce mutations and has been shown to have a high predictive value with rodent carcinogenicity tests [28].
The activity of e-liquids, SLT and NRT extracts in the Ames assay is shown in Figure 1B. The control e-cig sample containing water/glycerol and the PBS control sample (SLT and NRT) did not induce any revertants above baseline and were within the variability range of this assay. No significant induction in the activity over respective controls was observed for all e-liquids and extracts (Figure 1B). The level of e-liquids as high as 15-fold higher than SLTs and NRT extracts did not induce any activity. No evidence of cytotoxicity, as determined by the background bacterial lawn, was observed for all e-liquid, SLT and NRT samples at all doses tested.
3.3. E-Liquids, Smokeless Tobaccos (SLTs) and Nicotine Replacement Therapy (NRT): Genotoxicity
The results of in vitro MN formation assay are shown in Figure 1C,D). The MN assay conducted in CHO-K1 cells, identifies clastogenic and aneugenic chemicals which essentially cause a DNA-damaging event that leads to the disruption or breakage of chromosomes and ultimately results in sections of the chromosome being deleted, added, or rearranged upon cell division (mitosis) [29].
A sample dose range which does not produce cytotoxicity of more than 55 ± 5% (compared to control) was utilized in the MN formation assay [24]. The control e-cig, e-liquids, SLT and NRT extracts did not induce any significant cytotoxicity at all dose levels tested since cell-viability remained around 100% of control at all concentrations (Figure 1D). No significant induction in the MN formation over respective controls was observed for all e-liquids and SLT and NRT extracts (Figure 1C).
3.4. E-Liquids, Smokeless Tobaccos (SLTs) and Nicotine Replacement Therapy (NRT): Inflammation
Airway epithelial cells are the first line of defense in the airways to respond to any external stimuli and secrete specific chemo-attractants and pro-inflammatory cytokines, for example IL-8, monocyte chemotactic protein-1, and IL-1ß, in order to activate the secondary response for neutrophils and macrophage infiltration [30,31]. Instead of measuring downstream acute or chronic phase inflammation specific cytokines, this study measured an upstream pro-inflammatory cytokine, IL-8.
The effects of 24 h exposures of e-liquids and SLT and NRT extracts on IL-8 release in A549 cells are shown in Figure 1E. The control samples for e-cig, SLTs and NRT did not induce any significant IL-8 release. No significant IL-8 release was observed for most of the products, with the exception of the blu MM-Ø, blu MM-High and blu CT-Ø treatments which resulted in higher IL-8 release only at extremely high doses of 6.9–13.8 mg/mL. When compared to the IL-8 release induced by conventional cigarette samples (Figure 3E), any significant IL-8 release as a result of the blu MM e-liquid treatments occurred at doses approximately 42-fold higher than the conventional tobacco cigarettes. It has been suggested that the toxicity of e-liquids may change when the same e-liquids are heated to produce the inhaled aerosol [26]. The evaluation of e-cig aerosol toxicity is essential since the intended use of e-cigarettes is through aerosol inhalation. Additionally, it is proposed that different e-liquid formulation ingredients may evaporate differently, leading to changes in concentrations in the generated aerosols as well as the possibility that components may undergo modification when subjected to the heat used to generate the aerosol; therefore, the final composition of the aerosol may be different when compared to the e-liquid [9]. In the light of that, the purpose of the study was to also characterize the aerosol toxicity as delivered by heating the e-liquid.
3.5. E-Cigarettes and Conventional Cigarettes
In order to study the comparative toxicities of the e-cig aerosols and tobacco smoke, all products were smoked by the standardized CI profile with the aerosols or smoke from each product being collected on a pad as described in the Experimental Section. The pad-collected tobacco smoke matter was extracted in DMSO because it has been widely applied as a vehicle for in vitro assays of test articles of limited water solubility due to its excellent solvent properties for both polar and non-polar compounds and its moderate toxicity to test organisms [32,33]. The reasoning for the concentration ranges utilized in this study was to limit the level of DMSO in order to avoid any solvent specific effects on the assays [32]. The toxicological responses of the pad-collected e-cig aerosols and cigarette smoke are shown in Figure 3A–E.
3.6. E-Cigarettes and Conventional Cigarettes: Cytotoxicity
The cytotoxicity of e-cig pad-collected aerosol is shown in Figure 3A. The e-cig pad-collected aerosol was not cytotoxic at all tested levels. For comparative purposes, different levels of WTPM from tobacco cigarettes were also tested. A dose-dependent increase in cell death was observed for 3R4F, 1R5F and Marlboro Gold cigarettes with up to 90% cell death at the 0.5 mg/mL maximum applied dose. The WTPM mediated cytotoxicity results are in agreement with previously reported studies [12,34]. It was not possible to quantify the comparative cytotoxicity in terms of traditional EC50 values (a dose which induces 50% cell death) since no cell death was observed at any concentration used for all e-cig samples (Table 2 and Figure 3A).
There was an observed increase in cellular viability in cells treated with e-liquids (Figure 1A) and lower doses of pure nicotine (Figure 2A). Also treatment with e-cig aerosols resulted in a similar increase in cellular viability (Figure 3A). This observed increase in cellular viability for pure nicotine and both e-cig liquids and pad-collected aerosols could be related to nicotine's effect on cellular proliferation and protection [27].
|Pad-Collected Matter: Smoke and Aerosols
|NRU EC50 (mg/mL)
|Marlboro Gold
|Control e-cig
|blu CT-Ø
|blu CT-High
|blu MM- Ø
|blu MM-High
Similar findings were reported for aqueous extracts of aerosols from various commercial e-cigs studied in cultured mammalian fibroblast and myocardial cells [9,10]. Both studies also reported that some aqueous extracts of e-cig aerosols showed cytotoxicity related to flavors, but were significantly less cytotoxic than cigarette smoke extracts. This study evaluated two flavored e-cigs, with and without nicotine (Table 1).
With e-liquids and pad-collected aerosols, no nicotine or flavor specific cytotoxic effects were evident with e-cigs without nicotine, blu MM-Ø, and blu CT-Ø, and with nicotine as high as 24 mg/mL, blu MM-High and blu CT-High (Figure 1A and Figure 3A). The cytotoxicity and inflammatory response of L-nicotine in this cell culture system (Figure 2) was also tested. No cytotoxicity and inflammation (IL-8 release) were observed below 2.5 mg/mL and 1.0 mg/mL nicotine, respectively (Figure 2A,B). The highest level of nicotine in e-liquids tested was about 0.5 mg/mL (Table 1), which was below the concentrations of L-nicotine required to induce cytotoxicity and IL-8 release in this experimental method. In addition, the WTPM from tobacco cigarettes at 0.5 mg/mL was extremely cytotoxic (Figure 3A), corresponding to a nicotine concentration of approximately 0.04 mg/mL, which was well below nicotine mediated toxic levels, demonstrating that WTPM induced cytotoxicity was not mediated by nicotine.
3.7. E-Cigarettes and Conventional Cigarettes: Mutagenicity
The mutagenicity of pad-collected smoke and aerosols of tobacco cigarettes and e-cigs, respectively, is shown in Figure 3B. No activity was observed for control e-cig samples in the Ames assay. The specific activity for all tobacco cigarettes was in the range of 1600–1850 and 500–750 revertants/mg WTPM for TA98 and TA100, respectively (Figure 3B). Historically, WTPM prepared under the same smoking conditions has been shown to have similar levels of specific activity (revertants/mg) [35].
No increase in Ames activity was observed for any e-cigs used in this study and the revertants/mg was extremely low and within assay background measurements (< 2 revertants/mg). It was not possible to quantify the specific activities for e-cig aerosols since no increase in revertant counts was observed with increasing doses for all tested e-cig samples (Figure 3B).
3.8. E-Cigarettes and Conventional Cigarettes: Genotoxicity
The cell viability and clastogenic effects of WTPM and e-cig pad-collected aerosols are presented in Figure 3C,D. The pad-collected aerosol from the control e-cig containing glycerol/water and the solvent (DMSO) control did not induce any MN formation. A significant dose-dependent WTPM mediated induction in MN formation was observed with all tobacco cigarettes (3R4F, 1R5F and Marlboro Gold). No increase in the MN formation was observed for pad-collected aerosols from e-cigs at all doses tested (Figure 3C). The maximum induction in the MN formation with tobacco cigarettes was about 2.5 to 3-fold over background at about 0.12 mg/mL WTPM. A sharp decrease in the WTPM-induced MN formation was observed at dose levels higher than 0.12 mg/mL WTPM due to the decrease in cell viability (Figure 3D). Similar MN findings have been reported [31]. The dose at which tobacco cigarette WTPM induced maximum MN formation is approximately 166-fold lower than the maximum e-cig pad-collected aerosol dose (20 mg/mL) tested, which had no observed induced MN formation.
3.9. E-Cigarettes and Conventional Cigarettes: Inflammation
The inflammatory responses, as measured by IL-8 release from cells treated with tobacco WTPM and e-cig aerosols are presented in Figure 3E. No IL-8 release was observed for control samples. The pad-collected aerosols from all e-cigs did not induce any IL-8 release at all doses tested (Figure 3E). In contrast, a WTPM mediated dose-dependent increase in IL-8 release was observed for all tobacco cigarettes. A sharp decrease in the IL-8 level at WTPM levels over 0.3 mg/mL was noticed (data not shown) since significant cytotoxicity was observed at those doses (Figure 3A).
The WTPM dose at which a significant IL-8 release was observed (0.15 mg/mL) was about 20-fold lower than the maximum e-cig pad-collected aerosol tested dose (3.2 mg/mL), at which no inflammatory effect was observed. The release of IL-8 in cultured cells by different cigarette smoke preparations has been reported [36] and this inflammatory response has been associated with oxidative stress due to the free radicals present in cigarette smoke [37].
At the lower doses of e-cig pad-collected aerosols utilized in this study, compared to the control, a lower release of IL-8 was observed (Figure 3E). That effect was also evident in cells treated with lower doses of pure nicotine (Figure 2B). This phenomenon of a lower release of an inflammatory cytokine (IL-8) is associated with the anti-inflammatory effects of nicotine [38]. There may be an association between the lower nicotine present in e-cig pad-collected aerosols and anti-inflammatory effects.
3.10. Nicotine Equivalence
Assessment of in vitro responses observed in this study was also calculated based on the level of nicotine present in the test samples. The level of nicotine concentrations measured in the prepared samples are shown in Table 1 but varied depending on sample volume and toxicity endpoint measured in this study. The upper limit of nicotine measured in tobacco cigarette WTPM was about 0.025 mg/mL, e-cig pad-collected aerosol was about 0.223 mg/mL and e-liquid was about 0.522 mg/mL. Thus, the nicotine concentration was about 10 to 20-fold higher in e-cig samples as compared to conventional cigarette samples. No nicotine mediated cellular toxicity was observed at 2.5 mg nicotine/mL (Figure 2A). At low doses up to 2.0 mg/mL, L-nicotine in fact increased the cellular proliferation as indicated by the higher cell viability than the control (Figure 2A) indicating a cellular protective response [27] as well as lower release of IL-8 in the media than control (Figure 2B) suggesting the anti-inflammatory properties of nicotine [38].
The average human exposure to nicotine on a 10-puff basis from a typical tobacco cigarette (tar 11.4 ± 0.1 mg/cig) is about 2.0 mg and from an e-cig product (labeled 24 mg nicotine) is about 0.23 mg under the similar CI smoking profile used for this study [39]. Therefore, it was evident that the nicotine levels in e-cig treatments were well below the toxic level of L-nicotine and represent comparative nicotine levels present in the tested e-cig and conventional cigarette samples. In addition, based on literature on the beneficial role of nicotine, relative to e-liquids and pad-collected aerosols used in this study and pure nicotine effects, there may be an association between lower levels of nicotine present in samples used in this study and cellular protection as well as anti-inflammatory effects [27,38].
Under the experimental conditions used to evaluate traditional tobacco burning cigarettes, e-cigs did not produce any meaningful toxic effects as measured by four in vitro endpoints. These results demonstrate the potential for e-cigs to significantly reduce the toxicological impact when compared to traditional tobacco burning cigarettes.
3.11. Comparable Human Exposure: Conventional and E-Cig
The comparative human exposure to tobacco cigarette smoke and e-cig aerosol is important in order to assess e-cig mediated reduced exposure and reduced harm. It has been reported that a smoker with one pack-a-day tobacco cigarette consumption inhales on average about 261 mg/m3 cigarette tar [40], equivalent to about 271 µg/mL or 0.271 mg/mL [40]. Internal study indicated the range of e-cig aerosol delivery to be in the range of 0.5–1.5 mg/puff under Canadian Intense conditions (39). Assuming similar e-cig use as a conventional tobacco cigarette (200 puffs), the upper limit of human exposure to e-cig aerosol is approximately 300 mg or approximately 250 µg/mL or 0.25 mg/mL. The range of e-cig pad-collected aerosol used in the present study was 3.2–20 mg/mL. No adverse toxicological events were observed in this study even when the e-cig aerosol levels used were about 12–78 times higher than expected with normal e-cig use.
3.12. Contribution of Findings to Tobacco Harm Reduction and E-Cigs
The concept of Tobacco Harm Reduction (THR) has been advanced as a pragmatic approach to achieving reductions in the adverse public health impacts of cigarette smoking in the near term; in parallel with social, educational, and regulatory strategies intended to reduce and discourage cigarette smoking, particularly among adolescents [4,41,42,43].
The use of non-combustible SLT products such as Swedish-style snus and traditional moist snuff are demonstrably on the order of 98% less harmful in terms of risks for lung cancer, COPD, CVD, and other cancers, (including oral cancers) as compared to cigarette smoking [11,41,44,45].
Similarly, NRT products such as dermal patches and chewing gums have been shown to be safe and efficacious in clinically-managed and over-the-counter consumer usage. Therapeutic nicotine vapor inhaler devices and aerosol sprays for nasal and oral use have to date demonstrated similar benefits and low risks in facilitating smoking cessation [46]. The efficacy of such conventional NRT cessation aids has, however, proven in practice to fall short (~7% cessation success) of what is needed by a considerable number of smokers [47]. These smokers consistently report that taste, sensory and behavioral components experienced in the act of cigarette smoking are substantial motivators of the smoking behavior and may well comprise a population that could achieve substantially higher success in quitting through use of products that mimic the behavior element of smoking as well as the delivery of nicotine. Therefore, the use of e-cigs that provide some of the taste, sensory and behavioral components of conventional tobacco cigarette smoking may hold substantial promise in defining the potential benefits of the THR paradigm [48].
Despite the absence of long-term epidemiologic data on any chronic disease risk, a growing body of recent literature is consistent with an expectation that the use of e-cigs is unlikely to raise serious health concerns [49,50], particularly in comparison to those that result from the smoking of conventional cigarettes [7]. This conclusion is currently based, and further supported by this study and on a growing number of independent analyses of commercially-available e-cig liquids and product aerosols from markets around the world, that have consistently reported very low or undetectable levels of most tobacco smoke constituents that are known or suspected to play a prominent role in the etiology of serious tobacco-related diseases. [7,51,52,53,54,55,56,57,58,59].
There are various essential and contributory components to the THR framework, including product use and behavior, taste, nicotine delivery, product chemistry, toxicity and clinical safety. This study shows that neither the e-cig liquids nor collected aerosols produced any meaningful toxic effects in widely used in vitro test systems. These findings add additional value to the increasing body of scientific weight-of-evidence supporting the potential inclusion of e-cigs into THR paradigm.
4. Conclusions
In summary, this comparative in vitro toxicity study of e-cigs, SLT, NRT and tobacco cigarette products demonstrates the following:
- (1)
E-cigs vs. Tobacco WTPM: At doses up to approximately 100-fold higher than typical cigarette smoke exposures, blu e-cig liquids and pad-collected aerosols had no-to-extremely low in vitro activity (NRU, Ames, MN and IL-8) when compared to WTPM from tobacco burning cigarettes. WTPM activity was up to approximately 6,000 times higher than e-cigs.
- (2)
E-cigs vs. SLT and NRT: blu e-cig liquids demonstrated similar no-to-extremely low in vitro activity as aqueous extracts from a commercial nicotine lozenge (NRT) and commercial SLT products (snus and snuff).
- (3)
Effect of Nicotine: In vitro activities (NRU, Ames, MN and IL-8) measured for blu e-cig exposures, with and without nicotine, were similar for all sample types, indicating that the presence of nicotine, at the levels tested, did not contribute to any toxicological effects, confirmed by the lack of cytotoxicity and inflammation response of L-nicotine at comparative levels.
- (4)
Effect of Flavors: In vitro activities (NRU, Ames and MN) for the commercial blu e-cigs were indistinguishable from control (glycerol/water); indicating these flavors (CT and MM), at the levels tested, had no detectable impact on the cytotoxicity and genotoxicity endpoints utilized in this study. There was some observed IL-8 induction for some e-liquids, albeit at the highest doses tested.
- (5)
Liquid vs. Pad-Collected Aerosol: In vitro results for blu e-cigs, in this study, were similar for the different exposure methods (e-liquids and pad-collected aerosol); demonstrating no detectable impact on the in vitro toxicological responses when the e-liquids were aerosolized.
- (6)
SLT vs. Tobacco WTPM: SLT extracts added to the test systems at levels up to 54-fold higher than those used for Tobacco-WTPM generated by burning cigarettes was markedly less cytotoxic and mutagenic, and evoked a significantly lower IL-8 response at all dose levels evaluated. The effects of the SLT extracts in the assays were statistically indistinguishable from those of the e-cig and NRT preparations.
With respect to the study, lack of any meaningful in vitro acute toxicity for blu e-cigs and extremely low levels of chemical constituents measured in blu [39] and the analysis of known reduced risk products such as NRT and SLT has the potential to demonstrate a decreased human health impact as compared to conventional tobacco-burning cigarettes.
The authors would like to thank Edward Robinson, Dan J. Heck, Sherwin Yan and Carl D'Ruiz for critical review of the manuscript and Mark Sackfield for technical assistance in sample preparation for toxicological testing.
Author Contributions
Manoj Misra: Participated in study design and execution of the study, conducted cytotoxicity (NRU) and IL-8 release measurements (e-liquids and pad-collected matter from e-cigs and tobacco cigarettes, aqueous extracts of SLTs and NRT) and related data collection and interpretation, and constructed manuscript as principal writer.
Robert D. Leverette: Participated in study design and execution of the study, coordinated sample preparation (e-liquids, pad-collected aerosols and smoke condensates, SLT and NRT aqueous extracts), conducted mutagenesis Ames test measurements (e-liquids and pad-collected matter from e-cigs and tobacco cigarettes, aqueous extracts of SLTs and NRT) and related data collection, compilation and interpretation and presentation of data (graphs and tables).
Bethany T. Cooper: Conducted MN formation measurements (e-liquids and pad-collected matter from e-cigs and tobacco cigarettes, aqueous extracts of SLTs and NRT) and related data collection.
Melanee B. Bennett: Maintained and provided cultured cells, A549 and CHO cells, for the study and assisted in conducting cytotoxicity (NRU) measurements (e-liquids and pad-collected matter from e-cigs and tobacco cigarettes, aqueous extracts of SLTs and NRT).
Steven E. Brown: Participated in study design and critical review of the manuscript.
Conflicts of Interest
The authors are Lorillard Tobacco Company employees and declare no conflict of interest with respect to the research, authorship, and/or publication of this article.
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© 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).


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There's no easy way of retrieving the Managed Path for a Site Collection (SPSite) through the SharePoint 2010 object model.
Therefore, I wrote this method, to retrieve it for you. It should work with both wildcard inclusion and explicit inclusion Managed Paths, including nested managed paths (i.e. /sites/, /sites/projects/, /sites/depts/, etc.).
private Microsoft.SharePoint.Administration.SPPrefix GetManagedPath(SPSite site) { if (site == null) throw new ArgumentNullException("site"); string relativeUrl = site.ServerRelativeUrl; if (relativeUrl.Length == 0) throw new Exception("Invalid ServerRelativeUrl for this SPSite."); foreach (Microsoft.SharePoint.Administration.SPPrefix prefix in site.WebApplication.Prefixes) { switch (prefix.PrefixType) { case Microsoft.SharePoint.Administration.SPPrefixType.ExplicitInclusion: if (relativeUrl == "/" + prefix.Name || relativeURL == prefix.Name) return prefix; break; case Microsoft.SharePoint.Administration.SPPrefixType.WildcardInclusion: // WildCard Inclusion prefixes can be nested (i.e. /sites/ , /sites/projects/, /sites/depts/). // Thus, we remove the site collection's name and compare against the whole string, in stead of using .StartsWith() if (relativeUrl.Substring(0, relativeUrl.LastIndexOf("/")) == "/" + prefix.Name) return prefix; break; } } // A prefix should've been returned by now. throw new Exception("No SPPrefix (Managed Path) found for this SPSite"); }
The method returns an SPPrefix class, which contains the Name and PrefixType properties of the Managed Path. If the Site Collection is located at the root of the Web Application, the SPPrefix.Name property will be empty and of the type Explicit Inclusion.


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Request a Performance by the PGMC
So, you have an event and need musicians?
The Providence Gay Men's Chorus can fulfill your music needs!
Many of your questions can be answered by reviewing the Performance Request form.
Please make your request a minimum of 60 days (2 months) in advance.
Click here to download the request form
Submit the Performance Request form by mail to:
Or, submit electronically by emailing the completed form to:


text:
KEN DOUGALL discovered first hand how important it is to find the right nursery for your child.
His first experience of daycare saw his baby daughter twice go unfed for a full day, neglected by the staff to whom he had entrusted his only child.
Ken's daughter, Robyn, was six months old when she started at a nursery in Edinburgh.
Ken, 58, recalled: "When we first saw the nursery it seemed fine.
"She was only there for a few weeks but in that time I went there and found twice they hadn't given her any food.
"At that age you bring the food in and the food hadn't been touched."
Learning that his daughter had gone unfed was upsetting enough but a further incident proved to be the final straw.
Ken said: "I went to pick her up one day and I found she had a mark on her face. It was the shape of an ice cream tub and she'd been left to fall asleep face down in it.
"Of course, they made up all sorts of nonsense that it wasn't the case and that it was a pillow that had caused the mark, but you don't get a distinct mark like that from a pillow so we took her out pretty quick."
The distress he experienced led Ken to set up a website dedicated to helping parents find the right nursery for their child – a place where they can leave them safe in the knowledge they'll be fed, cared for and stimulated.
It's the kind of information Ken wished he had when he was choosing a nursery for Robyn.
He said: "It was difficult to know if the nursery was any good in the first place. There were things that seemed a bit strange. There was an atmosphere you discovered after a few weeks and thought 'I'm not sure about this'.
"The duty of care wasn't there."
Just weeks after they withdrew Robyn, who is now 14, Ken started up scottishnurseries.com, which has grown to become a comprehensive directory of nurseries, enabling parents to find information and images of all the daycare services in their area.
He said: "There are some horror stories, but there are so many great nurseries as well. This site means parents can get an overview."
While the vast majority of nurseries in Scotland work to high standards of care, there have been some worrying cases in recent years that suggest there is still some way to go.
The Channel 4 Dispatches documentary last week, How Safe Is Your Child's Nursery? reported on the death of toddler Rhiya Malin in 2007. The two-year-old died after becoming trapped in a wooden playhouse in the garden of an Essex nursery.
And last summer, a five-year-old boy was left behind by a Greenock nursery during a day trip to Largs.
Although such horror stories are extremely worrying for parents, thankfully they are rare.
Glasgow-based architect Pam Heap has a four-year-old daughter, Chloe, and a son, Will, who is one.
She found nursery worked well for her oldest child, but she removed her baby son.
Pam, 38, said: "All the staff we'd built up a rapport with when they were apprentices had become qualified nursery nurses so the nursery didn't keep them on. They then hired new girls and they just didn't have that same rapport with us. When we read the report of what my son had done that day it was like reading a script and sometimes you'd get the feeling they didn't actually know what he'd done.
"You know it's not going to be 100 per cent perfect, but he was sick all the time and he kept picking up conjunctivitis.
"One day I walked into the room and all the kids were sitting there with red eyes and the staff said, 'Well, their parents just bring them'.
"I'm self-employed and I need to be in the office every day but I was having so much time off it just wasn't going to work.
"I decided to nanny share with a friend. We found someone through the Tinies agency and it's worked out much better."
The different experiences of parents only serves to emphasise the importance of making the right decision around daycare.
Where problems do arise and are not addressed, families are encouraged to contact the Care Inspectorate, the organisation responsible for regulating and inspecting care services in Scotland.
A spokesman said: "We inspect 15,000 care services in Scotland and the majority perform well with good or excellent grades. In most cases, our inspectors arrive unannounced and grade services on key themes, which include the quality of care offered.
If parents have concerns about the care their children receive, we strongly encourage them to speak to the service managers first, but people can also make complaints to us direct.
"We accept anonymous complaints in cases where those raising an issue prefer not to be identified."
The Care Inspectorate works to a six-point grading scale with one being unsatisfactory and six being excellent.
The spokesman added: "If any care services scores grades of one or 2, we require changes to improve standards of care. If a service fails to improve, we can take enforcement action and – in extreme cases – have powers to close services down.
"All our inspection reports are published online at careinspectorate.com for parents and carers to read."
But to avoid a situation where parents find themselves having to complain, it's best to carry out some simple checks before deciding on the best placement for your child.
Jan Davidson, development director for the Association of Quality Nurseries in Scotland, suggests that parents should look closely at staff and children when first visiting a daycare provider to see how they are interacting.
She said: "See what reception you get when you first walk into the nursery if you haven't made a prior appointment – are they happy to see you, what kind of welcome do you get?
"Look at as many nurseries as possible and don't just follow a friend's recommendation.
"What suits one family might not suit another. When you're visiting a nursery, you're looking to see happy children who are safe and stimulated.
"You want to see a hive of activity, not children who are sitting around looking bored. There should be plenty of staff interaction where appropriate and staff getting down to a child's level, looking them in the eye.
"And the staff should look happy, they shouldn't be standing rolling their eyes.
"For babies, the ratio should be one member of staff to three children. For two to threes it's one member of staff to five children and three to fives it's one member of staff to eight. But high staff turnover is a huge problem at the moment and that's something parents have to be wary of."
MUM-OF-TWO, Dr Zenab Ali, 33, from Glasgow, says her son Faaris, now three, was perfectly happy at nursery but her one-year-old daughter Sofia did not do as well.
Zenab said: "Sometimes she would come home filthy, but you appreciate a nursery's not going to take care of your child the same way you are and it is more difficult when you've got 15 babies and only three or four staff.
"Often when I went into the baby room a lot of the kids would just be sitting there. It's difficult because you're only getting a five-minute snapshot and this wasn't a bad nursery at all, but it just seemed there were too many babies in the room and not enough staff.
"A mother can struggle with two kids, can you imagine a room of 15?"


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Posted by Jenny Zhang
If you've ever left your dorm, you've probably encountered secondhand smoke at one point or another. Whether you're the smoker taking a puff in front of the Burgess Caf??, or the passerby that witnesses the crowds forming around the benches anterior to the residence halls, news of a potentially smoke-free Skidmore might come as a shock to you.
According to Rochelle Calhoun, dean of Student Affairs and co-chair of the subcommittee on Student Affairs from the Institutional Policy and Planning Committee (IPPC), discussions about the potential of the College becoming a smoke-free campus stem from a Student Government Association Senate meeting that took place last year. SGA President Matthew Walsh '13, who also serves as co-chair with Calhoun on Student Affairs, attended a senate meeting where senators chose smoking as an issue for the IPPC to look into.
"We started by doing some reading about smoke or tobacco-free campuses. We also had a conversation with a woman who works with the Cancer Society," Calhoun said. "She talked to us about trends and higher education, about going smoke free. In the middle of first semester last year, we learned that the Environmental Health and Safety committee was also looking at the issue. We combined forces and had a conversation on how to begin to explore the issue."
Conveniently, Christine Kopec, currently a visiting assistant professor for the Department of Management & Business, was also teaching a business ethics class at the time, in which one of the students' objectives was to explore an issue in the community. Kopec asked her class to take up the issue of smoking on campus.
Kopec's class investigated the question of being a smoke-free campus. Students referenced other institutions that went smoke or tobacco-free, and tried to understand why they made their decision by examining the processes they followed. At the end of the course, the class was asked to offer their perspective on whether the College should become a tobacco or smoke-free campus, and answered in the affirmative.
When Student Affairs and the Health and Safety committee coalesce this year, members will review the report from the business ethics class once again.
"It really has been a conversation in committee at this point. Our goal this year is to make it a campus conversation," Calhoun said. She added, ""There is a range of options for us. We want to know what they are and be in a community dialogue about it."
Walsh reviewed smoking policies of close to 15 institutions that he said the College considers "peer and aspirant." Only one was on its way to becoming smoke-free. Others had specific policies about various parameters around buildings past which students and faculty could not smoke.
In addition, surveys were administered by Health Promotions to find out more about students' behaviors around smoking. Calhoun said if the surveys are sufficient, the committee will review them.
Enforcement of potential smoking policies is a topic of much discussion on college campuses. While some universities see a ban as a violation of the school's policies, others have made it a communal responsibility to uphold the decree. At various schools, literature that serves as a reminder of tobacco or smoke-free school environments was printed and distributed throughout campus.
Calhoun predicts that if the decision to make the College smoke-free is final, it should take 18 months to two years before the policy can fully take effect.
"Folks who are interested in exploring it span both students, staff and faculty," Calhoun said. "I can certainly say there is community interest in having this conversation."


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I am a little odd...I know. I think it started a long time ago. I was walking through the cheese aisle in the grocery store yesterday and while browsing my eyes meet one of my favorite childhood snacks - Port Wine Cheese Spread. The thought that came to me right away was "yes, I have to bring that home - I have not had that in forever!". I brought it home and ate a bit too much of it. With my craving subsided the thought that came to me this morning when I saw it in my fridge was "what an odd thing to be a childhood favorite." I mean, what child should look forward to sitting down to Port Wine Cheese Spread, Genoa Salami, Gourmet Honey Mustard and some crackers? So maybe that is where it all started.
Have you ever had that spread, if not, you should try it.
Here is another favorite.
Ginger Ale feels fancy to me. It is my drink of choice whenever we are on a plane. I know a can of soda is one of the least special things, but whenever I taste it I whisked hundreds of miles up into the clouds on my way to somewhere fabulous.
What are some of your odd childhood favorites?


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Jim's fraction is -2/9 and Bob's fraction is -4/7.
Who do you think is closer to zero?...
-2/9 is closer because if u find it's decimal value it is: -0.22(repeating)
-4/7 decimal value is: -0.57.
Where is the Half point for 2/3?
Homework for tonight is: 3 questions that ask you to compare the fractions using the denominator. The fractions that you have to compare are
1/2 and 1/3
1/5 and 2/4
2/3 and2/4
Besides that we also have section 2.1 Math Link (the worksheet Mr.B gave us)
Well I have said what we did in class so I guess that means I am done my scribe.
For the next scribe I am not going to choose another guy because it has been only guys that have been doing scribes...Next is Nichole! Good Luck
Remember the Halloween dance is tomorrow so if you don't have all of your work in make sure you get it done so you can go. Oh yeah I almost forgot: COMMENT!!!


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Saturday, November 17, 2012
Vintage French pins...
Dear readers,
In order to celebrate the first shop anniversary ( does one month really count? YES! ), I'm giving away a free pin from my collection with your purchase!
These metal pins were really popular in the '70s and '80s and represented pretty much the French norm.
Shiny, metallic, campy and colorful, everyone had to have one. Or a few!
Just add a comment to seller in Etsy and specify your choice.
Thank you!
Subscribe to: Post Comments (Atom)


text: I keep hearing that ICS is great, except for a few little bugs. I never hear what the little bugs are. Maybe these bugs are important to some. Does anyone have a list of things that are a problem in the different builds? I have a few questions. For instance does the video cam still have concert mode recording? Its actually one of the main features I bought a moto phone for. Or maybe the default can handle loud concerts so it doesn't matter. The other issue I hear about is flash. It may be a diminishing issue but it is still an issue that can matter a lot. So lets hear about what horrible problems these release candidates must have so we can understand why they haven't been rolled out yet


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American Bazaar is having a birthday celebration hunt starting Sept 1st! Details Below!
Find some of these great prizes hidden in the amazing stores that are participating in this hunt!
In September, AMERICAN BAZAAR is going to celebrate it's first year anniversary! YAY! Celebrate this event by participating in a big party hunt with AB! ♥
Name of the hunt: AMERICAN BAZAAR BIRTHDAY HUNT (ABBH)
Date: September 1rst to 30th
Theme: Celebration, party, glam!
Blog: http://americanbazaarfashion.blogspot.com
Nails: Studio Nails - Mehndi (Not Free)
Skin: Apple May Designs - Atalise (Not Free)
Hair: The Alice Project - Elise (Lucky Board Prize)
Dress: Sakide - (ABBH Prize)
Face Piercing: Doomsday - Darky Piercing (ABBH Prize)
Poses: Bent! - White Tie Affair at Fashionably Late (60L)


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Stay posted for event pictures. For any other questions, please contact Julie Voutour at email@example.com or 519-748-0848 ext 5223.
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