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Kerry says US has proof sarin used in Syria attack
US Secretary of State John Kerry said yesterday the United States now had evidence of sarin gas use in Syria and said that "the case gets stronger by the day" for a military attack.
A day after US President Barack Obama stepped back from his threat to launch an attack, Kerry said in a series of TV interviews that the administration learned of the sarin use within the past 24 hours through samples of hair and blood provided to Washington by first responders in Damascus.
Kerry said he was confident Congress would give Obama its backing for an attack against Syria, but he also said the president has authority to act on his own if Congress doesn't give its approval.
But he stopped short of saying Obama was committed to such a course if lawmakers refused to authorize force.
Congress is due to return from a summer break next Monday.
Obama, who has talked repeatedly of US reprisals against President Bashar Assad for the alleged use of chemical weapons against his own people in Syria's protracted civil war, said on Saturday that he had decided to defer any immediate action in order to seek congressional authorization.
"The case hasn't changed and the case doesn't change at all. The rationale for a military response is as powerful today" as it has been, Kerry said.
"This case is going to build stronger and stronger," he said on NBC's "Meet the Press." But he also said he thinks "the people of America should be celebrating that the president is not acting unilaterally."
Kerry maintained there is no weakness in the US case underscoring Obama's about-face, saying instead that "the president believes that we are all stronger as a nation when we act together."
He said that Assad "has now joined the list of Adolf Hitler and Saddam Hussein" in deploying chemical weapons against his population and that "the case remains the same" for a US response.
Asked on CNN's "State of the Union" if the US obtained its new information from UN weapons inspectors who had visited Syria, Kerry responded: "No, it is independent. ... But it is confirmation of the signatures of sarin."
He added: "In the last 24 hours we have learned through samples that were provided to the United States, that have now been tested, from first responders in east Damascus, and hair samples and blood samples have tested positive for signatures of sarin."
He was asked repeatedly what Obama would do in the event that Congress refuses to give its consent, Kerry said, "The president has taken his decision."
"I think this is a smart decision by the president. He is not trying to create an imperial presidency," Kerry added.
"I believe that in the end, Congress will do what is right," Kerry told "Fox News Sunday."
Administration officials have said Obama appeared set on ordering a strike until last Friday evening. After a long walk around the White House grounds with Chief of Staff Denis McDonough, Obama told his aide he had changed his mind.
The officials said Obama initially drew pushback in a two-hour session attended by Vice President Joe Biden, Defense Secretary Chuck Hagel, Director of National Intelligence James Klapper, CIA Director John Brennan, national security adviser Susan Rice and homeland security adviser Lisa Monaco. They declined to say which of the participants had argued against Obama's proposal.
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Chole also known as Chana Masala is a chickpea dish cooked in a spicy tomato gravy.
Serves 2 to 4.
- 1 15 oz can of chickpeas (kable chana, Garbanzo beans)
- 3 tablespoons oil
- Pinch of asafetida (Hing)
- 1 teaspoon cumin seeds
- 1 tablespoon Besan (gram flour) (available in Indian grocery stores)
- 1 large tomato chopped
- 1 teaspoon ginger paste
- 1 teaspoon chopped green chilies
- 2 teaspoons coriander powder
- 1/2 teaspoon turmeric
- 1/2 teaspoon red chili powder
- 1 teaspoon salt
- 1/4 teaspoon garam masala
- 1 teaspoon chopped cilantro (hara dhania)
- Thinly sliced tomatoes for garnish
- Drain chickpeas and wash well.
- Blend the tomatoes, green chilies and ginger to make a puree.
- Heat the oil in a saucepan. Test the heat by adding one cumin seed to the oil; if seed cracks right away, oil is ready. Add the asafetida and cumin seeds. When cumin seeds crack, add the gram flour and stir-fry for a minute.
- Add the tomato puree, coriander powder, turmeric, and red chili powder. Cook about four minutes on medium heat. The tomato
mixture will separate from the oil and reduce to about half in quantity.
- Add chickpeas, salt, and one cup of water. Cook, covered, for seven to eight minutes on medium heat.
- Press the chickpeas with a spatula to soften. Add more water as needed to keep the gravy consistency to your liking, and let it cook
on low heat a few more minutes.
- Add the garam masala and cilantro. Let it cook for another minute.
- Garnish with thin tomato slices.
Serving Suggestions
- Chana Masala goes well with any Indian flat bread, and can also be served with Western bread or pita bread.
- Chana Masala is also a delectable treat over plain rice.
- This is a healthy, nutritious dish for vegan and gluten-free diets.


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Gaston: GOP 'holding a gun to the head of our country'
So former state Sen. Dan Debicella ("Himes' partisanship hurting families," Sept. 24) thinks that Congressman Jim Himes -- not Speaker Boehner, not the Tea Party -- is to blame for "offering insults rather than bipartisan solutions" to our nation's problems? Is he the least bit aware that Republicans and their extremist Tea Party caucus -- not Jim Himes -- have controlled the House of Representatives since 2010? Mr. Debicella takes the congressman to task for calling the GOP "radical obstructionists" and "out of touch with the real world.'' But these statements are not insults; they are demonstrably true.
What party in touch with "the real world," however you define it, would threaten to plunge our economy into the abyss if it didn't get its way on repealing Obamacare? What party would jeopardize the full faith and credit of the country, and sink us into default, all to prevent tens of millions of people from receiving essential health care? That sounds pretty radical to me!
Nowhere in Mr. Debicella's column does he mention this outrageous hostage-taking by House Republicans, nor its irresponsible brinksmanship. Nowhere does he mention that Republicans ran in 2012 on abolishing Obamacare, and lost by 5 million votes. Nowhere does he mention that President Barack Obama's signature initiative was passed by both houses of Congress, and upheld as the law of the land by a conservative Supreme Court. As Jonathan Chait of the New Republic has said of today's GOP: "The fact that a major party could even propose anything like this is a display of astonishing contempt for democratic norms ... is there an example in American history of a losing party issuing threats to force the majority party to implement its rejected agenda?"
The dead giveaway to the lack of seriousness and cynicism of Mr. Debicella's argument is his plea for both sides to "talk to each other rather than call each other names." But he knows full well that what passes for "negotiation" in today's Washington, D.C., is one where Republicans regard "compromise" as giving in to their demands. Republicans are holding a gun to the head of our country to extract concessions in exchange for not unleashing economic mayhem that will hurt all of us. And for Congressman Himes to call such behavior "radical" is not an "insult." It is deadly accurate, and calls out an unconscionable stain on the Republican Party.
Anytime you hear a politician like Mr. Debicella airily urging one side to agree to "responsible spending cuts," as he urges Democrats to do, demand that he specify what cuts he has in mind. If he can't or won't identify those cuts, then you know he is not serious.
As for "partisanship hurting families," Mr. Debicella has been suspiciously silent on the mean-spirited partisanship of House Republicans voting in unison to chop $40 billion in food stamps, at a time of grinding poverty for millions of American families. That kind of "partisanship" hurts American families a lot more than the "blame and attack" culture he ostensibly rails against in Washington -- while he, of course, blames and attacks Congressman Himes.
Bill Gaston is a vice chairman of the Greenwich Democratic Town Committee.


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For Pam and JaVale McGee, basketball is a family business. Pam McGee is the first WBNA star to have a son play in the NBA, and now, she and JaVale are appearing in a new show called "Mom's Got Game," airing this month on the Oprah Winfrey Network.
"The Kennedys do politics. The McGees, we do basketball," Pam says.
A former WNBA Hall of Famer, Pam is known for being domineering both on and off the court. JaVale, a center for the Denver Nuggets, has a reputation for being a colorful and eccentric character -- and also one with incredible athleticism and skill. "Mom's Got Game" will explore the dynamic relationship between these two larger-than-life basketball superstars.
However, Pam isn't just 25-year-old JaVale's mother; she's also his business manager. As Pam works to keep her own busy life on track, she's also determined to keep a tight rein on the glitz and girls that come with the life of an NBA star.
The series premiere of "Mom's Got Game" airs Saturday, Jan. 18, at 10 p.m. ET on OWN.


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With Valentine's Day circled in red on most calendars (don't forget!), February has long been known as the month for lovers. In the Bluff City, it's also a time for food lovers, since the Memphis Restaurant Association will celebrate the 50th anniversary of its annual gala on February 23rd at The Peabody.
The MRA actually began back in 1947 as a chapter of the Tennessee Restaurant Association. In the late 1960s, the MRA became an independent group to support the pending liquor-by-the-drink legislation, and over the years its 400-plus members — many of them mom-and-pop eateries located in just about every neighborhood here — have supported such events and organizations as Feed the Need, Zoo Rendezvous, Youth Villages Soup Sunday, and the Memphis Food Bank.
On these pages, we offer some vintage postcard views that illustrate the wide range of dining establishments available throughout our city over the years. Happy 50th, MRA.
The first president of the Memphis Restaurant Association was Speros Zepatos, whose family has been associated with Memphis' oldest restaurant for decades. Located at Main and G.E. Patterson, with Central Station across the street to the west and the old Arcade Hotel to the north, and used as a location in the cult classic Mystery Train, this may be the most photographed street corner in town. Although it's famous for all sorts of great food and a truly classic interior, note that the old postcard touted only one benefit of eating here: "Air Conditioned."
For years, Harry Glaser was one of this city's best-known restaurateurs. Not only did he own the famous Embers Restaurant, on Park just west of Getwell, but he also installed another Embers on the top of White Station Tower, one of the first rotating restaurants in the city. The original Embers, shown here, could seat more than 340 diners in four separate dining rooms. The best place of all, of course, was the Waterfall Room, with water cascading down a back wall of rough stone. Despite the 360-degree views from atop White Station Tower, or the waterfall in the main dining room, the Embers' slogan was "Where Fabulous Food Is the Show!"
Some of the best places to grab a bite to eat weren't always fancy restaurants. Case in point: the popular Park Avenue Lounge, located on Union across the street from The Peabody. It's never been clear to me why a place called Park Avenue was never, apparently, located on Park Avenue, but I guess that didn't matter to anyone searching for (as the postcard says on the back) "Memphis' Finest Restaurant." Not only could you get a good lunch here, and wash it down with an ice-cold bottle of Schlitz, the postcard also promised "Entertainment," without going into any details.
Sometimes it's nice to just pick out your own food, and Memphis has had plenty of fine cafeterias: Piccadilly, Britling's, and Morrison's come to mind. But none of them had the downhome charm, if you ask me, of the Mark Twain Cafeteria on Summer, easy to locate by the bright neon sign of Tom Sawyer pulling fish from a lazy river. Inside, diners would eat inside the pilothouse of a riverboat, or just admire the nice murals showing scenes from the books of Samuel Clemens. The restaurant is long gone, but the murals were saved and moved to Mud Island's Mississippi River Museum.
Willie King was apparently quite a character. In the 1940s, he opened a busy liquor store at 597 Madison, and painted a sign outside reading, "Women — If you drive your husband to drink, drive them HERE." He also opened popular eateries around town, such as Willie King's Restaurant on South Bellevue, and the well-known Pitchfork on South Second. The postcard proclaimed that they offered "exclusively barbecue, chicken, and beans." And look — even the china was made in Memphis. In later years, the Pitchfork became home to Erika's German restaurant.
If you were shopping at "Memphis' Greatest Store," you didn't have to leave when you got hungry. The downtown location offered a rather nice restaurant on the top floor. The postcard even proclaimed that the "beautiful restaurant is the ONE and ONLY eating place in any Memphis department store recommended by Duncan Hines." Oh, and for the menfolk, the back of the postcard discreetly noted that "Goldsmith's features a private Men's Grill reserved for gentlemen only." Ladies? Well, you're on your own, I guess.
I wish I knew more about this place. Among other things, the name alone intrigues me, and I really love the huge signs. The only clues come from the old postcard, which shows it was located on "Bristol Highway No. 70," otherwise known as Summer Avenue. Primarily a tourist court "with modern brick cabins and hot or cold showers," the place also had a café, and a roadside sign urged travelers to "Stop, Eat, and Drink." Squint closely at the card, and you'll see that the Owl offered Clover Farms Ice Cream and Bottled Milk Chocolate. You could enjoy a Big Boy Cone for just 10 cents, and a malted milk for 20 cents.


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SelfShelf Bookshelf by Nicole Van Schouwenburg
For those of you who loved This Into That's "Book Shelves", here's another cute little play on the same visual pun. Dutch designer Nicole Van Schouwenburg presents Selfshelf, a single book shelf that lets you stack up to 4 Kg of books in a "floating pile" on your wall. When we spoke to the designer, she was fairly sure that the plywood used is sustainably sourced. In any case, minimal use of materials and a simple, durable construction makes this a winner where embodied energy is concerned.
:: SelfShelf bookshelves [by DM]


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Meet the Beatles and the 1960s
The music of the Beatles in the context of 1960s counter-culture: rock and roll rebellion, Dylan and psychedelic drugs, recording studio techniques, Eastern religion and the anti-war movement. One course.
105 Mary Duke Biddle Music Building
Campus Box 90665
Durham, NC 27708
Tel: (919) 660.3300
Fax: (919) 660.3301


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Todas las Noticias
« Back
Towards a fully ecumenical, global and sustainable online library
The international governing body of the Global Digital Library on Theology and Ecumenism, also known as GlobeTheoLib, met from 9-10 September 2016 in Geneva.
Twenty participants from member associations attended the Consortium. Amélé Ekué, Professor of Ecumenical Social Ethics at the World Council of Churches and Andreas Waldvogel, Programme Executive Online Library at Globethics.net, led the meeting along with Obiora Ike, Executive Director of Globethics.net. Consortium Committee member Martha Smalley from the Foundation for Theological Education in South East Asia said that: "It was exciting to learn about new resources available through GlobeTheoLib".
The new 2017-2020 Strategy, the 2017-2019 Budget and the Consortium agreement were on the agenda during the meeting as well as updates on new developments.
Some future projects were presented, with the idea that the library be "fully ecumenical, global and sustainable". "GlobeTheoLib is useful, especially for Eastern Europe countries where physical libraries are not so rich" Ivan Dimitrov from the Conference of Orthodox Theological Schools commented. André Karamaga from the All Africa Conference of Churches confirmed: "I am happy that so many African users can have access to these online resources".
GlobeTheoLib was launched in 2011. This 5th anniversary was marked on Friday 9 September 2016 with the launch of a new online collection on 'EcoTheology, Climate Justice and Food Security' together with a book published in the Globethics.net Global series on the same topic containing presentations and a report of the international consultation.
- Go to the 'Eco-Theology, Climate Justice and Food Security' online collection
- Download the "Eco-Theology, Climate Justice and Food Security" book (PDF)
About GlobeTheoLib
GlobeTheoLib, a joint project of the World Council of Churches and Globethics.net, is a free online library hosted on the Globethics.net platform that provides theological resources for education and ecumenical dialogue.


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VF Corp is exploring strategic options for its denim business that could include a sale or spin off of its Lee and Wrangler jeans brands, the Wall Street Journal reported on Friday.
VF Corp is exploring strategic options for its denim business that could include a sale or spin off of its Lee and Wrangler jeans brands, the Wall Street Journal reported on Friday.
Levi Strauss has announced a new climate action strategy, which sets aggressive targets for reducing carbon emissions across its owned-and-operated facilities and global supply chain by 2025.
The LA-based fashion label has teamed up with the major league soccer club to provide custom suiting and fashion looks for its players when they are off the pitch for the next three years.
American Eagle's latest fall back-to-school denim campaign follows the brand's commitment to celebrating real consumers, showcasing 12 "real people," including an AE retail store associate.
Tommy Hilfiger has launched Tommy Jeans Xplore, a line of smart chip-enabled pieces that reward you with points when you wear them. The points are redeemable for gift cards, signed product and exclusive pieces.
VF Corp-owned denim brand Lee has announced the appointment of its new creative director Michael Kampe, who joins the brand from Hugo Boss.
Shop Direct, the owner of online fashion retailers including Very.co.uk and Littlewoods, has announced changes to its executive board to be more customer-centric.
The Smiley Company and major denim brand Lee Jeans have linked up for a new collection launching at retail across Europe with unusual treatments blending the Smiley icon and Lee logo.
Guess has joined forces with digital payment platform Alipay to offer Chinese customers a simplified payment option when visiting the US. The Alipay app can now be used at 50 Guess stores across the country.
The LA-based clothing brand launched its Fall/Winter advertising campaign on Monday, revealing an earth-toned homage to classic Guess campaigns shot by fashion photographer Josh Ryan.


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Women seek strength.
Strangely how so many cannot distinguish between strength and violence, yet underneath it all, the women in Western culture are drawn to strength and its manifestations.
Remember that understated strength is always preferred to the brute display of power. The latter can turn many off, as it borders too closely to violence, and violent people can never be trusted to channel their aggression.
Another words, if a woman sees that a man who is prone to violence, she will suspect that he will soon become violent toward her, and that is (or should be) a big warning sign.
"But what really attracts you is his strength and air of purpose. The way other men obey, and follow and fear him. The air of command, of power and with it, success" (Wilbur Smith)


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NovaStor's NovaBACKUP products for small to medium-sized businesses are ready to protect critical servers, business applications, and virtual environments on servers running Windows Server 2012.
Agoura Hills/ (CA) USA, September 4, 2012 – NovaStor announces the immediate support of Windows Server 2012 by NovaBACKUP backup software products. NovaBACKUP is a complete family of products that offer comprehensive and easily scalable data protection for businesses of every size and need. From a single file server to a sophisticated network of application servers, virtual machines, and workstations, NovaBACKUP enables users to protect all their critical business data with its line of Server, Business Essentials, and Business Essentials Network products.
An efficient and secure IT infrastructure is a critical necessity for large and small business alike in today's competitive marketplace. By supporting Microsoft's new Windows Server 2012 operating system from day one NovaStor ensures its customers using the latest server technology can also easily protect their vital business data with professional backup methods.
100% Server Protection Including Virtual Machines, Exchange and SQL Support
NovaBACKUP Business Essentials offers comprehensive protection for all the different types of business data distributed throughout the IT infrastructure. In addition to file and disaster recovery protection, NovaBACKUP Business Essentials enables the backup and restore of Microsoft Exchange and SQL data as well as unlimited virtual machines based on Hyper-V and VMware ESXi / vSphere.
Centralized Network Management of Backup Protection
NovaBACKUP Business Essentials Network offers centralized management of data protection for your entire network. The number of virtual machines is unlimited and Exchange, SQL, and SharePoint support does not require additional licenses. NovaBACKUP Business Essentials Network allows the IT administrator to use one solution with an intuitive web interface to easily administer and protect all critical business data from a central location.
Product information and free evaluation versions of NovaStor's backup software products for Windows Server 2012 are available from the respective product pages on NovaStor's website.
Related Links for Backup Software Server 2012
NovaBACKUP Server (Windows Server Backup)
NovaBACKUP Business Essentials (SQL/Exchange Server Backup)
NovaBACKUP Business Essentials Network (Centralized SQL/Exchange Server Backup)
About NovaStor
NovaStor (www.novastor.com) is a leading international provider of software solutions for data protection and availability. NovaStor provides software, SaaS solutions and services for local and online backup, restore and retention of business-critical data. Clients include home, mobile, and SMB users, service providers as well as inter-national corporations. NovaStor's cost-effective solutions are platform- and hardware-independent and ensure that optimal technological and economical use is gained from the customer's existing and future IT environment. NovaStor is headquartered in Switzerland (Zug), has offices in Germany (Hamburg) and the USA (CA, Agoura Hills), and is represented in numerous other countries through partnerships.
For Further Information:
Mike Andrews
29209 Canwood Street
Agoura Hills, CA 91301
Tel.: +1 (0)805 579 6700
Fax: +1 (0)805 579 6710
E-Mail: email@example.com


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The national polling numbers have not been good recently for President Obama. Many have him still ahead a point or two, but most of those use very questionable samples. Gallup's latest 7-day tracking poll has the race tied. Rasmussen has Romney ahead by 3. With the exception of Rasmussen, almost all of these polls are of registered voters. Nate Silver at The New York Times predicts the eventual switch to a likely voter screen will boost Romney by 2.3 percentage points. So, on balance, Romney is probably slightly ahead now nationally.
Of course, the Presidency isn't won in a national vote, but by winning individual states to collect 270 electoral college votes. There are roughly twelve states considered "battlegrounds" this year. Almost all the resources of both campaigns will be focused in these states. The Hill, today, looked at polling averages in these swing states and decided that Obama has the definite edge going into November.
Taking the polling averages used by Nate Silver in the New York Times, the president is ahead in 10 of the 12 vital states. If those polls were borne out on Election Day, Obama would coast to victory with 332 electoral college votes. Only 270 votes are needed to win the presidency.
Awarding Obama only the states in which he now leads by 3 percentage points or more in the polling averages still sees him safely home.
I have no doubt this kind of analysis comforts the reporter, the newspaper, and many of its readers. And, they do have a point; polling in the swing states is ultimately much more meaningful than what the national polls say. But there is no way to objectively look at the data they are citing and conclude that Obama has a clear edge in these states.
1. These are registered voter polls. Polls of likely voters are much closer to the actual voting results. Factoring in Silver's prediction that Romney will get, on average, a 2.3 percentage point boost from a likely voter screen, Obama's lead almost disappears in many of these states.
2. Obama has enjoyed a 3-1 funding advantage over Romney the past two months in these battleground states. Obama went for an early kill-shot, while Romney conserved his resources. That Obama can only register small leads in these swing states while enjoying such a spending disparity should be disconcerting for the Obama campaign. After all, Obama won't enjoy that spending edge over the rest of the campaign.
3. In almost all the polling averages, Obama is under 50%, a dangerous place for an incumbent. (Only in New Mexico is his polling average above 50%…barely, though, at 50.2%. In most swing state polls, Obama is polling around 45-47% in a head-to-head match up. His numbers here actually match Gallup's latest national approval rating for Obama. In other words, he is doing no better in the swing states than he is nationally.
Interestingly, The Hill states that Republicans are growing uneasy about the state of the race in the battlegrounds. But, none of the GOP strategist they cite raise any serious alarm bells. Its almost as if they're just making up that point.
I know these kinds of analyses are comforting to the media, but they are only doing a disservice to themselves. Yes, the battle for the swing states is close and will likely remain close throughout the election. But, you could just as easily argue that Romney has the edge in the swing states, as Obama's huge spending advantage has failed to boost his approval ratings.
99 days of the media's silliness to go.
Follow me on twitter here.


text: Do you need promotional products fast? Peak Incentives is proud to offer over 500 promotional items available in 24 hours. Place your order today and we'll ship your order tomorrow with no additional charges. No Fees - No Rush Charges -- Its That Easy! Our 24 Hour service is the fastest in the industry. Give us a call today and ask how we can help with your last minute project.


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When we walked out the door to go to school this morning, we saw a black helicopter hovering about 2 blocks away.
The girls were freaked out.
As was I.
When we got to the school, we saw that the teachers were hustling all the kids inside. Given the sunny day, this is rather odd. (We can't even get them to let the kids inside on 20 degree winter days!)
Here's the reason…
Seems that one of the cars driven by the suspected terrorists who were detained in Florida was registered to someone who lives in my town.
I am SERIOUSLY freaked out!


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Frozen Lemon Cheesecake
Frozen Lemon Cheesecake with Mad Millie Cream Cheese
My first attempt at making Mad Millie Cream Cheese was a great success! With my Mad Millie Cream Cheese I was able to make this exquiste Lemon Cheesecake. It tastes delicious and so easy to make. Enjoy!
- 75g butter, melted
- 1 250g packet malt or plain sweet biscuits
- 393g can sweetened condensed milk
- 500g Mad Millie Cream Cheese
- 2 tsp finely grated lemon rind
- 1/2 cup lemon juice
- Place the biscuits into a food processor and pulse until crumb consistency.
- Add melted butter to the biscuit and pulse again.
- Press crumbs over the base and sides of a 24cm removable based flan dish.
- Mix together condensed milk, cream cheese, lemon rind and juice until smooth
- Pour mixture over the biscuit base and freeze until set.


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Research September 2014 | Volume 122 | Issue 9
Early Postnatal Exposure to Ultrafine Particulate Matter Air Pollution: Persistent Ventriculomegaly, Neurochemical Disruption, and Glial Activation Preferentially in Male Mice
Joshua L. Allen,1 Xiufang Liu,1 Sean Pelkowski,1 Brian Palmer,1 Katherine Conrad,1 Günter Oberdörster,1 Douglas Weston,1 Margot Mayer-Pröschel,2 and Deborah A. Cory-Slechta1
Background: Air pollution has been associated with adverse neurological and behavioral health effects in children and adults. Recent studies link air pollutant exposure to adverse neurodevelopmental outcomes, including increased risk for autism, cognitive decline, ischemic stroke, schizophrenia, and depression.
Objectives: We sought to investigate the mechanism(s) by which exposure to ultrafine concentrated ambient particles (CAPs) adversely influences central nervous system (CNS) development.
Methods: We exposed C57BL6/J mice to ultrafine (< 100 nm) CAPs using the Harvard University Concentrated Ambient Particle System or to filtered air on postnatal days (PNDs) 4–7 and 10–13, and the animals were euthanized either 24 hr or 40 days after cessation of exposure. Another group of males was exposed at PND270, and lateral ventricle area, glial activation, CNS cytokines, and monoamine and amino acid neurotransmitters were quantified.
Results: We observed ventriculomegaly (i.e., lateral ventricle dilation) preferentially in male mice exposed to CAPs, and it persisted through young adulthood. In addition, CAPs-exposed males generally showed decreases in developmentally important CNS cytokines, whereas in CAPs-exposed females, we observed a neuroinflammatory response as indicated by increases in CNS cytokines. We also saw changes in CNS neurotransmitters and glial activation across multiple brain regions in a sex-dependent manner and increased hippocampal glutamate in CAPs-exposed males.
Conclusions: We observed brain region– and sex-dependent alterations in cytokines and neurotransmitters in both male and female CAPs-exposed mice. Lateral ventricle dilation (i.e., ventriculomegaly) was observed only in CAPs-exposed male mice. Ventriculomegaly is a neuropathology that has been associated with poor neurodevelopmental outcome, autism, and schizophrenia. Our findings suggest alteration of developmentally important neurochemicals and lateral ventricle dilation may be mechanistically related to observations linking ambient air pollutant exposure and adverse neurological/neurodevelopmental outcomes in humans.
Citation: Allen JL, Liu X, Pelkowski S, Palmer B, Conrad K, Oberdörster G, Weston D, Mayer-Pröschel M, Cory-Slechta DA. 2014. Early postnatal exposure to ultrafine particulate matter air pollution: persistent ventriculomegaly, neurochemical disruption, and glial activation preferentially in male mice. Environ Health Perspect 122:939–945; http://dx.doi.org/10.1289/ehp.1307984
Address correspondence to D.A. Cory-Slechta, 601 Elmwood Ave., Box EHSC/Room 2-6810, Rochester, NY 14642 USA. Telephone: (585) 275-7060. E-mail: email@example.com
This work was supported by National Institute of Environmental Health Sciences grants ES019105 and ES019852 (D.A.C.-S.), ES001247 (G.O., M.M-P., and D.A.C.-S.), and T32 ES007026 (J.L.A. and B.P.).
The authors declare they have no actual or potential competing financial interests.
Received: 10 December 2013
Accepted: 22 May 2014
Advance Publication: 5 June 2014
Final Publication: 1 September 2014
- Supplemental Material (700 KB) PDF
Air pollution has been associated with adverse neurological and behavioral health effects in children and adults. Recent epidemiological studies have reported associations between exposure to air pollutants and increased risk for autism (Becerra et al. 2013; Volk et al. 2011, 2013), cognitive decline (Power et al. 2011; Weuve et al. 2012), ischemic stroke (Lisabeth et al. 2008; Wellenius et al. 2012), schizophrenia (Pedersen et al. 2004), and depression (Lim et al. 2012). Exposures—in particular to ultrafine ambient particulate matter (UFP; < 100 nm in aerodynamic diameter), identified as potentially the most toxic constituent of air pollution (Oberdörster 2000)—are pervasive and ubiquitous. Increases in neuroinflammation, oxidative stress, and glial activation have been identified as putative mechanisms by which air pollution exposures may impair central nervous system (CNS) function in adults (Block and Calderón-Garcidueñas 2009), but such exposures in the context of early brain development—a time frame considered crucial to causation of autism, schizophrenia, and cognitive development—remain largely unexplored. Given the potential public health importance of the reported epidemiological associations, it is imperative that the biological plausibility of such early developmental exposures to produce CNS dysfunction and disease be examined. Thus, we hypothesized that exposure of mice to UFP during early postnatal development—a period of rapid brain growth and differentiation—should adversely influence CNS development by mechanisms identified as subserving air pollutant effects.
Materials and Methods
Animals, reagents, and exposures. Eight-week-old male and female C57BL6/J mice were purchased from Jackson Laboratories (Bar Harbor, ME) and allowed to acclimate in the housing room for 1 week before breeding. Monogamous pairs of mice were bred for 3 days; males were then removed and dams remained singly housed with litters until weaning. Weanling mouse pups were exposed to ultrafine concentrated ambient particles (CAPs; < 100 nm) using the Harvard University Concentrated Ambient Particle System (HUCAPS) described previously (Allen et al. 2013). Briefly, animals were exposed to ambient UFPs in real time postnatal days (PNDs) 4–7 and on PNDs 10–13 for 4 hr/day for 4 days/week between 0700 and 1200 hours—the times corresponding to peak vehicular traffic outside the intake valve of the instrumentation. Particulates were concentrated approximately 10-fold the level in ambient outdoor air. The HUCAPS system is fitted with a size-selective inlet and a high-volume (5,000-L/min) UFP concentrator that concentrates ambient particles. CAPs- and filtered-air (FA)–treated animals received identical experimental manipulation. Because of the presence of the particle impactor in the HUCAPS system, animals in the CAPs-exposed chamber may have been held at a slightly higher negative pressure compared with animals treated with FA; however, the flow of CAPs-enriched or filtered air was maintained constant in both chambers. Room air was filtered by HEPA filtration (99.99% effective) for FA-exposed animals. Relative humidity and temperature in exposure chambers were maintained at 35–40% and 77–79°F (25–26°C). Particulate mass concentration and counts are shown in Figure 1. We obtained particle counts using a condensation particle counter (model 3022A; TSI, Shoreview, MN), and we calculated mass concentration using idealized particle density (1.5 g/cm3). On PND14 and PND55, the animals were euthanized by rapid decapitation to avoid the known effects of anesthetics on neurochemistry, allowing us to assess the immediate and persistent effects of CAPs exposure on the developing and young adult mouse CNS. An additional group of brains, from male mice euthanized at PND270 (from a separate exposure study), was examined for ventricle area. Exposure characteristics for the PND270 group were similar to those for the PND14 and PND55 groups. Details have been reported previously (Allen et al. 2014b). To preclude litter-specific effects, in the present study we used only one pup per sex per litter per time point. All mice used in this study were treated humanely and with regard for alleviation of suffering, and the study protocol was approved by the University of Rochester Institutional Animal Care and Use Committee.
Figure 1 – Mean particle counts and particle mass concentration for each day of exposure. Inset: mean diameter for each day of exposure. Error bars represent SDs.
Glial fibrillary acid protein (GFAP) and ionized calcium-binding adapter molecule 1 (IBA-1) immunostaining and image analysis. Brains were extracted and placed into 4% paraformaldehyde for 24 hr and then into 30% sucrose until they sank. The brains were sectioned on a freezing microtome (Microm HM 440 E; GMI Inc., Ramsey, MN) at 40-μm thickness in cryoprotectant (30% sucrose, 30% ethylene glycol in 0.1 M phosphate buffer) and stored at –4°F (–20°C) until immunostaining. Every sixth section was stained for GFAP and IBA-1 to assess the global activation of astrocytes and microglia, respectively. Briefly, the brain sections were washed of cryoprotectant and placed into primary antibody solutions for GFAP (AB5804, 1:4000 dilution; Millepore, Billerica, MA) or IBA-1 (016-20001, 1:5000; Wako Chemicals USA, Richmond, VA) for 24 hr. For GFAP, the tissue was then placed into a biotinylated secondary antibody solution (BA1000, 1:200 dilution; Vector Labs, Burlingame, CA) for 1 hr, and the stain was visualized using DAB (3-3´-diaminobenzidine). For IBA-1, the tissue was placed into a fluorescent-labeled secondary antibody solution (A-11012, 1:400 dilution; Life Technologies, Grand Island, NY). Immunolabeled tissue was mounted onto Superfrost Plus micro slides (48311-703; VWR, Radnor, PA) and coverslipped using Cytoseal 60 (for chromogenic tissue) (23-244257; Fisher Scientific, Pittsburg, PA) or ProLong Gold Antifade Reagent (P36930; Life Technologies).
Three images of each of following brain regions were obtained: corpus callosum, cortex, ventral midbrain, dentate gyrus, hippocampus (CA1/CA2), and striatum. Relative immunoreactivity was determined using Image Pro Plus version 7.0 (MediaCybernetics, Rockville, MD). All images underwent contrast enhancement before utilization of the count/size method. Briefly, immunoreactive cells on two or three sections per brain region were enumerated using the count/size feature of Image Pro Plus version 7.0 across three equally sized fields per brain region [method modified from Cao et al. (2012)]. Data are reported as percentages of time point– and sex-matched controls.
Lateral ventricle and aqueduct of Sylvius area determination. The area of the lateral ventricles (approximate bregma range: 1.10–0.38 mm) and aqueduct of Sylvius (approximate bregma range: –3.88 to –4.84 mm) was determined by tracing the outline of the area of interest in at least four adjacent sections of slide-mounted brain tissue using Neurolucida (MBF, Villiston, VT). We used Neurolucida software to enumerate the area of interest area in square micrometers. Lateral ventricle bregma for the PND14 brains are approximate, given that, to the knowledge of the authors, no atlas for that point in early postnatal brain development exists. To examine the persistence of lateral ventricle dilation in CAPs-exposed male mice, the ventricle area was quantified in brain tissue harvested at approximately PND270 from another group of identically, but not concurrently, exposed males. Unlike the mice from which brains were obtained at PND14 and PND55, mice from which PND270 tissue was harvested had undergone behavioral testing (reported by Allen et al. 2014b).
Neurotransmitters quantification. Briefly, brains were extracted and dissected, on an ice-cold plate, into the following regions: olfactory bulb, hippocampus, midbrain, striatum, hypothalamus, cerebellum, and cortex. We used HPLC coupled with an electrochemical detector (for monoamines) or a fluorescent detector (for amino acids) to quantify dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), norepinephrine (NE), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), glutamine (GLN), glutamate (GLU), and γ-aminobutyric acid (GABA), expressed in nanograms per milligram protein. Dopamine turnover (DA TO) was calculated as DOPAC/DA concentrations. Method details are available elsewhere (Cory-Slechta et al. 2004, 2013; Virgolini et al. 2008).
Cytokines. Interleukin 1-beta (IL-1β), tumor necrosis factor-alpha (TNFα), and IL-6 in the striatum, hippocampus, olfactory bulb, midbrain, cortex, and cerebellum were quantified using custom multiplex plate–based chemiluminescent ELISA (Quansys Biosciences, Logan, UT). Briefly, tissue was quickly sonicated in 0.1 M PBS, pH 7.4, containing 1% protease inhibitor cocktail (P8340; Sigma, St. Louis, MO). Twenty-five microliters of brain homogenate was loaded per well and run in duplicate according to the manufacturer's instructions. The chemiluminescent signal was visualized using the Q-view Imager and analyzed using Q-View Software (Quansys Biosciences). Cytokine levels were normalized to the total protein content of the same region as determined by the bicinchoninic acid method.
Statistical analyses. Statistical analysis was carried out using JMP10 (SAS Institute Inc., Cary, NC). Lateral ventricle dilation was characterized by the statistical interaction of postnatal CAPs × sex; thus, all statistical analyses were separated by sex and included two-way analyses of variance with age of sacrifice and treatment group as the independent factors. Fisher's least significant difference post hoc analysis was used in the event of an age of sacrifice × treatment interaction. All analyses were performed as two-tailed tests, and p < 0.05 was considered statistically significant.
Mice were exposed on PNDs 4–7 and 10–13 for 4 hr/day, from 0700 to 1200 hours: the times corresponding to peak vehicular traffic and particle concentration levels near the intake valve. The mean CAPs count across the 8 days of postnatal exposure was approximately 200,000 particles/cm3, and the mean particle mass concentration was 96 μg/m3 (Figure 1). Particles remained in the UFP-size range for all exposure days (Figure 1 inset).
To address the potential of CAPs exposure to elicit immediate CNS effects and to determine the persistence of such effects, mice were euthanized at two time points after cessation of exposure: on PND14 (24 hr postexposure), and on PND55 (young adulthood). Notably, CAPs-exposed male, but not female, mice had significantly enlarged lateral ventricles compared with air-exposed controls (Figure 2A,B), as indicated by the treatment × sex interaction [F(1,32) = 10.0559, p < 0.01] and main effect of CAPs exposure for male mice [F(1,16) = 10.3298, p = 0.0054] and female mice [F(1,16) = 0.2455, p = 0.6270]. This observation was confirmed by Neurolucida (MBF Bioscience)–quantitated increases of lateral ventricle areas: 380% and 178% at PND14 and PND55, respectively (Figure 2E). On PND14 only, a single CAPs-treated female showed enlarged lateral ventricles as indicated by increased variability in Figure 2E for CAPs-females at that time point; however, this effect failed to reach statistical significance. Lateral ventricle size in mice (sex unspecified) has been reported to increase out to 90 days of age, with more rapid growth up to about 40 days of age (Mandell et al. 2010), although separate determinations by sex reveal that males show a decline in area between 1 and 3 months of age (Mandell et al. 2010). Figure 2A shows representative images of lateral ventricles of PND14 male air-treated (Figure 2A) and CAPs-treated (Figure 2B) animals at similar bregma. CAPs exposure did not affect the aqueduct of Sylvius (Figure 2E). To further evaluate persistence, brains from identically exposed males obtained at PND270 were subjected to ventricular tracing and increased lateral ventricle size was confirmed by a two-tailed t-test (p = 0.04; Figure 2C,D).
Figure 2 – Images of lateral ventricle from air-exposed (A,C) and CAPS-exposed (B,D) male mice at PND14 (A,B) or at approximately PND270 (C,D). Bars = 10 μm. Quantification of lateral ventricle on PNDs 14 and 55 (E) and PND270 (F). The aqueduct of Sylvius area is shown for PNDs 14 and 55 (E). Data reported as group mean area ± SE. TX, main effect of CAPs treatment. n = 5 animals/sex/treatment/time point.
*p < 0.05, by two-tailed t-test.
To assess glial activation as a potential mechanism of neurotoxicity in CAPs-exposed mice, we immunostained brain sections for GFAP and IBA-1, markers for astrocytes and microglia, respectively. CAPs exposure altered the astrocyte state in a sex- and regionally dependent manner (Figure 3A–C). Data are presented as percent time point– and sex-specific FA control values. In males, CAPs exposure reduced GFAP immunostaining in the corpus callosum [main effect of CAPs: F(1,15) = 4.5986, p = 0.048], at both PND14 and PND55, and reductions in GFAP immunoreactivity in the hippocampus occurred only at PND14 [time point × treatment interaction; F(1,15) = 5.200, p = 0.0376, p < 0.05] (Figure 3A,C). In contrast, females showed increases in GFAP in the hippocampus [CAPs by time point: F(1,16) = 9.1589, p = 0.008], corpus callosum [CAPs by time point: F(1,16) = 5.8066, p = 0.0284], and anterior commissure [CAPs by time point: F(1,16) = 12.76, p = 0.018] (Figure 3B,C) that were restricted to PND14 relative to PND14 air-treated females (all p-values < 0.05), but not at PND55, indicating a transient astrocytic response to CAPs exposure that was present on PND14 but resolved by PND55. Data were also normalized to sex-specific PND14 FA control to allow for the examination of the trajectory of GFAP changes across the study period (see Supplemental Material, Figure S1).
Figure 3 – Representative images of GFAP immunoreactivity in the corpus callosum and hippocampus of air- and CAPs-exposed male (A) and female (B) mice at PND14, with (C) relative quantification of GFAP in those regions and in the dentate gyrus, cortex, midbrain, striatum, and anterior commissure immediately adjacent. (D) Representative images of IBA-1 immunoreactivity in the hippocampus and corpus callosum of male mice at PND55. (E) Relative quantification of IBA-1 immunoreactivity in the anterior commissure at PND14 and hippocampus of male mice at PND55. Data reported as percent sex-specific control by time point ± SE. Abbreviations: TX, main effect of CAPs treatment; TP × TX, statistical interaction between CAPs treatment and time point. Bar = 50 μm. n = 5 animals/sex/treatment /time point.
*p < 0.05, compared with time point– and sex-specific control, by two-tailed t-test.
CAPs exposure altered IBA-1 immunostaining in the anterior commissure and hippocampus only in males (Figure 3D,E). Data are presented as percent time point- and sex-specific FA control. Despite the larger increase at PND14, statistical analyses indicated that CAPs exposure increased IBA-1 immunostaining (approximately 25%) in the anterior commissure at both time points [main effect of CAPs: F(1,15) = 5.75, p = 0.03], indicating persistent microglial response in the white matter. In contrast, CAPs exposure increased IBA-1 immunoreactivity in the hippocampus only at PND55 [CAPs by time point: F(1,15) = 4.8791, p = 0.043] relative to FA-treated controls (p < 0.05). Data were also normalized to sex-specific PND14 FA control to allow for examination of the trajectory of IBA-1 changes across the study period (see Supplemental Material, Figure S2).
CAPs exposure modified CNS neurotransmitter levels in a sex- and region-dependent manner. CAPs exposure increased hippocampal GLU [F(1,26) = 5.5383, p = 0.0246], midbrain DA TO [F(1,26) = 6.6590, p = 0.0159], and cortical DA TO [F(1,18) = 8.4456, p = 0.0106] in males at both time points (Table 1). CAPs exposure increased cortical NE in males only at PND55 [CAPs by time point: F(1,26) = 5.13, p = 0.03] (Table 2). No treatment-related differences in levels of CNS neurotransmitters were observed in the olfactory bulb or hypothalamus nor in levels of DA, DOPAC, HVA, 5-HT, or 5-HIAA in the midbrain, striatum, cortex, or hippocampus (data not shown).
Table 1 – Neurochemical disruption and cytokine changes (group mean ± SE) in hippocampus, cortex, midbrain, and striatum of CAPs-exposed male mice.
Table 2 – Neurochemical disruption and cytokine changes (group mean ± SE) in hippocampus, cortex, midbrain, and striatum of CAPs-exposed female mice.
In females, CAPs exposure reduced hippocampal GABA [F(1,28) = 4.22, p = 0.049], but increased midbrain HVA [F(1,29) = 4.92, p = 0.035] and DA [F(1,29) = 6.9, p = 0.013] and hippocampal 5-HT [F(1,29) = 6.46, p = 0.017] at both time points (Table 2). In addition, cortical NE was increased only at PND55 [CAPs by time point: F(1,29) = 6.37, p = 0.017], whereas hippocampal DA TO [CAPs by time point: F(1,26) = 4.90, p = 0.036] was increased, and midbrain DA TO was reduced [CAPs by time point: F(1,29) = 9.52, p = 0.004], but only at PND14. No treatment-related differences in neurotransmitter levels in the olfactory bulb, cerebellum, or hypothalamus were observed (data not shown).
In males, reductions in hippocampal IL-6 [F(1,28) = 4.69, p = 0.039], and in striatal IL-1β [F(,1,28) = 6.48, p = 0.017] and TNFα [F(1,28) = 5.00, p = 0.033], were observed at both time points, with a similar trend in hippocampal IL-1β [F(1,28) = 3.59, p = 0.069] (Table 1). Hippocampal GLU in CAPs-exposed males was positively correlated with hippocampal IL-1β (R2 = 0.233, p = 0.039) and IL-6 (R2 = 0.361, p = 0.01). In males, midbrain IL-1β [CAPs by time point: F(1,28) = 4.76, p = 0.038] and TNFα [CAPs by time point: F(1,28) = 5.448, p = 0.027] were reduced at PND14, but increased at PND55 (all p-values < 0.05) (Table 1). We observed no treatment-related differences in central cytokines in the male olfactory bulb or cerebellum (data not shown).
In CAPs-exposed females at PND55, cortical IL-6 was reduced [CAPs: F(1,18) = 5.78, p = 0.027] but midbrain IL-6 was increased [CAPs by time point: F(1,28) = 5.92, p = 0.022] (Table 2). We detected no IL-6 in the female cortex at PND14. Midbrain TNFα [F(1,28) = 7.05, p = 0.013] and IL-1β [F(1,28) = 6.65, p = 0.016] were increased in CAPs-exposed females at both time points (Table 2). In contrast, striatal IL-6 was decreased at PND14, but not at PND55 [CAPs by time point: F(1,28) = 8.61, p = 0.007, all post hoc p values < 0.05] (Table 2). No treatment-related differences in cytokine concentrations were observed in the olfactory bulb or cerebellum (data not shown).
We exposed mice to human-relevant levels of UFP. As indicated in Figure 1, the average particle count was approximately 200,000 particles/cm3. Ambient UFP counts near roadways in Los Angeles, California (Westerdahl et al. 2005) and Minneapolis, Minnesota (Kittelson 2004) have been reported to be as high as 200,000 and 400,000 particles/cm3, respectively, with peak episodic counts reaching 2,000,000 particles/cm3 in Minneapolis (Kittelson 2004).
We observed a persistent dilation of the lateral ventricles, but not of the aqueduct of Sylvius, that occurred preferentially in CAPs-exposed male mice. Lateral ventricle dilation is a predictor of poor neurodevelopmental outcome (Laskin et al. 2005; Tatli et al. 2012). It has been associated with multiple developmental CNS disorders, including autism and schizophrenia (Barttfeld et al. 2011; Bigler 1987; Fannon et al. 2000; Movsas et al. 2013; Sanfilipo et al. 2000; Schulz et al. 1983; Wright et al. 2000), idiopathic mental retardation, periventricular leukomalacia (Volpe 2001, 2003, 2005), fragile X syndrome, and attention deficit disorder and, in the absence of other CNS abnormalities, to developmental delays (Gilmore et al. 2001, 2008). Its consequences can include progressive hydrocephalus, gray matter migration abnormalities, loss of parenchymal brain tissue, agenesis of the corpus callosum, and delayed or abnormal maturation of white matter, that is, reduced MBP (myelin basic protein) expression, diminished total axon volume, trisomies, and microcephaly (Bigler 1987; Gilmore et al. 1998, 2001, 2008; Griffiths et al. 2010; Kuban et al. 1999; Kyriakopoulou et al. 2014, Manfredi et al. 2010). Ventriculomegaly is associated with such deficits, persists after birth (Gilmore et al. 2001), and is more prevalent in males (Gilmore et al. 1998). Our observation of male specificity of the lateral ventricle dilation is consistent with literature suggesting that males are more likely to be diagnosed with a number of neurodevelopmental and neuropsychological disorders of childhood, including autism, earlier onset schizophrenia, attention deficit hyperactivity disorder, conduct disorder, and learning disabilities (Boyle et al. 2011; Centers for Disease Control and Prevention 2007; Erskine et al. 2014; Kirkbride et al. 2012). Although the mechanism(s) underlying the male specificity of this effect are as yet undefined, they likely reflect sex differences in neurodevelopment such as the sex differences in microglial colonization of the brain already seen by PND4 [at which time males show a more activated morphology (Schwarz et al. 2012)], a possibility that is consistent with the observation that changes in IBA-1 were found only in males. Although we observed a single CAPs-exposed female that appeared to have enlarged lateral ventricles at PND14, the effects were not statistically significant, further suggesting male specificity of the lateral ventricle dilation. However, future studies should address whether females may be rendered susceptible at higher particle concentrations or at longer durations of exposure. Obstruction of the aqueduct of Sylvius is a common mechanism of lateral ventricle dilation (James 1992), but that was not seen in the present study. Whether an earlier transient obstruction occurred cannot be ruled out, however. Future studies of a similar nature should include the use of a repeated-measures design in rodents exposed to CAPs. Use of magnetic resonance imaging to track the trajectory of central ventricular system changes in the same animal across time would assist in illuminating the mechanism(s) by which such changes occur in CAPs-exposed male mice and may inform the sex dependency of this effect. Global patterns of glial changes in the brain indicate that females mount a transient astroctyic response—but no microglial response—to CAPs exposure, whereas males show both astrocytic and microglial dysfunction that persists into early adulthood.
Our previous work indicates that significant disruption of adulthood neurotransmission in response to CAPs exposure in mice persists at least to almost 1 year of age (Allen et al. 2014a, 2014b). To determine the etiological role of such disruption in CAPs-associated neuropathology, we examined regional levels of DA and its metabolites, DOPAC, HVA, NE, 5-HT and its metabolite 5-HIAA, as well as GLN, GLU, and GABA. Notably, the sustained increase in hippocampal GLU may indicate the contribution of an excitotoxic mechanism of CAPs that persists until early adulthood. In addition, increased DA metabolism, as evidenced in our animals by increased DA TO, has been associated with oxidative stress (Cohen 1983; Graham 1978; Hastings 1995; Schulz et al. 2000). Interestingly, a loss of GABAergic neurons in the hippocampus, which is consistent with the decreased hippocampal GABA observed in females in the present study, has been implicated in both schizophrenia and bipolar disorder (Benes et al. 1998). Moreover, disrupted CNS neurotransmission is associated with both autism (Cook 1990) and schizophrenia (Grace 2012).
Early cytokine changes were also sex and brain-region dependent (Tables 1 and 2). In the female midbrain, IL-6 was increased only at PND55, whereas TNFα and IL-1β were persistently increased across both time points. IL-6 in the female striatum was increased only at PND14. A protracted profile of changes, as observed for female midbrain IL-6, may indicate adverse effects on the ontogeny of microglial development that later results in a neuroinflammatory profile; whereas changes that were restricted to PND14 only, such as was observed for female striatal IL-6, likely indicate a transient response.
Decreases, as opposed to increases, in male hippocampal IL-6 and striatal IL-1β/TNFα and in female cortical IL-6 were unanticipated, but perhaps suggest that microglia, a major source of brain cytokines, are dysfunctional or lost. Brain cytokines have multiple important roles in the developing nervous system (Deverman and Patterson 2009), such that any alteration in their levels during the early postnatal period would have deleterious effects on the CNS. Indeed, IL-1β, TNFα, and IL-6 have been implicated as having roles in synaptic plasticity in the hippocampus (Balschun et al. 2004; Goshen and Yirmiya 2009; Schneider et al. 1998) and can activate astrocytes that modulate synaptic plasticity. Furthermore, IL-1 receptor antagonist polymorphism has been implicated in ADHD (attention deficit hyperactivity disorder) etiopathogenesis (Segman et al. 2002), and disrupted attention has been observed previously in our male CAPs-exposed mice (Allen et al. 2013). Furthermore, hippocampal GLU in CAPs-exposed males was positively correlated with hippocampal IL-1β/IL-6, likely indicating a mechanistic link between excitotoxicity and neuroinflammatory responses. Fogal and Hewett (2008) have proposed IL-1β as a bridge between neuroinflammation and excitotoxicity. This correlation was absent in air-exposed control males and in females regardless of exposure group.
Collectively these data show a dramatic susceptibility of male mice to environmentally relevant levels of early postnatal air pollution exposure, with effects that persist into adulthood and cause permanent neuropathology characterized by ventricular enlargement, a pathology not seen in females. Lateral ventricle dilation (ventriculomegaly), is a strong predictor of poor neurodevelopmental outcome in children and a pathological hallmark observed in both autism and schizophrenia. Thus, the findings we present here provide biological plausibility for the reported associations in epidemiological studies of air pollution with autism (Becerra et al. 2013; Volk et al. 2011, 2013), schizophrenia (Pedersen et al. 2004), and ADHD (Siddique et al. 2011). Moreover, the heightened sensitivity of males to CAPs effects parallels the greater prevalence of these disorders in males.
Although ventricular enlargement is not observed in female mice exposed to CAPs, CAPs-exposed females exhibit biochemical and neurochemical alterations that are nevertheless significant and represent protracted neurotoxicity in response to early postnatal CAPs exposure. CAPs-exposed males and females show significantly altered neurochemical changes in multiple brain regions, including areas that comprise the mesocorticolimbic dopamine tracts, regions critical to cognition and attention. CAPs-exposed males have increased levels of the major excitatory neurotransmitter GLU in the hippocampus, a sign of excitotoxicity in that region. CAPs-exposed females show a decrease in hippocampal GABA, the major inhibitory neurotransmitter of the CNS. GABA alterations in the hippocampus have been implicated in both schizophrenia and bipolar disorder (Benes and Berretta 2001). The functional/behavioral significance of these changes remains to be fully determined; however, impairment in behaviors involving the hippocampus, such as learning and memory, would be predicted. These changes in neurotransmitters along the mesocorticolimbic pathway may underlie the increased preference for immediate reward observed in CAPs-exposed males that we previously reported (Allen et al. 2013). In interpreting these findings, inherent differences between murine and human brain development must also be considered. The early postnatal period in both humans and rodents is marked by substantial brain development; however, the exact nature of the development is different. As a rough estimate, rat brain development at PND7 has been determined to approximate human brain development at birth (Clancy et al. 2007); thus our paradigm for exposure from PND 4–7 and 10–13 in mice, in terms of neurodevelopment, probably best approximates what would be the perinatal period in the human, encompassing the time frame shortly before and after birth. Taken together, these data suggest that exposure to CAPs in the early postnatal period, at human- and environmentally relevant levels, may represent a far greater public health concern than has previously been recognized as a risk factor contributing to intractable neurodevelopmental disorders such as autism and schizophrenia.
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Goshen I, Yirmiya R. 2009. Interleukin-1 (IL-1): a central regulator of stress responses. Front Neuroendocrinol 30:30–45.
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Kittelson DB. 2004. Nanoparticle emissions on Minnesota highways. Atmos Environ 38:9–19.
Kuban K, Sanocka U, Leviton A, Allred EN, Pagano M, Dammann O, et al. 1999. White matter disorders of prematurity: association with intraventricular hemorrhage and ventriculomegaly. The Developmental Epidemiology Network. J Pediatr 134(5):539–546.
Kyriakopoulou V, Vatansever D, Elkommos S, Dawson S, McGuinness A, Allsop J, et al. 2014. Cortical overgrowth in fetuses with isolated ventriculomegaly. Cereb Cortex 24(8):2141–2150.
Laskin MD, Kingdom J, Toi A, Chitayat D, Ohlsson A. 2005. Perinatal and neurodevelopmental outcome with isolated fetal ventriculomegaly: a systematic review. J Matern Fetal Neonatal Med 18(5):289–298.
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Siddique S, Banerjee M, Ray MR, Lahiri T. 2011. Attention-deficit hyperactivity disorder in children chronically exposed to high level of vehicular pollution. Eur J Pediatr 7:923–929.
Tatli B, Ozer I, Ekici B, Kalelioglu I, Has R, Eraslan E, et al. 2012. Neurodevelopmental outcome of 31 patients with borderline fetal ventriculomegaly. Clin Neurol Neurosurg 114:969–971.
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Clarivate Analytics released the 2018 Journal Citation Reports, which tracks citations for articles published in 2015 and 2016. EHP's new Journal Impact Factor is 8.31, with a 5-Year Journal Impact Factor of 9.81. (more…)
We are pleased to present new and improved author guidelines! (more…)


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Created on 09-05-2013 at 00:00 AM
Gerd 'Der Bomber' Müller of course, but also Karl-Heinz Rummenigge, Roland Wohlfarth, Giovane Elber, Roy Makaay, Luca Toni... many a striker has become a Bayern crowd hero over the decades. But this season, the home faithful at the Allianz Arena have come to know and – judging by the frenetic applause – also to love a different kind of front man, a player who is a striker and the first line of defence: Mario Mandzukic.
It's because he always tracks back to the edge of his own penalty box; the way he robs opponents of possession in midfield; the way he never shirks a challenge; and his tireless, unceasing effort for the team, his harrying of opposing players, and his creating space for team-mates. It is an exceptional combination. "He played as a striker, midfielder and right-back. It was unbelievable!" declared Javi Martínez after the Champions League quarter-final home leg against Juventus. Mandzu is a fighter – "Football is a man's game. You get stuck in. I love it," he says - and he scores goals too, 21 in total this term, level with Thomas Müller at the top of the club's scoring chart.


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The Zoo is open year round except Christmas Day.
April - October
November - March
9 a.m. - 4 p.m.
In the event of severe weather, the Zoo's operating hours may change. See the weather forecast for Asheboro, NC. To plan your Zoo visit, please check the Zoo's homepage for updates or call 1-800-488-0444. Ticket sales end one hour prior to closing.
Some of the North Carolina Zoo's animals, particularly the African species, are unable to tolerate very cold weather. For this reason, certain animals may not be on exhibit if temperatures or wind-chill factors are below 45 degrees F. Precipitation can also impact animal-exhibit status. If temperatures exceed the 45-degree minimum, affected animals may be placed on exhibit later in the day. Animals in indoor exhibits are not impacted by temperatures and may be enjoyed by visitors year round.


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Parents definite all the time alter them in focusing on their preschool youth workforce,except for they must appealing start another time to be betrothed in supporting their kids' authoring and evaluating job all all above fundamental to high school. They must always hints their youth by tool of apartment house suit literacy demeanor aside from assisting them in their exploring in the school.
prosperous land literacy behavior are as follows:
reading stories aloud to children
evaluating along along furthermore the children and personality attentive to them while they read
letter of invitation your children the topics that they are electing up in school
leaving sensing materials such as books and magazines in the home
making ways for the tykes to examined selected books independently
Monitoring your teenagers when they do their training and assignments
Bringing the adolescents to libraries and check on books and a few multimedia materials
providing anywhere to boot magazines,helpful comics and magazines as presents
granting them the occasion,uncertainty and materials they hunger for them to be converted into competent at and be in communiqué at home
evoking a seat-in talk within reach to the books they are recently reading
Emphasizing the right crave of literacy and the flavor of helpful attainment.
There are teachers who are operating and ancient students and they will be predisposed to blow up the parent and counselor partnerships by without hardship coming to parents on how to inquire into the books that their adolescents are currently reading,hurl in comments and report to the writings they made ready,and monitoring them when they do and full their experiment and assignments.
Teachers have prior to now stepped convey large quantity of fruitful and positive domicile literacy demeanor for students that procure twists of future for parents jointly as anyways as their kids to do sensing and inscribing.
They must maneuvers reading and inscribing look around the information superhighway for the excuse that computers have prior to now been a share of each daylight hours human being living,and it is really creative for parents and kids to peep as regards to and search the planet wide cyber web to collect concentration,comprehended prolific articles that are posted on infobahn contented,goes wordy and literacy games,and motivating their childrenbecome suit additionally emails and immediate messaging technology.
Parents must still be provoked to reading aloud to adolescent recruits every sunbeams,and have a demonstration and be a focus for to profitably understood aloud by by road of interactive materials.They must absorb how to contain appropriate books and request types and order to have their tykes be more joined up and interconnected and the books,such as missive of invitation queries,whistling about the illustrations and making deduce.This all makes for at all rounded arrangement.


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New boat launch at Crescent Bar, with limited parking, opens May 26
EPHRATA, Wash. – Local residents and visitors will have a number of outdoor opportunities along the Columbia River this summer recreation season.
Grant PUD operates 19 recreation sites on or near the Columbia River. Recreation sites with boat launches include the Priest Rapids Recreation Area, Buckshot, Huntzinger, Wanapum Dam Lower, Wanapum Dam Upper, Vantage, Frenchman Coulee and Apricot Orchards. The new Chinook Park boat launch located off-island at Crescent Bar, will open to the public on May 26. Fuel will also be available at the Chinook Park boat launch when it opens.
Boaters should be mindful that, because of on-going construction in the Crescent Bar area, parking is limited at the Chinook Park boat launch. Those with off-site parking are encouraged to use that option.
The two-lane launch and boat dock is the first of several new and enhanced amenities that will be free and open to the general public visiting the Crescent Bar Recreation area. The new RV campground and other facilities, including parks, beaches and walking trails, are expected to open by late June to early July following several months of construction. The golf course is also now open throughout the season.
Grant PUD's recreation sites offer day-use visitors free, family-friendly fun in the sun and are one of the many ways Grant PUD powers our local way of life. During the Memorial Day weekend, overnight camping, which requires a fee, will also available at four campgrounds: Priest Rapids Recreation Area, Sand Hollow, Rocky Coulee and Jackson Creek Fish Camp. For information about Grant PUD's recreation options, visit http://grantpud.org/recreation.
Grant PUD wants everyone to enjoy a safe time along the river by following these safety guidelines:
- Water released from the dams can create hazardous boating conditions. Sudden water level fluctuations can impact the shoreline. Make sure your boat stays wet and anchor well off shore.
- Safety barriers located above both Wanapum and Priest Rapids dams are there to keep everyone safe. Do not go beyond the safety barriers under any circumstances. If someone gets in trouble and goes beyond the barriers, call 911 immediately.
- Check the weather forecast before starting out. Watch for any wave, wind and cloud changes that signal bad weather is heading your way.
- Make sure water and weather conditions are safe before entering the water. Cold water reduces body heat 25 times faster than air at the same temperature. The Columbia River can be cold enough to cause serious harm. Wearing a life jacket increases your survival time.
- There are no lifeguards on duty at our recreation sites. Please be careful.
# #
Established by local residents over 75 years ago, Grant PUD generates and delivers energy to millions of customers throughout the Pacific Northwest. What began as a grassroots movement of public power has evolved into one of the premiere providers of renewable energy at some of the most affordable rates in the nation. For more information visit www.grantpud.org or follow us on Facebook and Twitter.
Public Affairs
(509) 754-5035 / firstname.lastname@example.com


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This Fairline Targa 44 GT Hardtop For Sale is a class leader with superb styling and curvaceous lines. The hard top with electric opening sun roof converts the cockpit into a bright and airy outside lounging, entertaining and driving area. The finish in the interior is completed to the highest standard including a fabulously galley and luxurious accommodation in large and comfortable master and guest cabin. This boat has had one owner only from new and has minimal hours on the engines. Her inventory is extensive and to a good standard. She has been fastidiously maintained, presented in pristine condition throughout and ready for the season. We highly recommend a viewing of this boat to confirm her excellent condition. VAT paid in France. Ready for the season. Please contact us for more information
The Fairline Targa 44 offers a luxurious accommodation both above and below deck, which includes a sumptuous master cabin with access to en suite bathroom, as well as an aft guest cabin with two single beds which can be converted to a double berth and with an en suite bathroom. Cabins and lower saloon are fitted with LCD TV & DVP player. The well equipped galley includes panoramic hull windows. The main deck has a very sociable cockpit which comprises of a large sun pad at the stern, a cockpit dinette with a large teak table to sit 8 people serviced by a full wet bar.
Air conditioning
Battery charger
Bimini Top
CD player
Cockpit cover
Cockpit cushions
Cockpit shower
Cockpit speakers
Cockpit table
DVD player
Deep freezer
Electrical Circuit: 24V
Electric bilge pump
Electric head
Electric windlass
Hydraulic gangway
Manual bilge pump
Microwave oven
Navigation center
Shore power inlet
Swimming ladder
Teak cockpit
Sunseeker London Group presents the information and the details of this Vessel in good faith and does not expressly or impliedly guarantee or warrant the accuracy of this information nor expressly or impliedly warrant the condition of the Vessel. All information and details are intended as a guide only and are not binding and do not constitute part of any terms and conditions. A prospective purchasers should instruct his agents, or his surveyors, to investigate such details in order to validate all information. All prospective purchasers should be aware that the ""Manufacturers Model Year"" varies from builder to builder and does not necessarily correspond to the Vessel's year of build. This Vessel is offered subject to prior sale, price change, or withdrawal without notice. It is noted that this information may be displayed in various languages; however, the interpretation of the language that shall take precedence shall always be UK English.
The Quay Portomaso Marina
Portomaso St. Julians


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JERSEY CITY, New Jersey - (Reuters) - The International team have been so outplayed at the Presidents Cup that it perhaps would have been appropriate had the United States delivered the knockout punch on Saturday.
Instead, the coup de grace will be delivered at Liberty National on Sunday, probably sooner rather than later, leaving the visitors to conduct a probably uncomplicated post-mortem.
Sometimes one team is simply better than the other and the International team's record over the first three days makes ugly reading.
Only two matches won out of 18, one of them a generous four-foot concession by American Kevin Chappell on the final hole on Saturday that allowed a relieved Indian Anirban Lahiri to avoid having to make the knee-knocker in a howling wind.
The U.S. have won 101 holes to 61, while the bellicose crowd have upset some of the International team players.
"We're fighting not only these guys who are the best players in the world but we're fighting the crowds," said Day. "It's tough."
Former world number one Day played the 2015 event exhausted after winning his first major at the PGA Championship a couple of months previously. He went 0-4-2 and this time has gone 0-3-1.
Another former world number one, Adam Scott, is 0-3-0 this week, while Hideki Matsuyama, the top-ranked player on the International team, has earned just half a point.
"That one full point has been quite elusive this week," said Lahiri. "We feel terrible about this being Nick's last captaincy, and we've not played well and the Americans have played great. So this is not the way we'd like him to leave.
"We can compete. We haven't this week."
Assistant captain Ernie Els said it had been a perfect storm.
"Just based on pure form running into this week, the timing of their form has been exceptional," he said of the Americans.
"And then you look at their talent on the team, it's pretty exceptional, too. They had a lot going for them this week."
Reporting by Andrew Both


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Hands & Hearts Ministries, Inc. – Solomon's Porch
The Lord's Hands & Hearts Ministries, Inc. is a volunteer driven organization that seeks to reach the lost and broken with the love and compassion of God to address issues of poverty, addiction, oppression, discouragement, and hopelessness. We believe the whole person must be ministered to and healed in order to see lasting freedom; body – spirit – soul.
We have been blessed to be a part of God's work in the lives of several men and women who have come up and off the streets and are in healthy and productive lifestyles and are giving back to the community.
Hands & Hearts currently serves over 1,000 people each month. Services and programs offered include transitional housing, hunger relief through Solomon's Porch and Pauline's Pantry supplying food and hygiene products to low income families and the homeless, Christian teaching and counseling to the homeless, residential poor and children living in shelters, clothing relief for the homeless, and food assistance for our ministry partners also serving the homeless.


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My name is Sajid. I have always been interested in Islamic Art and specifically art inside the the Holy Rawda and Riyadh ul Jannah.
Having been in Saudi Arabia for nearly 2 years I started out building on my Arabic Language- which is still on going – the second hobby I took up and try to work on regulary is the study of calligrapy found inside the Two Holy Masajid. My knowledge of Islamic history has helped me but I realised how little I actually know about our glorious past.
I am also an avid fan of collecting, viewing and documenting old photographs and images of the Haramain pre 1924. To this end I have managed to view hundreds of photos stored in the King Abdul Aziz Public Library archives in Riyadh . Although it took me nearly 15 months to see the photos due to Saudi red tape and politics, I managed to view them.
The images were a wonderful reminder of a bygone age where the visitors to the Holy Grave would have been able to visit without being hassled and interrogated!
I hope you like this site and enjoy it, If you have any advice please inform me.
Your brother


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"Dear White People" actor Justin Dobies has signed with Paradigm and Inphenate for representation.
"Dear White People" premiered to positive reviews at the Sundance Film Festival earlier in the year and premieres tonight at the L.A. Film Festival.
The Roadside Attraction/Lionsgate co-production bows domestically on Oct. 17.
The pic was Dobies' debut after graduating from the Yale School of Drama.


text: Every day when Robin settles in to her one-of-a-kind workspace, she is reminded how lucky she is to spend her days in such a creative cocoon! Even in the long, cold days of winter, her studio is where the sun shines in, allowing her creative vision and capable hands to transform latent objects into vibrant pieces of assemblage art. This metamorphosis takes ordinary (and often overlooked!) rusty metal bits and bobs and brings them to life!


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Top 10 Best Upright Vacuum Cleaner Reviews in 2017
Are you looking for the best upright vacuum cleaner? We got you covered! We will identify ten of the best options that you can consider. We will have short upright vacuum cleaner reviews to tackle some of the models that we are recommending, as well as their features.
We will also take a quick look at some of their pros and cons. Our goal is to make it easier for you to come up with a decision.
Top 10 Best Upright Vacuum Cleaners on the Market
Here are ten of the models that we have hand-picked and reviewed. We took a look at some of their notable features, as well as what other people have to say.
- Lightweight
- Comes with Automatic Cord Rewind
- Impressive Suction
- Has Multiple Attachments
- Can Easily Tip
- No On-Board Storage
Essential Factors to Consider
To help you in making the right decision, make sure that the following factors will be taken into consideration:
- Ease of Use: If the upright vacuum is complicated to use, you will most probably feel too lazy to use it. Besides, it is meant to make your life easier and not harder. With this, it is important that it is user-friendly. The controls should be easily accessible. Another thing that can contribute to ease of use would be its weight. Choose a vacuum that is as lightweight as possible, but make sure that it won't be prone to slanting when it is in an upright position.
- Performance: The motor of the unit will be the one indicative of its performance. With a powerful motor, it will be able to deliver dependable performance. One of the most important is for such to have no loss suction, which means that even when dealing with the toughest dirt, it will not lose power.
- Capacity: You do not necessarily need an upright vacuum that comes with generous capacity. You will be good enough with a small tank if you only have a small home. If you leave in a large place, however, it would be best to choose a larger canister, which will allow you to clean continuously and without the need for frequent emptying.
- Filters: Some lower end models are equipped with replaceable filters. Nonetheless, they are not recommended because they are expensive in the long run because you have to buy new filters. A better option would be one that comes with washable filters. They can be used all throughout the functional life of the unit. You just need to have them rinsed when needed.
- Attachments: It will also be a good thing if you choose an upright vacuum that comes with multiple attachments or accessories. A crevice tool, for instance, will help you to clean even compact spaces, such as under the furniture and stairs. A brush attachment is also good so that you can have it used for cleaning upholstery. You will also benefit from having an on-board storage, which will make it easy to organize the accessories and will provide you with easy access to such when you need it.
In sum, the best upright vacuum cleaner is not necessarily the cheapest option that is available in the market. The ones that are feature-rich can be expensive, but they will surely be worth every dollar that will be spent. To help you make the right choice, go back to the things we have mentioned above and read the short upright vacuum cleaner reviews that we have discussed. For sure, it will be easier for you to make the right choice. Do your research to thoroughly evaluate the options that are available.


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oh, hello. I'm sarah!
My name is Sarah Anne and I grew up in the suburbs of Seattle and picked up a camera somewhere around the age 15. I studied traditional film photography for 4 years before switching entirely to digital photography. I continued my schooling in a two-year commercial photography program after my BA, where I specialized in fashion portraiture. Falling in love with photographing people and telling their stories has set me on the path I'm on today.
There is something particularly special about photographing someone. It is the moment you capture them in which they will never be the same. A smile, a laugh, a tear, all held captive in a single frame. That is my purpose when I photograph my clients. I want to hold captive in my frames, the moments that are truly special to them. From the light, to the color tones, to the expression on their faces, it is all centered on the idea of seeing a moment as it ever was and will never be again.
When I'm not behind my camera or glued to my computer screen, I'm am with my wonderful husband watching movies, while enjoying wine and playing with our beautiful kittens Zara & Finn.