text:
You can easily experience confusion and frustration when you apply for disability benefits in Port Huron. You have many hoops to jump through and hurdles to clear. You may get discouraged and feel like giving up. However, giving up is not an option when these benefits are your lifeline to making ends meet.
You should seek help immediately from Disability Attorneys of Michigan. Our knowledgeable legal team helps residents in Port Huron, MI and throughout Michigan to overcome the challenges they face in the disability benefits process.
Our skilled disability attorneys are known for:
- Extensive experience. We have more than 100 years of combined experience. We have built up vast knowledge and insights into the complicated Social Security disability and VA disability systems. We use that knowledge to our clients' advantage.
- Compassionate service. We treat every client as if they are a member of our family. Our concern for our clients doesn't stop when their case is over. That caring attitude leads many of our clients to refer their friends and family members to us for help. We consider referrals to be the highest compliment a client can pay us.
- Comprehensive approach. We know that many of our disabled clients need more than just benefits. We go the extra mile to help clients to find housing assistance programs as well as free and low-cost health care clinics. We want our clients to get the well-rounded support they need.
If you or a loved one needs help applying for Social Security disability or VA disability benefits in Port Huron, contact us today. Our skilled disability attorneys can help with your initial application and the appeals process.
How Our Attorneys Help People with Disabilities in Port Huron, Michigan
Many law firms try to cover a lot of practice areas. Our firm focuses solely on helping people who need disability benefits. We help our clients by:
- Applying for Social Security disability benefits. When you meet with us, we will explain what you should expect from the SSD benefits application process and determine what types of disability benefits you may need. We will take the time to ensure your claim is thoroughly documented, which will improve your chance for approval.
- Pushing claims through the process. Many applicants spend months or years waiting for their SSD benefits claim to be processed. We focus on providing claims reviewers with every bit of information they need. We want to prevent your application from hitting a snag. We will also keep track of your claim's progress and push for updates every step of the way.
- Appealing claims that have been denied. The majority of SSD benefits claims are denied the first time, including valid claims. Our attorneys can help you to navigate the complicated appeals process and fight for the benefits you deserve.
- Standing up for veterans. Many veterans do not realize that they may be entitled to SSD benefits in addition to VA benefits. We will pursue every possible source of compensation for you. We have extensive experience with appealing denied VA benefits claims and low disability ratings.
"Mandy and her staff helped me work through this trying process and kept me informed with all of my questions and guidance needed. I would highly recommend the staff for their effort. Thank you." – Anthony.
Click here to read more client testimonials.
To schedule a free consultation with one of our attorneys, fill out the contact form below, or call the Law Offices of Disability Attorneys of Michigan today at 1-800-949-2900.
Disability Resources near Port Huron, Michigan
We want our clients to have access to all of the resources they need to maintain a good quality of life. Our attorneys make it a point to identify disability resources in Port Huron and make those connections. Some of the local programs that you may find useful include:
Department of Veterans Affairs
200 Grand River, Suite 104
Port Huron, MI 48060
600 Grand River Ave
Port Huron, MI 48060
1530 Pine Grove Ave # 7
Port Huron, MI 48060


text:
It's one of the most immediately recognizable photographic sequences ever made: Ralph Morse's dizzying pentaptych capturing the July 16, 1969, liftoff of Apollo 11. Here, in five narrow frames, we witness—and celebrate—a distillation of the creativity, the intellectual rigor, the engineering prowess and the fearlessness that defined the best of the Space Race.
[See the complete LIFE special issue on the Apollo 11 triumph, 'To the Moon and Back']
But for all of their emotional and historical heft, Morse's pictures also call to mind, in almost anyone who encounters them, a straightforward and pressing question: How the hell did he do that?
Morse, now 97 years old, recently spoke with LIFE.com, and briefly described how the sequence came about.
"You have to realize," he says, "that the rocket had to go through the camera, in a sense. It had to go through the camera's field of view. It took me two years to get NASA to agree to let me make this shot. Now, RCA had the camera contract at Cape Canaveral at that time, and they had a steel box—with optical glass—attached to the launch platform. We negotiated a deal with them and I was able to put a Nikon, with maybe 30 or 40 feet of film, inside the box, looking out through the glass. The camera was wired into the launch countdown, and at around minus-four seconds the camera started shooting something like ten frames per second.
"It was probably less than an hour after liftoff when we rode the elevator back up the launch tower and retrieved the camera and film from inside that steel box."
Finally: Below is a picture of Neil Armstrong's wife, Jan, with sons Erik and Mark, watching the launch of Apollo 11—from the deck of a boat rented for them by LIFE magazine. The scene, as captured by LIFE's Vernon Merritt III, is a quiet reminder that the mission to the moon was not only an epic public spectacle. It was also a deeply personal and private adventure, shared by the astronauts and those closest to them in ways, and with an intensity, that the rest of us can hardly imagine.

subset: commoncrawl


text: The Pepsi USBC Youth Championships is a nationwide tournament open to all USBC Youth members.Beginning with qualifying during their leagues, youth bowlers have the opportunity to advance to a state finals event and earn scholarships, where they can compete against bowlers from across their state. Last year, more than $500,000 in scholarships was awarded across the country as part of this tournament.Be sure to ask your youth program director when your league will be participating in the Pepsi.CONTACTZach BartonTournament ManagerIBC Youth Tournaments Manager800-514-BOWL, ext. firstname.lastname@example.com


text:
On behalf of the faculty, staff, and administration of Irvine Valley College, I am delighted to welcome you. As you navigate our website, I hope you will get a taste of who we are and all we offer to help our students flourish.
From its early years as a satellite campus to its independence in 1985 to the present day, IVC has been driven by a commitment to academic excellence and responsiveness to students. We are proud to be at the forefront of community colleges in the nation working to ensure student success and completion rates. We are proud of our students' achievements and our standout transfer rates—No. 1 in the state of California. We are proud of the services we offer to help keep students on track, through both the highs and the challenging moments of their college life.
The faculty at IVC—who include authors, scientists, artists, designers, musicians, Fulbright scholars and entrepreneurs—are passionately committed to their students. Our wonderful staff is, above all, student centered. Our beautiful campus offers a friendly, relaxed atmosphere, and our classrooms and labs are equipped with the latest technology to prepare you for advanced study or career advancement. We stress the importance of designing an educational plan so you can accomplish your highest goals.
I know that some of you will be making the transition from high school to college. Others will be returning from active military service or an interval of time away from school. Some of you will seek to upgrade your job skills, and many others will be getting your undergraduate preparation before transferring to a four-year school. I have witnessed how IVC transforms lives, and I am confident we can give you the education, training and tools you need to move forward, whatever your path.
The Latin motto on our college seal—a posse ad esse—translates to "from possibility to reality." It affirms our commitment to help you, our students, imagine, plan for, and achieve your educational goals. We are here for you.
Sandy JefferiesOffice of the President, Manager
T: 949-451-5210 O: A100 BuildingComments or Feedback?


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Forest tax – sometimes called timber tax – is an excise tax that began in 1971, when the Legislature excluded timber from property taxation. In place of a property tax on trees, timber owners pay a 5 percent excise tax on the stumpage value of their timber when it is harvested. In 1982, the Forest Tax was extended to timber harvested from state and federal land, in addition to private land.
Timber from private land: The person who owns the timber at the time of harvest is responsible for paying forest tax. Contractors performing labor and services for the timber owner are not responsible for the forest tax. When the owner of the timber cannot be determined, the landowner at the time of harvest will be responsible for the tax.
Timber from public land: The owner is the first person (other than the public entity) to acquire title or possessory interest to the timber.
The revenue is split between the counties and the state general fund. The timber is taxed at 5 percent, with 4 percent going to the county where the harvest occurred and 1 percent going to the state general fund.
Most timber harvests on private land require a permit from the Department of Natural Resources.
A copy of your approved permit will be sent to the Department of Revenue. The Department will then mail tax reporting forms and instructions to you. If you do not receive a return, call the Department of Revenue at 1-800-548-8829.
If a permit is not required, you must call the Department of Revenue at 1-800-548-8829 to register and pay your tax.
Forest tax is due at the end of the month following the end of the quarter when the timber was harvested (see chart below).
For delinquent taxes paid on or after August 1, 2015, new penalty rates apply (9%, 19%, 29%). See Special Notice - Late Payment Penalties Increase for additional information.
There are two ways to file: online or by mail.
File online: Now you can file your forest tax return online where you file your business and occupation (B&O) taxes. Revenue's free E-file system does the calculations for you, remembers your information, and gives you more ways to pay.
To get started, you'll need your Tax Reporting Account Number (TRN) and Pre-Assigned Access Code (PAC). Both numbers are located on your forest tax return you received in the mail.
If you aren't signed up for My Account, register for a free account. Once logged in, click "File a Return," then click "Forest Tax" to begin filing
Once you file your first forest tax return online, you will no longer receive a paper tax return. Instead, you will receive an email notification each quarter when your tax return is ready.
File by mail: Unless you have previously filed a forest tax return online, a return will be mailed to you each quarter. All first-time filers will receive a return in the mail. Send the completed return and your payment to the Department of Revenue at the address listed on the return. Blank forms are also available online.
If you do not receive a return, call the Department of Revenue at 1-800-548-8829.
If you have questions or need assistance from a Revenue forester, call 1-800-548-8829 Monday through Friday from 8 a.m. to 5 p.m. or e-mail us.
Q&A for Small Harvesters filing their B&O tax returns
Forest Land Values
Local Offices
Log Export Regulations
Understanding Washington's Timber Excise Tax (pdf)
Damaged timber adjustment application (pdf)
Forest tax forms
Forest tax publications
Laws & Rules
Join the Forest Tax Email List
Sign up to receive email notifications about forest tax draft rules, meetings/public hearings, rules agendas, etc.


text:
Azure International is a leading investment and advisory company focused on China's cleantech energy sector. Founded in 2003, we have a team of 20+ local and international professionals based in China with backgrounds in engineering, marketing, manufacturing, consulting, policy, government relations and finance. In addition to deep advisory capabilities in renewable energy, energy efficiency, carbon management, and energy finance, we have proven capability to invest in and accelerate the development of clean energy companies. Our portfolio and partner companies have achieved both significant commercial success and returns to investors. Azure provides the necessary expertise and execution capabilities in China to lead relationship development with government and strategic partners, project execution, sourcing, sales and technology development – all with deep understanding of Chinese and international requirements.
For further enquiries or if you are interested to
learn more about how we can collaborate, please
contact us directly at:
Azure International
Tel: +86 10 8447 7053
Fax: +86 10 8447 7058
E-mail: email@example.com


text: In 1867, ASB was founded by a mysterious criminal figure. It was a private corporation with its sole purpose being global domination. Its intentions were masked to the public by the legitimate packaging business it had as a front. Another mysterious figure, rich, powerful and clever enough to deduce that ASB was behind the recent crime wave, founded WEC, a corporation whose sole task was to prevent the ASB from achieving their goal. Since then, an invisible war was fought between these two private corporations. Over the years, WEC had been slowly disrupting the ASB's operations and preventing their plans from being materialised. After destroying most of the ASB's assets, WEC sent their best Agent to the heavily guarded ASB Base in order to destroy both it and what was left of the ASB once and for all.


text:
Gift Registry Login
Returning Customers
• required
If you are a registered user, please enter your email and password.
Log in using your account from
Find Someone's Gift Registry
• required
You can also search for other people's Gift Registry using the Gift Registry Search
New Customers
Creating an account is easy. Just fill out the form below and enjoy the benefits of being a registered customer.


text:
This weeks Chopped Challenge Mystery Basket included beer, almonds, tomatoes and marshmallow fluff… again!
I combined the beer and almonds to make one of my favorite side dishes, onion rings.
I then combined the marshmallow fluff and tomatoes to make a side of BBQ sauce for dipping.
The final result of "Chopped Challenge Thursday" Week Ten: Beer Battered Almond Crusted Onion Rings with a Sweet Marshmallow BBQ Sauce
Ingredients (BBQ Sauce – makes 2 cups)
- 2 tbsp honey
- 2 tbsp molasses
- 2 tbsp marshmallow fluff
- 1/4 cup apple cider vinegar
- 1/4 cup beer
- 1/4 cup brown sugar
- 2 tsp dry mustard powder
- 1/2 tsp garlic powder
- 1/2 tsp onion powder
- 2 tomatoes (chopped)
- 1 can (6 oz) tomato paste
Combine all ingredients in a blender or food processor.
Puree until a thick sauce forms.
Place in the refrigerator while preparing the onion rings.
Ingredients (Onion Rings – makes app. 30)
- 2 yellow onions
- 1 egg
- 1 cup milk
- 1 cup beer
- 2 cups cornmeal
- 1/2 cup almonds
- 2 cups flour
- 1 tbsp cayenne pepper
- 1 tbsp kosher salt
Begin by slicing the onions into 1/4 inch rounds.
Next, whisk together the egg, milk and beer. Pour the mixture over the onions.
Next, blend together the almonds and cornmeal in a food processor.
Place in a shallow dish. Combine the flour, salt and cayenne pepper in a separate shallow dish.
Next, heat a small amount of olive or canola oil in a large skillet over medium heat, then pre-heat the oven to 400° and prepare a baking dish topped with cooling racks on the side of the skillet.
Now, you're ready to go!
Begin, by moving the onions from the milk and beer mixture to the flour mixture, coat well, then toss them back into the milk and beer, then into the cornmeal almond mixture. Coat well then place into the skillet and cook on each side for 1-2 minutes.
Remove from the skillet and place on the baking sheet.
Bake for 6-8 minutes then remove from the oven.
Serve with the Sweet Marshmallow BBQ Sauce for dipping.
This is the perfect way to eat your favorite crispy side dish without the guilt of eating fried foods!


text:
Nation & World
With al Qaida's Nusra Front leading, Islamists seize control of Syria-Turkey border crossing
Al Qaida-linked Syrian rebels took control Monday of a key border crossing connecting Turkey to a Syrian province considered the heart of support for the government of President Bashar Assad, in heavy fighting that took the lives of three members of Assad's family.
Syrian state television accused both the rebels and Turkey of using the Turkish side of the Kasab border crossing to ambush government forces on Friday. That sparked a broader confrontation that saw both sides heavily reinforce their positions over the weekend.
The offensive has been led by the Nusra Front, al Qaida's official Syrian franchise, and the Islamic Front, a broad coalition of Islamist fighters that includes the al Qaida-linked group Ahrar al Sham. Adding to the radical flavor of the fighting is a unit of Chechen-led fighters aligned with the rogue Islamic State of Iraq and Syria, a jihadist group made up largely of non-Syrians that has been criticized for its brutal rule in the parts of Syria it controls.
On Monday, the official social media accounts of the Islamic Front released photos of its fighters taking control of the border crossing, although reports said that fighting for control of the area was continuing.
The crossing provides access to the coastal province of Latakia, the ancestral home of the Assad family and its fellow Alawite Muslims, where support is strong for the Assad government and its militia, the National Defense Force, a paramilitary group trained by Iran to bolster the thinly spread Syrian army. Latakia has both symbolic and strategic importance, connecting the rest of Syria to the Mediterranean Sea. Russia maintains a military facility at the Latakia port city of Tartus.
The importance of the region to the Assad regime is reflected in the command structure of the National Defense Force there. On Sunday, Syrian state television announced the death in the fighting of the local defense force commander, Hilal Assad, a distant cousin of the president.
On Monday, Syria announced the deaths of two other cousins of the president, Ali and Kifah Assad, though it was unclear if they were killed separately of Hilal, who died when rockets fired by rebels targeted his command post. Both men were rumored to have been in command positions in the National Defense Force and could have been killed in the same incident.
A group that is part of the Islamic Front, Jaysh al Islam, issued a statement detailing how Hilal Assad was killed.
"The first rocket was fired around 7:15 p.m., followed by another five minutes later," the statement said. "The rockets targeted a house where Hilal was holding a meeting with other members of the National Defense Force."
The Syrian charge that Turkey was helping the Islamists came one day after Turkish jets downed a Syrian fighter-bomber as it attacked rebel positions along the border. Turkey alleged that the MiG-23 had entered Turkish airspace, a charge Syrian state television denied. Video shot by a Turkish news crew showed the MiG-23 crashing into a mountainside inside Syria.
The fight for Latakia, which had been dormant since last summer as the regime successfully recaptured key rebel held areas in Homs, Qusayr and the border with Lebanon, has often been characterized by extreme sectarian violence.
An investigation by Human Rights Watch, an advocacy group, accused Islamist fighters of killing at least 190 civilians and kidnapping 200 others in fighting last summer in Latakia.
The Syrian Observatory for Human Rights, a pro-rebel monitoring group with investigators around Syria, said that at least 80 fighters on both sides have died in fighting for the border crossing since Friday. The group also said that heavy rocket fire by rebels had begun to strike key cities throughout the province, with multiple casualties.


text:
idealists needed a new logo design and created a contest on 99designs.
A winner was selected from 130 designs submitted by 19 freelance designers.
A hot, new, free adults only, sex, dating website for Australia.
Adults looking for hot, fun times.
We are looking for a logo (and favicon) for a new Australian, adult dating site, SexSeeker.com.au
approx, 310x77px
Something hot, fresh, and not cheesy, and some spice!
flames in the logo are cool, MAYBE like::
If you have a better idea..don't hesitate to try it.
But please keep to the colours, background is black. please only use colours, red [rgb(165, 10, 24)], white, yellow.
think fling.com logo but hotter
also shadow or reflection is nice
any questions, please ask.
we require the logo in both original PSD, with layers, text as editable font, plus also web friendly format for site.
Also a favicon that somehow links into the design of the logo.
Find out how a design contest works or learn more about our logo design services.


text:
Sector groups
Experts in 17 key sectors from all across the Enterprise Europe Network have teamed up to provide you with customised support.
The Network's Sector Groups combine international business expertise with local knowledge. We can help your business grow through tailored support and new partnerships. We can also advise you on how to find partners to apply for EU-funded joint research projects.
Learn how to benefit from our specific support for your sector by selecting the respective Sector Group.


text:
U.S. Department of the Interior, National Park Service
Researching a historic property for National Register nomination differs from researching a property for other purposes. Information collected must be directed at determining the property's historical significance. When evaluating a property against National Register criteria, significance is defined as the importance of a property to the history, architecture, archeology, engineering, or culture of a community, a State, or the nation. Significance may be based on association with historical events (Criterion A); association with a significant person (Criterion B); distinctive physical characteristics of design, construction, or form (Criterion C); and potential to yield important information (Criterion D).
Every National Register nomination must place a property in its historic context to support that property's significance. Historic context means information about the period, the place, and the events that created, influenced, or formed the backdrop to the historic resources. The discussion of historic context should describe the history of the community where the property is located as it relates to the history of the property.
Two other considerations affect evaluation of significance: association and period of significance. Association refers to the direct connection between the property and the area of significance for which it is nominated. For a property to be significant under historic events (Criterion A), the physical structure must have been there to "witness" the event or series of events; they must have actually occurred on the nominated property. For a property to be significant for an association with an individual (Criterion B), the individual should have lived, worked, or been on the premises during the period in which the person accomplished the activities for which the individual is considered significant. Period of significance refers to the span of time during which significant events and activities occurred. Events and associations with historic properties are finite; most properties have a clearly definable period of significance.
Lastly, a property is evaluated for its integrity: the authenticity of physical characteristics from which properties obtain their significance. When properties retain historic material and form, they are able to convey their association with events, people, and designs from the past. All buildings change over time. Changes do not necessarily mean that a building is not eligible; but, if it has radical changes, it may no longer retain enough historic fabric, and may not be eligible for the National Register. Historic integrity is the composite of seven qualities: location, design, setting, materials, workmanship, feeling and association.
The National Register nomination form records the property at the time of its listing and justifies how the property qualifies for National Register listing. In addition, the form contains other data elements that should be reviewed before research is initiated. They include the location, size, and boundaries of the property; category and numbers of contributing resources; historic and current functions; architectural classification and materials; area and period of significance; and bibliography.
One of the most challenging tasks of research is knowing when you have gathered enough material. You are ready to complete the National Register nomination form when the following questions can be answered:
|National Register Home | Publications Home | Previous Page | Next Page


text:
Hey all,
I'm sure everyone is frantically backing up favorite galleries, but we should be a little systematic about it. I'd hate to see a hundred back-ups of Hachi's folder but no backups of Obi-Juan-Kenobi's, just to pick two great castle builders. Add to this thread the names of any galleries you've backed up. Even if someone else has already backed up that gallery, let us know. The format I propose is this:
1. Gallery name (back-up #1), (back-up #2), etc
2. Gallery 2 (back-up #1)
If you have your own stuff backed up, add (self) as the backer-upper. We'll keep updating the list so we know what galleries are safe and identify any key builders who are missing, focusing on castle builders of course, but include anyone you back up.


text:
Hi all! I'm Rebecca Silbaugh from Ruby Blue Quilting Studio. I'm pleased to introduce you to my Charmed Living Runner design. This is my first project for the Moda Bake Shop (Thanks Moda!) and I could be more excited to share it with you. It's a great project to make for you or as a gift. With the variety of charm packs available, you can make this out of any fabric and it will look spectacular. Also included are optional applique instructions. Feel free to change the applique to suit your fabrics or leave it out entirely.
I hope you enjoy this pattern and have as much fun making one as I have. For more information on who I am and what other patterns I have designed, please check out my blog at rubybluequilts.blogspot.com. Also, for wholesale inquiries or more information on where my patterns are sold, please e-mail me at firstname.lastname@example.com.
* 1 Moda charm pack
* Backing – 3/4 Yard
* Binding – 1/4 Yard
If you decide to add an applique embellishment to your table runner you will need:
* 16″ square scrap for the flower petals
* 4″ square scrap for the large flower center
* 2″ x 4″ scrap for the small flower center
* 6″ square scrap for the leaves
* 1 Yard Green 1/2″ ricrac for flower stems
* Threads to match
Begin by separating each of the charm squares into piles. There will be a pile for each piece that will need to be cut. This is a good planning step to make sure you distribute the colors.
You will need one pile with 3 squares, one with 18 squares, one with 11 squares, and one with 8 squares. Keep in mind it might be helpful to use smaller prints in the pile with 11 squares since they will be cut the smallest.
Cut each of the 3 squares from the first pile into 4 equal 2-1/2″ squares.
Trim the next 18 squares to 5″ x 4-1/2″ pieces. Re-trim each of these into 2 pieces measuring 2-1/2″ x 4-1/2″.
Cut the next 11 squares into 9 pieces, 1-1/2″ square each.
Cut last 8 squares into 2 pieces each: 1-1/2″ x 5″ and 3-1/2″ x 5″. All of these pieces will be used in the borders. Set them aside for now.
Pair together two 1-1/2″ squares at random, designating one as a "light" and one as a "dark". Make 48 pairs pressing the seam to the "dark".
Match two of the pairs shown above. Offset the "darks" to create a scrappy four patch. Do this for all pairs, creating a total or 24 four patches.
Sew a 2-1/2″ square to the side of a four patch. Make 12.
Sew a 2-1/2″ x 4-1/2″ strip along the bottom of each of the 12 units from above.
Stitch another 2-1/2″ x 4-1/2″ strip along the side of each block being made.
Sew each of the remaining four patches onto the end of a 2-1/2″ x 4-1/2″ piece. Make 12.
Sew the strip segment made above along the bottom of the block. Repeat this step for all 12 blocks. Each block should measure 6-1/2″ square.
Stitch all of the blocks together in a 3 x 4 setting, rotating blocks as you lay them out.
Pair each of the border pieces (set aside earlier). Alternate fabrics, designating one as the "dark" like we did making the four patches earlier. Four small pieces need to be "darks" and four of the bigger pieces need to be "darks". Press seams toward the "darks".
Alternate the small and large "dark" pieces by sewing 4 units together side to side. Make 2 borders. Each border should measure 4-1/2″ x 18-1/2″.
Stitch the borders along both ends of the runner. At this point you can choose to embellish the runner with applique or leave as is.
This is the same runner once the applique has been added.
Here's a close up of the applique along the bordered edge of the runner. Now all that's left is to quilt and bind! Quilt as elaborate or simple as you like (I usually "over-quilt" my table runners in case I want to set "stuff" on it. It seems to help the "stuff" from being wobbly. Less wiggle room!)
One table runner measuring 18″ x 32″, perfect for anyone! It's so quick and easy I can promise you that once you've made one, you'll want to make more! For color options of this pattern, please visit my blog at rubybluequilts.blogspot.com.
If you create one of these incredible table runners, please e-mail me at firstname.lastname@example.com and I will post your picture on my blog! Thanks again and I hope you enjoyed my tutorial!


text:
If you're not big into the summer Olympics because track and field just doesn't get you going, infamous pranksters Improv Everywhere have a nice alternative for you. Their latest MP3 experiment takes on the Olympic games in a characteristically bewildering style.
Over 4,000 participants showed up at New York City's Governor's Island on July 15th to participate in this year's MP3 experiment, the 9th of its kind. Donning headphones and simultaneously taking commands from the same pre-recorded omnipotent voice, pseudo-Olympians took part in several ridiculous games which included implements like bed-sheets and time-honored skills like water-marksmanship.
The Improve Everywhere Games may not have had their own torch, or medals, but they were on tape-delay. And that's how the professionals do it, right? [YouTube]


text:
Your success. Our priority.
Columbia Threadneedle Investments is a leading global asset
manager. We know investors want strong and repeatable risk-adjusted
returns and we aim to deliver this through an active and consistent
investment approach that is team-based, risk-aware and
Better insights
Our talented investment teams around the world work together to
uncover investment insights. By sharing knowledge across asset
classes and geographies we are able to generate richer perspectives
on global, regional and local investment landscapes.
Better decisions
The ability to exchange and debate investment ideas in a
collaborative environment enriches our teams' investment processes
to ensure our best insights are applied to portfolios. More
importantly, it results in better-informed decisions for our
Better outcomes
Our broad range of investment strategies and solutions are
designed to meet the evolving needs of our clients, whether they
are individuals, advisers or institutions. We are committed to
first class client service and investment excellence. We have a
dedicated team of more than 2,000 colleagues across the globe, all
with a common goal.
Your success is our priority.
Columbia Threadneedle Investments is the global asset management
group of Ameriprise Financial, Inc. (NYSE:AMP), a leading US-based
financial services provider.
Columbia Threadneedle Investments is the global brand name of the
Columbia and Threadneedle group of companies.


text:
Note: This item is more than seven years old. Please take the publication date into consideration for any date references.
Print – Plain Text – Permalink
News Release
Media Contact: TPWD News, firstname.lastname@example.com, 512-389-8030
March 29, 2012
TPWD to Sell Portion of Palo Duro Canyon's Fortress Cliff Ranch
AUSTIN – The Texas Parks & Wildlife Commission has approved a real estate deal that calls for the Texas Parks and Wildlife Department to sell 2,014 acres of the state-owned, 2,867-acre Fortress Cliff Ranch, while retaining roughly 850 acres to expand Palo Duro Canyon State Park.
Under the sales contract, Sooter Ranch Ltd. will pay $2.4 million for the property that includes a modern ranch house, roughly 1,500 acres of grassland and mixed brush, a side canyon and a quarter mile of the canyon rim.
TPWD, working with the Trust for Public Land, acquired the valuable ranchland overlooking the almost 29,000-acre park in a dual transaction straddling several years ago primarily to protect the state park's view shed.
The sales contract mandates that the purchased property be placed under a perpetual conservation easement held by TPWD to ensure that the land's important wildlife conservation values are protected and to protect views from the park of seven miles of the canyon rim that had been targeted for possible development into small, canyon-front home lots, Ted Hollingsworth, TPWD's land acquisitions program manager, told commissioners Thursday.
TPWD determined through the use of computer modeling and site visits to map park views that the portion of the ranch being sold did not contribute significantly to the mission of TPWD or the state park. TPWD also evaluated recreational access and public use options in making the determination. The retained acreage will be integrated into existing resource management and the park's public use plan one day is expected to allow visitors to hike from the canyon floor up to the rim to enjoy the spectacular views.
"By selling much of the Fortress Cliff property to a conservation buyer, the agency is staying true to its original stated intent and plan to sell the ranch house and uplands at a future date to protect the cliffs and the park's view shed, and make the best use of our limited funds," said Carter Smith, TPWD executive director. "The sale proceeds will allow us to acquire high-priority state park property elsewhere in Texas."
The Fortress Cliffs property, formerly Tub Springs Ranch, is located about 15 miles southeast of Amarillo in Randall and Armstrong counties.
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The Government is facing renewed heat over its relationship with SkyCity after claims the casino operator lobbied it over a deal with China Southern Airlines to fast-track visas for wealthy Chinese visitors.
Immigration Minister Nathan Guy was forced to hastily announce the deal - which reduces visa requirements for wealthy China Southern Airlines passengers - after NZ First leader Winston Peters produced internal Immigration NZ emails revealing concerns it would allow criminals into the country.
Yesterday in Parliament, Mr Peters pressed his attack further, tabling an article which appeared in an online version of New Zealand TravelTrade magazine in August last year.
In the article, SkyCity's president of international business, Ejaaz Dean, was reported as saying the casino was "working closely with China Southern Airlines to bring VIP gamblers into Auckland seamlessly".
He "confirmed the casino was in talks to make the visa process easier", the article said.
In response to a question from Labour MP Trevor Mallard, Mr Guy said he was not aware of any SkyCity involvement in the deal.
Mr Peters said the arrangement, made after Mr Guy met airline representatives in April, "means that a casino and a communist government airline have ... now acquired privileges for their customers not available to any other group of people anywhere else in the world".
The Auditor-General is investigating how the Government sought proposals for an Auckland convention centre after SkyCity won out over rival bids with an offer to foot the entire $350 million bill, in return for changes to gambling laws.
In light of that and the TravelTrade article, Mr Peters said the Government's relationship with the casino company was "totally incestuous, giving them special deals and special arrangements even changing our border security routines to favour these people".
Finance Minister Bill English dismissed Mr Peters' claims, saying: "The Government discusses laws with commercial entities and large scale public entities all the time."
SkyCity spokeswoman Kelly Armitage said the company had "ongoing discussions with all airlines" and was "always talking to the Government" about how to make to make visa requirements for customers easier, but it wasn't involved in discussions on the China Southern Airlines arrangement.
She said TravelTrade's article was incorrect.
"Whatever Ejaaz said to the reporter has been misrepresented somehow."
The deal
* China Southern Airlines' Gold and Silver frequent flyer card holders will not have to produce evidence of sufficient funds to support themselves to get a visitor's visa
* Visitors will still have to meet health and good character requirements, as well as evidence of onward travel
* Immigration Minister Nathan Guy says those eligible are "considered to be low-risk as they travel regularly for business or leisure"


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Department of Mathematics
Meet the Platonic Solids: Icosahedron
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If you would like to learn more about Platonic solids, you can start here.
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- Epidemiology
- Risk for HIV-Associated Pneumonias
- Symptoms
- Bacterial Pneumonia
- Pneumocystis Pneumonia
- Tuberculosis
- When to Seek Medical Evaluation
- Medical Evaluation
- Conclusion
- Selected Sources
Respiratory symptoms, including cough, shortness of breath, labored breathing, and chest pain, are common complaints in the setting of HIV infection. The spectrum of respiratory infections ranges from mild, self-limited viral upper respiratory infections to severe, life-threatening pneumonias requiring urgent hospitalization and treatment. In the United States, bacterial pneumonia and Pneumocystis pneumonia (PCP) are the two most common HIV-associated pneumonias. Although less common in the U.S., tuberculosis (TB) is the leading HIV-associated pneumonia worldwide.
While the overall incidence of opportunistic infections has decreased since the introduction of highly active antiretroviral therapy (HAART) in 1996, HIV-associated pneumonias remain a significant source of illness, and any respiratory complaint that may be due to pneumonia must be taken seriously. This review focuses on the most common HIV-related pulmonary infections -- bacterial pneumonia, Pneumocystis pneumonia, and tuberculosis -- and will provide an overview of the epidemiology, characteristic clinical and chest radiograph findings, diagnosis, treatment, and prevention of these pneumonias.
Following the introduction of HAART and the use of preventive antibiotics for PCP, the prevalence of different HIV-associated pneumonias has changed. From the beginning of the HIV/AIDS epidemic through the early 1990s, PCP was the most common pneumonia seen in most U.S. institutions. At San Francisco General Hospital (SFGH), for example, approximately 25 cases of PCP were diagnosed monthly in 1992. In the mid-1990s, HAART became available and cases of PCP declined. Today, bacterial pneumonia is the most common HIV associated pulmonary infection seen at SFGH, with significantly fewer cases of PCP -- roughly three or four cases per month. (Unfortunately, over 20% of the people diagnosed with PCP at SFGH in the post-HAART era are unaware of their HIV positive status at the time of presentation with PCP, emphasizing the need for early HIV testing.)
Globally, TB is the major pulmonary infection associated with the HIV epidemic. In sub-Saharan Africa, TB is probably the most common pulmonary complication of HIV infection: approximately one-third of persons with TB in Africa are also HIV positive. In contrast, as reported in the January 2002 issue of AIDS, TB accounted for less than 5% of pneumonias in a prospective study of 230 people admitted with HIV and pneumonia to an academic medical center in Atlanta, Georgia.
Risk for HIV-Associated Pneumonias
The relative health of the immune system, as measured by the CD4 cell count, is the most important factor in assessing the risk for various opportunistic pulmonary infections (Table 1). Typically, the severity of HIV infection can be stratified by CD4 cell count into several stages: above 500, 200-500, 50-200, and below 50 cells/mm3. A CD4 cell count above 500 cells/mm3 is indicative of a relatively intact immune system, and is typically seen in early HIV infection or after initiation of HAART and successful immune reconstitution. A CD4 cell count between 200 and 500 cells/mm3 signals immune suppression. When the CD4 cell count decreases below 200 cells/mm3, HIV infection has progressed to AIDS as defined by the U.S. Centers for Disease Control and Prevention (CDC).
Table 1. HIV-Associated Opportunistic Respiratory Infections
Risk Increased at
Any CD4 cell count
Bacterial pneumonia (community-acquired pneumonia)
CD4 <200 cells/mm3
Pneumocystis pneumonia
Cryptococcus neoformans pneumonia, usually associated with disseminated disease
CD4 <100 cells/mm3
Toxoplasma gondii pneumonia, usually associated with disseminated disease
CD4 <50 cells/mm3
Endemic fungal pneumonia: Histoplasma capsulatum or Coccidioides immitis pneumonia, usually associated with disseminated disease
Cytomegalovirus pneumonia
Mycobacterium avium complex pneumonia, usually associated with disseminated disease
Aspergillus species pneumonia
Among the various opportunistic pulmonary infections, bacterial pneumonia and TB are unique in that HIV infection increases the risk of contracting both illnesses even if the CD4 cell count is relatively preserved (above 500 cells/mm3). In addition, the overall risk of contracting bacterial pneumonia or TB increases as the CD4 cell count decreases. In contrast, pulmonary infections such as PCP, fungal pneumonias, Toxoplasma gondii pneumonia, and cytomegalovirus (CMV) pneumonia are typically seen only in the setting of severe immune suppression, after the CD4 cell count falls below 200 cells/mm3.
In addition to the CD4 cell count, several key factors increase and decrease the likelihood of pulmonary infection. Injection drug use increases the risk of bacterial pneumonia. A prior diagnosis of PCP is a significant risk factor for subsequent PCP infection, while prophylactic use of trimethoprim-sulfamethoxazole (TMPSMX, Septra, Bactrim) when the CD4 cell count falls below 200 cells/mm3 substantially decreases the risk of subsequent PCP. Cigarette smoking has been linked to increased risk of bacterial pneumonia and TB in both HIV positive and HIV negative individuals.
HIV infection is a risk factor for progression of latent tuberculosis infection (LTBI) to active tuberculosis disease. LTBI indicates prior infection with Mycobacterium tuberculosis and is defined by a positive purified protein derivative (PPD) skin test (which involves injecting 0.1 ml of sterile M. tuberculosis proteins under the skin of the forearm and assessing for swelling at the injection site 48 to 72 hours later), along with a normal chest radiograph (X-ray) and no symptoms con cerning for active TB. HIV positive individuals who have LTBI face a 10% per year risk of progressing from latent to active tuberculous disease, compared with an approximately 10% lifetime risk in the general population. Thus, all HIV positive persons are advised to be screened annually for LTBI, and those diagnosed with LTBI should receive therapy.
While there is no one sign or symptom that indicates a pulmonary infection, a cluster of complaints that suggests the need for further evaluation includes the presence of fever, cough, fatigue, or shortness of breath. Chest pain worsened by breathing or a decrease in the ability to exercise or perform usual daily activities are concerning as well. The duration and acuity of symptoms is important to note (Table 2). For example, bacterial pneumonia classically presents with the rapid onset of fevers, chills, cough, and shortness of breath over the course of three to five days, whereas PCP typically presents with the sub-acute, gradual progression of fever, cough, and shortness of breath over the course of two to four weeks. The production or non-production of sputum (material discharged from infected airways) is also noteworthy. While PCP typically causes a dry, non-productive cough, bacterial pneumonia is often associated with the production of thick, purulent (puscontaining) sputum. These observations, however, are generalizations, and exceptions to the rule can and do occur. For example, cases of PCP have presented with a productive cough (though usually of thin, clear sputum), and bacterial pneumonia can on occasion present with a sub-acute onset of symptoms over one week or more.
Table 2. Signs and Symptoms of Common HIV-Associated Pulmonary Infections
Clinical Features
Bacterial Pneumonia
Pneumocystis Pneumonia
Streptococcus pneumoniae, Haemophilus species, Pseudomonas aeruginosa, and others
Pneumocystis jirovecii
Mycobacterium tuberculosis
Signs and symptoms
Cough with purulent sputum, fever, chills
Acute onset, symptoms <1 week
Nonproductive cough, shortness of breath, fever
Gradual onset, symptoms >2 weeks
Cough, fever, night sweats, weight loss, swollen lymph nodes
Gradual onset, symptoms >2 weeks
The presence of non-pulmonary signs and symptoms must also be noted, as these can be related to a primary pulmonary infection. Prolonged fevers over weeks to months, drenching night sweats, loss of appetite, and weight loss are commonly seen in the setting of active tuberculosis, Mycobacterium avium complex (MAC) that is disseminated (spread to other organs besides the lungs), and endemic fungal infections such as Coccidioides immitis (the causal pathogen of "Valley Fever," common to the California Central Valley and the American Southwest). The common portal of entry for these organisms is the lungs, and disseminated infection can present with pneumonia. Confusion and headache may indicate both neurologic and pulmonary involvement by the fungus Cryptococcus neoformans. Blurry vision and abdominal pain may herald concurrent CMV infections of the eye, gastrointestinal tract, and lung. Finally, it must be emphasized that two or more opportunistic infections may present concurrently in the setting of HIV infection, especially with advanced immune suppression. For example, simultaneous infection with two different entities -- such as PCP and bacterial pneumonia -- may occur. The following sections discuss in more detail the three most common HIV-associated pulmonary infections: bacterial pneumonia, PCP, and TB.
Bacterial Pneumonia
HIV positive persons are at greater risk for bacterial pneumonia than are HIV negative individuals. Bacterial pneumonia is a frequent complication of HIV infection, and it often precedes other opportunistic infections. In many people, bacterial pneumonia may be the first manifestation of undiagnosed HIV infection.
In HIV positive people, bacterial pneumonia is frequently recurrent; in fact, recurrent bacterial pneumonia, defined as two or more episodes within 12 months, became an AIDS-defining illness in the CDC's 1993 Expanded Surveillance Case Definition for AIDS Among Adolescents and Adults. Persons with multiple episodes of bacterial pneumonia may develop bronchiec tasis (permanent destruction and dilatation of the bronchial airways) and other irreversible damage to their lungs.
In 1995, the Pulmonary Complications of HIV Infection Study group (PCHIS) published a paper describing the increased risk of bacterial pneumonia in the setting of HIV infection. The PCHIS was a multicenter study with six sites across the United States, one of which was SFGH. The study authors found that the rate of bacterial pneumonia was higher in the HIV positive population, even when the CD4 cell count was greater than 500 cells/mm3. In addition, the rate of bacterial pneumonia increased as the CD4 cell count declined. In this study, the incidence of bacterial pneumonia among injection drug users was significantly higher than the rates found among both female heterosexuals and men who had sex with men. Among persons with CD4 cell counts less than 200 cells/mm3, those who smoked cigarettes had a higher incidence of bacterial pneumonia compared with non-smokers.
Many bacterial pathogens have the potential to cause HIV-associated pneumonia. Studies have found that two of the most common bacteria are Streptococcus pneumoniae and Haemophilus influenzae. "Atypical" organisms, such as Mycoplasma, Legionella, and Chlamydophila, can also cause pneumonia. Pseudomonas aeruginosa and Staphylococcus aureus are both reported as community-acquired pathogens seen with an increased frequency in HIV positive persons. However, it is not uncommon to never identify the infectious organism despite culturing samples of blood and sputum. In the aforementioned Atlanta study, which investigated the microbiologic cause of 230 cases of HIV-associated pneumonia, the authors were unable to isolate the causative organism in 33% of cases. Nevertheless, in the majority of cases of "culture-negative" bacterial pneumonia, symptomatic improvement and recovery occur with antibiotics appropriate for the diagnosis of bacterial pneumonia.
Clinical and Radiographic Presentation
The clinical and radiographic presentation of bacterial pneumonia in HIV positive persons is similar to that in HIV negative individuals. Persons with pneumonias due to Streptococcus pneumoniae and Haemophilus species characteristically present with an acute onset (three to five days) of symptoms, including fevers, chills, rigors, chest pain, cough productive of purulent sputum, and dyspnea (labored breathing). The patient's white blood cell (WBC) count is usually elevated. Persons with bacterial pneumonia characteristically present with unilateral (on one side only), focal (having a clear focus), segmental (located in a specific segment of the lungs), or lobar (located in a specific lobe, or side, of the lungs) consolidation on chest radiograph (Figure 1). However, the frequency of these typical radiographic findings may depend on the underlying bacterial pathogen. HIV positive persons may present with multifocal or multilobar involvement and with parapneumonic effusions -- accumulations of fluid between layers of the membrane that lines the lung and the chest wall -- more frequently than HIV negative individuals.
|Figure 1: Chest radiograph of an HIV positive individual with a CD4 cell count above 200 cells/mm3, revealing right upper lobe consolidation. Sputum and blood cultures were positive for Streptococcus pneumoniae. Courtesy of Laurence Huang, MD.
The evaluation for bacterial pneumonia typically involves an attempt to isolate the infectious pathogen in cultures of blood, sputum, and potentially other sterile areas such as pleural fluid (fluid accumulating in the pleural space, which surrounds the lungs in the chest cavity). While it is quite uncommon for PCP to disseminate and cause infection outside of the lung, pathogens responsible for bacterial pneumonia can often invade the lung barrier to gain access to the normally sterile bloodstream. From there, these bacteria can cause widespread infections of not only the blood (bacteremia) but also the heart valves (endocarditis), the pleural space (empyema), and the tissue layer surrounding the brain, or meninges (meningitis). In the setting of disseminated disease, the sequelae of infection can be quite morbid -- long-term neurologic defects following S. pneumoniae meningitis are seen up to 25% of the time, and surgical replacement of infected heart valves is required in some instances of endocarditis.
Treatment approaches for bacterial pneumonia differ based on whether the illness is severe enough to warrant hospital admission. Outpatient treatment for mild cases of bacterial pneumonia can be accomplished and usually involves seven to ten days of oral antibiotics. In the hospital setting, intravenous antibiotics are typically administered. The U.S. Public Health Service and Infectious Diseases Society of America recommend that HIV positive persons with suspected or confirmed bacterial pneumonia and who are being treated as inpatients should receive an intravenous betalactam antibiotic plus either a macrolide or doxycycline. The preferred betalactam antibiotics are ceftriaxone (Rocephin), cefotaxime (Calforan), or ampicillin (Omnipen, Polycillin, Principen).
Because of the increased risk of disseminated disease with bacterial pneumonia, it is recommended that all HIV positive adults with a CD4 cell count greater than 200 cells/mm3 receive the 23-valent polysaccharide pneumococcal vaccine (PPV). The PPV works by stimulating an antibody response against sugars in the protective capsule of S. pneumoniae. The PPV may lose some efficacy if given after the CD4 cell count falls below 200 cells/mm3, as a protective immune response may fail to mobilize. In these persons, revaccination may be considered if the CD4 cell count rises above 200 cells/mm3, as a result of HAART.
Pneumocystis Pneumonia
Pneumocystis pneumonia (PCP) is caused by the fungal pathogen Pneumocystis jirovecii (formerly known as P. carinii). PCP is the most common AIDS-defining opportunistic infection in the United States and typically causes disease only when the CD4 cell count falls below 200 cells/mm3. PCP research has been hampered by the inability to culture this organism.
On the basis of antibody testing, it is believed that the majority of people are infected with Pneumocystis early in childhood. The conventional theory is that PCP results from reactivation of this latent childhood infection, but studies suggest that PCP may also result from a recent exposure and infection. The route of transmission of PCP and its natural reservoir are incompletely understood, though a respiratory route of infection has been implicated in well-controlled animal studies. Currently, there is evidence that person-to-person transmission does occur, and recent molecular studies have shown that the organism can reside in the lungs without causing symptoms (referred to as "colonization"). The significance of colonization is unknown. Nevertheless, unlike management of TB, respiratory isolation for PCP is not routinely recommended at this time.
Clinical and Radiographic Presentation
The clinical presentation of PCP in HIV positive persons differs from the presentation in other immuno-compromised persons; in general, HIV positive individuals present with a sub-acute onset (two to four weeks) and a longer symptom duration. Classically, PCP presents with fever, cough, and shortness of breath. The cough is usually dry and non-productive unless a concurrent bacterial infection is present. The cough may be exacerbated by deep breathing and occasionally accompanied by "chest tightness." Symptoms are often subtle at the onset but are gradually progressive and may be present for weeks and occasionally months before diagnosis.
No current laboratory test is specific for PCP. The serum lactate dehydrogenase (LDH) is usually found to be elevated; however, the LDH can be elevated in response to a variety of pulmonary and non pulmonary conditions. On chest radiograph, persons with PCP characteristically present with bilateral (on both sides), reticular (network-like), or granular (grainy-looking) opaque areas, or opacities (Figure 2).
|Figure 2. Chest radiograph of an HIV positive person with a CD4 cell count below 200 cells/mm3, demonstrating the characteristic bilateral granular opacities of PCP. Bronchoscopy with bronchoalveolar lavage fluid microscopic examination revealed Pneumocystis cysts and trophic forms. Courtesy of Laurence Huang, MD.
Occasionally, persons with PCP may have a normal or minimally abnormal chest radiograph and may undergo high-resolution computed tomography (HRCT) of the chest for further evaluation. On chest HRCT, persons with PCP characteristically present with bilateral, patchy areas called "ground-glass" opacities (Figure 3).
|Figure 3: Chest high-resolution computed tomography (HRCT) scan of an HIV positive person with a CD4 cell count below 200 cells/mm3, whose chest radiograph was normal. Chest HRCT scan revealed the characteristic patchy ground-glass opacities of PCP. Induced sputum microscopic examination revealed Pneumocystis cysts and trophic forms. Courtesy of Laurence Huang, MD.
There is no universally agreed-upon approach to the management of HIV positive persons with suspected PCP. Many institutions treat persons with suspected PCP based solely on the patients' symptoms and chest radiographic presentation, while other institutions (such as SFGH) pursue a definitive microscopic diagnosis. Because Pneumocystis cannot be cultured, the diagnosis of PCP relies on microscopic examination of the characteristic cysts and/or trophic forms (different stages of the pathogen's life cycle) on respiratory specimens that have been stained to make their microscopic structures more clearly visible. Typically, these respiratory specimens are obtained from sputum induction (a procedure to stimulate sputum production through the inhalation of hypertonic saline mist) or bronchoscopy with bronchoalveolar lavage (BAL; a procedure, performed by a pulmonary specialist, in which a fiberoptic bronchoscope is passed into the throat and wedged deep into an airway, saline is instilled, and fluid is aspirated back and sent for study). Several studies have examined the utility of applying a sensitive and specific molecular assay (e.g., polymerase chain reaction, or PCR) to a simple, non-invasive, 60-second procedure called oropharyngeal washing (OPW) to collect specimens for PCP diagnosis. However, although results indicate that PCR with OPW is a sensitive and specific test for PCP, it is mainly a research tool at present.
Unfortunately, the health consequences of PCP infection can be severe. Outpatient treatment may be appropriate in cases of mild infection but most people with PCP require hospitalization and close observation. Indications for hospital admission include low oxygen saturation of the blood, severe shortness of breath, and persistent or worsening symptoms despite the use of appropriate oral PCP treatment. In the HIV positive population, PCP remains the most common reason for respiratory failure and need for mechanical ventilation ("breathing machine"). While the number of PCP infections has declined substantially since the introduction of PCP prophylaxis and HAART, mortality from severe PCP requiring admission to an intensive care unit and subsequent mechanical ventilation remains high (>50%).
First-line therapy for PCP is the fixed-dose combination drug trimethoprim-sulfamethoxazole (TMPSMX). Typically, PCP treatment is for a total duration of three weeks. Common side effects of therapy include gastrointestinal upset (nausea, vomiting), rash, fever, and bone marrow suppression (anemia). In cases of moderate to severe PCP, corticosteroids are indicated to decrease the inflammatory reaction in the lung and subsequent respiratory failure, and have been shown in controlled trials to decrease mortality. Secondline therapy includes intravenous pentamidine (Nebupent), clindamycin (Cleocin) plus primaquine (Primaquine); trimethoprim (Trimpex, Proloprim, Primsol) plus dapsone (Dapsone); and atovaquone (Mepron) suspension.
Prevention of PCP, also called PCP prophylaxis, should begin when the CD4 cell count falls below 200 cells/mm3. Other indications for PCP prophylaxis include a diagnosis of oral thrush or following a documented episode of PCP. The most effective prophylaxis regimen is daily TMPSMX with either a double-strength or single-strength tablet. One double strength tablet three times a week is an alternative prophylaxis regimen. Unfortunately, some persons are allergic to or intolerant of TMP-SMX. In these persons, dapsone with or without pyrimethamine, atovaquone suspension, and monthly aerosolized pentamidine are potential options. Rigorous adherence decreases the risk of PCP infection substantially, but no preventive regimen is 100% effective. PCP has been known to occur despite antibiotic prophylaxis, especially in the setting of severe immune suppression. PCP prophylaxis can typically be stopped when the CD4 cell count has risen above 200 cells/mm3 for a period of three months as a result of antiretroviral treatment.
The widespread use of TMP-SMX for PCP prophylaxis has led to increasing concerns about the potential for TMP-SMX drug resistance. Unfortunately, the inability to culture Pneumocystis has precluded the demonstration of drug resistance in vitro. Several studies using molecular and epidemiologic tools have found a strong association between the use of TMP-SMX for PCP prophylaxis and the presence of specific mutations in Pneumocystis, and have found in some instances that the presence of these mutations is associated with increased mortality and increased TMP-SMX PCP treatment failure. However, the clinical significance of these Pneumocystis mutations is unclear at present, since these studies also have noted that the majority of persons with these mutations still respond to TMP-SMX therapy.
Coinciding with the onset of the HIV epidemic, there was a surge in cases of Mycobacterium tuberculosis infection in the 1980s and early 1990s, and like recurrent bacterial pneumonia, pulmonary TB became an AIDS-defining illness in the CDC's 1993 Expanded Surveillance Case Definition for AIDS. While various public health and infection control measures have subsequently decreased the number of TB cases per year in the U.S., HIV remains a major risk factor for TB infection.
M. tuberculosis is a bacterium spread by person-to-person transmission via respiratory droplets. Transmission of infection typically requires close proximity of several hours or more to a person who has active pulmonary tuberculosis and is coughing. Among HIV negative persons, exposure to and subsequent infection with M. tuberculosis is asymptomatic in at least 90% of cases, resulting in LTBI, a prolonged carrier state in which dormant bacteria with the potential to cause future infection remain in the body for life. Primary progressive TB, an active pneumonia following initial exposure to the bacteria, is quite rare. The lifetime risk of progressing from LTBI to active tuberculosis is approximately 10% in HIV negative people. In contrast, people living with HIV are at an increased risk of progressing from LTBI to active tuberculosis at a rate of approximately 5%-10% per year. In addition, HIV increases the risk of primary progressive TB and development of an active pneumonia following initial exposure to tuberculosis.
Clinical and Radiographic Presentation
There are several features which are notable in HIV-associated tuberculosis. First, the chest radiograph is less likely to show the "classic" upper lung zone cavitary (chest cavity) disease (Figure 4), and the absence of the typical radiographic appearance may delay diagnostic evaluation for TB and the initiation of TB therapy. In HIV positive persons with advanced immune suppression, the chest radiograph may reveal disease in the middle and/or lower lung zone (Figure 5), nodules (aggregations of cells), or a "miliary" pattern characterized by numerous small lesions. Persons with TB may also present with pleural effusions on chest radiograph. While most cases of active tuberculosis will have some abnormal findings on chest radiograph to suggest presence of infection, even a normal radiograph does not rule out the diagnosis of tuberculosis in the setting of HIV infection. Second, much like bacterial pneumonia, HIV-associated tuberculosis has a tendency to cause widespread, disseminated disease. Tuberculosis can spread to almost any organ in the body, but commonly will affect the lymph nodes, pleural space, meninges, pericardium (the tissue layer surrounding the heart), and bone marrow.
|Figure 4. Chest radiograph of an HIV positive individual with a CD4 cell count above 200 cells/mm3, revealing right upper lobe consolidation with areas of cavitation. Multiple sputum acid-fast bacillus stains were smear microscopy-positive and mycobacterial cultures grew Mycobacterium tuberculosis. Courtesy of Laurence Huang, MD.
|Figure 5.Chest radiograph of an HIV positive person with a CD4 cell count below 200 cells/mm3, revealing right lower lung zone consolidation without cavitation. Sputum acid-fast bacillus stains were smear microscopy-negative but mycobacterial cultures grew Mycobacterium tuberculosis that was mono-rifampin-resistant. In this case, the key to the diagnosis of TB was knowledge of the person's CD4 cell count and understanding that TB can present with this chest radiographic picture in an individual with a CD4 cell count below 200 cells/mm3. Courtesy of Laurence Huang, MD.
Since TB is transmitted from person to person, individuals who are admitted with suspected TB should be placed in respiratory isolation while undergoing diagnostic evaluation. Sputum acid-fast bacilli (AFB) smears and mycobacterial culture are the standard diagnostic tools used to evaluate suspected TB. Sputum is obtained on three consecutive days, ideally from the first specimen produced each morning. Serial sampling of expectorated sputum is appropriate for persons with a productive cough; sputum induction should be performed in persons with a non-productive cough. Occasionally, bronchoscopy with BAL and transbronchial biopsies is performed to diagnose TB. Thoracentesis (a procedure to remove fluid from the space between the pleura, the lining of the outside of the lungs, and the wall of the chest) with pleural biopsies may be performed to diagnose pleural TB.
Effective treatment of active tuberculosis requires multiple antibiotics taken for a minimum of six months. If the infecting M. tuberculosis is susceptible to all antibiotics tested in sputum samples or tissue cultures, HIV infection does not significantly change the type or duration of recommended anti-TB therapy. A typical regimen would involve treatment with isoniazid (INH; Niazid, Nydrazid), a rifamycin drug (RIF; commonly rifampin [Rifadin] or rifabutin [Mycobutin]), pyrazinamide, and ethambutol (Myambutol) for two months, followed by four additional months of INH and RIF. All of these antibiotics can be given as oral medications, without the need for injections. These general guidelines must be tailored to each individual case; the type of antibiotic may be changed and duration of therapy lengthened if there is any indication that the TB infection is not being adequately treated.
HIV-associated tuberculosis has been reported to have similar outcomes (rates of cure and disease relapse) compared with HIV negative cases when the tuberculosis organism is antibiotic susceptible, although overall mortality (from both TB and other AIDS-related illnesses) is higher in HIV positive persons. A recently published retrospective analysis of TB cases in San Francisco, however, described higher rates of TB relapse in people with HIV. While these findings may eventually lead to changes in recommended therapy for patients with both TB and HIV, further research is necessary to clarify this important clinical question.
When undergoing treatment for active tuberculosis, it is extremely important to adhere strictly to recommended therapy and avoid missed doses of antibiotics. One of the greatest risks for developing drug-resistant TB is intermittent antibiotic use and failure to comply with recommended TB therapy. Intermittent exposure to antibiotics will select for TB organisms that are resistant to first-line antibiotics, making further treatment more difficult (often requiring the use of intravenous or injectable antibiotics) and lengthening the duration of therapy. While the treatment period for drug-susceptible TB is approximately six months, treatment for different strains of drug-resistant TB may take two years or longer and typically involves combinations of four to six or more medications, one of which is usually injected. The treatment of multidrug-resistant TB requires the use of second-line antibiotics, which have decreased efficacy compared to first-line drugs like INH and RIF and more side effects. Despite these intensified regimens for drug-resistant TB, treatment failure rates and mortality are increased, especially in the HIV positive population. For these reasons, directly observed therapy (DOT) is recommended for all cases of HIV-associated TB. DOT is defined as a situation in which a health care provider observes a person taking their medications. In various studies, DOT has been shown to decrease rates of drug resistance as well as relapse of TB disease.
Multidrug-Resistant TB and Extensively Drug-Resistant TB
Multidrug-resistant TB (MDR-TB) is defined as infection with an organism resistant to the two main first-line drugs, INH and RIF, while extensively drug-resistant TB (XDR-TB) is defined as infection with an organism resistant to INH, RIF, any fluoroquinolone, and at least one of the injectable antibiotics used in TB therapy. In the U.S., where new cases of TB and drug-resistant TB must be reported to state health departments and the CDC, there were 121 cases of MDR-TB in 2005 and 15 cases of XDR-TB between 2000 and 2005. In San Francisco, typically one to four cases of MDR-TB are diagnosed yearly, and the overall number of newly diagnosed active TB cases declined to 120 in 2006 -- an all-time low.
Drug-resistant TB can be acquired either by primary infection from another person with resistant TB, or when a previously sensitive organism becomes resistant, usually through inadequate treatment or nonadherence to treatment. Drug resistance occurs because any TB-positive individual harbors a mixed population of tuberculosis organisms, some with inherent, natural resistance to various antibiotics. Thus, the rationale for combination antibiotic therapy is based on the extremely low likelihood that any one organism is resistant to two or more antibiotics. However, if drug therapy is taken sporadically or if prescribed treatment is inadequate, selection for the antibiotic-resistant strains will occur.
In published studies of drug-resistant TB, concomitant HIV infection is seen in disproportionate numbers. Multiple outbreaks of drug-resistant TB were reported in U.S. hospital and jail settings in the early 1990s, with most cases occurring in HIV positive individuals. In contrast to the outcomes seen with antibiotic-susceptible TB, mortality was extremely high in cases of HIV co-infection with MDRTB, ranging from 72% to 89%. In a case series of all people with MDR-TB treated at SFGH between 1982 and 2000, the cure rate and survival in HIV negative people was 97% (32 of 33 cured); in contrast, all 11 of the HIV positive individuals died of either TB or another AIDS-related illness during the study period. All of the HIV positive participants in this study had advanced AIDS, and only two were on HAART. Fortunately, outside of institutional outbreak settings,which were attributed to poor infection- control practices, there has not been a consistent association to suggest that HIV infection increases one's risk of acquiring MDR-TB.
Highly Active Antiretroviral Therapy
In addition to anti-TB medications, HIV positive persons may also require HAART to treat their underlying HIV infection. While there are varying opinions on when to start HAART, most guidelines advocate earlier initiation in settings of more severe immune suppression. Thus, anti-HIV and anti-TB treatment may need to be given concurrently if the CD4 cell count is less than 200 cells/mm3, whereas it may be a better option to defer antiretroviral therapy until TB treatment is completed in those persons with higher CD4 cell counts. One recently reported study of HIVassociated TB found that initiation of HAART during TB treatment led to decreases in HIV viral load, AIDS-related illnesses, and mortality. This study enrolled 188 people, all of whom had severe immune compromise, with a median CD4 cell count of 90 cells/mm3. Unfortunately, concomitant use of HAART and anti-tuberculosis therapy was associated with an increase in medication side effects, sometimes requiring cessation or changes in therapy. Similar results were noted in a 2007 retrospective study of 264 patients with HIV-associated TB in San Francisco, in which the authors found that use of HAART was associated with a decrease in mortality.
Several factors can complicate the co-administration of anti-tuberculosis and antiretroviral agents. Toxicities and side effects of HAART and anti- TB medications are common and can overlap (Table 3). In general (and when possible), it is wise to initiate anti-tuberculosis therapy first and ensure that it is well tolerated for a period of at least two weeks before starting HAART. Second, there are complex drug-drug interactions between the rifamycins, which represent a cornerstone of TB therapy, and two classes of antiretroviral medications -- the protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). These interactions can lead to increased blood levels of rifamycin and decreased blood levels of the PIs and NNRTIs. Clinically, this change in blood levels can increase the risk for rifamycin side effects and potentially require discontinuation of this important medication. In addition, decreased drug levels of PIs and NNRTIs can lead to resistance to both classes of drugs and seriously complicate future attempts to treat HIV. Fortunately, there are regimens which can simultaneously treat TB and HIV which minimize the likelihood of side effects and drug-drug interactions (although these problems remain significant in resource-limited settings, where fewer antiretroviral drugs are available). For the highest chance of success, it is strongly recommended that cases of HIV-associated TB be treated by health care providers who have significant experience in these fields.
Table 3. Common Antibiotics for Tuberculosis, and Possible Side Effects
Side Effects
Additional Information
First-line drugs
isoniazid (Niazid, Nydrazid)
Hepatitis, neuropathy
Vitamin B6 (pyridoxine) supplementation recommended to decrease risk of neuropathy.
rifamycin (rifampin [Rifadin], rifabutin [Mycobutin])
Hepatitis, rash, itching
Orange discoloration of body fluids (saliva, urine, tears, sweat) is normal and to be expected. Rifabutin has fewer interactions with common antiretroviral drugs.
Hepatitis, joint pains, gout flare, rash
ethambutol (Myambutol)
Decreased visual acuity or color discrimination
Eye exam recommended prior to treatment and following any changes in vision.
Second-line drugs
amikacin (Amikin)
kanamycin (Kantrex)
capreomycin (Capastat)
Hearing loss, renal failure (kidney injury)
levofloxacin (Levaquin)
moxifloxacin (Avelox)
All fluoroquinolones can be taken orally, and are commonly used to treat non-tuberculosis related bacterial infections
Because antibiotic therapy can substantially decrease the risk of progression from LTBI to active tuberculosis, annual screening for LTBI in those with HIV infection is strongly advised. The recommended screening exam is the PPD skin test, described above.While false positives and negatives are possible (the latter especially in the setting of advanced HIV), the PPD skin test cannot cause tuberculosis infection. In HIV positive persons, a diagnosis of LTBI is typically confirmed by the presence of a 5-mm or larger patch of hardened or inflamed skin at the site of the PPD test 48 hours following the injection.
An alternative screening exam for LTBI is the interferon-gamma release assay (IGRA), which is a blood test; unlike the PPD, the IGRA does not require a repeat visit for interpretation. While the IGRA has been approved by the U.S. Food and Drug Administration to assist in the diagnosis of tuberculosis infection, its accuracy in HIV positive persons has not been well characterized. Prior to initiating antibiotic treatment for LTBI, active tuberculosis disease must be excluded, with a chest radiograph and medical exam by a health care provider experienced in tuberculosis diagnosis and treatment. Recommended regimens for treatment of LTBI in the setting of HIV infection include nine months of isoniazid, rifampin for four months, or rifabutin for four months.
When to Seek Medical Evaluation
While HIV does increase the risk of serious pulmonary infections, it is also quite common (and normal) to experience relatively minor episodes of cough, runny nose, sore throat, and other respiratory symptoms which may indicate the "common cold," bronchitis, or related viral upper respiratory infections. When is it important to seek medical care? Gauging both the severity and duration of symptoms is key to answering this question. High fevers, severe shortness of breath, and cough are extremely worrisome even if symptoms are of short duration. Similarly, low-grade fevers and progressive shortness of breath and cough are concerning if symptoms persist for more than one week. Erring on the side of caution is advisable; early diagnosis and prompt initiation of appropriate treatment will result in improved outcomes for all HIV-related pulmonary diseases.
Medical Evaluation
A battery of tests assists the health care provider in arriving at the correct diagnosis. As mentioned above, basic blood work and cultures of sputum and blood may be performed. An arterial blood gas test may be conducted to evaluate the levels of oxygen and carbon dioxide in the arteries. A chest radiograph will provide a significant amount of information, as each HIV associated pneumonia has a characteristic pattern. If the diagnosis remains unclear with these initial tests, a computed tomography (CT) scan of the chest can provide additional diagnostic information. If PCP is suspected, sputum induction and/or bronchoscopy with BAL may be performed; bronchoscopy requires specialized equipment and is usually performed by a pulmonary specialist. If active tuberculosis infection is suspected, hospital admission and respiratory isolation is usually indicated. The diagnosis of TB requires submission of daily sputum samples to search for M. tuberculosis organisms.
Pulmonary complications of HIV are common and can range from minor upper respiratory infections to life-threatening pneumonias. Because of the health consequences of a delayed or incorrect diagnosis, empiric therapy (often with antibiotics) is not recommended and pursuit of a definitive microbiologic or pathologic diagnosis is encouraged whenever possible. The most common HIV-associated pulmonary infections in the United States are bacterial pneumonia, PCP, and tuberculosis. While drug-resistant TB is not a particularly common problem in the U.S., the consequences of developing MDR-TB in the setting of HIV infection are severe. Treatment of HIV and TB co-infection should be done by a health care provider with significant experience in both of these fields.
While regimens to treat HIV and TB can be quite complex and require multiple medications, it is extremely important to adhere to the recommended medication schedule to prevent development of antibiotic resistance. Because the risk of HIV associated pneumonias typically increases with a progressive decline in CD4 cell count, antiretroviral therapy and appropriate use of preventive antibiotics are highly recommended in the appropriate clinical setting.
Matthew Fei, M.D., is a clinical fellow in the Division of Pulmonary and Critical Care Medicine at San Francisco General Hospital and the University of California, San Francisco.
Laurence Huang, M.D., is a Professor of Medicine at the University of California, San Francisco, and an attending physician in the Division of Pulmonary and Critical Care Medicine and the HIV/AIDS Division at San Francisco General Hospital. He is actively involved in clinical research studies on HIV-associated pneumonias, including PCP, TB, and bacterial pneumonia.
Selected Sources
Centers for Disease Control and Prevention. Guidelines for preventing opportunistic infections among HIV-infected persons -- 2002 recommendations of the U.S. Public Health Service and the Infectious Diseases Society of America. Morbidity and Mortality Weekly Report 51(RR08):1-46. June 14, 2002.
Centers for Disease Control and Prevention. Treatment of tuberculosis, American Thoracic Society, CDC, and Infectious Diseases Society of America. Morbidity and Mortality Weekly Report 52(RR11):1-77. June 20, 2003.
Hirschtick, R. and others. Bacterial pneumonia in persons infected with the human immunodeficiency virus. New England Journal of Medicine 333(13):845-51. September 28, 1995.
McIlleron, H. and others. Complications of antiretroviral therapy in patients with tuberculosis: drug interactions, toxicity, and immune reconstitution inflammatory syndrome. The Journal of Infectious Diseases 196:S63-S75. August 15, 2007.
Nahid, P. and others. Treatment outcomes of patients with HIV and tuberculosis. American Journal of Respiratory and Critical Care Medicine 175:1199-1206. June 1, 2007.
Onyebujoh, P. and others. Treatment options for HIV-associated tuberculosis. The Journal of Infectious Diseases 196:S35-S45. August 15, 2007.
Rimland, D. and others. Prospective study of etiologic agents of community-acquired pneumonia in patients with HIV infection. AIDS 16:85-95. January 4, 2002.
Wells, C. and others. HIV infection and multidrug-resistant tuberculosis -- the perfect storm. The Journal of Infectious Diseases 196:S86-S107. August 15, 2007.
World Health Organization. TB/HIV: A Clinical Manual, 2nd edition. 2004.


text:
Wednesday, January 9, 2013
British Crime Novelist Martin Edwards
Martin will be featured in the forthcoming book, The Mystery Writers, along with Sue Grafton, Lawrence Block and many others.
Martin, what does membership in the Murder Squad entail?
It's a group of six Northern crime writers, set up by Margaret Murphy. Members include Ann Cleeves and Cath Staincliffe, who have both had their books televised in recent years. We do events either jointly, in duos, or singly, all around the UK. We've produced an anthology, ingeniously entitled Murder Squad, and a CD sampler of our work. We have a website, www.murdersquad.co.uk I'm proud to be part of such a super gang.
How do crime novels in the UK differ from those written in the US?
Difficult to generalise, I think. We have plenty in common,, and I am certainly delighted with feedback on my books from the US. Americans like Deborah Crombie write very good crime novels set in the UK. Lee Child is a Brit who sets his bestsellers in the States. I suppose that there are fewer good private eye novels in the UK, and perhaps not quite as many serial killers – though we are catching up!
What was it like growing up in Knutsford, Cheshire, England, and did you write as a child?
I was born in Knutsford, famous as Elizabeth Gaskell's Cranford (a Victorian era novelist and short story writer], though in fact I grew up a few miles away in Northwich. I still live close by. It's a terrifically attractive market town, packed with history and there's plenty of culture too. I've featured the town briefly in one novel, and more extensively in a short story featuring Mrs. Gaskell. I did write as a child. I think my first detective story was written when I was about 10, heavily influenced by the Basil Rathbone Sherlock Holmes films.
Are you still practicing law in Liverpool and how has your legal background influenced your novels?
Yep, I still have the day job. My first series, featuring Harry Devlin, also a lawyer, was set in Liverpool, a truly unique and fascinating city which everyone should visit! The most recent book, Waterloo Sunset, is a personal favourite. My legal background also influenced a stand alone novel of psychological suspense, Take My Breath Away, but it is less relevant to the Lake District Mysteries, although sad to say, a lawyer does meet a very unpleasant fate in The Serpent Pool.
You're involved in a number of crime writer organizations. Tell us about them.
I was elected to the Detection Club a couple of years ago, which was gratifying, because of its fantastic history and the fact that almost all the members except me are superstars of the genre.
I've been a member of the Crime Writers' Association for over twenty years, and I edit their annual anthology. I'm also chair of the CWA Cartier Diamond Dagger nominations committee. It was via the Northern Chapter of the CWA that the members of Murder Squad first met. It's a very good social organisation.
You have an interesting, informative blog site titled, "Do You Write Under Your Own Name?" How did the name come about and has blogging helped sales of your books?
Glad you like the blog! When people – such as clients – meet me and learn that I write books, they often ask if I write under my own name. A polite way of saying they have never heard of my novels! I'm sure blogging has been good for my profile. Since it started I have won a Dagger and been elected to the Detection Club, but I'm not sure it's cause and effect...
Tell us about your series and your latest novel?
My main current series is the Lake District Mysteries. The first book in the series, The Coffin Trail, was shortlisted for the Theakston's prize for best crime novel of 2006. The series features cold case cop DCI Hannah Scarlett and the historian Daniel Kind. The developing relationship between them is a key element in the series, and so are the landscape, history and literature of the Lakes. The fourth and latest book in the series is The Serpent Pool, which draws on Thomas De Quincey's years in the Lakes and above all on his fascination with murder as a fine art, has received terrific reviews since publication earlier this year.
What's the most important ingredient in a crime novel?
Tricky question, but I'm tempted to say the key ingredient is making the reader want to keep turning the pages.
What's your writing schedule like?
Overloaded! Because I work full time, I tend to write whenever I can snatch a few minutes in the evening and at weekends.
Advice to fledgling crime writers?
Keep at it, and don't be disheartened too much by rejection.
Thanks, Martin. You can visit Martin Edwards at his website:
http://www.martinedwardsbooks.com/ and his blog blogsite: www.doyouwriteunderyourownname.blogspot.com/
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Dolly Parton has spoken of her relief after a dog she offered to adopt when it was left behind at Glastonbury was reunited with its owners.
The country superstar said there was some sadness that she would not be able to look after the white lurcher but she was "glad" she was back with her family as the animal was too old to travel back to the US with her.
The dog was found in a tent during a clean-up after thousands of festival-goers left the site and taken in by the nearby Happy Landings animal shelter, with 68-year-old Parton later offering to give her a home.
However the Jolene singer said the shelter had called to say the owners had come forward.
"Everybody feels good about it. I did not get to take her home - I was looking forward to it. I was gonna rename her Glassy because of Glastonbury, I was going to say 'Glassy Come Home'," she joked.
"But [the owners] wanted her and they feel good about that and I have been very instrumental in making sure that the dog has been well taken care of all the way through. She's 15 years old, they thought at one point she was seven, but she's 15, and so everybody's happy to be back. I feel kind of sad because I was looking forward to taking her home, but I'm glad she's back where she belongs.
She continued: "My heart went out to this particular dog, I just thought it was meant to be somehow, it was just so touching to me that she got lost there at the festival where we were..
"I'm very happy she's back where she'll be comfortable and safe. They told me also at the end that she would have been too old to have travelled, I would not have been able to take her had they not found the owner because she was not in great health."
Parton - who is promoting a new "best of" album Blue Smoke - also rubbished suggestions that she had mimed during her performance on the Pyramid stage a little over a fortnight ago.
"Every time I go on tour I hear that. I want people to just come and watch, see what I do and then you tell me what you think. I'm right there, I'm Dolly and I'm singing, and somebody's always going to have something negative to say and so I just roll with the punches."
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