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MIAMI, FL – 11/2/2016 (PRESS RELEASE JET) — Big Cheese, Inc. d/b/a The Grilled Cheese Truck, a Trilogy Capital Group portfolio company, announced today that it has entered into an employment agreement with fast food industry veteran Al Hodges as Chief Executive Officer and President. Mr. Hodges will assume the position on completion of the company's current round of financing. The announcement was made by Trilogy Chief Executive Officer A.J. Cervantes.
The Grilled Cheese Truck is being positioned as a national brand with a focus on grilled cheese products. The Grilled Cheese Truck intends to capitalize on its established brand through the rollout of gourmet food trucks, small-footprint retail, pop-ups, kiosks and food carts.
"At end of day, the success of any emerging growth company is a function of the quality and experience of management," stated Mr. Cervantes. "Al's extraordinary successes in the QSR industry bode well for the future of The Grilled Cheese Truck brand."
Mr. Cervantes continued, "Al brings over 35 years of experience with successes that includes P&L responsibility for over 4,600 Dunkin' Donuts' stores with $5 billion in revenues, annually opening 150 to 350 locations throughout the nation. Additionally, Al has served as Vice President of Marketing / Vice President of Operations Special Concepts with Cinnabon, Inc., repositioning the brand, as well as eight years as National Director of Food Operations for Target Stores."
"The Grilled Cheese Truck is a proven brand with extraordinary consumer acceptance," said Mr. Hodges. "Given the historic success Trilogy Capital has had building major companies, I am firmly convinced that the combination of a great brand, Dave Danhi's extraordinary talent and his contributions as our Chief Creative Officer and the strength of the Trilogy Capital management team, is a winning formula for not just success – but success in the future as a major public company."
Reg A+ Crowdfunding Offering
Management of The Grilled Cheese Truck intends to file a Reg A+ offering statement with the Securities and Exchange Commission pursuant to which it will raise capital to fund the execution of the national rollout. The Reg A+ offering is made possible as the result of recent changes in the federal securities laws that permit entrepreneurs to engage in crowdfunded finance. Interested investors can contact firstname.lastname@example.com to receive more information. Please see the important notice below regarding Regulation A+ offerings.
Big Cheese, Inc. and The Grilled Cheese Truck Brand
The Grilled Cheese Truck is a nationally recognized American brand and an entrepreneurial "emerging growth" company with a brand and menu that has been widely followed throughout the nation including the Rachel Ray Show, The Price is Right, ABC Channel 7 (Top Food Truck in Los Angeles), NBC News, Fox News.com, USA Today, Los Angeles Times (Best Food Truck in LA and Southern California), The Cooking Channel, Food &Wine (Best grilled cheese in the U.S.), The Travel Channel, Klout.com (Top 10 Most Influential Food Trucks – 2011), BBC Travel, MSN.com (The Best Food On Wheels), and Zagat Guide.
The Company's business strategy includes the objective of becoming the largest operator in the gourmet food truck space. The Company is pursuing multiple sales channels while building market share in the gourmet food truck industry. The Company is targeting customers, social media followers and general media attention all attracted to The Grilled Cheese Truck's established brand. The Company's business strategy includes The Grilled Cheese Truck offerings in gourmet food trucks, small footprint retail, kiosks, food carts, stadiums, military bases, universities, casinos and related venues, festivals, motorsports, action sports, team sports, large outdoor events/concerts, large churches and schools. Management has extensive experience and success in managing rapid roll-ups in early stage, highly fragmented industries. The Company seeks to operate both company-owned and franchised The Grilled Cheese Truck operations with an emphasis on franchised rights to Veterans as part of its growth strategy. For more information about The Grilled Cheese Truck, please visit www.thegrilledcheesetruck.com
Please clink on this link for The Grilled Cheese Truck corporate video: https://www.youtube.com/watch?v=iAEozG_d6cQ
About Trilogy Capital Partners
Trilogy Capital Group, LLC is a Miami-based private equity group principally engaged in the development of a series of private-to-public companies on a sector agnostic basis. Trilogy acquires or develops domestic and international companies pursuant to a buy and build or consolidation business model. Trilogy Capital Group and its predecessor company, Trilogy Capital Partners, have been engaged in private equity, merchant banking and strategic advisory services since 2002. For more information about Trilogy Capital, please visit www.trilogy-capital.com
About Algie Hodges, Chief Executive Officer and President
Mr. Hodges, 58, brings over 35 years of operational expertise as a veteran executive with extensive experience in strategic planning, profit/loss accountability, marketing, sales growth, rapid unit growth, acquisitions, change management and business turnarounds in the retail food service industry, quick service restaurants, fast casual restaurants and organizational growth to his CEO role. Mr. Hodges served as Vice President of Domestic and International Operations for Smoothie King Franchise, Inc., Vice President of Food and Beverage for Mapco Mart Express and as Vice President of Operations Fazoli's System Management, Inc. Mr. Hodges also served as Dunkin' Brands Region Vice President and Vice President Eastern Seaboard where he lead a two-year operations initiative known as "Dunkin Wins," that restructured the field organization, established metrics for outcome-based performance drivers and implemented guest satisfaction measures that corrected three years of negative same-store sales and declining customer transactions. His executive leadership position at Dunkin' included multi-site operations and strategic business planning for over 4,600 stores with $5 billion in revenues, annually opening 150 to 350 locations throughout the nation. Previously, Mr. Hodges held multi-unit executive positions with the RTM Restaurant Group as a Region President/Partner and franchisee owner where he acquired and built over 200 restaurants concepts. He served as Vice President of Marketing / Vice President of Operations Special Concepts with Cinnabon, Inc. repositioning the brand. Mr. Hodges spent a sixteen-year career at Target Stores that included many acquisitions, re-branding and the opening of 10 to 28 stores at time, with eight years as National Director of Food Operations as a key member of the team that developed the first Super Target concept, helping the chain to grow from 80 locations to nearly 800 in his career. Mr. Hodges has served on the Board of Directors of the American Cancer Society, the United Cerebral Palsy, and the Alabama Sports Foundation and presided as Chairman of the Board for Kid One Transport, an organization that provides transportation to the doctor for those that could not afford to do so in the black belt of Alabama. He also served on the Presidents Council for the University of Alabama. Mr. Hodges has been a featured speaker at both the MUFSO and COEX Conventions as a Retail Food Service Specialist. He attended the University of Missouri at St. Louis and Jarvis Christian College in Hawkins, Texas.
Important Notice Regarding Regulation A+
Big Cheese, Inc. d/b/a The Grilled Cheese Truck is "Testing the Waters" under Regulation A of the Securities Act of 1933. We will only be able to make sales of securities to you after we have filed an offering statement with the Securities and Exchange Commission, or SEC, and the SEC has qualified the offering statement. The Information in that offering statement will be more complete than the information that we are providing to you now and it could differ in important ways. You must read the offering statement and documents filed with the SEC before investing in our company. No money or other consideration is being solicited, and if sent, will not be accepted. No sales will be made or commitments to purchase accepted until the offering statement is qualified. Any indication of your interest to invest in our offering is non-binding.
Forward-Looking Statements
Statements in this press release and of the management or representatives of Big Cheese, Inc. in connection therewith that relate to beliefs, plans, objectives, goals, expectations, anticipations, intentions and future financial condition, results of operations or business performance constitute "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. These forward-looking statements are based on management's current expectations about future events. These statements can be identified by the fact that they do not relate strictly to historical or current facts, and by words such as "may," "could," "should," "would," "believe," "expect," "project," "anticipate," "estimate," "intend," "plan" or other similar words or expressions, and include statements regarding the our ability to commence a significant level of operations and develop the Grilled Cheese Truck brand into a nationally recognized brand, our ability to develop a successful and profitable business model that includes both company-owned and franchise grilled cheese truck operations, our ability to raise capital in a Regulation A+ or other securities offering, our ability to execute our proposed national rollout through multiple sales channels, our ability to rollout gourmet food trucks, small-footprint retail, pop-ups, kiosks and food carts. Any or all of the forward-looking statements in this press release may turn out to be inaccurate or wrong. This can occur as a result of inaccurate assumptions or as a consequence of significant known or unknown risks and uncertainties, including the risks related to the Company's ability to raise necessary capital to fund its growth, operate its business successfully given the lack of track record and early stage of operations, manage growth effectively, comply with regulations applicable to its business, compete successfully given the high level of competition, and retain and engage talented employees and key personnel necessary to execute the company's business plan. Because of these risks and uncertainties, the Company's actual results may differ materially from those that might be anticipated from its forward-looking statements. Therefore, you are cautioned not to place undue reliance on such forward-looking statements. The Company undertakes no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by applicable law. All trademarks and logos referenced herein belong to their respective companies.
Full News Story: http://pressreleasejet.com/news/the-grilled-cheese-truck-engages-al-hodges-as-chief-executive-officer-and-president-food-industry-veteran-to-architect-national-brand-rollout-through-multiple-sales-channels.html
Distributed by Press Release Jet
Media Contact
Company Name: Big Cheese, Inc. d/b/a The Grilled Cheese Truck
Contact Person: A.J. Cervantes
Email: firstname.lastname@example.com
Phone: 786.749.1221
Country: United States
Website: trilogy-capital.com


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An Appraisal of Nigerian Newspapers Coverage of Women's Participation in 2007 General Elections
The professionalism of media is crucial at all times especially during election periods to promote fair, safe and professional media election coverage. It is a truism that the media play an indispensable role in the proper functioning of a democracy. Discussion of the media's functions usually focuses on their "watchdog" role: by unfettered scrutiny and discussion of the successes and failures...
Oyesomi, Kehinde Opeyemi
OYESOMI Kehinde Opeyemi » Dr. OYESOMI, Kehinde Opeyemi, nee Farinde, is a lecturer at the Department of Mass Communication, Covenant University, Ota, Ogun state, Nigeria. Her responsibilities as a lecturer include teaching, advising, project supervision, research and community activities. she teaches Journalism and Public Relations courses. she has the task of developing the content of these courses, identify reading... view full profile
Female Genital Mutilation and its challenges for Nigeria's development in the 21st century: A communication perspective.
Effective Use of Information Sources for Breast Cancer Care: Interplay of Mass Media and Interpersonal Channels
Where is the African culture? Assessing the uniqueness of indigenous communication in galvanising women's political participation at the local level

subset: commoncrawl


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Customer service is important for any business to succeed. If you own a gym, your revenue source will be directly linked to your membership base. In order to ensure that your gym business survives and remains competitive in today's fitness industry market, you have to consistently provide your members with high quality service. Customer service plays a vital role in member acquisition and member retention. Gym members that are satisfied with the service being provided by your fitness business will automatically come back to your gym and spread the word to their family, friends, and co-workers. For service providers, like fitness facilities, it is imperative that quality of customer service is always the top priority.
How to provide quality assurance to potential customers
Getting customers into a gym can be a really tedious task. To attract customers gym owners have to assure their customers that the services that they are offering have a good first impression. The first way of assuring your customer that you set the service standards high is to provide tasteful marketing and promotional campaigns. Be sure not to alienate a particular segment of your target population because you really do not understand the full connotations of a trendy meme.
How to provide good customer service to existing members
When looking at the quality of service that is provided to a member, you have to take a cold hard look at your employees because they are the ones that are providing the service. They are the face of your business. The main focus of trainers, nutritionists, fitness instructors, and administrative staff should be to ensure that the member is satisfied and on a direct path to achieving their fitness goals. Before opening a gym it is important for owners to train their staff about the basics of customer communication and how to interact with the new and loyal members alike.
The first step to ensure good customer communication is to appearance standards. A member will have a difficult time communicating a particular need or concern to a staff member if they cannot identify them as gym employee or if the gym member is too distracted by the employee's disheveled appearance. Hence, it is important for all employees to wear the gym's uniform as it gives the member the impression that the establishment is unified and professional.
The next step is to ensure that the member and your staff are on a first name basis. It is important for employees to familiarize themselves with all the members who regularly visit the gym. This way the member feels comfortable while training and does not feel left out or alienated. Make sure that your employees names and titles are visible in the form of a tag or a badge on the uniform. So, if members need specific help from a trainer or the manager, they will not have any problem in approaching them.
Not only is it important to be able to open the lines of communication by taking tearing down any inapproacha
ble barriers, but you also need to consider how your employees communicate with your members as this is an important measuring stick for the quality of the service provided. TechRepublic posted an article by Attorney Calvin Sun, who does a fantastic job at outlining 10 effective ways to communicate with customers. Although the article's language is directed at the tech industry, his tips can be easily transferred to the gym industry. Take a few moments and check it out!
Go the Extra Mile
New and loyal members alike are always happy when a business goes the extra mile and does something special to make them happy. Gyms can send welcome letters, call and send birthday cards, and congratulatory notes whenever the member celebrates his birthday, gets a promotion, or has reached a particular fitness goal respectively. If a member finds out that these are the extra services being provided by your gym, there will be no hesitation that they are being provided with high quality service. Your members will also not hesitate to talk or tweet about it either.
Over to you…
How to go the extra mile for your members?
How do you educate your employees on effective communication tactics?


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|Project by Jay Gerig
|posted 02-20-2016 05:56 AM
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These shelves are made from 3/4" mahogany. I based them on this plan here (though I altered all the dimensions to suit my taste and needs): http://www.vintagerevivals.com/2015/05/15-simple-diy-shelf-seriously-cute.html
-- "This is hell, but I planned it, I sawed it, I nailed it, and I will live in it until it kills me." - Alan Dugan


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Condo Building of the Week
Over the next few weeks, we'll be revisiting a blog feature from August 2012 – "Top 10 High Rise Condo Buildings," which highlighted several of Philadelphia's luxury properties. This time around, we'll take more of an in-depth look at each building's history, along with updated information on current sales & vacancies. Last week, we featured "The Murano," in Logan Square. This week, we continue with The Residencies at the Ritz-Carlton.
[caption id="attachment_13591″ align="aligncenter" pool, gym, washer/dryer & more. Just steps from Suburban Station.
Available Units: http://bit.ly/12VqWpd
Center City Real Estate Blog, The Residencies at the Ritz Carlton, Wikipedia
This is brought to you by Philadelphia Real Estate Blog
To view every Philadelphia Real Estate Listing, including Philadelphia Condos visit www.CenterCityRealEstate.com
Twitter: @CenterCityPHL | Instagram: @CenterCityPhilly | Pinterest: @CenterCityPHL


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Weight Loss Programs for Cincinnati & NKY
Trying to lose weight, but getting frustrated? Are you not losing fast enough? Or maybe you've lost weight, but you just can't seem to keep it off? Your journey to health and wellness begins here and now!
Rejuvene offers a variety of weight loss programs to fit your needs!
Weight Loss Program
The Optimal You Plan is the first step in your weight loss journey. With this diet you'll experience the momentum push you've been looking for with your weight loss. More importantly, you will learn the tools and lifestyle modifications you'll need to keep your weight off long-term.
This plan has been adapted utilizing patient experiences, findings, and research by Dr. Sillins and research done by A.T.W. Simeons, MD as conveyed in his manuscript, Pounds and Inches: A New Approach to Obesity.
We offer programs tailored to your lifestyle that encompass 4-phases: 23-day, 30-day and 40-day, based on the amount of weight you would like to lose and to ensure the most effective conditioning for immediate weight loss and long-term weight management after Phase 2.
Diet Counseling
Consult with a Doctor to share your weight loss goals and to review your current eating patterns. Healthy nutrition and successful weight loss techniques can be confusing. Analyze your food choices and clear up confusing nutrition information so you can be successful with your weight loss efforts. Together you'll design a plan that will help you lose weight, but will also be realistic and include some of your favorite foods. You'll also learn and practice behavior techniques that will help keep your weight off. Meet with the Dietitian only once or set up regular visits to help keep you motivated and on track.
* Expert counseling from our Doctor and staff.
* Enjoy your favorite foods
* Realistic healthy eating for weight loss and weight maintenance
Intense Weight Loss Program
If you desire a fast-paced weight loss, then our Optimal You program may be what you are looking for!
The diet program is a 4, 6, or 10 week eating regimen that will maximize your weight loss in a short period of time. After that, you will transition you into a higher calorie level and more normal eating and food choices. Through the transition, you will learn behavior modification techniques and skills to keep your weight off. Weekly accountability will help you meet your goals.
What are you waiting for? Call today to get started 859-429-3333


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Fully catalogued Work in progress
Barrie House
1937Architect: Osborne Howard Leicester
Borough: Westminster
Building named after J M Barrie, the author of Peter Pan. Flats vary from two to seven bedrooms. The access is single core but with one main stair and three service stairs. There is a basement garage. The contractor was Griggs and Son...


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Kevin Martin is the director of the Kalish visual editing workshop. Previously Martin was the photo director at the North State Journal, a new newspaper based in Raleigh, North Carolina, a photo editor for the Associated Press in New York, visuals editor at the Knoxville News Sentinel and a photo editor at the San Antonio Express-News and The Advocate in Baton Rouge, Louisiana. Martin has a master's degree in photography from Ohio University and a bachelor's degree in journalism from Eastern Kentucky University. Before seeing the light of picture editing, he was a staff photographer at The Augusta Chronicle in Georgia.
Martin is also is a past-president of The Associated Press Photo Managers and a past executive board member of the National Press Photographers Association. In 2014 and 2015 he was a juror for the Pulitzer Prize in news and feature photography.


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The goal of the Lighthouse Catechism is to guide children with the light of the gospel and guard them from false teaching. Take advantage of this resource by helping your children memorize some of the most crucial doctrines of the Christian faith.
Through TCKids, we want to shepherd children to treasure Christ
by helping them know the gospel, show the gospel, and grow in the gospel.
We would love to see you and your family visit TCKids at The Church at Trace Crossing this Sunday.
Join the fun and experience a world where kids learn the truth about Jesus
in a way they enjoy and understand.
sunday mornings
Every Sunday morning, babies through preschoolers experience safe, age-appropriate environments where they are taught and shown the love of God in Jesus.
wednesday evenings
During the Fall and Spring semesters, children (babies through grade 6) break off into age-appropriate, gospel-centered equipping classes where they are introduced to Christian doctrine and practice.
sunday evenings
During the Fall and Spring semesters, children (babies through grade 6) meet together at our campus from 5:30-7:30pm where they are taught biblical truth based on Trace Crossing's current sermon series.
Upcoming Events
Hang tight while we look up scheduled events...
planning to visit tckids?
Your First Visit
Look for a Trace Crossing Greeter. He or she will escort you to the Preschool Wing. We'll meet your family, check your child into our database system, and one of our volunteers will lead your child to their age-appropriate room. We'll ask for your family's contact information and any special instructions (allergies, special needs) for your child.
how check-in works
After your first visit, a TCKids team leader will help you check in your child at the welcome desk in the Preschool Wing. Team Leaders will print matching identification tags that are exclusive to your family and visit. After the service, you'll return to your child's classroom and show your tag in order for your child to be released back to you.
the ride home
On your way out the door, be sure to pick up a Big Truth Card. It highlights the main point for today's Bible story and gives you the memory verse for the month. As you drive home, ask your child, "What did you learn about Jesus in today's story?" It's our goal that every child can answer this question every week.


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Gov't to Review Cases That Used NSA Data
Attorney General Eric Holder announced Friday that the Justice Department will begin examining criminal convictions made with evidence obtained through the National Security Agency's warrantless "surveillance" programs. Holder's announcement follows on the heels of a similar case last month, when the Justice Department notified a defendant — an immigrant from Uzbekistan — that some of the evidence against him had been gathered by the NSA's spy programs. This was the first time such information had been made public. Like in the Uzbekistan case, if the upcoming review finds that evidence against specific defendants had been gathered using NSA programs, these defendants will be informed.
"We have a review underway now," Holder informed the Washington Post. "We will be examining cases that are in a variety of stages, and we will be, where appropriate, providing defendants with information that they should have so they can make their own determinations about how they want to react to it."
So, what options would the defendants then have? Well, if NSA data collection did lead to a conviction, experts believe that the Justice Department's notification of NSA involvement could provide a legal challenge to the surveillance programs. WaPo reports that the Supreme Court has previously declined to hear such a challenge, because there was no proof that the noticeably warrant-less surveillance had led to any convictions. Basically, no one had legal justification to sue.
In the case of the Uzbek who was notified that the spy data will be used against him, he's suspected of providing material aid to a terrorist group, and will soon face trial. It's unclear if he will act on the information the Justice Department gave him about NSA-supported evidence. His case was the first, but there will be more: the notifications will come on a rolling basis as the Justice Department learns of the individual cases.
Everyone remembers how this all started: Files exposing the NSA surveillance programs were leaked to journalists by former NSA contractor Edward Snowden. In addition to collecting metadata, as well as contact lists and subject lines, from the correspondence of U.S. citizens, the NSA also apparently spied on the leaders of Brazil, Mexico, and Germany. Later, the British government, which was also implicated in large chunks of the spy programs, detained the partner of American journalist Glenn Greenwald while he was transferring flights in London. They said that Greenwald's partner, David Miranda, was thought to be carrying files that might endanger the lives of Secret Service agents.
Throughout the scandal, President Barack Obama has maintained that he was not aware of the extent of the spy programs. As Bustle has noted, it seems peculiar, to say the least, that spy agencies were running amok without the president's knowledge. And it would be even more odd that, if this were true, there haven't been any high-profile firings — considering how much damage the leaks have done to Obama's international image.
In any case, it's promising that the Justice Department is looking into how the data obtained by the NSA is used. Because the program was shrouded in so much secrecy — and because the heads of spy agencies exhibited such contempt for oversight by democratically elected officials — it's good to have hope that the Supreme Court might finally set some guidelines about what is and is not allowable. Plus, it'll be an interesting showdown in the court: What side will arch-conservatives who claim to have a deep-seated belief in personal liberty take?


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Why Did the U.S. Allow Its Cities to Decline?
Gruber explains how "cultural bias against the city" had an effect:
"In Europe during the same period of economic and technological change cities largely retained their primacy for the middle and upper classes, while the suburbs became the home of the working-class and poor. In the U.S., the single-family house in a faux rural setting became the norm for the middle-class, and even in metropolitan areas that remained relatively prosperous the middle-class largely abandoned central cities. To say that suburban sprawl happened because of favorable governmental policies only begs the question why those were the policies. Did they reflect a bias against cities, rooted in Jeffersonian rural populism?"
Gruber notes the impact of automobiles, but points out that other nations have managed to incorporate cars without destroying their urban centers. He also considers the impact of immigration and racism, and the ideological shift that came from modernism.


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You may need to install Flash or enable it on your browser to play the puzzles.
Can't see the Full Screen puzzle? Your pop-up blocker probably prevented it from opening. Click here to relaunch the pop-up.
Still can't get it to work? Please contact us for additional help
Jigsaw of white, woolly sheep grazing in a green grassy field. The field is high up in the mountains.


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Pochettino: Negotiating with Levy is easy!
Tottenham boss Mauricio Pochettino has said that he found negotiating with club chairman Daniel Levy much easier than others have in the past.
Pochettino does not have an agent and negotiated his own contract - a lucrative £8.5m-per-year deal.
And the Argentine joked that he found the talks easy to conduct, despite Levy's reputation for being difficult to do business with, summed up by Sir Alex Ferguson's famous quote that bartering with him was "more painful than my hip replacement".
"For me, it's the opposite," Pochettino said.
"For me, if there was one person that was easy to do business with, it was Daniel.
"Historically, other managers were the opponent of Daniel, they always fight with him. I think it's only me maybe that has a good relationship with him.
"It was not difficult, I think it was more difficult for him than me. It was difficult because I am the manager and he cannot upset me. If we are talking about extending a contract or giving me more money, you need to be careful.
"With agents, you can talk very openly and say anything you want and the agent will manage the situation. But when you are talking directly to your manager, you need to be careful because one word can change the negotiation or change your mind. For him, that was new and it was tough every time he needed to talk to me."
Tottenham are set to endure a second successive transfer window with no new arrivals and Pochettino explained that poaching talent from smaller clubs is not as easy as it used to be.
"It's true that today the Premier League is so competitive and today for Tottenham to go to, I don't know, to Southampton and sign a player like they used to do, like with Bale – today, it's so difficult.
"It's the same situation that happens with big clubs. Like you say, the example of Manchester [United] picking players from Tottenham, Tottenham picking players from whoever, so I think everything has changed."
Spurs face Manchester United at Wembley on Sunday afternoon, hosting a club who are reportedly intent on luring Pochettino away in the summer.


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NPR Cuts Jobs, Cancels Programs
Folkenflik reports on the NPR layoffs, on 'All Things Considered'
National Public Radio has announced the elimination of 64 filled and 21 unfilled positions as part of cuts throughout the organization. Two shows, News & Notes and Day to Day, were canceled.
ROBERT SIEGEL, host:
Like many industries, the news business is struggling in these tough economic times. There have been layoffs at Gannett's newspapers, and even a bankruptcy filing at the Tribune Company. As NPR's David Folkenflik reports, NPR is not immune.
DAVID FOLKENFLIK: NPR announced today it is canceling two daily national shows, "Day to Day" and "News & Notes," as part of a sweeping effort to close a projected $23 million budget gap. NPR is reducing its workforce by 7 percent. Dana Davis Rehm is NPR's senior vice president for strategy and partnership. She says it is hard to lose valued, capable colleagues.
Ms. DANA DAVIS REHM (Senior Vice President for Strategy and Partnership, National Public Radio): This is driven entirely by the economic crisis that's sprawling around us and every other organization and company in America and maybe the world.
FOLKENFLIK: The two California shows will air their final broadcasts in March. In all, 64 NPR employees will be laid off, including 34 from the news division. Another 21 empty jobs will be eliminated. For all that, a newsroom of roughly 300 journalists will remain. Interim CEO and President Dennis Haarsager says NPR sought to tailor these cuts to do the least harm to the core mission of news gathering, and that officials haven't given up their ambitions for NPR.
Mr. DAVID HAARSAGER (Interim CEO and President, National Public Radio): I think once this recession has passed, we'll be able to revisit those aspirations and move forward in a very positive way. Unfortunately, we don't know how long that's going to be.
FOLKENFLIK: Some notable NPR hosts and correspondents were among those that were laid off today. They included Madeleine Brand [and] Jacki Lyden. The ironic thing is that the audience for NPR shows is growing. Ratings estimates show that NPR news programs attracted record levels of listenership last spring. Dana Rehm.
Ms. REHM: There is significant evidence that NPR is more important to audiences on air and online than ever as people seek to understand the extraordinary events that are occurring around us.
FOLKENFLIK: Corporations sought to reach those listeners with increased underwriting in recent years, and that helped to spur growth. NPR added new beats, new bureaus, and kept up one of the most expansive foreign operations of any American news outlet. But now, much of that underwriting has withered along with the fortunes of the financial companies and car manufacturers that paid for it. Expected revenue from investments evaporated as the value of publicly traded stocks tanked. NPR's board has authorized a $15 million drawdown from the company's operating reserves, much of which came from a bequest from the late Joan Kroc. The larger endowment created from her gift remains untouched. David Folkenflik, NPR News, Washington.
Copyright © 2008 NPR. All rights reserved. Visit our website terms of use and permissions pages at www.npr.org for further information.
NPR transcripts are created on a rush deadline by Verb8tm, Inc., an NPR contractor, and produced using a proprietary transcription process developed with NPR. This text may not be in its final form and may be updated or revised in the future. Accuracy and availability may vary. The authoritative record of NPR's programming is the audio record.
NPR Announces Cuts To Staff, Programs
The Press Release
NPR News announced Wednesday that it is canceling two daily radio programs — Day to Day and News and Notes — as part of a broader effort by the company to close a projected budget shortfall of $23 million for its current fiscal year. Overall, NPR will cut 7 percent of its work force and slash expenses further around the company.
"It's a very difficult time for us all, but NPR is not exempt, unfortunately, from the recession that has covered our country in the last several months," Dennis Haarsager, NPR's interim president and CEO, said at its corporate headquarters in Washington, D.C. "We simply must react to it in a responsible way — and that's what we've tried to do."
The two shows will go off the air on March 20, and 22 journalists working for them will lose their jobs, including hosts Madeleine Brand and Farai Chideya. The shows are both based in Culver City, Calif., at NPR West, a major satellite operation.
Day to Day was designed as a midday complement to mainstays Morning Edition and All Things Considered, while News and Notes, a successor to The Tavis Smiley Show, was intended to draw more African-American listeners. Beyond the two shows, another 12 journalists will lose their jobs throughout NPR News.
Companywide, NPR is laying off 64 people and eliminating 21 other positions that are currently vacant. NPR News will still have more than 800 employees on staff, including about 300 journalists.
The shortfall was driven in large part by the erosion of corporate underwriting, Haarsager said. Earlier this year, budget planners counted on receiving $47 million from those corporate spots and online ads. Now, he said, the company projects that it will receive just $32 million in revenues for the current fiscal year.
Interest payments from an endowment created from the bequest of the late Joan Kroc, which have typically paid out about $10 million a year to NPR, were wiped out by the sharp downturn in the financial markets. However, NPR's board authorized the company to draw down $15 million from the company's operating reserves, most of which also came from the Kroc gift.
In interviews, company officials said they decided to try to make big, specific cuts to mitigate their effect on NPR's ability to gather and report the news.
NPR has grown mightily in the past dozen years, thanks to the Kroc bequest but also to sharp rises in listening audiences and corporate underwriting. NPR has expanded beats and added domestic and foreign bureaus at a time when many of its peers and competitors have scaled back their journalistic ambitions. It has been among the few American news organizations to have correspondents based both in Iraq and Afghanistan.
"This is a hard day for NPR," said Ellen Weiss, NPR's senior vice president for news. Despite the bad news on the revenue front, the on-air and online audience for NPR is up significantly, she said. "At many levels, NPR's best resources are its people. There isn't a single individual person who isn't going to feel pain today," Weiss said. She spoke while traveling in California to meet with employees at NPR West.
But she stressed that canceling the shows should protect NPR's journalistic core and its mainstay news magazines, including All Things Considered and Morning Edition. Haarsager says it is his hope that these cuts forestall future ones down the line, but he says he believes the economic pressures will continue to confront NPR for several more years.
The moves constitute a marked but not total retreat from the big growth at that California facility during the past five years. Journalists for Morning Edition and the news division's national desk will continue to work at NPR West.
Public radio consultant John Sutton says NPR's embrace of funds from corporate underwriters during boom times makes it more subject to market forces than it has ever been. He argues that spending is too high throughout the larger public radio system, and he foresees, if anything, more of a shakeout in how that system is funded.
"Public radio as a whole is still largely based on an infrastructure that is still 20 years old," Sutton says. "It is probably bigger than it should be, given the technology and the way the media marketplace is going."
Until recently, however, NPR seemed to many analysts largely insulated from the severe economic shocks buffeting newspapers and other media companies.
Newspapers have undergone waves of layoffs and buyouts. The Tribune Co., owner of such newspapers as The Los Angeles Times, The Chicago Tribune and The Baltimore Sun, along with 23 local television stations, declared bankruptcy earlier this week. And The New York Times Co. announced that it would borrow up to $225 million against the worth of its new headquarters in midtown Manhattan.
By that scale, NPR's reckoning is far smaller. But executives say they recognize that offers no solace to staffers, listeners and member stations.
"We would not have made this decision to cancel News and Notes and Day to Day" in normal times, said Dana Davis Rehm, NPR's senior vice president for strategy and partnerships. "This is driven entirely by the economic crisis that's swirling around us and every other company in the nation and maybe the world."


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Sierra Avery |
Nursing | Brighton, MI
Best Memory of SVSU
My best memory of SVSU is working at Career Services. I have met some of the most wonderful people through this job and the office acts more like a family.
What Excites Me Most About Commencement Day
I am most excited about finally finishing my education and becoming a nurse.
Plans After graduation
After graduation I plan on being a registered nurse hopefully in a pediatric unit.


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Botanical name: Salvia officinalis
Sage has aromatic, wrinkled silvery green leaves and purple flowers that appear in autumn.
Use Sage in vegetable and meat dishes. Excellent in stuffing for chicken or turkey.
Growing Sage
Sage needs to be grown in very well-drained soil and full sun.
Trim back after flowering.


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Thick and Chewy Gingerbread Cookies
These thick and chewy cutout gingerbread cookies have an intense gingerbread flavor with a delicious and surprising soft chewiness.
Gingerbread is a classic Christmas flavor. I love it. But I have to admit I'm not a huge fan of thin and crispy gingerbread cookies. I've always wanted a gingerbread cookie similar in texture to a really good sugar cookie.
This recipe fits the bill.
These cookies are packed with gingerbread flavor but the texture has a delicious and surprising softness and chewiness that keeps me going back for just one more gingerbread man.
The dough requires chilling and freezing in order for the cookies to keep their shape, but the time invested is well worth it. And as a sidenote, the cookies are egg-free in case that happens to be an allergy you are working around.
These cookies are such a favorite, we make them every holiday season. One taste, and I think you'll know why.
As with all cutout cookies like this, you can get as fancy as you like decorating the cute little shapes.
You can see I leave the decorations pretty simple (that might have something to do with the fact that I'm usually juggling a child or three while making and decorating).
And you don't have to feel pressured into only using a gingerbread person cookie cutter, either! Obviously, you can use whatever shape of cookie cutter your little heart desires.
As I mentioned above, because the texture of the dough is a little different than other cutout gingerbread cookies, it's important to chill the dough per the recipe so the cookies don't spread or flatten.
One last note, the baked and cooled cookies freeze great! I stack them in large tupperware-like containers with sheets of parchment or wax paper inbetween the layers.
As an Amazon Associate and member of other affiliate programs, I earn from qualifying purchases.
Thick and Chewy Gingerbread Cookies
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* This race will be decided by ranked-choice voting. If no candidate wins more than 50 percent of total votes, the Maine secretary of state will conduct a second ballot tally at a later date to determine the winner.
0% reported- Race has been called
- Candidate has been eliminated


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Orange Grove Charter School is one of the two schools in the Charleston County School District (CCSD) which elected to become autonomous and be governed by an independent board of directors. It left the CCSD with an Average rating in 2007 and attained an Excellent rating by 2010. The school has maintained the Excellent rating ever since.
As a charter school, Orange Grove Principal John Clendaniel has the flexibility to select curriculum materials, hire faculty and implement programs. The school started its middle school program during the 2015-2016 school year at the former Oakland Elementary School building on Arlington Drive. The school currently enrolls 1020 students and will expand to 1150 students next school year when it adds an eighth grade class. There are currently 360 students on the school's waiting list.
Orange Grove Middle School just had its lease extended at its Oakland campus by the Charleston County School Board with the option to eventually move into the former Middleton High School building on William Kennerty Drive. A successful fundraising program has enabled the school to equip each of its middle school students with a Chrome books tablet.
Satisfaction with the school is incredibly high. In an end-of-year survey from the past school year, 96% of students and parents indicated that they are satisfied with the school. The school has a 95% teacher retention rate. A walk down the school's orderly hallways reveals many smiling students and teachers.
Orange Grove Elementary uses the SRA self-paced reading program in kindergarten through second grade. Students typically spend 90 minutes per day on reading and math. They also receive Spanish language instruction starting in kindergarten.
The school places an emphasis on individualized learning. Teachers are trained to interpret student test scores and give them more work in the skill areas which most need emphasis. There is an Academic Specialist at each grade level who works with students in small groups to boost their skill development.
Principal Clendaniel aims to create a family atmosphere in the school. "I want everyone in the school to feel safe, loved and respected," he says. "It's not all about test scores. We have a lot of fun at Orange Grove." As an example the students participated in a costume parade in the Sandhurst neighborhood the Friday before Halloween.
There is a strong emphasis on character development at the school and students receive recognition for displaying exemplary behavior as part of the Character Cub program (the school mascot is a tiger). The school also focuses on career opportunities and holds several career day programs during the year.
Enrollment for the 2017-2018 kindergarten class will take place in January. Applications are available at http://www.ogesc.com.


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netCommons at UNESCO
The netCommons project, together with members of its advisory board visited on January 30, 2018, the offices of UNESCO in Paris for a discussion on the potential impact of Community Networks for several Internet Universality Indicators.
Leonardo Maccari, Maria Michalis and Melanie Dulong de Rosnay did three presentations to the UNESCO staff with focus on the technical feasibility and social impact of CNs, the perception of CNs from interested people and the impact of the legal system on CN respectively. All three themes produced an informed discussion with the UNESCO working group on the Internet Universality Indicators which was extremely fruitful to enlarge the interest on CNs to a wider community, and to improve the indicators. The netCommons project was asked to participate at the consultation on the indicators, and to produce a formal feedback.
This was a superb achievement, since the Indicators will be used by UNESCO and other international bodies as the base criteria to evalaute national policies regarding Internet connectivity, and, most of all, their impact on human rights. CNs should have a say on this, as they represent the forefront of a movement of re-appropriation of communication means, with a strongly ethical component, and netCommons tries to make sure that their importance is reflected in the Indicators.
We worked on targeted suggestions, modifications and additions to the Indicators and our proposal is now submitted, and will be presented in more detail in a dedicated post.


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There's no doubt that Windows PCs have become inherently more secure since the days when Windows XP was the corporate operating system of choice. As far back as 2010, official reports revealed that the malware infection rate for Windows 7 was nearly five times lower that the rate for XP (source: CNET ).
However, with the best will in the world, there will always be times when the malware authors and hackers get a few steps in front of Microsoft and the Internet security vendors. Often, nowadays, they do so by using social engineering techniques to trick those less competent users into installing something they shouldn't. When this happens, you're left with a cleanup job.
As an MSP owner, you and your staff are, inevitably, going to find yourself in situations where you need to clean up a client PC. So, here's a guide to how best to tackle it.
Often, customers will have no idea how deeply malware can bury itself into a computer's operating system. Files can hide themselves, move around and morph, and often (especially on Windows PCs), a single malware attack can leave multiple infections. Ensure customers understand that a cleanup can take time so that they don't become impatient, which they may - even if it was them who opened the suspicious attachment!
There comes a point in every malware cleanup where it becomes more time-effective to reinstall and rebuild than to continue attempting to clear every trace of infection. Decide up-front how long should be spent on a cleanup, so you don't invest multiple hours and then reinstall anyway.
If you've identified an infected computer get it straight off the network. If you have any suspicion that cross-infection could have taken place, test-scan some other PCs to be sure.
Some of the very best malware removal software can miss certain infections. Every IT professional should have two or three reliable removal tools in their armory.
Many malware infections can hide themselves away only to reappear after a couple of reboots. Never assume an infection is completely clear until after extensive double / triple checking and rescanning.
If you can ascertain how a malware infection entered a client PC, educate your clients to minimize the chances of it happening again. At the same time, know that sometimes you may never find the root cause, and be ready to explain this to clients. They are often extremely surprised that Internet security software is less than 100% effective.
Be sure to take notes during a comprehensive malware cleanup. Add the documentation to your MSP's internal knowledge base or, even better; share it online with the wider technical community.
Get the latest MSP tips, tricks, and ideas sent to your inbox each week.


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Merren & Chris - Berlin wedding
The #mcwoodswedding
What more could you want than to shoot an awesome Aussie couple in Berlin?
Merren and Chris moved to Berlin for an 'adventure', which was supposed to last a year or two. Three+ years later, and with the addition of little Hayley to the fam, they seem to have settled into the Berlin life for good.
Merren and Chris wanted to show off their Berlin life to all their friends and family, and took guests on a tour of the city by through venue hops and walking routes. It was super thoughtful and full of unique and quirky touches (cue mini schnaps bottle favors).
There was a sweet pre-ceremony reveal at Museum Island, where bike tour guide Merren often takes visitors. Merren's colleages from Fat Tire bike tours even dropped some bikes down for a photo opp! We then headed to the absolutely stunning Clärchen's Ballhaus Spiegelsaal (aka Hall of Mirrors), for a heartfelt ceremony, including ballad vows! A walk down to a local Späti for beer and pretzels followed, and then a short trip on the Ubahn took guests to the reception at Schönwetter beer garden.
Merren and Chris's happiness was overflowing and contagious, and made for the most amazing day! We are so lucky to have been a part of it!
Sunshine, glorious florals, and classic English styling in Oxfordshire.
What more could a photographer want?
Well, I was lucky enough to shoot Anisha and Arun's intimate wedding ceremony at the Old Swan Minister Mill as my first U.K. wedding earlier this year and it was nothing short of stunning.
Anisha reached out to me shortly after moving to Oxford asking me to cover her special day that was only to be attended by close family and friends; a special affair that required a candid and discrete approach across the afternoon.
Honestly, I could not have wanted for a more picture perfect couple who executed classic style in such an honest and down-to-earth manner. Just two people in absolute love celebrating it with a sincere gathering of wonderful people in a picture perfect setting.
Much love to you awesome folk!
Another awesome U.K. wedding wrapped up and also the smallest one I have had the absolute pleasure to capture!
Lara and Mark's day was a simple affair where they exchanged vows at the local Register Office in Hammersmith, which also just happens to be situated right near the river Thames. Their day was witnessed by two of their dear friends and the wonderful people who had me come along to capture it all, Sara and Tom. The ceremony was an absolute cracker of an affair with the two city officials and celebrants fighting to hold themselves back from dancing to the Motown music playlist that the wedding party had loaded up.
One of the great things about the U.K. are the ample pubs that even without a plan you can find, grab a drink or three in and have a great time. All of 100m away from the town hall was the gorgeous little pub known as The Dove that sits beside the river Thames. The champagne was popped and several pints of ale were drunk by all, which sparked everyone's enthusiasm to get dirty by walking into the low tide of the river for photos. Did we ruin our shoes in the muck? Sure did! Was it worth it? Well, look ahead and tell me what you think in the comments below. This truly was a celebration of love and true friendship.
Much love all you awesome folk!
- Mathieu
Take note, grooms who think they can DIY at their wedding. If you're not prepared to custom build an altar and a tree-house for your big day, then you've got nothing on Joseph.
Liz and Joey's wedding was a perfect example of paying homage to young love, and creating a relaxed celebration centered around family, friends, and pets! Every wedding should have pets! Even if they break out of the fence frequently during inopportune times.
Set in the beautiful beach side suburb of Portalrlington where Liz and Joey grew up and got together as a couple, each part of their day was only ever a small walk or drive away, and the collection of classic Aussie muscle cars made each short trip a totally stylish blast! Perhaps one of the sweetest parts of the day though was returning to the street lamp that Liz and Joey got together underneath years before for a few quiet moments. So simple yet so significant. Love it!
My sincerest appreciations go out to Liz & Joey for having me capture such a wonderful, warm day in Australia. Every bride and groom could learn from these two about how to rock it in relaxed DIY style.
Much love,
From start to finish, Anna & Chris created one of the most memorable and fun weddings I've ever had the pleasure of being a part of. They won me over even more by feeding me a deluxe meal, not once, but twice! Yep, it's that simple with me.
But seriously!
Having spent a few occasions getting to know Anna & Chris before their big day (engagement session here) I knew they'd just have an amazing vibe to their wedding - chilled, full of smiles, food, and oh so much love! The elegant and stylish simplicity of their attire, the jovial loving bounce they had for each other all day, and an absolutely blistering first dance! It truly was the perfect balance of organised and footloose fun. I cannot thank them enough for having me capture it all!
Much love and one big ol' blog post of joyful images,
Shout out to the fine venue folk at The Farm Cafe for being on point and keeping me well hydrated!
February 2019


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Class: Cars, Custom — Model origin:
The vehicle is part of the movie
◊ 2006-06-16 22:38
◊ 2006-06-16 22:40
◊ 2006-06-17 06:22
|That is a pretty cool car. I love that evil look!
◊ 2006-07-04 20:19
|They smash the hood and grille to make it more sinister looking.
◊ 2007-01-16 01:59
|It looks looks like something from a cartoon.
◊ 2007-01-16 02:08
|I'd love to have this car, complete with clattering valves and burned-out glasspack mufflers. Slower traffic would move over FAST.
◊ 2007-01-23 22:01
|i loved the movie i hope they make another.make the car come back.
◊ 2007-01-23 22:05
|i wish i had that car,it is cool,i watch it a lot.make the car come back from hell.
◊ 2007-09-11 07:03
|When I first watched this movie I wanted this car.
◊ 2008-04-01 14:56
◊ 2008-09-12 02:15
|One thing about this movie i never did understand is did that old charger driving by itself or is somebody in there?
-- Last edit: 2008-09-12 02:16:36
◊ 2008-10-16 00:18
|Awesome car
◊ 2012-01-08 05:42
someone was driving it because a car cannot pull you into itself.
◊ 2012-03-28 07:29
|I should make my 74 SE look like this one
◊ 2012-06-02 23:42
|wait but at some points the inner headlights seem to be broken but when the car is circling the house they are both on but's that's the only time the inner headlights are on even at night
◊ 2012-06-27 01:47
|I noticed that the shot where the charger goes off a cliff was used in the Taking Back Sunday music video "MakeDamnSure."
◊ 2012-12-14 14:50
|Knows anybody where the car now is? or whats happen with the car after the movie?
◊ 2014-03-10 13:24
|Yes, this car is very well have altered the radiator grille. Looks, I think even better than the normal Charger.
I think one, his front now a bit like the Dodge Coronet 1970? ))
◊ 2015-08-16 12:21
Someone was driving the Charger and he was a murderous pedophile who had a thing for young girls, what his MO was that he picks his target and stalks them and then abducts them for his sick fetish and when he was done with them, he would dump them alive or if they put up a fight, he would sometimes kill them.
The FBI Behavioral Analysis Unit would profile him as:
. A white male.
. Aged in his late 30s, early 40s.
. Most likely had a failed relationship.
. Most likely had a juvenile record for minor sexual offences that was later sealed either on his 18th or 21st birthday.
. Most likely started as a peeping tom in his teens.
. Most likely has limited means based on the state of the car.
. Most likely done this in other states as his hunting ground is on the main highways.
-- Last edit: 2020-04-28 13:42:29
◊ 2017-08-06 18:47
|I don't get why the cops couldn't identify this car by its make and model, and yet could only identify it by the year it was built.
Is this town just not familiar with what a Dodge Charger is? If so, then they obviously never watched Bullitt or The Dukes of Hazzard.
-- Last edit: 2017-12-29 16:53:47
◊ 2017-10-01 04:25
|looks like one of the (too numerous ) car-related flaws in scripts ...
◊ 2017-11-11 05:28
Not to mention, they called this car a sedan, even though it is clearly a coupe. It wouldn't be until 2006 when the Dodge Charger would become a sedan.
◊ 2017-12-06 17:07
|Do those windows need to be so heavily tinted? I mean, I get the idea that we're not supposed to see the villain, but just because you don't want us to see him, it doesn't mean you should put heavily tinted windows on his car. Seriously. The tint on those windows is so heavy, it looks like not even the driver can see through them.
Look at the Peterbilt from Duel, the movie that this movie is obviously ripping off. That truck's windows weren't tinted, and yet we still never saw the driver. All we ever saw of him were his shoes, hands, and his silhouette. Here, we can't even get a good glimpse of this guy's silhouette. However, I somehow managed to see his silhouette through the windows. But because of the film's poor quality, it's pretty hard to see.
-- Last edit: 2019-06-25 23:37:16
◊ 2019-08-16 06:12
|What a BEAUTY. Love the Chargers from that Era, that Evil front looks sick.
◊ 2019-08-16 06:13
The synopis from the film says that a dude drives it. And rapes girls with it. But no one knows who's that guy driving it.
◊ 2020-08-30 05:53
|1974... the last year the Dodge Charger would be a cool-looking car until 2005.
-- Last edit: 2020-08-30 05:53:47


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Author(s): Christopher Kelly
A mesmerizing debut novel of vengeance.
Tortured by memories of being bullied all through school, Ben Reilly sets out to finally put his demons to rest. Although Terrence O'Connor, the beautiful boy who was his tormentor, is now a successful writer in Manhattan, he is also a man searching out his own identity. As Ben and Terrence form an unlikely friendship, hidden motives and long-kept secrets bubble to the surface. Does Ben realize he's fallen in love with Terrence? And can Terrence admit to his own confused feelings? Darkly disturbing and brilliantly written, here is a chilling depiction of the once-victim who unwittingly becomes the bully.


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brm256 | undergraduate
Retail Personnel Management
- Overview
- Topics
- Costs
This undergraduate-level course is 5 This course is available as part of a degree or certificate program. To enroll, speak with an Enrollment Representative.
Course details:
topic title goes here
Measuring Employee Performance in a Retail Organization
- Determine methods to coach employees in developing career-related skills and knowledge.
- Determine performance appraisal techniques for retail employees.
- Develop strategies to resolve employee conflict.
Compensation, Benefits, and Incentives
- Determine strategies to motivate employees.
- Develop benefits and incentives that align with retail industry standards.
- Develop compensation strategies to meet organizational objectives.
Training the Retail Team
- Develop the components of a training program.
- Create work schedules that meet the needs of retail personnel, consumers, and organizational objectives.
Retail Staffing
- Align individuals with jobs based on personal characteristics, work experience, and skill sets.
- Identify sources of qualified applicants.
- Forecast staffing requirements.
Legal and Ethics Issues in Retail Personnel Management
- Describe the legal and ethical considerations of the employment termination process.
- Identify the legal and ethical aspects of managing employees.
- Identify the legal and ethical aspects of the hiring process.
Please ask about these special rates:
Teacher Rate: For some courses, special tuition rates are available for current, certified P-12 teachers and administrators. Please speak with an Enrollment Representative today for more details.
Military Rate: For some courses, special tuition rates are available for active duty military members and their spouses. Please speak with an Enrollment Representative today for more details.
The University of Phoenix reserves the right to modify courses.
While widely available, not all programs are available in all locations or in both online and on-campus formats. Please check with a University Enrollment Representative.
Transferability of credit is at the discretion of the receiving institution. It is the student's responsibility to confirm whether or not credits earned at University of Phoenix will be accepted by another institution of the student's choice.


text:
We will be sending out a further briefing on the key aspects of the report shortly. The pre-budget report focussed on key themes of investment in transport, housing and skills. The PBR drew heavily on all the recent government commissioned reports - further information on these can be found below;
No major tax changes were announced;
The Chancellor has stated that his efficiency programme is on track. Baseline savings will be at least 3 per cent per year across local and central government whilst administrative budgets will be cut by at least 5 per cent over the 2007 CSR period. This will release an extra £26bn;
£9.6bn planned investment in transport in 2007/08;
Inflation-only rise in road fuel duty of 1.25p per litre from midnight; Increase in air passenger duty from 1st February 2007 from £5 to £10 in recognition of the environmental costs of flying; £8bn planned investment in housing; A time-limited stamp duty exemption on all new zero carbon homes;
Capital investment in education to rise from £8.3bn in 2007/08 to £10.2bn in 2010/11;
A four-year educational investment settlement was also announced - a total of £36bn is to be invested in educational institutions over the period;
A further £130m will be given directly to schools in England in 2007/08 to support personalised teaching and extended services;
From the 1st of April 2007, landfill tax will increase by £3 to £24 per tonne; A series of measures to tighten the tax avoidance regime were announced plus further strengthening of strategy relating to the Missing Trader VAT fraud;
The Government is taking action against Managed Service Company (MSC) schemes which avoid paying employed levels of tax and NICS;
Some modernising of the tax system were announced - simplification of tax rules governing life assurance companies and the introduction of a Construction Industry Scheme which aims to help the construction industry comply with their tax obligations whilst reducing regulatory burdens;
Improving the enforcement of the National Minimum Wage to tackle non-compliance and raising penalties for those who are seriously non-compliant; and Individual Savings Accounts (ISAs) will become permanent beyond 2010.


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Metro Pulse, June 12, 2013- An organization has been formed to find and support a candidate against U.S. Sen. Lamar Alexander in next year's Republican primary. The Real Conservative National Committee will have volunteers canvassing the five major metropolitan areas of Tennessee on Saturday (June 15), organizing a ground game as part of its "Beat Lamar" campaign. The goal is to knock on a total of 5,000 doors in Memphis, Nashville, Chattanooga, Knoxville, and the Tri-Cities.
Alexander has been expecting a challenge from the right and has been amassing a campaign war chest. FreedomWorks, a conservative Super PAC, has been around the state interviewing potential candidates, including Knox County Mayor Tim Burchett.(link)
The Real CNC invites you to participate in Beat Lamar Alexander Ground Game Day Saturday, June 15, 2013
The Real CNC - Join conservative activists throughout Tennessee in this day of door to door canvassing. This is the first step you can take to help conservative candidates challenge incumbent RINOs in the House and Senate in the 2014 Republican primaries! The Real Conservatives National Committee intends to change the way the Republican primary election game is played so as to give qualified, boat-rocking conservative candidates like Ted Cruz and Rand Paul far better chances of defeating establishment Republicans.(link)
Who will run against Lamar?
|Glenn Thomas Jacobs, AKA "Kane"
If the best they can come up with to run against Lamar is the professional wrestler known as "Kane," I don't think Lamar has anything to worry about. Glenn Jacobs is a libertarian and a Ron Paul supporter. He considers the tea party "too Republican" for his taste (link). He blogs, mostly on economic issues, and advocates going back on the gold standard and abolishing the Federal Reserve. You can find his blog at this link:Adventures of Citizen X.
Top Stories


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Intestinal microbiota comprises microbial communities that reside in the gastrointestinal tract and are critical to normal host physiology. Understanding the microbiota's role in host response to invading pathogens will further advance our knowledge of host-microbe interactions. Salmonella enterica serovar Typhimurium was used as a model enteric pathogen to investigate the effect of intestinal microbiota perturbation on host susceptibility to infection. Antibiotics were used to perturb the intestinal microbiota. C57BL/6 mice were treated with clinically relevant doses of streptomycin and vancomycin in drinking water for 2 days, followed by oral infection with Salmonella enterica serovar Typhimurium. Alterations in microbiota composition and numbers were evaluated by fluorescent in situ hybridization, differential plating, and Sybr green staining. Antibiotics had a dose-dependent effect on intestinal microbiota composition. The chosen antibiotic regimen did not significantly alter the total numbers of intestinal bacteria but altered the microbiota composition. Greater preinfection perturbations in the microbiota resulted in increased mouse susceptibility to Salmonella serovar Typhimurium intestinal colonization, greater postinfection alterations in the microbiota, and more severe intestinal pathology. These results suggest that antibiotic treatment alters the balance of the microbial community, which predisposes the host to Salmonella serovar Typhimurium infection, demonstrating the importance of a healthy microbiota in host response to enteric pathogens.
Intestinal microbiota, or intestinal normal flora, is composed of a highly complex community of various microorganisms, among them bacteria. Members of the bacterial community contribute to many aspects of intestinal tract development and provide metabolic contributions well in excess of the human genome (14, 31, 32). A healthy microbial community is essential for the health of the host; conversely, imbalances of the microbiota have the potential to promote illness and contribute to the establishment and persistence of various diseases.
Bacteria comprising the intestinal microbiota cluster within a number of phyla. Firmicutes and Cytophaga-Flavobacterium-Bacteroidetes (CFB) are the two phyla that make up over 90% of both the human and murine intestinal microbiotas (12, 24), with Proteobacteria, Actinobacteria, Verrucomicrobia, and Cyanobacteria comprising a much smaller portion. While the compositions of intestinal microbiotas at the phylum level are similar among individuals, and even between humans and mice, high numbers of different species are found within each phylum, with a lot of interindividual variations (12, 14, 24).
Many diseases have been linked to imbalances in the intestinal microbial community, including obesity (41), inflammatory bowel disease (13), colorectal cancer (46), and even atopic diseases (25, 34). For most of these associations, however, it is not clear whether the microbial imbalance is a predisposing factor that precedes the onset of the pathology or is the result of the pathological condition. Diseases such as vaginal candidiasis and Clostridium difficile colitis frequently start following a course of antibiotic therapy that disrupts the microbiota balance (11, 39), which favors the hypothesis that the imbalance precedes the onset of pathology. However, whether this conclusion can be extrapolated to all disorders in question is not known. Furthermore, little is known about the effect of perturbations in the intestinal microbiota on host susceptibility to invading pathogens. It has recently been demonstrated that enteric pathogens interact extensively with the intestinal microbiota (4, 21, 27, 40), thereby prompting the hypothesis that different microbiota compositions, as a result of perturbations in the microbial community, affect the outcome of enteric infections.
To investigate this hypothesis, we disrupted the murine intestinal microbial community with various doses of streptomycin and vancomycin and characterized the achieved perturbations. The effect of antibiotics on intestinal microbiota has been poorly evaluated beyond studies of induction of resistance (26, 35, 47). Additionally, most previous studies used culture techniques to evaluate the effect of tested antibiotics on microbiota (17, 36, 45), severely limiting the scope of assessment. Our evaluation involved culture-independent techniques, providing a novel glimpse at the extent of antibiotic-induced changes in the intestinal microbiota. Streptomycin was chosen as a nonspecific broad-spectrum antibiotic and vancomycin as an antibiotic with a gram-positive spectrum of activity. Both antibiotics are used in clinical practice for a wide variety of infections (Table 1).
After the antibiotic treatment, mice were infected with Salmonella enterica serovar Typhimurium to investigate the effects of the preinfection perturbation on the outcome of infection. Salmonella serovar Typhimurium is the causative agent of enteric salmonellosis in humans and is often used as a model of typhoid fever in mice. It was chosen as the model pathogen since the normal intestinal microbiota of mice provides a barrier to Salmonella serovar Typhimurium-induced intestinal disease (37), making the effects of any perturbation in the microbial community more obvious and easier to evaluate. The doses of antibiotics used in this study were considerably lower than those used in the conventional streptomycin Salmonella serovar Typhimurium infection model (5, 40) and did not significantly reduce the total number of intestinal microbes, providing a better insight into their role in Salmonella serovar Typhimurium-induced disease.
We found that the degree of antibiotic-induced microbial perturbation prior to infection was associated with the ability of Salmonella serovar Typhimurium to colonize the mouse intestinal tract, further perturb the intestinal microbiota, and induce intestinal pathology. A change in the composition alone of the intestinal microbiota (in the absence of significant changes in total numbers of intestinal microbes) prior to Salmonella serovar Typhimurium infection was sufficient to make mice more susceptible to Salmonella serovar Typhimurium, indicating that different subsets of the microbiota may play protective roles or enhance susceptibility to enteric infections.
Mice.C57BL/6 female mice (Jackson Laboratory, Bar Harbor, ME) were housed in the animal facility at the University of British Columbia (UBC) in accordance with guidelines of the UBC Animal Care Committee and the Canadian Council on the Use of Laboratory Animals and infected at 4.5 to 5.5 weeks of age. Mice were fed a standard sterile chow diet (Laboratory Rodent Diet 5001, Purina Mills, St. Louis, Missouri) ad libitum throughout experiments. Control mice received sterilized but not acidified water throughout the experiment.
Bacterial strains. Salmonella serovar Typhimurium strain SL1344 (16) was grown at 37°C with shaking (200 rpm) overnight in Luria-Bertani (LB) broth supplemented with 100 μg/ml streptomycin. The strain is resistant to vancomycin and streptomycin.
Mouse infection.Mice were treated with streptomycin (Sigma) at 150, 300, and 450 mg/liter and vancomycin (Sigma) at 50 and 100 mg/liter in drinking water for 2 days. As mice drink, on average, 3 ml of liquid per day (6), the average consumed dose of antibiotics was calculated (Table 1). Control mice were given drinking water without antibiotics. After 2 days, the antibiotics were withdrawn and mice were infected with 2.7 × 108Salmonella serovar Typhimurium CFU/mouse by oral gavage. Uninfected control mice were given 100 μl of sterile LB broth. At 3 days postinfection, the mice were euthanized by CO2 asphyxiation and tissues were harvested aseptically for further evaluation.
Tissue collection and bacterial enumeration.Ceca and colons were collected in 1 ml of sterile phosphate-buffered saline on ice and homogenized with an MM 301 mixer mill (Retsch, Newtown, PA). Serial dilutions of the homogenates were plated on LB or xylose-lysine-deoxycholate (Oxoid) agar plates containing 100 μg/ml streptomycin to enumerate Salmonella serovar Typhimurium colonization. Serial dilutions were plated on LB, MacConkey (Oxoid), kanamycin-esculin-azide (EMD Chemicals), and Rogosa (Oxoid) agar plates to enumerate colonization by culturable aerobes, Enterobacteriaceae, enterococci/group D streptococci, and lactobacilli, respectively. All plates except Rogosa were incubated aerobically at 37°C overnight; Rogosa plates were incubated in anaerobic chambers with GasPack Plus anaerobic system envelopes (BD) for 2 days.
Histopathology.Cecal tips were fixed in 10% neutral buffered formalin overnight and then placed into 75% ethanol. Fixed tissues were embedded in paraffin and cut into 5-μm sections. Tissues were stained with hematoxylin and eosin (H&E), using standard techniques by Wax-it Histology Services (Vancouver, BC, Canada) and the UBC Histology Laboratory. Pathological scores were assigned as previously described (9). Pathology images were taken using a Zeiss Axioskop 2 microscope.
Fluorescence microscopy.A 1:10 dilution of each organ homogenate was stored in 3.7% formalin at 4°C until use. Two to 40 μl of the samples was stained with 0.25 μl Sybr green (Invitrogen) as previously described (27) and viewed with an Olympus 1X81 microscope. Three fields were randomly chosen; the numbers of cells were counted and averaged. The counts were made in a microscope field of a known diameter and corrected to the volume of sample used. For fluorescent in situ hybridization (FISH), as previously described (27), 5 to 100 μl of the samples (with 100 μl of sample being the limit of detection) was hybridized to 250 ng of the general EUB338 probe (5′-GCT GCC TCC CGT AGG AGT-3′) (2) fluorescently labeled with Texas Red and 250 ng of either CFB286 probe (5′-TCC TCT CAG AAC CCC TAC-3′) (43) or GAM42a probe (5′-GCC TTC CCA CAT CGT TT-3′) (28) labeled with fluorescein and viewed and counted as described above. The percent compositions of the CFB and Gammaproteobacteria phyla were determined by dividing the numbers obtained for these phyla (CFB286 and GAM42a probes, respectively) by the numbers obtained for all eubacteria (EUB338 probe). The percent composition of Firmicutes and "other" bacteria was determined by subtracting the results obtained for CFB and Gammaproteobacteria from 100%.
ELISAs.Cecum homogenates were centrifuged twice for 10 min at 13,000 × g, and the supernatants were collected and stored at −80°C. The levels of tumor necrosis factor alpha (TNF-α), monocyte chemotactic protein 1 (MCP-1), interleukin-6 (BD Biosciences), and keratinocyte chemoattractant (R&D Systems) were determined by enzyme-linked immunosorbent assays (ELISAs) according to the manufacturer's instructions. Cytokine levels were normalized to the total protein levels in the samples, as determined by the Bradford assay (7a).
Statistical analysis.One-way analysis of variance (ANOVA) with Bonferroni's posttest or Kruskal-Wallis with Dunn's posttest was performed using a 95% confidence interval. All analyses were performed using GraphPad Prism version 4.0. Differences were considered to be significant at P values of <0.05.
Antibiotic treatment modifies the microbiota composition in an antibiotic- and dose-dependent manner but does not significantly change the total numbers of intestinal microbiota.To evaluate the effects of streptomycin and vancomycin on the intestinal microbiota of mice, we employed FISH and differential plating methods. FISH provides a good overview of the distribution of the major phyla in the intestinal microbiota and was previously shown to correlate well with the results of the more laborious and expensive sequencing method (27). Differential plating provides an evaluation of a selection of bacteria at a finer genus level. Colonic microbiota of antibiotic-treated uninfected mice was evaluated. Mice were treated with increasing doses of streptomycin and vancomycin, administered in drinking water for 2 days. The dosage was either within the range of or lower than what is used in clinical practice for several indications (Table 1).
As demonstrated in Fig. 1A, the treatment of mice with increasing doses of streptomycin gradually increased the proportion of CFB bacteria in their colonic microbiotas in a dose-dependent manner. At the genus level, the numbers of lactobacilli and enterococci/group D streptococci significantly decreased with streptomycin treatment (Fig. 2A), consistent with a gradual decrease in the proportion of Firmicutes and "other" bacteria as evidenced by FISH evaluation.
The effect of vancomycin on the microbiota was strikingly different from the effect of streptomycin (Fig. 1A). The low vancomycin dose caused a dramatic reduction in the proportion of CFB bacteria and a small increase in the proportion of Gammaproteobacteria. With a higher vancomycin dose, the proportion of the CFB bacteria was still reduced, and that of the Gammaproteobacteria increased to nearly 50% of the microbiota. At the genus level, vancomycin treatment adversely affected both lactobacilli and enterococci/group D streptococci and promoted the overgrowth of Enterobacteriaceae and culturable aerobic bacteria in a dose-dependent manner (Fig. 2A). Overall, the evaluation of bacteria at the genus level for all groups of mice showed variation between mice, consistent with the fact that individuals display variation in their microbiota composition at the species level (12, 14, 24). The effect of the selected antibiotics on lactobacilli, although statistically significant, was not as dramatic as the effect on other bacterial groups and potentially not as significant biologically.
Treatment with antibiotics alone did not significantly change the total numbers of microbiota (as determined by Sybr green staining), although treatment with vancomycin had a greater effect on the total numbers of microbiota than treatment with streptomycin (Fig. 3A). However, even the largest reduction in numbers of microbiota observed was less than a log different from numbers observed for the control group.
Preinfection alterations in the microbiota promote further infection-induced modifications.Next, the intestinal microbiota of mice following infection with Salmonella serovar Typhimurium was examined, using the methods described above. When untreated and antibiotic-treated mice were infected with Salmonella serovar Typhimurium, a striking feature was an increase in the proportion of Gammaproteobacteria in all infected groups (Fig. 1B and C). Examination of both the colonic and cecal microbiotas yielded very similar results at both the phylum and genus levels. The increase in Gammaproteobacteria was higher in mice that were pretreated with antibiotics prior to infection and was dose dependent for both the streptomycin- and vancomycin-pretreated groups. The treatment of mice with the intermediate and high doses of streptomycin and the high dose of vancomycin resulted in a statistically significant increase in the proportion of Gammaproteobacteria, compared to that in the untreated infected group (P < 0.05). An examination of infection-induced changes in the microbiota at the genus level demonstrated that the numbers of Enterobacteriaceae and culturable aerobic bacteria were increased in all of the examined antibiotic-pretreated infected groups and that the numbers of enterococci/group D streptococci were increased in the vancomycin-pretreated groups, compared to those in the untreated infected mice (Fig. 2B and C).
These data clearly indicate that the preinfection intestinal microbiota composition has an impact on the ability of the infectious agent to further interact with and modify the microbiota. More-significant perturbations in the microbiota of uninfected mice resulted in more-significant shifts when Salmonella serovar Typhimurium was introduced.
Antibiotic treatment does not significantly change the total numbers of intestinal microbiota but promotes infection-induced reduction in the total numbers of microbiota, concurrent with an increase in pathogen colonization.To investigate the reasons for alterations in postinfection microbiota composition observed by FISH and differential plating evaluation, we examined the total numbers of intestinal bacteria and Salmonella serovar Typhimurium colonization.
Infection with Salmonella serovar Typhimurium caused a dramatic reduction in the total numbers of microbiota of antibiotic-pretreated mice, compared to those of untreated infected mice (P < 0.05), in both colons and ceca (Fig. 3B and C). The total numbers of microbes in antibiotic-treated uninfected mice 3 days after the withdrawal of antibiotics did not differ significantly from the levels in untreated uninfected mice, except for the colonic microbiota of mice pretreated with 300 mg/liter of streptomycin and 100 mg/liter of vancomycin (Fig. 3B and C). The magnitude of the reduction in total numbers of microbiota as a result of infection (Fig. 3B and C) was associated with the extent of preinfection perturbation in microbiota composition (Fig. 1A). Moreover, greater Salmonella serovar Typhimurium intestinal burdens (Fig. 4) were associated with a greater infection-induced reduction in total numbers of microbiota (Fig. 3B and C). Therefore, the increased proportion of the Gammaproteobacteria in the microbiota of antibiotic-treated infected mice (Fig. 1B and C) was due to a combination of a decrease in total numbers of intestinal microbes in these mice (Fig. 3B and C) and increased colonization by Salmonella serovar Typhimurium (Fig. 4), which also belongs to Gammaproteobacteria. Consequently, the magnitude of the preinfection perturbation of the microbiota steady state was directly linked to the increased susceptibility of the host to Salmonella serovar Typhimurium colonization and to Salmonella serovar Typhimurium-induced perturbations of both the composition and total numbers of the microbiota.
The degree of Salmonella serovar Typhimurium-induced intestinal pathology correlates with the extent of preinfection microbiota perturbation.To examine how increased Salmonella serovar Typhimurium burdens and greater microbiota perturbations correlate with Salmonella serovar Typhimurium-induced intestinal disease, H&E-stained cecal necropsy specimens were examined. Ceca were chosen for histopathological evaluation, as they are the focal point of Salmonella serovar Typhimurium-induced intestinal pathology in mice. Tissues from uninfected mice, both untreated and antibiotic treated, showed no signs of intestinal disease, indicating that treatment with antibiotics alone did not induce a pathological response in the mouse intestinal tract (Fig. 5A). There were no signs of edema, no presence of inflammatory infiltrate, and no alterations in the epithelial architecture. When infected tissues were examined, signs of intestinal disease were observed in all but the untreated infected group (Fig. 5A). Mice pretreated with increasingly higher antibiotic doses prior to infection exhibited increasingly advanced pathology, starting with mild edema and minimal alterations to the epithelial layer and progressing to copious inflammatory infiltrate, severe edema, and complete loss of epithelial architecture. Although all mice infected with Salmonella serovar Typhimurium appeared sick (ruffled fur and sluggish movements) at the time of sacrifice due to Salmonella serovar Typhimurium systemic infection (Salmonella serovar Typhimurium was present in the spleens of all infected mouse groups [data not shown]), mice with more extensive intestinal pathology were more moribund (seemingly more lethargic) than those in other infected groups.
Pathological scoring (9) demonstrated that while tissues from uninfected animals were healthy (minimal pathology scores), Salmonella serovar Typhimurium-infected animals showed overt signs of intestinal pathology that correlated with the extent of preinfection microbiota perturbation (Fig. 5B). Pathological indices were increased in all of the tissue sections of antibiotic-pretreated infected mice, becoming significantly greater than those of the untreated infected group (P < 0.05).
The severity of typhlitis in antibiotic-treated mice correlates with the levels of inflammatory cytokines in the diseased ceca.To evaluate the infiltrating inflammatory cells in cecal inflammation (typhlitis), a panel of four inflammatory cytokines and chemokines was examined: TNF-α, MCP-1, keratinocyte chemoattractant, and interleukin-6. Together, these inflammatory mediators function to activate and/or attract a wide array of inflammatory cells to the site of injury or infection, such as macrophages, neutrophils, and T and B cells (1, 19, 20), and their presence can therefore be used as an indication of the inflammatory infiltrate.
None of the uninfected ceca had elevated levels of any of the examined inflammatory mediators present (Fig. 6). Thus, antibiotics alone did not induce an inflammatory milieu in the intestinal tract of the treated mice. Similarly, untreated infected ceca had negligible levels of all of the examined inflammatory mediators, consistent with the fact that regular mouse microbiota provides its host with protection from Salmonella serovar Typhimurium-induced intestinal disease. Conversely, ceca of infected mice that have been pretreated with streptomycin or vancomycin had high levels of all the examined inflammatory mediators, indicating that more-severe typhlitis observed in cecal necropsy specimens (Fig. 5) was due to increased inflammatory infiltrate in the infected tissues. The increase in inflammatory mediators was dependent on the dose of antibiotics that mice received prior to infection and consequently on the extent of preinfection microbiota perturbation.
Intestinal microbiota is the collection of microorganisms inhabiting the intestinal tract of the host. Numerous functions of the microbiota and its contributions to the physiology and anatomy of the intestinal tract make these bacteria an invaluable partner to their eukaryotic host. However, despite our appreciation of the microbiota's importance, the specifics of its contributions to various disease states are not well understood. Moreover, the effect of microbiota perturbations on predisposition to and progression of various diseases is not well known.
While examining the effects of antibiotics on the intestinal microbiota, we were surprised to see that although vancomycin's spectrum of activity is exclusively gram-positive bacteria (33), gram-negative bacteria (CFB phylum) appeared to be adversely affected by the treatment. Perhaps certain gram-positive bacteria that were resistant to the effects of vancomycin were able to dominate the niches of their more sensitive relatives, as a result making the overall colonic environment more hostile to the members of the CFB phylum. However, vancomycin treatment promoted the proliferation of gram-negative bacteria of the Gammaproteobacteria phylum, specifically the Enterobacteriaceae. The main effect of streptomycin on microbiota was in promoting the growth of CFB bacteria at the expense of other phyla. As this effect was dose dependent, it was likely due to a selective inhibition of a microbial population whose vacated niche CFB organisms were then able to colonize.
After infection with Salmonella serovar Typhimurium, it was observed that the pretreatment of mice with increasing doses of vancomycin resulted in an increase in the proportion of Gammaproteobacteria postinfection. A higher variability in response to Salmonella serovar Typhimurium was observed in infected mice treated with the low vancomycin dose than in those treated with the higher vancomycin dose. Streptomycin-pretreated mice exhibited a more uniform response to Salmonella serovar Typhimurium infection than vancomycin-pretreated mice. This could be due to the fact that streptomycin, unlike vancomycin, did not encourage the growth of commensal Enterobacteriaceae, thus preventing the potential competition between them and Salmonella serovar Typhimurium. Bacteria of the CFB phylum were more adversely affected during infection with Salmonella serovar Typhimurium than bacteria in Firmicutes and other phyla (Fig. 1B and C), a result that is similar to that noted by Stecher et al. during Salmonella serovar Typhimurium infection in a high-dose streptomycin pretreatment model (40). The higher sensitivity of bacteria belonging to the CFB phylum could be due to the inflammatory changes observed during Salmonella serovar Typhimurium infection. The presence of reactive oxygen species during inflammation could be detrimental to the strictly anaerobic CFB bacteria.
The increased susceptibility of mice to Salmonella serovar Typhimurium infection as a result of treatment with selected antibiotics could be due to a number of factors, such as alterations in the host immune response due to a disturbance in the microbiota (as it is known that the microbiota contributes to the establishment of intestinal immunity) (29), a selective removal of a group of bacteria that usually provide a barrier to Salmonella serovar Typhimurium colonization and/or persistence, or a combination of these two options. At least two groups of bacteria, lactobacilli and enterococci/group D streptococci, were selectively inhibited by both antibiotics used in the study. Both of these bacteria belong to the gram-positive Firmicutes phylum, and it has previously been shown in vitro that gram-positive fecal isolates are better able than gram-negative ones to inhibit the growth of Salmonella serovar Typhimurium (15). Further studies focusing on detailing the effects of antibiotics on different species making up the microbial community could shed more light on which members are specifically needed for protection against various invading pathogens. To date, most studies on the contribution of particular members of the bacterial population to the inhibition of enteric pathogens focused on probiotic bacteria in epithelial cell models (8, 10, 15). Our studies highlight the importance of the microbiota in host response to infection in an animal model and identify potentially important groups of microbiota that could become the focus of future studies.
Greater Salmonella serovar Typhimurium burdens in mice treated with increasing doses of antibiotics were also associated with more-profound intestinal inflammation and pathology, as well as with greater postinfection alterations in microbiota, as evidenced by both a reduction in total numbers of bacteria and a larger proportion of Gammaproteobacteria making up the intestinal microbiota. The enhanced intestinal inflammation and pathology were likely due to a greater activation of the host immune system by higher numbers of Salmonella serovar Typhimurium. The cytokine profile was indicative of infiltration by neutrophils and macrophages, which is consistent with the current knowledge of the innate immune response to Salmonella serovar Typhimurium infection (44). Additionally, the cytokine profile was reminiscent of that observed for inflammatory bowel diseases (increases in TNF-α and MCP-1) (3, 38), which are also characterized by disturbances in intestinal microbiota (13), particularly an increase in colonization by Gammaproteobacteria. We have previously shown that a strong inflammatory response acts to reduce the total numbers of intestinal microbiota (27), which is likely the reason for a reduction in total numbers of bacteria observed postinfection. As well, a strong inflammatory response was shown to benefit the growth of enteropathogens (27, 40) and nonpathogenic aerobic bacteria (27). Salmonella serovar Typhimurium-induced inflammation was previously shown to adversely affect the members of murine cecal microbiota, promoting the overgrowth of the pathogen (40), which is also confirmed by our results.
Most previous studies looking at murine Salmonella serovar Typhimurium-induced colitis utilize extremely high doses of antibiotics (20 mg streptomycin/mouse) (5, 7), eliminating 90 to 98% of the intestinal microbiota prior to infection (40). Thus, it was ambiguous which component of the antibiotic-induced perturbation of the microbiota was responsible for the disruption of resistance to Salmonella serovar Typhimurium colitis: a change in the composition of the normal flora or the reduction in total numbers of bacteria. We have shown that a perturbation in the composition alone is sufficient to increase the susceptibility of the murine host to Salmonella serovar Typhimurium colitis. A recently published study (23) has also found that even when bacterial numbers returned to normal levels after antibiotic treatment, mice still remained more susceptible to Salmonella serovar Typhimurium infection. This study, however, did not examine the shifts in microbiota composition either pre- or postinfection and did not conclusively demonstrate the correlation between the perturbations in microbiota composition and increased susceptibility to Salmonella serovar Typhimurium.
Our results demonstrate profound perturbations in the composition of the intestinal microbiota as a result of antibiotic treatment. Furthermore, they show that microbiota imbalance predisposes the host to more severe enteropathogenic infection. These observations could be part of the explanation for the high rates of nosocomial infections, where antibiotics are abundantly used. In fact, nosocomial Salmonella enterica infections, particularly with multidrug-resistant strains, are a concern in developing countries (22, 42) and occasionally even happen in developed countries (18, 33). Although our findings cannot be indiscriminately extrapolated to all diseases where microbiota imbalance has been implicated in the etiology, they show that, at least in infectious colitis, microbial imbalance precedes the onset of pathology rather than being the result of it. Consequently, the initiation of pathology could be averted or corrected by maintaining a balanced microbial community.
Antibiotic usage is extensive in our society, both in hospitals and in the community. However, the effect of antibiotics on the intestinal microbiota has not been extensively scrutinized other than in studies on the induction of antibiotic resistance in commensal bacteria following treatment. The demonstrated perturbations in the microbial community as a result of antibiotic treatment warrant further detailed investigation of the effects of the most frequently used antibiotic regimens on the composition of microbiota and attempts to find prebiotic or probiotic supplements that would offset these perturbations.
We thank members of the Finlay laboratory for helpful suggestions and discussions of the manuscript.
This study was funded through the CIHR Michael Smith Prize and a CIHR operating grant for Salmonella. I.S. is supported by the UBC-CIHR Translational Research in Infectious Diseases and Vancouver Coastal Health Research Institute M.D./Ph.D. Studentship Award and the Michael Smith Foundation for Health Research (MSFHR) Senior Graduate Fellowship. C.L. was a Canadian Association for Gastroenterology and MSFHR postdoctoral fellow.
None of the authors have any potential conflicts of interest regarding this work.
- Received 11 March 2008.
- Returned for modification 10 April 2008.
- Accepted 28 July 2008.
- Copyright © 2008 American Society for Microbiology