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In fact, when I asked an elderly gentleman on Salina, about my Cafarella family, he noted that they had the best honey on the island. Don't know if he was pumping sunshine up my skirt or what, but it does prove that honey is a good choice in Italian cooking. For centuries, there was not much choice for sweet foods...It was honey or nothing.
This is a good recipe for onion haters. It is unlike anything else.
Cippolini onions are not the easiest onions to find, and not the easiest to peel. If you have never seen them, they are rather flattened onions. You could, of course, use any small onion. You just need to keep them in a size range that will cook in the prescribed time.
If you go to the Salumerie in Little Italies all over the country, you will find these little onions available, all prepared, but you will pay through the nose for them. They are usually a little crunchy compared to most recipes, and perhaps a bit more tart, as they do not always use balsamic vinegar. You may wish to experiment over time with different vinegars and proportions of vinegar and sweeteners to get what you really want. Also, you may prefer different vinegars and degrees of sweetness with different meats, or just alone with cheese, olives and bread.
I used to get a small container of these when I first moved to the Boston area, along with a loaf of unsliced Scala bread, a container of mixed olives, a chunk of Provolone, a Genoa Salami(I love Fiorucci, but it is a bitch to find) or if I was feeling rich, a few slices of Prosciutto Crudo. I would sit with a friend or two on the banks of the Charles River in Cambridge and have a picnic overlooking the Boston skyline. Add a glass of red wine and a bunch of green(for me) grapes, and life is beautiful.
I do not know about you, but I must have unsliced bread, torn apart by hand, into large chunks. Slather with butter, or dip into a little cup of oil, grating cheese, salt and pepper and pepperoncini. Mix them together and allow to sit for a few minutes to blend the flavors.
Anyway...Back to the onions.
I have a stand of Egyptian onions that produce the tiny bulbs at the top of the stalk...those might work with reduced roasting time. Pickling onions would be good, shallots(If you can afford them) or just sort out the runts when you harvest onions from your garden.
Cut the top and bottom off the onions(You can leave the root end if you want, but rub off the dried up root with your fingers.) and plunge them into a pot of boiling water for just a few seconds. Remove with a slotted spoon and cool till you can handle them. The skin should come right off.
Place your onions in a single layer in a heavy skillet(cast iron or enameled would be good) or casserole.
Mix a tablespoon of honey or white sugar, balsamic(or red wine) vinegar, a tablespoon of herbs like rosemary, basil, oregano, mint or thyme (your favorite), a few tablespoons of olive oil, salt and pepper. Cloves are a classic choice with onions. Sprinkle a few in with the onions, or if the onions are on the larger size, stick one clove into each onion. This is easy to over-do, so be careful.
Mix together and stick your pinkie in. Taste critically. Look for a pleasant sweet and sour that will satisfy you(remember that the onions will add sweetness). Agro Dolci is a widespread favorite in Italy. Pour over the onions. Cover tightly with a lid or with foil, and roast for 20 minutes. Remove the cover and stir. Return to the oven and continue to roast for an additional 20 minutes or to the desired degree of doneness(I know you will just hate tasting these a few times till they are done enough, but be brave.) Serve them warm or cold. 400 to 450 degrees F is a good range for the oven.
The vinegar, sugar etc. will become syrupy, and if the onions become too dry, add a bit of wine, or more of the original mixture.
You will find exact measurements in various recipes on line, but you should develop your unique blend through trial and error. The thing about this, as in many other recipes from Italy, is that they just did not measure. They dumped in about as much as their mother did, and they altered the recipe by taste with each batch or weight of onions or strength or variety of vinegar.
You could easily just drop these onions into a cast iron pan with a little olive oil. Dump on the herbs, honey and vinegar etc. as the onions are grilling at a fairly low temperature. Turn with a big spatula a few times till the sauce reduces. Taste for the degree of doneness you like(I love them apple crisp, just as much as soft and sticky), and remove to a bowl to cool.
This would be just as good with carrots, and you could add mushrooms late in the roasting process.
You could easily add cloves of garlic to the pan, or stir in a bit of cream at the end of the process and reduce in the last few minutes of the roast time.
Thanks Wikipedia for the image of Cippolini Onions. Here they are shown peeled, with residual tops still attached. You could leave them on and have a convenient handle to nibble out of hand. Just remember to rub off the roots if not cutting them off. They are perfectly edible, but a little like grit floating around in the sauce.


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Can i have my games chat logs please?
I just had a nationalist/racist garbage in my team keep talking about black people and how skin color matters,about politics and other random shit he had in his head and all i want is the chat logs to sent them on support,can i have them ?Its the only way to prove that these psychopaths(like this xin i had on my last game) ruin the game with every possible way.You cant just imagine what he was saying,it was the most disgusting chat i ever saw on a multiplayer game.
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subset: commoncrawl


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Kay. he lies down on the floor, closes his eyes, and starts to snore. Loudly.
The baby looks at him, startled.
The baby looks at me for an explanation.
I play along, saying, "Look! he's sleeping!"
The baby looks back at Seth. Wide eyes. It walks toward him to investigate.
It approaches his head.
Seth: (opens his eyes and bares his teeth.) "RAAARRRRRR!!! RAARRRRR!!! RAAAAARRRRRRRRRR!!!!!"
Baby: cries for half an hour.
Tuesday, February 17, 2009
4 comments:
- The Boob Nazi said...
hahahahaha loved it!
- February 17, 2009 at 10:03 PM
- rychelle said...
Thankfully he was never that scary with my kids!!!
- February 18, 2009 at 9:09 AM
- LJ said...
I'm going to have to share this with Adam.
- February 18, 2009 at 2:38 PM
- TD Quong said...
Are you worried about your children? Or do you think they will just really like dinosaurs?
- March 25, 2009 at 8:20 PM
Subscribe to: Post Comments (Atom)


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Whether you are in one among our 123 stores or connecting with our quickly increasing online neighborhood, you'll know that Sportsgirl is at the forefront of Australian style and culture. For example, set a extremely particular goal like talking to five folks every week till you might have a proposal, publicly decide to the aim, and promise to make a forfeit in the event you miss it. We know one job seeker who, though he's liberal, promised to donate to the Trump marketing campaign if he missed his goal. To get extra sensible tips on the right way to motivate yourself, take a look at the guide The Motivation Hacker by Nick Winter. If your personal circumstances have changed since your claimant dedication was last discussed, and it has an affect on the type or hours of work you could possibly do, you may be able to get your claimant dedication changed For instance, in case your child has began school you may need to cut back the hours you could possibly work.
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Go to our profession reviews and scroll to the tip of the profile to see customized advice for every kind of job. Vocational Rehabilitation and Employment Program for assist with job coaching, employment lodging, job-searching for skills teaching and individualized career counseling. Full of expert performers (also including John C. McGinley, Jorge Garcia, John Cho, Greg Germann, Seth Morris, Jay Pharaoh and others), all of whom have seen higher material, Get a Job" is brisk and slick but soulless. You can also sign up for tailor-made Job Alerts, which suggests you'll by no means miss that dream opportunity and we'll never miss out on you. The odds are significantly higher to get an interview by way of OCI than within the open job market. Most individuals are so glad to get a job, or awkward concerning the idea of negotiating, that they by no means attempt.
A new study has confirmed true the oft-repeated saying that it's easier to land a job when you have already got one. Website to study a career guidance and recruitment journal, on-line job board and career expos. After two internships at L.A. Weekly, Will has been promised a job upon commencement, Will shows up on the workplaces bursting with ideas and power — only to be instructed by an editor (John Cho) there isn't any longer room for him at the newspaper. Get a Job will have a simultaneous restricted theatrical and on-demand release, although Teller (who shot this earlier than Whiplash) and Kendrick might hope no one notices. If you'll be able to't get the job you need immediately, consider applying to a different place within the organization – like a freelance position, or a position one below the one you actually need. Honestly, it would probably have been higher for nearly everybody involved—particularly Kidd—had Get A Job been left on the shelf completely.
Whether or not you possibly can refuse a job offer or pay enhance is determined by what's in your claimant commitment. If the job offer is much less hours, lower pay or a distinct type of job to what you agreed in your claimant commitment, you may nonetheless be anticipated to take it. These will not be thought-about good causes for refusing a job provide, until you'll be able to argue that your travel or childcare prices will likely be too high to make a decrease paid job worthwhile. The job search could also be one of the hardest stuff you've ever executed — you've got most likely by no means been rejected 30 occasions in a row before.


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Healthy Lifestyle Discounts
Healthy Life Option (HLO) – Healthy Plus Option (HPO) – Multi-App Discount
At Asteron Life, we believe insurance should do more than just help clients at claim time – it should also be affordable.
That's why our Healthy Lifestyle Discounts are making a difference by offering eligible clients the opportunity to save on the costs of their insurance premiums.
Rewarding healthy living with savings of up to 25%*
Our Healthy Lifestyle Discounts apply to clients that meet key eligibility criteria, which includes:
- Entry age
- HLO - 30 to 55 (age next birthday)
- HPO - 30 to 50 (age next birthday)
- Body mass index (BMI) ≤ 28
- Non-smoker for at least 5 years
If Income Protection or Business Expenses Cover is bundled with a Lump Sum Cover, your client can also gain our 5% Multi-App Discount on top of the savings they receive from either HLO and/or HPO. This means your client could benefit from:
- Up to 25% worth of discounts on Life Cover
- Up to 15% worth of discounts on TPD cover, and/or
- 5% discount on Trauma
We've streamlined the application process to make it easier for you to apply the Healthy Lifestyle Discounts and see exactly what each benefit entails. Our system helps save valuable time so you can focus on continuing to provide the best advice for your clients.
*25% savings relates to a client applying for and issued a Life and Income Protection or Business Expense cover with our 20% Healthy Plus Option savings and 5% Multi-App Discount. Discount is applied before stamp duty and policy fees.
Healthy Life Option (HLO)
Our Healthy Life Option provides eligible clients on stepped premiums the opportunity to reduce premiums by 10% off their Life Cover and/or new TPD Cover**. If your client meets all criteria, they will automatically receive their discount for the life of the policy with no additional assessments required.
**The 10% HLO TPD Discount is not available for customers who applied for and issued cover on/or before 9 April 2017. In addition, to be eligible the policies for Life and/or TPD Cover need to be offered at standard rates without any loadings or exclusions.
Healthy Plus Option (HPO)
Clients who take a QuickCheck, MBA blood test and lifestyle questionnaire may be eligible for 20% off their Life Cover under our Healthy Plus Option. This offer can provide substantial savings, and is enduring when your client completes a yearly QuickCheck and MBA blood test.
If your client chooses not to supply annual health checks, their discount will reduce by 1% annually (to a guaranteed minimum of 10% for the life of the policy). Clients can reapply for the full discount anytime up to the age of 55.
Multi-App Discount
Our Multi-App Discount offers a further 5% off premium costs if Income Protection or Business Expenses Cover is bundled with at least one Lump Sum cover.
Making insurance more affordable
Our healthy lifestyle discounts reward eligible clients with reduced premiums so they can enjoy all the benefits a healthy lifestyle has to offer.
When our Multi-App Discount is applied to our HPO and/or HLO, your client can save quite a sum over time.
Healthy Lifestyle Discounts - how your clients can be rewarded
#The 20% HPO discount has additional assessment requirements (QuickChek and MBA blood test) and will not be automatically applied.
Get a quote and apply today
Take advantage of these Healthy lifestyle discounts for your client today or call us on 1800 739 641 for more information.
New to Asteron Life?
To find out more about our Healthy Life Option for your clients please contact your Asteron Life Business Development Manager.
Apply for a log in to access our online quoting tool.
Important note
This information is current as at January 2019 and may be subject to change. This information is general advice and does not take into account a person's objectives, financial situation or needs. A person should consider the appropriateness of the advice, the Product Disclosure Statement (PDS) and Policy document for Asteron Life Complete (ALC PDS) and SPDS available at www.asteronlife.com.au and consider obtaining financial advice before making any decision about this product.
ALC PDS is issued by Suncorp Life & Superannuation Limited ABN 87 073 979 530 AFS Licence No 229880, with the exception of an interest in the Suncorp Master Trust ABN 98 350 952 022 RSE Fund Registration No R1056655 SFN 1400 429 47 which is issued by Suncorp Portfolio Services Limited ABN 61 063 427 958 AFS License No 237905 RSE License No L0002059 who will hold the policy on your behalf, as a member of the Fund. This product is not a bank deposit or other bank liability. Products and services are provided by different entities in the Suncorp Group and each entity is not responsible for, does not guarantee and is not liable in any respect for products or services of other Suncorp entities.


text: Getting approved for a mortgage involves proving to lenders that you're willing to repay your home loan as agreed and that you're capable of doing so. Your ability to repay is determined by your income, but many borrowers who can afford to pay their bills don't actually do so. This is why mortage lenders look at credit scores when deciding if they will land you money.Read more


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Kevin Remde welcomes back Yuri Diogenes to the show as they continue their discussion around the benefits, challenges and considerations businesses must make around Bring Your Device (BYOD) and how IT organizations can support it.
- [2:46] Why don't you give us a summary on the concept of BYOD?
- [6:20] I understand that recently you and your team have published some really useful resources to the Microsoft TechNet online documentation. What have you created for us?
- [9:26] How should one use the BYOD Design Consideration Guide?
- [13:51] Can you give us an example of how an IT organization can use this guide in a real-world BYOD scenario?
Check out the FREE "BYOD Design Considerations Guide"
Shortened URL if you would like to share on Twitter or Facebook, etc.


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Join us this Monday Night as we host two of San Diego's own industry bartenders! Veronica and Brittany. Come party with us! $155 select bottles at the "Home of the most beautiful girls in San Diego". San Diego industry, your cover is waived at the door!
Pacers Industry Monday Nights – Guest Bartenders Veronica and Brittany
August 1, 2016 - August 2, 2016
3334 Midway Drive
San Diego, CA 92110 United States
San Diego, CA 92110 United States
- This event has passed.


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Musings on pedal extenders
Yesterday I took a spin on the trike round the Innerleithen Loop. Weather was not too bad, a little bit of drizzle but otherwise warm and nice to be out after Saturday's pouring rain. In my recent review of the Sprint I talked about the speed I am able to achieve round this loop which


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Nu s-au găsit proiecte
Ne pare rău că nu am găsit proiectul care te interesa.
Aici poți găsi cele mai recente proiecte:
We need to have this list turned into an xml file of all of the records. [conectează-te pentru a consulta linkul URL] XML record would be: CODE FROM DATE TO DATE DESCRIPTION A few comments; - Not every record has a 'FROM Date' - Not every record has a 'TO Date' - Date should be converted to DD MMM YYYY format - Any quotation marks should be removed
I need someone who can records some words Maximum 20 minutes work. 1 person for 1 work only Rs. 100 for 20 minutes. One time project. interested people send name, age, city and voice notes of " Hi , I believe in you." on mail [conectează-te pentru a consulta linkul URL]@gmail.com. offer till 15th Dec.
I need an Android and iOS app. I already have a design for it, I just need it to be built. reference: Delivery App
i want a full website similar to [conectează-te pentru a consulta linkul URL] with all tools included
Must have access to own googlemaps API key and be familar with Excel / VBA / googlemaps API need freelancer to make changes to the attached excel application - add in your API key into the project to get it to work to the first stage. What is then needed is 1. change to Oauth 2.0 setup so API key isnt included in VBA 2. need to create application that uses google address auto complete - this...
I need an Android app. I would like it designed and built.
Need Billing with vat. View all purchase,sales and profit reports
My book will be related to health industry, about how to be healthy without medicine. What are diseases actually are.
I am looking for a person who is experst with python specially pandas
Are you good at English or Russian? I need new freelancer that is student .


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[Korean Stars' Real Personality] Uee
Uee is a consistent person. Even after becoming very popular because of her sexy thighs, she didn't put on airs. Actually, she was already 21 when she debuted in 2009. Unlike other k-pop idols who usually debut when they're teenagers, Uee has lived as an ordinary student till she became 20. Of course, she was a swimmer in her school days, but I mean, she didn't receive a special k-pop training in her teenage life, and it's a notable difference between her and other idols because that's why she acts differently from them. She acts like an ordinary young girl in her waiting room and gets along well with anyone. She's not prim-minded at all.


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Im posting this, as I know of at least 2 posters who are in this class and hopefully more who lurk! Our class is having its 50th reunion Saturday, Nov.
17,2018 at the Barrister Gardens Banquet Center in St. Clair Shores. Cost is $68 per ticket. No tix sold at door. Please send me a private message for contact info.


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Press & News
RGI in "Quaderno del Premio Camillo e Adriano Olivetti"The Spille d'oro association organized a special ceremony to present the "Quaderno del Premio Camillo e Adriano Olivetti"
Career Day "Incontro Aziende studenti"Today December 4th we are at Career Day "Incontro Aziende studenti" in Bari
IOLAVORO Job FairToday December 4th and tomorrow December 5th we will participate at IOLAVORO Job Fair in Turin
NOVUM-RGI at Messekongress "IT für Versicherungen"We are truly excited to inform you that today November 26th and tomorrow 27th NOVUM-RGI will take part together with its customer "Die Bayerische" at the Expert conference "IT for insurance"in Leipzig
NOVUM Cloud Platform nominated for eco://award 2019 in the Cloud categoryThe NOVUM Cloud Platform was nominated by a top-class jury as one of three solutions in the Cloud category
RGI at Insurance Summit - Il Sole 24 OreRGI will be the technological partner of the yearly must-attended event of the industry - Insurance Summit
Person-first interaction: technology needs humans to generate value"Hyper-personalization" is the keyword for the Insurers evolution according to RGI
RGI at Tour AL-LavoroWe are very happy to participate today at the Tour AL-Lavoro organized by Almalaurea in Milan
RGI at "Wooooow! Io e il Mio Futuro"We are thrilled to attend the "Wooooow! Io e il Mio Futuro" event at Officine H in Ivrea
RGI at IOLAVOROToday we are attending at "IOLAVORO"at Officine H, in Ivrea
RGI at PUNTO IMPRESAToday we are participating at "Punto Impresa" organized by Università degli Studi dell'Insubria
AmTrust Assicurazioni partners with RGI for the Italian MarketIt took only 4 months for the go-to-market management of Healthcare TPL insurance
Job Fair 2019 at Scuola Superiore Sant'AnnaToday we are eager to participate to the Job Fair 2019 held at Scuola Superiore Sant'Anna in Pisa
NOVUM-RGI at the Career Forum in SalzburgTake the first step into your career and get to know us today, October 22 at the Career Forum in Salzburg.
NOVUM-RGI will participate in the "DAV" meetingNOVUM-RGI will take part in the "DAV" (Deutsche Aktuarvereinigung e. V.) meeting organized by the Insurer Alte Leipziger - Hallesche
NOVUM-RGI at IT Optionen for VersicherungenOn October 10 and 11 in Düsseldorf, NOVUM-RGI will take part in the congress "IT Optionen for Versicherungen"
NOVUM at the "MOI-Magic of innovation" in ViennaNOVUM was selected by the advisory board as one of the ten most innovative companies to present its NOVUM Cloud Platform in the "Insury Business Trophy" session
RGI back to school at the XIX Italian Olympiad in InformaticsRGI, the software vendor leader in the digital transformation of the European insurance market, supports the young IT talents in the XIX Olympiad in Informatics.
RGI announces the new release of PASS_Insurance 4.0Innovative technology, Cloud and paperless are the pillars for the platform with the largest European customer base
Press ReviewRGI ACQUIRES DACH SOLUTION PROVIDER NOVUM
RGI ACQUIRES DACH SOLUTION PROVIDER NOVUMTransaction supports RGI's European market development strategy to expand to DACH countries
RGI HAS BEEN SELECTED AS ONE OF THE 50+ MOST INNOVATIVE INSURTECHS AT DIA AMSTERDAM 2019Amsterdam, 27 June 2019. RGI is again on the stage of the DIA Amsterdam 2019, the must-see Insurtech event, taking place from 25 to 27 June in Amsterdam
KAPIA-RGI NEXT France, 27 June, 2019Today Thursday 27 of June 2019, we are very pleased to host our French Clients and Partners in the exclusive KAPIA-RGI NEXT event at the HUB INSTITUTE in Paris
KAPIA-RGI strategic Dinner, 26 June 2019 at the Ritz ParisFor the second consecutive year, KAPIA-RGI is organizing the new edition of the private dinner "La rencontre stratégique KAPIA-RGI"
We have been selected to speak as one of the most 50+ innovative insurtechs at DIA Amsterdam 2019The DIA Amsterdam is the biggest global event for insurtech and innovation in insurance
RGI Compliance JourneyToday Thursday 20th June in RGI Academy, we have the pleasure to host our clients at the RGI Compliance Journey meeting
#ENERGIE GAMES: A SPORT AND SOCIAL RESPONSIBILITY EVENT PROMOTED BY RGIRGI People took the challenge to raise funds for the Insuperabili Academy
Open Day Data ScienceToday May 27, RGI is attending the Open Day of the YTiA Data Science course, the great free Training project of Manpower realized in collaboration with Tree, in Milan.
Career Day - Porte Aperte alle ImpreseToday May 22th, RGI will attend the Job meeting and Career Day Porte Aperte alle Imprese
Today KAPIA-RGI participates to the TEKPLACEToday April 16th, 2019, KAPIA-RGI attends the Insurance TEKPLACE held in Paris at Espace Etoile Saint Honoré.
Job Fair 2019RGI will attend the Job Fair on April 9th at the MO25 Engineering Department "Enzo Ferrari" in Modena
RGI new majority shareholder of UNIMATICAThe group increases its share from 31% to 56%, assuming the role of majority shareholder and taking company control
Rendez-vous de Casablanca de l'assurance 2019RGI will attend Rendez-vous de Casablanca de l'Assurance 2019
RGI Next PartnersRGI is pleased to announce the second edition of RGI Next Partners
Infostage '19RGI will attend, February 19, to the Job Fair at Politecnico of Turin.


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Court Reporter in Frio County, TX | 866.357.1796 | Texas Stenographers
Our court reporting agency is a full-service agency that provides apt court reporters and stenographers to help clients attain %accurate and easily accessible transcripts of all legal hearings such as arbitrations, mediations and depositions. If you're an lawyer who is looking for a certified court reporter, you can trust that we have everything you'll require to meet your needs. We come full equipped with videoconferencing technology and online services to attorneys and those who need to give or take a deposition.If you're looking for a certified court reporter in TX, Houston, New York, Philadelphia, Atlanta or anywhere else in the United States, turn to us for all your needs. We've been around for over two decades and have a successful track-record of not only meeting expectations, but exceeding them for our clients.
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Video is a powerful document in legal matters, particularly when those matters reach the courtroom and must be argued in front of a judge or jury. If you need a court reporting service to record and transcribe your deposition, make sure that they employ expert videographers with technology that can capture the most important visual details – positive or negative body language, facial expressions that don't match the tone of voice, and even the slightest gestures that might indicate witness coaching. A single nuance captured on video could make all the difference in the world when it comes to a settlement negotiation or a courtroom presentation.
Frio County Texas
Get Automated Reminders of Upcoming Deposition Dates | TX
Our staff is dedicated to providing you with excellent service and ensuring that no one "drops the ball" on important deadlines. That's why you will receive reminders of upcoming depositions in automated emails to ensure that all parties know scheduled start times and locations.
Contact Us Today to Schedule Your Next Deposition
You've got enough to do without having to worry about whether the parties in the case are aware of upcoming deposition dates. Let us handle the deposition scheduling details and other administrative tasks in your case so that you can focus on what matters most: winning for your client.
Frio County Texas
Court Reporters and Legal Videographers in Texas
For unrivaled service, we can help you in Texas. Our support staff is fully knowledgeable in helping clients manage their transcripts once the deposition has wrapped up. In addition to our competent support staff, who are accessible to help clients with technology consulting, we also provide litigation support to ensure that your transcripts are properly organized and remain accessible through our online document database. Regardless of where you are based, contact us for all your court reporting needs. We have a demonstrated track record of serving clients for over two decades and are eager to work with you!


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Cops ease rules on tattoos, turbans, beards
NEW YORK — The Joe Friday look is out. Tattoos, turbans and beards are in.
Police departments, compelled by a hiring crisis and eager for a more diverse applicant pool, are relaxing traditional grooming standards and getting away from rules that used to require a uniformly clean-shaven, 1950s look.
More officers are on the job with tattoos on their forearms, beards on their chins or religious head coverings like hijabs and turbans in place of — or tucked beneath — their blue caps.
"My turban is a part of me," said Mandeep Singh, among 160 Sikhs in the New York City Police Department who last month were allowed to wear navy blue turbans in place of the standard-issue police caps. "This opens a gate for other potential candidates who felt they could not be a police officer because they would have to choose either the job or their faith."
That followed a 2014 move by the St. Paul, Minnesota, police to create a special hijab for its first female Somali Muslim officer.
Muslim NYPD officer Masood Syed, who grows a beard for religious reasons, was suspended for its length and sued his department last year over a rule requiring beards to be trimmed to within a millimeter of the skin. As a result, the department changed the length to a half-inch and reinstated him. Syed's suit is still pending, though, because he said the length is arbitrary and it should be case by case, depending on the officer's needs.


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Graduation ceremonies conclude Emporia State's spring 2019 semester
May 3
Hats off to the nearly 1,100 candidates for graduation at Emporia State University.
ESU Summer Theatre Closes Season with 'The True Story of the 3 Little Pigs'
ESU Summer Theatre closes its 65th anniversary season with its annual family-friendly production, "The True Story of the 3 Little Pigs."
Jul 23
ESU Summer Theatre Presents 'The Complete Works of William Shakespeare (abridged)'
Actors rapping to "Othello" is just one of the featured moments as ESU Summer Theatre continues its 65th anniversary season with its third producti...
Jul 5


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This article discusses four features of islands that make them places of special importance to environmental conservation. First, investment in island conservation is both urgent and cost-effective. Islands are threatened hotspots of diversity that concentrate unique cultural, biological and geophysical values, and they form the basis of the livelihoods of millions of islanders. Second, islands are paradigmatic places of human–environment relationships. Island livelihoods have a long tradition of existing within spatial, ecological and ultimately social boundaries and are still often highly dependent on local resources and social cohesion. Island cultures and their rich biocultural knowledge can be an important basis for revitalizing and innovating sustainable human–nature relationships. Third, islands form a global web that interlinks biogeographic regions and cultural spaces. They are nodes in a global cultural network: as multicultural island societies, through diaspora islander communities on continents and through numerous political and trade relationships among islands and between islands and countries on continents. Fourth, islands can serve as real-world laboratories that enable scientific innovation, integration of local and generalized knowledge and social learning and empowerment of local actors. We conclude that island systems can serve as globally distributed hubs of innovation, if the voices of islanders are better recognized.
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Now that you have braved the perils of tax season, it is time to make use of that rebate. Upgrading your home security system is not only a responsible way to allocate the funds from your tax refund, but it can also be fun. By integrating your alarm system with a virtual assistant like Amazon Echo or Google Home, you … Read More
6 Tips to Properly Secure Your Business
In business you always want to make more money than you're spending. Theft and loss can take a big portion of that profit out of your business. Unfortunately, the biggest culprit of theft and inventory loss can happen internally. According to Statistic Brain, 75% of employees have stolen from their employer at least one time. Increase your business protection with … Read More
Ensure Your Business and Employees are Safe in the Event of Fire
Recipe for Safety Keeping your business and employees safe in an emergency is a multifaceted undertaking. Taking measures to prevent fires is an excellent first step to tackle. Here are some of our top tips for fire prevention and preparation: Install smoke detectors and replace batteries at least once a year. Have working fire extinguishers available throughout your facility. Develop … Read More
Emergency Preparedness: Building Your Natural Disaster Kit
This past year across the United States has been filled with fires, floods, and storms. A lot of people have been left in the dark with nowhere to go and no preparation. If you have a natural disaster plan, review this list of must haves to make sure you are prepared for anything! If you live in a high risk … Read More
Choose the Right Home Security Camera with this Helpful Guide
Tips for Choosing the Right Home Security Camera Today's world is so rushed and busy that few people are home for long periods of time. When they are home, they are likely indoors working through a mile long to-do list. The appearance of an unoccupied home can leave you at risk for burglary. Home security cameras go a long way … Read More
Stay Safe on St Patrick's Day! 5 Tips to Celebrate Safely
St. Patrick's Day is a day to celebrate the rich and fruitful Irish culture. While going out can be fun and exciting, it's important to take your personal safety seriously. Here are some tips on how to stay safe at any event while you're out on St. Patrick's Day. Arm your alarm monitoring system before you leave: Before you leave … Read More
The Position of Your Home Can Determine if Thieves Will Strike
Buyer Beware: Your Home's Position Can Determine If a Burglar Targets You By doing a bit of research, you might learn that you're better off buying your home when it's cold outside. During the warmer months of the year, home sales increase, and so do your chances of having to fight off other buyers. As the temperature drops, take your … Read More
Feature: Resolution IGM Flex Cellular Module
The Resolution IGM Flex cellular alarm communicator is one of the most popular products Alarm Relay offers. And it's popular for good reason, with so many advanced capabilities aimed to enhance security for users what's not to like?! Alarm Relay started offering the Resolution Flex module to provide customers an easy, DIY cellular alarm module that can be connected to … Read More
The Rescu App in a Hostage Situation
"If you had a gun to your head…" is a saying we often light-heartedly use to ask family and friends silly 'would you rather' questions. But what if having a gun to your head was a real possibility? Do you have the resources to counteract a hostage situation? Imagine yourself sleeping soundly and comfortably, maybe you live alone, or maybe … Read More
Why Cellular Alarm Monitoring is the Most Reliable Form of Communication
With technology advancing so rapidly, we're all ditching our landline (or ditched it ages ago!). Most people primarily rely on their cell phone for communication. Why should it be any different when it comes to your alarm system? Many burglars know they can cut your phone line to disrupt alarm communication. How can you avoid having your alarm monitoring service … Read More


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Posted: Jan 20, 2018
MILWAUKEE (WLCSports.com) – After holding a 10-point halftime lead, the Wisconsin Lutheran College men's basketball team suffered an 82-73 setback against the visiting Concordia Wisconsin Falcons Saturday afternoon inside the Recreation Complex. With his free throw at the 10:17 mark in the second half, Chase Nowak (Milwaukee, Wis.) became the 21st member of the 1,000-point club at WLC.
- Final Score: Concordia Wisconsin 82, Wisconsin Lutheran 73
- Records: Wisconsin Lutheran (2-14, 2-10 NACC), Concordia Wisconsin (10-8, 8-5 NACC)
- Location: Recreation Complex, Milwaukee, Wis.
- Tyler De Young (Waupun, Wis.) opened the scoring for the Warriors, connecting on a triple from the top of the key, while Nowak buried a mid-range jumper to put WLC ahead 5-3 with 17 minutes to play in the first half.
- Moments after a rejection from Nowak, Collin Kennedy (Holmem, Wis.) knocked down a corner three to put Wisconsin Lutheran ahead 10-6 with 11 minutes on the clock in the first half.
- Randy Johnson Jr. (Milwaukee, Wis.) entered the game and immediately got on the board with a three-pointer, then Caleb Goldstein scored a driving layup to put the Warriors ahead 20-12, forcing CUW to take a timeout with 8:36 left in the half.
- Goldstein stole an inbound pass and took the ball the length of the floor for a layup and the foul, then De Young knocked down a corner jumper on the ensuing possession, giving the Warriors a 28-15 lead and forcing the Falcons to take a timeout with 5:28 to play in the half.
- The two teams traded baskets in the final minutes of the half, but WLC maintained a 37-27 advantage at halftime.
- Nowak buried a three from the wing to push the Warriors lead to 11 with 16 minutes left in the second half, but CUW answered with five straight points to cut Wisconsin Lutheran's lead to six, 44-38.
- Two straight baskets brought the Falcons within three points, but Mack Knueppel (Jackson, Wis.) answered with a three from the top of the key to put WLC back ahead by six points with 9:30 remaining.
- Concordia Wisconsin used a barrage of three-pointers to take a 62-61 lead, its first lead since the 18:55 mark in the first half.
- CUW continued its hot shooting from deep, pushing its lead to four with four minutes to play in the contest.
- The Falcons increased their lead to eight, but Nowak answered with a corner three to bring the Warriors within five with two minutes left to play.
- Nowak and Knueppel scored baskets on the next two WLC possessions, but CUW answered with a fast-break dunk, forcing the Warriors to foul to stop the clock.
- The Falcons converted two free throws in the final minute of the contest to ice the game, earning the 82-73 victory.
- Nowak and Knueppel led the way for the Warriors with 15 points apiece, while Goldstein added 12 points.
- Collin Kennedy added 11 points and corralled eight rebounds, while De Young chipped in nine points and eight boards.
- WLC shot 40.9 percent (27-of-66) in the contest and connected on 45 percent (9-of-20) of its outside shots.
- The hosts controlled the rebounding advantage 42-27, including 15 offensive rebounds, their highest-total of the season.
- Josh Erickson led a balanced CUW attack with 19 points, while Jordan Johnson added 16 points.
- Noah Gosse scored 14 points and pulled down a game-high 10 rebounds, with Josh Hau adding 12 points, five rebounds, and five assists.
- The visitors shot 53.6 percent (30-of-56) from the field and knocked down 47.6 percent (10-of-21) of their three-point attempts.
- Concordia Wisconsin out-scored WLC 38-26 in the paint and received 25 points from its bench players.
- The Warriors travel to River Forest, Illinois, Tuesday evening to take on the Concordia Chicago Cougars (2-14, 1-11 NACC) for the first of three games next week. The Cougars picked up their first NACC win of the season Saturday afternoon against Dominican by a score of 77-63. In their initial matchup earlier this season, WLC earned a 106-98 victory over CUC. Live stats and video for the contest will be available at WLCSports.com.


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If you're looking for a skin tightening anti-aging treatment that can be performed at any time of year and gives you lasting results, TempSure™ Envi might be right for you. Dr. David Zweiback and his team at Zweiback Medical Associates offer TempSure Envi treatments to help you achieve your skin tightening goals. Call the office in Jenkintown, Pennsylvania, or schedule an appointment online today to get tighter, younger looking skin.
TempSure Envi is a laser treatment that uses radiofrequency to boost collagen and elastin which can help with skin firmness, wrinkles, and cellulite. The treatment can be performed in under an hour and is effective on any and all skin types. The treatment helps with:
There are no restrictions to sunlight exposure so you are free to walk out of the office with no downtime, however, sunscreen is always important.
TempSure Envi works as a laser treatment that uses therapeutic heat temperatures to break down the cells of the targeted area. This then causes surrounding cells to work overtime to heal the area which causes an increase in collagen and elastin in the skin. This means that you will notice brighter and tighter skin.
The simple in-office procedure is completed in under an hour, and you can resume your normal activities post-treatment.
Your safety and comfort is the top priority for Dr. Zweiback. He uses TempSure Envi because of the safety features on the device, such as a safety timer. The safety timer alerts Dr. Zweiback when optimal temperatures have been achieved, and this allows him to give you beautiful and safe results. The team at Zweiback Medical Associates work hard to make sure you have a pleasant, soothing experience.
TempSure Envi is for any adult who wants improvement in their skin elasticity. The ability to be able to have the treatment done during any time of year makes it a great option with limited restrictions. Dr. Zweiback has a comprehensive background in advanced laser treatments, making him an expert in the field for you to discuss your skin care goals and find out which skin tightening treatment will work best for you.
Call Zweiback Medical Associates or schedule an appointment online today to see how TempSure Envi skin tightening treatments can help you achieve your skin care goals.


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The Perks of Having An Oversize Planner
It is not weird to find people who would prefer to have their set of activities for today and the following days stored in their mind. Although this would give you the ultimate privacy to your plans, it is not the most ideal as this is what makes individuals prone to missing out on some of their plans or not being able to fulfill other responsibilities they have for the day, week or months. To get rid of the potential problems, you'd surely be better off looking into the direction of oversize planners.
With the existence of technology, you may think that an oversize planner or a big calendar you could use to plot your activities and plan is not going to be as useful as others may claim but, you'll surely proven wrong when you experience some of the benefits it could provide you with. Still, knowing that it is beneficial may not immediately get you sold to it and if that is the case, you can always read on and find out more about what this specific benefits are, which could certainly end up convincing you right away that it is an option that you should never pass up on.
The first evident benefit of having an oversize planner stuck right into the wall of your home is that it would allow you to always be aware of the responsibilities you have to attend to in the foreseeable future. You don't even have to worry if you're having some problems memorizing what you need to do for the day or the week, since as long as you place the calendar in an easily accessible area, you could easily remember the whole suite of activities you need to answer to immediately.
The oversize planner in the form of a giant calendar would allow you to view your responsibilities in the next few days. It's easier to understand and with its help, you could formulate the best plan on how you could go about every responsibility in your list in the most efficient and effective way possible.
Finally, there's also the advantage with the fact that it could even act as the record of things you've done and things you still haven't done. This way, if there are certain situations in the future where you may be required to think back on what you've done in a specific date, you can rest assured that you'll have a clear answer to the question at hand.
News For This Month: Calendars


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Brian and Dusty are joined by Thane Goetz for part 2 of our series breaking down the NFL Draft by position. Thane and the guys discuss Nelson & Cobb's contract situations, where the Packers will be most improved next season & an interesting idea on how to solve the Aaron Rodgers contract situation.
Make sure to give Pack to the Future a review on iTunes and follow the guys Brian, Dusty, Jordan and
Check PackersTalk.com for a variety of Packers podcasts and follow Packers Talk on Twitter, Facebook, or subscribe over at iTunes.
Follow Packers Talk Radio Network: Follow @PackersTalkNet Add to Circleson
Jersey Al Bracco is the co-founder and editor of PackersTalk.com. He can be heard as one of the Co-Hosts on Cheesehead Radio and is the Green Bay Packers Draft Analyst for Drafttek.com.
More Packers News
Pack to the Future Episode 76: Scholastic
The guys spent Jordan's birthday discussing the Aaron Rodgers contract situation and what impact Matt ...read more
Pack to the Future Episode 73: Take Two
In our second attempt at making an episode this week and with almost the full ...read more


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Extra terms!
April 18, 2018
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Some more basic ballet terms, are tendu and dégagé.
To tendu, slide your foot to the front(side or back), Making sure to have a pointed toe.
A dégagé can be done, when passing through tendu, and then lifting your foot slightly off of the ground.
*Remember: every step can either be done fast or slow. In ballet terms that would be petite allegro(fast) and Adagio(slow or at ease).


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PayPal is Coming Soon to Google Pay
You got your Google Pay in my PayPal!
Do you use Google Pay? Do you use PayPal? In the next few weeks, you'll be able to use them both together.
Google and PayPal are partnering to allow users to add their PayPal account to Google Pay. This will allow users to utilize their PayPal funds at point of sale terminals wherever Google Pay is accepted.
At the offset of the program, users shall only be able to use their PayPal balance. But soon, users will be able to use their bank cards that they have linked to their PayPal account.
There are a number of users out there, who's banks do not work with Google Pay, but would like to use the service. This new setup will allow those users to be able to utilize Google Pay, while continuing to use their bank of choice.
I'll be honest, I don't use Google Pay. Call me old fashioned, but I am still uncomfortable with the idea. Do you use Google Pay on your BlackBerry? Will you be adding your PayPal account to the service?


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Azure Computers (Thailand) Co., Ltd.
Azure Computers (Thailand) with it's headquarters in New Jersey, USA, and operations in UK, Singapore, Australia, India and Thailand providing IT solutions in three major areas of Web/Mobile Solutions, Enterprise and IT Outsourcing Services.
As a BOI promoted company in Thailand, it has strong, strategic partner with best-in-class technology vendors like SAP, IBM & HP. AZURE Computers has been a dependable IT Consulting partner for many Thai and International companies over the last decade.
Read more about us at www.azurethailand.com
JAVA/Back End Developer
jobsDB Ref. JTH300003002097552
Employer Ref. ITN19
JAVA/Back End Developer
Required :
- 5+ years experience designing and developing web portals and eCommerce.
- Experience with Java including Java 6/7/8, Spring, JDBC, JSP, JSTL, Web services(SOAP/WSDL), JAXB, Ehcache, Maven, Tomcat server
- Experience with using tools such as Eclipse IDE, Git, /Jira, Subversion, Oracle Developer, Selenium QC, etc.
- English: Good (Required)
Optional :
- Experience with Web technologies including Javascript/Ajax, CSS, JSON, jQuery, HTML5, frameworks such as JQuery and Bootstrap.
- Strong Experience with an RDBMS (Oracle, MySQL, Postgres, etc) and working with data formats like XML.
- Strong problem solving, web application debugging and troubleshooting skills using latest tools a must.
- Multi-tasking with good follow through skills, good communication skills.
Interested candidates can submit your application by
AZURE COMPUTERS (Thailand) Co Ltd,
75/47, Ocean Tower II, 23rd Fl, Soi 19 Sukhumvit Road, Wattana, Bangkok 10110, Thailand
Tel : +662 258 4556-8, Fax +662 6657309
Keywords: Java Developer Java programmer IT Programmer Java Developer


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Beginning the new year with resolutions is a tradition - but how about reSEWlutions? Do you have sewing techniques or patterns that you have wanted to try and never built up the courage?
Speaking of courage, I took these pictures with my camera phone on selfie mode. In 19F "feels like 2 degrees" weather. You're welcome.
This week we're talking about plackets. Plackets are a "resewlution" that I see come up every so often, and I think they're an important technique to learn! Some of my favorite styles have plackets, and there are so many types that make them so versatile in garment sewing.
I started thinking about the Winter Wear Designs patterns I might want to sew, and settled on Blithe - mostly because I'd wanted to make it for a long time, and just hadn't got around to it! Opportunity. :)
The only problem with waiting this long was that now I had to make it maternity friendly. Well, that was easy enough. After poking around the internet a while for ideas, I found that one was simply to make the front longer. Since I mostly wear the same RTW size now that I did pre-pregnancy, but none of my shirts fit, I decided to try that. I cut Blithe using the front and back pieces given, but when it came to cutting the bottom of the front, I laid the back piece on top, lined up the armscyes, and cut the tunic length shirttail hem for both pieces.
As of press time I'm undecided about the length, but I've been told it looks good with leggings, so it'll stay - at least til after baby comes! One good thing about it - you can always shorten a garment. Harder to lengthen one. ;)
This placket though. I love plackets, like I said, but I often find myself getting puckered corners, or folding something the wrong way - they are one technique I use that I MUST refer to instructions, every. single. time. I don't know if I'll ever be good enough at them to just DO one without thinking.
If I ever am, it'll be because of this one. The corners are beautiful! The method used is so simple and so perfect, and I really can't praise it enough. I stopped in the middle of sewing just to point this out to Suzanne in the blogger group, because I was so enamored with my handiwork (thanks to hers!)
I probably could use a few more buttons, honestly, but that's the danger of using your stash - I was hard pressed to find even the three that matched, and I'm still not sure one of them is exact! Lol.
If you want a fun, breezy woven top with a beautiful (seriously, I can't say it enough) perfect placket, try Blithe. I'm in love. This is the first woven top I've ever sewn for myself, because I was never sure I wanted woven tops, but I do. OH I DO. And with a few more length, hem, and sleeve options, I won't get bored with it for a while either! I kind of love 3/4 sleeves though, so I might be "boring" and stick with those forever. We'll see!
Fabric is a fab blousewear crepe from my favorite LA Finch Fabrics. I want more. (I don't think there's more of this one, but now I have my eye on that Arboretum...)
Did you miss a day of placket sewing? All the links are below for your inspiration!
Did you miss a day of placket sewing? All the links are below for your inspiration!
January 29
Aurelie of Maglice&So (guest posting at WWD)
Laura of Custom Made By Laura
January 30
Laurie of The Bear and the Pea Atelier
Kristen (guest posting at WWD)
January 31
Alyssa of The Sewing Goatherd
Jessica of Jot Designs USA
Feb 1
Meriel of Elli and Nels
Livia of Liviality


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This one would be a Salute to the Music of James Bond and Secret Agent movies and shows.
Here's how the rundown of such an episode.....shaken and not stirred!
1. The James Bond 007 Theme - the orchestra
2. Thunderball - Jimmy Roberts
3. Goldfinger - Sandi Griffiths & Sally Flynn
4. Peter Gunn - orchestra featuring nice saxophone work by Russ Klein and trombone work by Bob Havens
5. Theme from The Avengers - dance routine by Jack Imel and Mary Lou Metzger
6. You Only Live Twice - Tanya Falan
7. The Man From U.N.C.L.E theme - the orchestra
8. Theme from Get Smart! - danced by Bobby Burgess and Cissy King
9. We Have All The Time In The World - Dick Dale
10. Diamonds Are Forever - Ralna English
11. Mission Impossible - the orchestra
12. Under The Mango Tree & Jump Up (from Dr. No) - The Curt Ramsey Quintet
13. Kingston Calypso (from Dr. No) - danced by Bobby Burgess, Jack Imel and Arthur Duncan
14. From Russia With Love - Joe Feeney
15. Casino Royale - the orchestra
16. Secret Agent Man - Ken Delo
17. Mr. Kiss Kiss Bang Bang - Mary Lou Metzger
18. The Saint - orchestra


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|1497 cc
|118 hp
|Anti-Lock Braking System
Interior comfort
Engine refinement
Lack of features
Slightly dated interiors
The 2018 Honda City facelift was recently released in the UAE. The sedan is available in a total three trim choices - the DX, LX, and EX. All the variants share a common powerhouse, i.e. a 1.5-litre SOHC i-VTEC petrol mill that generates 119 PS of maximum power and 145 Nm of peak torque. This mill comes mated to Honda new-gen CVT transmission and has a mileage rating of 20 kmpl. The facelifted model comes with a restyled exterior that includes a new honeycomb grille, LED DRLs, diamond cut alloy wheels, and revised tail lights.
Additions to the interior include a touchscreen display, cruise control, engine start-stop button, paddle shifters, automatic air-con system, and 60/40 split rear seat. The all-new City comes with a host of standard safety features like ABS with Brake Assist and Electronic Force Distribution, stability control, and SRS dual front airbags.
OTR Price
|1497 cc, 118 hp, CVT, Petrol
OTR Price
|1497 cc, 118 hp, CVT, Petrol
OTR Price
|1497 cc, 118 hp, CVT, Petrol
Ask from fellow City Owners and Zigwheels experts
Millions of people rely on the contributions like yours to decide which cars to buy
|Al Ain
|Ras Al Khaimah
City is available in 6 different colors - Crystal Black, Carnelian Red, Modern Steel Metallic, Lunar Silver Metallic, Nocturne Night and White Orchid.
Crystal Black
Carnelian Red
Modern Steel Metallic
Lunar Silver Metallic
Nocturne Night
Watch latest video reviews of Honda City to know about its interiors, exteriors, performance, mileage and more.
The Honda City has been one of the most successful models for the Japanese markets not only in the UAE, but also across the world. It is with this model that Honda has tried to expand its foothold in almost all the emerging markets all over the globe, and it has been successful in doing so. Unlike in other markets, in UAE, the Honda City serves as the range starting and the most affordable model for Honda in the country. Currently available in its latest guise, the UAE-spec Honda does miss out on some of the features available in the versions of City in other countries. The car is available in three different variants – DX, LX and EX.
The Honda City has always been praised for the plushness and comfort its interior cabin provides, and this latest generation Honda City is no different too. The overall cabin has been lifted off from the previous model, although the introduction of a couple of small features jazz up the interiors.
The three-spoke steering wheel with the generous use of silver finish in the lower portions of the spokes make it look chunky and good to feel. The three-pod instrument console looks simple, however, the blue backlit theme, chrome surrounds for all the three pods and the full TFT third pod for the MID lit it up. The asymmetric center console, like in all the Hondas, is slightly shifted towards the driver, which thanks to the heavy usage of silver and piano black around it, make it look rich and premium. The 7-inch touchscreen unit for infotainment system cover up the basics of the audio system as well as camera, however, it lacks in the modern smartphone connectivity options like Android Auto and Apple Carplay, which are now available in lower priced cars. Though, the full touch sensitive panel for climate control looks nice and provides a feel-good factor to the otherwise very simply laid out dashboard.
The UAE-spec City comes kitted with the basic features like rear AC vents, push button start with keyless entry, cruise control, 8-speakers, 60:40 rear fold down seats. We would have surely liked to see more features, considering the fact that its international versions, which are styled as same as this version, comes loaded with many more features, including the very popular sunroof. Also, the interior cabin has been here for a very long time, since the previous version of the City, and with no changes introduced here, it has started to show its age.
On the outside, the Honda City retains the arrow shot design philosophy of its previous generation model, although it has been tweaked to make it look as upmarket as possible, thanks to mild changes at the front and to the alloy wheels, which make all the difference.
At the front, the Honda City has got a thick single slat chrome grille, with redesigned air dams to make it look more aggressive than before. The angular headlamps are same as before, save for the introduction of new LED DRLs in its exterior corners. However, considering the competition has moved up in integrating projector or LED units for the main headlamp, the Honda City somewhat feels lacking here.
The side profile continues to be same as before, having an eye-pleasing aerodynamic profile. The sharp and thick crease running all the way from the middle of the front door towards the rear tail lamps adds some character to the side profile, while the 16-inch diamond cut alloy wheels make it look more sophisticated than before.
The rear of the Honda City has remained unchanged, with the swept back tail lamps being nicely styled, although like the front headlamps, they too miss out on LED units. The tail lamps are joined to each other with the help of a thin strip of chrome.
All in all, the Honda City still looks sporty and sophisticated at the same time, which is a balance hard to match.
The Honda City comes with McPherson Strut with Coil Spring at the front and Torsion beam axle with coil spring and anti-roll bars at the rear, which do sound basic, however, this suspension setup has been tuned for a very fine balance which does not compromise on either riding comfort or driving dynamics, thus set at a perfect balance. The 16-inch wheels have enhanced the overall driving dynamics by a small margin, which is a welcome addition.
The City still excels in the way its interior cabin space has been setup with the car still benchmarking in terms of legroom, headroom and shoulder room.
Hondas have always been known for its rev-happy and incredibly refined petrol engines, and the City too falls under the same category. Powering the Honda City is the manufacturer's smallest petrol engine for the country, a 1.5-litre four cylinder petrol motor, which has the ability to develop a maximum power output of 118 bhp and a peak torque output of 145 Nm. In all the three variants in which the City is being offered, this refined and smooth engine is mated to a simple CVT transmission, which do get the option of paddle shifters in the top-end variant for seamless yet enjoyable driving pleasure.
Considering the fact that it is an entry level model, we expect Honda City to cover only the basic safety features and miss out on other hi-fi electronic driving aids. Still, with the presence of dual front airbags, ABS with EBD and Brake Assist, Vehicle Stability Assist and Tire Pressure Monitoring System, the City feels safe and assuring enough for the passengers inside.
The Honda City has always been known for being that one model which sets and covers up all the basics of a car in a right manner. The UAE-spec car, in its latest iteration, might not have received much deal-braking changes, and it still misses out on many features that are available in its international versions. However, the car still manages to look athletic and premium at the same time, the engine still feels refined and powerful even after existing in the same form for a long time and the levels of interior space and comfort which the City offers is still second to none in the segment to which it caters.
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If there were 10 favourite cars of all time, Honda City would definitely make the cut for its reliable and loyal image. It is a thoroughly loved and powerful sedan in production since the last 20 years. This drives smoothly on all forms of terrain and beats all other rivals of the same segment such as Verna, Vento, Rapid, Altis.
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The experimental compound TMC207 is showing promise against infections caused by Mycobacterium tuberculosis both in a variety of animal studies and in the field. In this study, we used the guinea pig model, a species that shows several similarities to human tuberculosis, including the hallmark of primary granuloma necrosis, to determine the efficacy of a combination regimen combining TMC207 with rifampin and pyrazinamide. This drug regimen rapidly reduced the bacterial load in the lungs to undetectable levels by 8 weeks of treatment. This reduction was associated with a substantial improvement in lung pathology, but despite this effect areas of residual necrosis still remained. In the draining lymph nodes, however, tissue damage was rapid and not significantly reversed by the drug treatment. Approximately 10 to 11 months after the treatment had ended, the animals began to trigger a Karnovsky scale indicating bacterial regrowth and potential relapse, an event confirmed by the new development of both pulmonary and extrapulmonary granulomatous lesions. Interestingly, a similar rate of relapse was also seen in animals receiving 24 weeks of rifampin, pyrazinamide, and isoniazid standard chemotherapy. These data indicate that TMC207 could be a useful addition to current treatment regimens for tuberculosis.
The increasing incidence of drug-resistant forms of Mycobacterium tuberculosis, now thought to exceed half a million new cases a year (8, 10, 11, 26), further complicates the critical need to discover new antituberculosis drugs. Equally troubling, newly emerging evidence suggests that a significant percentage of new clinical isolates of M. tuberculosis are of extremely high virulence (8). Within the current drug discovery pipeline (12), a particularly attractive new candidate is the diarylquinolone TMC207 (2). This investigational drug potently inhibits the mycobacterial enzyme complex ATP synthase, thus interfering with energy production and homeostasis. As a consequence, TMC207 is highly active against both drug-sensitive and drug-resistant isolates of M. tuberculosis.
In animal studies, the majority of data has been obtained from the mouse model, where TMC207 has activity equivalent to, and synergizes with, standard rifampin, isoniazid, and pyrazinamide therapy (RHZ) (3, 13, 14, 17, 18, 30). However, although the mouse is an excellent and cost-effective screening tool (15), it lacks elements of the disease pathogenesis in humans, including granulomatous lymphadenitis, lymphangitis, and the development of both pulmonary and extrapulmonary lesions exhibiting caseous necrosis with dystrophic calcification (15). In contrast, the guinea pig model of tuberculosis mimics multiple elements of the pathogenesis of the disease in humans (4, 6, 7).
Virtually all studies evaluating drug efficacy in animal models utilize the laboratory strains M. tuberculosis H37Rv or Erdman. However, it is becoming increasingly apparent that newly emerging isolates are of very high virulence, including the W-Beijing family of M. tuberculosis, which is now globally distributed (8) and documented as a cause of major outbreaks of infection worldwide that often involve multidrug-resistant organisms. Because such high virulence now appears not to be unusual but rather the norm, we performed the studies here with the highly virulent Erdman K01 strain. Moreover, our recent studies with this and other virulent strains indicated that these infections are potent inducers of Foxp3+ regulatory T cells (23), a finding that further illustrates the need to find new drug regimens given the potential that this T-cell subset has the potential to subvert vaccine-induced immunity.
In an earlier study (16) we showed that TMC207 is highly active in the guinea pig model of tuberculosis, with low (∼50) numbers of bacilli detectable by culture in the lungs after 6 weeks of therapy. We noted, however, both in this case and in guinea pigs given much longer RHZ treatment (23), that remaining bacteria were extracellular within primary lesions with residual lesion necrosis. Preliminary work in our laboratory has allowed us to hypothesize that these remaining bacteria form extracellular biofilm-like communities which may explain their tolerance to chemotherapy, a possibility recently further supported by in vitro studies (20).
Moreover, regions containing persisting bacteria do not seem to develop rapidly but become apparent as the centers of primary lesions become necrotic, a parameter that seems to be driven by the induction of inflammation and the virulence of the M. tuberculosis isolate (24, 25). This raises the possibility that rapidly effective regimens could potentially sterilize these lesions before necrosis fully develops, thus preventing such biofilm-like communities from forming. The results of the current study show that a combination regimen of rifampin, pyrazinamide, and TMC207 (RZ/TMC207) appeared to rapidly render lungs culture-negative in just 8 weeks of therapy. Despite this, however, we observed that the RZ/TMC207 regimen failed to completely resolve primary lesions, leaving residual areas of necrosis and dystrophic calcification which we believe could potentially serve as the sites of disease relapse, an event that first became observable 10 to 11 months after the drug therapy had ceased. These data support the notion that TMC207 containing regimens have the potential to dramatically reduce the duration of treatment of tuberculosis, but relapse still is likely to occur.
Guinea pigs.Female outbred Hartley guinea pigs (approximately 500 g in weight) were purchased from the Charles River Laboratories (North Wilmington, MA) and held under barrier conditions in a biosafety level III animal laboratory. The specific-pathogen-free nature of the guinea pig colonies was demonstrated by testing sentinel animals. All experimental protocols were approved by the Animal Care and Usage Committee of Colorado State University. Guinea pigs were infected using a Madison chamber aerosol generation device, which delivered ∼20 M. tuberculosis strain Erdman K01 bacilli into the lungs.
Course of infections.Bacterial loads in the organs of guinea pigs (n = 5) were determined prior to the start of drug treatment on day 20 and then after 2, 4, and 6 weeks of treatment. As previously described (23), the bacterial loads in the organs of guinea pigs at each time point of the study were determined by plating serial dilutions of homogenates of lungs (right cranial lobe), spleens, and mediastinal lymph nodes on nutrient 7H11 agar and counting the CFU after 6 weeks incubation at 37°C. The bacterial load for each organ was calculated and converted to logarithms. The data were expressed as the mean log10 CFU plus the standard error of the mean (SEM) for each group.
Drug treatments.On day 20 of the infection, four guinea pigs were euthanized to determine the bacterial load prior to the start of treatment. The remaining animals were randomly assigned to three groups: an untreated control group, a group receiving the RZ/TMC207 treatment regimen, and additional animals set aside for relapse studies. Treatment with chemotherapy was administered 5 days a week for 8 weeks. Because of the challenging animal husbandry issues associated with drug treatment, described in detail elsewhere (23), animals were given 1-ml formulations containing 40% sucrose (wt/vol), 20% pumpkin (wt/vol) (Libby's 100% pure pumpkin) mixture supplemented with vitamin C (50 mg/kg) and commercial Lactobacillus (BD Lactinex) (all purchased from Walmart, Fort Collins, CO). Rifampin (50 mg/kg), pyrazinamide (100 mg/kg of mean body weight), and TMC207 (15 mg/kg) were incorporated into this sucrose/probiotic vehicle. Doses were chosen based on previous pharmacokinetic/pharmacodynamic studies (16). A split-feeding protocol in which pyrazinamide and TMC207 was given in the morning and rifampin in the afternoon was used to minimize drug toxicity interactions and to avoid the known antagonism between rifampin and TMC207. The relapse study animals treated with RHZ were treated with rifampin (50 mg/kg of mean body weight), isoniazid (30 mg/kg of mean body weight), and pyrazinamide (100 mg/kg of mean body weight), which was incorporated into the sucrose vehicle and then mixed with the same formulation as described above.
Animals were carefully monitored on a daily basis using a Karnovsky scale to indicate euthanasia as mandated by the IACUC of Colorado State University (23); usually, about a week or so after the drug treatment was started, animals began to go off feed, necessitating oral feeding by syringe with the nutrient-rich puree, vitamin C, and lactobacillus (the latter to help stabilize the cecal flora and to prevent gastrointestinal dysbacteriosis or antibiotic-associated enteritis). This was performed by gently cradling the animal in the crook of the arm and allowing the animal to consume the mixture from a 1-ml syringe. Two days prior to a necropsy time point, randomly selected guinea pigs were taken off drug therapy. These animals were then euthanized, and lungs, spleens, and mediastinal lymph nodes were removed. The number of viable organisms was determined by plating serial dilution of 10-ml organ homogenates on nutrient Middlebrook 7H11 agar plates (Gibco-BRL, Gaithersburg, MD). Bacterial colonies were then counted after 3 to 4 weeks incubation at 37°C.
Histology.The left caudal lung lobe, spleen, and lymph nodes from each guinea pig (n = 5) was collected at necropsy and fixed in 4% paraformaldehyde in phosphate-buffered saline (PBS). Randomly selected tissue sections were embedded in paraffin and cut to 5 μm on a microtome. Tissue sections were mounted on glass slides, deparaffinized and stained with hematoxylin and eosin and carbol fuchsin using the Ziehl-Neelsen method as previously reported (6). The lung and lymph node lesion area was quantified relative to normal tissue area using a stereology-based method referred to as the area fraction fractionator, with the investigator blind to all treatment groups.
The lung and lesion area was determined on representative hematoxylin and eosin. In addition, acid-fast-stained sections were evaluated. The area of inflammation relative to the normal tissue parenchyma was estimated from representative lung, lymph node, and spleen sections evaluated at a ×20 magnification. A total of 8 to 12 fields were selected randomly by the computer and a counting frame (2,000 μm2) containing probe points with a grid spacing of 200 μm was used to define the areas of interest (lesion and lung). The data are expressed as the mean ratio of lesion area to lung area of all of the animals within a treatment group. Lesions represented by photomicrographs represent the section that is closest to the mean value in each group.
Flow cytometry.To prepare single-cell suspensions for flow cytometry, the lungs were perfused with 20.0 ml of a solution containing PBS and heparin (50 U/ml; Sigma-Aldrich, St. Louis, MO) through the pulmonary artery, and the caudal lobe and portions of the lymph nodes were aseptically removed from the pulmonary cavity, weighed, placed in medium, and dissected as described before (22). The data acquisition and analysis was performed by using a FACSCalibur (BD Biosciences, Mountain View, CA) and CellQuest software (BD Biosciences, San Jose, CA). Analyses were performed with an acquisition of at least 100,000 total cellular events.
Flow cytometric analysis of cell surface markers.Single-cell suspensions from the lungs were prepared as recently described (23). Thereafter, cell suspensions from each individual guinea pig were incubated first with Serotec antibodies to CD4, CD8, pan-T-cell, CD45, MIL4, B-cell, macrophage. and class II antibodies at 4°C for 30 min in the dark and after washing the cells with PBS containing 0.1% sodium azide (Sigma-Aldrich). In addition, membrane permeabilization using Leucoperm (Serotec, Inc., Raleigh, NC) was completed according to the instructions prior to staining with macrophages and major histocompatibility complex (MHC) class II antibodies. The data acquisition and analysis were done by using a FACSCalibur and CellQuest software. Compensation of the spectral overlap for each fluorochrome was done using CD4 or MIL4 or CD3 antigens from cells gated in the FSClow versus SSClow, FSCmid/high versus SSCmid/high, SSClow versus MIL4+, SSChigh versus MIL4neg, and SSChigh versus MIL4+ regions, respectively. Analyses were performed with an acquisition of at least 100,000 total cellular events.
Relapse study.For relapse studies, guinea pigs were monitored by using a modified Karnovsky scale (6). Animals triggering this scale were humanely euthanized and relapse verified by histopathology. Relapse rates between animals receiving RZ/TMC207 or RHZ were compared by using log-rank statistics.
Statistical analysis.Data are presented using the mean values from four guinea pigs per group and from values from replicate samples and duplicate or triplicate assays. The Student t test was used to assess statistical significance between groups of guinea pigs.
Changes in bacterial load after chemotherapy.The effects of the combination RZ/TMC207 therapy in guinea pigs infected with M. tuberculosis are shown in Fig. 1. After 4 weeks of treatment, the bacterial loads in the lungs, lymph nodes, and spleens had dropped to barely detectible levels. No colonies could be detected in the lungs after 6 weeks, but a few colonies were noted in the draining lymph nodes and spleen at 4 and 6 weeks when homogenates were replated on 5% bovine serum albumin (BSA)/7H11.
Influence of chemotherapy on lung and lymph node histopathology.Representative photomicrographs of lung and lymph node from guinea pigs treated for 2, 4, and 6 weeks of combination drug therapy with RZ/TMC207 are shown in Fig. 2. The images in Fig. 2A to C are representative images of lungs and lymph nodes from guinea pigs prior to the initiation of drug therapy. Images from animals treated with RZ/TMC207 for 2 weeks (Fig. 2D to F), 4 weeks (Fig. 2G to I), and 6 weeks (Fig. 2J to L) are also shown. The images in Fig. 2M to O are from untreated control guinea pigs that received the sucrose carrier only, which were euthanized on day 76 after aerosol infection. Combination RZ/TMC207 therapy from 2 to 6 weeks decreased the percentage of lung affected by foci of granulomatous inflammation (Fig. 2D, G, and J), but lesions with central necrosis had a progressive increase in dystrophic calcification over the time of treatment (Fig. 2B, E, H, and K). Drug therapy with RZ/TMC207 had no benefit in reducing the lesion burden and the percentage of lesion with necrosis in lymph nodes (Fig. 2C, F, I, L, and O). There was almost complete effacement of the lymph node architecture as early as 20 days of infection (Fig. 2C), which remained unchanged in extent throughout the infection. There was marked progression of granulomatous inflammation in the lung (Fig. 2M and N) and lymph node (Fig. 2O) in untreated control animals receiving the sucrose carrier alone.
Analysis of lung lesion burden.The tuberculosis that develops in the guinea pig after aerosol exposure to M. tuberculosis can be divided into acute, subacute, and chronic stages of infection based on the pattern of bacterial growth and dissemination, as well as patterns of pulmonary and extrapulmonary pathology. During acute infection, an ∼2-week period of rapid bacterial proliferation occurs in the lung and draining lymph nodes and is characterized by progression of granulomatous inflammation and necrosis in the primary lesion complex of the lung and draining mediastinal lymph nodes. In the subacute stage, infection is established in multiple extrapulmonary sites, such as the spleen and liver, by hematogenous dissemination of bacilli. Concurrent with bacillemia and exponential bacterial growth in extrapulmonary sites, there is reinfection of the lung by the hematogenous route, creating a non-necrotic secondary lesion (22).
Treatment of infected guinea pigs with combination therapy consisting of RZ/TMC207 decreased the lung lesion burden but had no significant benefit in the draining lymph nodes. The data in Fig. 3 represent the mean percent lung area affected by granulomatous inflammation, as well as the percentage of lesion affected by necrosis and the percentage of necrotic foci that had dystrophic calcification in guinea pigs treated for 6 weeks with RZ/TMC207 combination therapy. Six weeks of RZ/TMC207 combination drug therapy reduced the area of lungs with lesions and the percentage of lesions with necrosis. Lesions with dystrophic calcification were first evident at 2 weeks of RZ/TMC207 therapy and were maximal at 4 weeks of therapy consistent with progressive healing of necrotic lesions. Treatment of guinea pigs out to 6 weeks had no additional benefit at reducing lesion burden and even showed a slight increase in lesion necrosis compared to 4 weeks of therapy.
Changes in cellular influx in the lungs after chemotherapy.In untreated control animals, we observed a steady increase in the numbers of activated CD4+ T cells expressing CD45+ (Fig. 4A), as well as CD4 and CD8 T cells expressing the homing receptor CT4+ (Fig. 4B and C). There were large numbers of MR-1+ macrophages brightly expressing MHC class II+ (Fig. 4D), as well as MIL4+ neutrophils (Fig. 4E) accumulating in the lungs over the course of the infection, but this influx was significantly reduced by drug treatment.
Relapse after chemotherapy.The remaining guinea pigs were monitored after completing either 8 weeks of RZ/TMC207 treatment, in parallel with a group of animals remaining from an earlier study that had been given 24 weeks of RHZ treatment. Bacterial quantification yielded culture-negative lungs after 6 weeks of RZ/TMC207 treatment and 24 weeks of RHZ treatment. After about 11 months, we started to see signs of distress in various individual animals, triggering our Karnovsky scale and hence warranting euthanasia. In the first animal to succumb, we noted considerable extrapulmonary dissemination, including multiple lesions visible in the lungs and around within the pericardium (data not shown). As more animals began to die, we consistently noted lung lesions, consisting of mixtures of granulomas that were relatively small and non-necrotic, and lesions showing considerable necrosis, with death resulting from lung consolidation. Overall, 23% (3 of 13) of these animals were euthanized, starting around 11 months after cessation of RZ/TMC207 therapy. We compared this rate to relapse in a parallel group of RHZ-treated guinea pigs (Fig. 5) and found that while relapse in the latter was higher (6 of 15 [40%]), this was not statistically different (P = 0.3).
There is increasing interest in using the guinea pig as a model to test drug regimens (1, 23), given the similarity of the disease process to that seen in humans (4). The results of the present study show that treatment of guinea pigs with a combination of RZ with TMC207 rapidly reduced the bacterial load in the lungs after infection of these animals by a low-dose aerosol exposure with the highly virulent Erdman K01 strain of M. tuberculosis. A 3-log drop was seen in the lungs after 2 weeks of treatment, and after 4 weeks only a few bacilli could be detected, even when using 7H11-5% BSA or LJ plates to account for protein binding by TMC207 and carryover dilution issues. These results are obviously superior to our previous results (23), in which we demonstrated that RHZ therapy of guinea pigs infected with the K01 strain was initially highly effective, reducing the bacterial load in the lungs > 3-log in just 14 days. This clearance rate then rapidly declined, and it took drug therapy for another 125 days before we could not longer detect bacilli in the lungs of these animals.
In the present study RZ/TMC207 caused rapid clearance of the secondary lesions that arise as a result of hematogenous dissemination (4) but failed to completely resolve primary lesions in which necrosis had already developed. More importantly, RZ/TMC207 failed to significantly reduce the progression of disease in the draining lymph nodes which, as in humans, is an important part of the primary lesion complex in guinea pigs following aerosol exposure (6). The significance of these observations is that we now have increasing evidence that these residual pulmonary and extrapulmonary lesions with necrosis harbor extracellular, drug-tolerant bacilli that serve as the source of disease reactivation after drug therapy is discontinued. These data further support our working hypothesis that the microenvironment created by the necrosis of host cells (particularly neutrophils) favors the persistence of drug tolerant biofilm-like communities in vivo.
Severe lung consolidation caused by cellular influx and granuloma formation is a central aspect of progressive disease in this animal model. Consistent with the histopathology data, analysis of the influx of various cellular phenotypes using flow cytometry revealed a substantial reduction in the numbers of activated cells accumulating in the lungs. It has to be conceded that at this time such analyses are very limited due to the lack of reagents, but some information can be gleaned by measuring the expression of CD45+ and the homing receptor CT4 (21, 22). Here, whereas the numbers of activated T cells expressing these markers continued to increase in untreated controls, the numbers were reduced in animals receiving treatment. A similar pattern was observed in the case of activated, MHC class II-expressing macrophages accumulating in the lungs, and also for numbers of MIL4-positive granulocytes. The latter observation is very important, given the central involvement of these cells in the process of necrosis development.
To expand on this latter issue further, guinea pig neutrophils ("heterophils") are important components of the early development of the granuloma in the lungs (29), and we have earlier postulated that degranulation of these short-lived cells may contribute to the development of lesion necrosis (28, 29). In addition, neutrophils are important early sources of oxygen free radicals, which may be the root cause of local vascular damage, further promoting necrosis and lesion hypoxia (4). These areas of necrosis harbor small clusters of bacilli (16), which we speculate may represent biofilm-like communities. This concept is further supported by in vitro models (20) and by preliminary data from our laboratory showing that cell debris generated by the death of these neutrophils can provide a key attachment matrix for extracellular bacilli and may even provide a trigger or signal for initial biofilm development.
Given the rapid clearance of the infection, it was somewhat surprising therefore to see evidence of potential relapse in the RZ/TMC207-treated animals, starting about 10 to 11 months posttreatment. For comparison purposes, we had kept aside a similar number of animals from a parallel study using RHZ; these animals also began to show evidence of relapse at much the same time. Relapse frequencies were a little higher in the RHZ group, but this was not statistically different. In the animals we were able to necropsy we consistently observed reactivation of extrapulmonary lesions. These observations in the guinea pig reflect what is seen in humans, in which relapse occurs up to 2 years after treatment. Since we think that reactivation in the RZ/TMC207-treated animals is arising from within primary lesion residual necrosis, this implies that even if necrosis is minimal it may still be sufficient to serve as a source of disease relapse.
It has been noted (17) that the bactericidal effects of TMC207 seem to increase over a few weeks of treatment. This bactericidal effect is suggested by PK studies in humans (27), suggesting that drug effects targets bacilli that undergo physiologic adaptations that favor extracellular survival in response to the stress conditions generated by host immunity. In our mode of extracellular persistent communities within necrotic lesions, these bacteria survive drug therapy even though the rate of replication is low. This microenvironment contains concentrated micronutrients such as ferric and ferrous iron that may serve as a source of nutrition for extracellular bacilli similar to what has been described for intracellular bacilli in infected macrophages (5). All such processes would require a certain level of energy generation, which TMC207 specifically interferes with. Furthermore, in the present study TMC207 was given for 6 weeks, and it would be interesting to see whether prolonging this duration of therapy might yield reduced relapse.
In addition to this limitation to the study design, we should acknowledge other limitations as well, all predicated by the extreme cost of these extensive studies. First, in addition to extending the treatment duration (the reader will note that neither the draining lymph nodes or spleen were completely sterilized at day 62), it would be interesting to see the degree to which RZ alone would have reduced the bacterial load, given the well-known antagonism between rifampin and isoniazid. Drug carryover in plating is also an issue in these types of studies, and so treatment stopped 2 days prior to the assays, and we only observed trace numbers of bacteria at day 62 when we plated on agar supplemented with BSA to try to account for protein binding. Another issue was related to the use of a Karnovsky scale to detect potential relapse. In classical studies, animals dying in any treatment group could then be assessed by microbiological assays to verify that they had active infection. In the current climate, however, animal usage regulations preclude this, and so we automatically euthanize animals triggering the scale. This arose from our vaccine studies over the past decade, and it is highly predictive of active tuberculosis. In fact, because of our confidence in this, we can use the harvested organs to answer other questions, such as the precise site or origin of regrowth. In the present study, we observed new primary lesions both in the lungs of relapsing guinea pigs, and in extra-pulmonary sites including the pericardium (data not shown). Thus, while the lack of culture data in the relapsing animals is a limitation, other interesting information can be obtained.
As has been noted here, most other animal studies to date have provided encouraging results using TMC207 as part of treatment regimens. Recent studies in mice, using high-dose intravenous infection, have looked at various regimens. These studies have included a comparison between RZ/TMC207 and RHZ, in which the results were comparable (14), although relapse rates were rather high (at 4 months after therapy). In a similar study (30), it was found that monotherapy with TMC207 gave better results than the experimental rifampin-like drug rifapentine and that RZ/TMC207 given just once weekly was better than RHZ daily. Taken in concert with our own results reported here, this suggests that RZ/TMC207 could potentially be used as intermittent therapy, reducing the cost of treatment even further, as recently suggested (19). The effectiveness of TMC207 has also been shown in the guinea pig model, both as monotherapy (16) and in combination with RZ in the studies described here.
The previous observation (18) that TMC207 also works well in combination with second-line drugs, coupled with good in vitro activity against drug-resistant strains (2), indicates that this drug may prove very useful in treating multidrug-resistant (MDR) TB. In this regard, a recent study (9) examined the effect of adding TMC207 to standard therapy (pyrazinamide plus kanamycin, ofloxacin, ethionamide, and cycloserine or terizidone) for MDR TB in a clinical trial in South Africa. The results were encouraging, with a reduction in time to sputum negativity in newly diagnosed MDR patients and increased numbers of patients that were sputum negative at 8 weeks. Given that the few clinical isolates of MDR M. tuberculosis thus far tested in the guinea pig model do not seem to have significantly lost virulence (24), new regimens for MDR TB could be readily tested in this animal model.
This study was supported by a grant from the Bill and Melinda Gates Foundation and NIH programs AI08385602 and IDP20D006450-01.
We thank Koen Andries for providing the TMC207 compound.
- Received 16 July 2010.
- Returned for modification 10 August 2010.
- Accepted 30 September 2010.
- Accepted manuscript posted online 11 October 2010.
- Copyright © 2011, American Society for Microbiology. All Rights Reserved.


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For as long as I can remember, I've kind of wanted to see a tornado. I don't know why, since I don't particularly want to be in an earthquake or hurricane, but I can't shake this little desire to see a tornado (from a safe distance). As a result, I've been dreaming about it for literally my whole life, and lately the dreams have gotten meta.
Once or twice a year, since I was a kid, I've had a dream where I see a tornado and am super excited (much happier than I would be in real life, since in real life I know I'd be terrified). In recent years, my subconscious has been remembering my previous dreams, because in the new tornado dreams I'm thinking "Finally! It's not a dream this time- I'm actually seeing a tornado!"
It reached a new level of meta last night, because in my dream I became aware of the fact that if I'm seeing a tornado, it must be a dream. In the dream I saw one forming in the distance, was excited, remembered all the other dreams, got even more excited that it wasn't a dream, but then started second guessing myself and trying to prove to myself (in the dream) that I for sure wasn't dreaming. I was actually pinching myself and looking for unrealistic things in the dream to prove that it really, truly, wasn't a dream, and I was actually seeing a tornado. Just as I convinced myself that it was real, I woke up.
Where is it going to go next time?


text: The children in Year 5 made coconut ice today. They were given the ingredients, utensils, and a recipe, and were left to work together to make enough for all the children in their group. They then made Christmassy boxes to put them in. We hope parents & carers got to try some rather than it all being eaten on the way home! Well done to all the children for working so well together. (The recipe we used has been added by popular request…)