text:
Here at Search Engine Watch, we wanted to reach out to the search community to get their reaction to the long-awaited search deal between Microsoft and Yahoo! Not surprisingly, marketers, search engine representives, and agencies had a lot to say on the matter. Below you'll find their initial reactions to this morning's announcement.
The deal is good for marketers and advertisers
Most agree with Search Engine Watch editor Kevin Newcomb, who earlier wrote today that the MSFT-YHOO deal is good for advertisers.
Ted Shergalis, co-founder and chief strategy officer of [x+1] thinks the deal raises the profile of search marketers, who, on the flip side, must be diligent in learning the terms of the deal as they unfold.
Ultimately i think it makes SEMs more relevant. Now, instead of doing the bulk of the work on each search engine, search marketers will now need to dedicate a bulk of time understanding new Bing/Yahoo! environment. At [x+1], we specialize in display, landing pages, and website personalization, so it will be interesitng to see if different type of user is coming through using the new Bing/Yahoo!
Brian Lewis, vice president at Engine Ready, emphasized the need for this type of improvement for search marketers, while recognizing the difficulty of capturing additional market share, which requires habitual change.
Although many specifics remain to be disclosed, my initial thoughts are that this alliance is just what the search industry needed to continue to provide improvements in the search experience for users as well as an advertising medium that offers profitable returns for savvy marketers. I think one of the biggest challenges for Yahoo/Microsoft will be changing user habits of automatically jumping to Google for search, and slowing the perception that Google and search have become synonymous.
Not an alternative to Google
Combining the number 2 and number 3 search engines may help advertisers in terms of traffic, but will the search landscape truly change? Other search engines know that to truly make waves in search, you need to provide value to searchers, which is not a guarantee in this deal.
Dr. Tomasz Imielinski, executive vice president of technology at Ask.com hints that their could be room for other players to move ahead while Microsoft and Yahoo! spend time implementing the terms of their deal.
This news is a solid indication that the search market is healthy and growing across the board, and a core foundation of the online medium. But as far as Microsoft and Yahoo are concerned, the primary focus for both for 2009 and into 2010 will need to be on search integration – and not on search innovation. At Ask, our core focus will continue to be innovating for success by putting consumers – and search products – first.
Ryan Hardy and Dan Giulvezan , Co-founders of Unurthme, echo that sentiment.
Everyone in the search industry has the same thing on their to-do list: beat Google. At Unurthme, we believe the more significant opportunity is to add value and innovation to search, thereby delivering users a superior search experience.
SEW Expert and WebCertain CEO Andy Atkins-Krüger thinks its a good time for smaller search engines to partner up with Google or Microsoft.
This deal is the best of both worlds. It creates a stronger competitor for Google, and an opportunity for regional search engines – such as Baidu, Yandex and Seznam – also to enter the fray thanks to the distraction this will create for Google and the negotiating position it opens up with them to partner with Microsoft or Google.
hakia CEO Dr. Riza Berkan thinks that Google has nothing to worry about, at least from this deal.
Our perspective is this deal does not really change anything from the search precision point of view. We think that Yahoo! is actually more precise. From the business point of view, it will create more advertising opportunities, since the share will be at 30%. The advertisers will feel better because the exposure is wider. But as for business as usual, I don't think there's a significant change. The search problem is still there and google is still dominating. this won't make a big diffference.
hakia, of course, employs Yahoo! search technology. Will this deal harm the semantic search engine? Berkan says no.
We don't rely on it. It helps us, but from what i have read so far, those services will be intact. But even if it wasn't, it really won't affect us at all.
It's natural for competitors to challenge the idea that the deal will work, but they're not alone. Vern Rowe, client strategy manager at OneUpWeb wonders if innovating existing search is even the answer. Perhaps the efforts seen lately in social media are the true future of search?
The Microsoft/Yahoo! deal is interesting from many aspects. Is it really about partnering to battle an adversary, or are we perhaps seeing a glimpse into a struggling profit center at Microsoft and a new Yahoo perspective that search is a dying technology (time to move on to the next thing-maybe social)? Whatever cord finally struck to get these two together, it might be a long road ahead of them with the Department of Justice before the deal is done. Then, if and when it gets cleared, there will most likely be another several months before there is a significant change from an advertiser's perspective.
So, you're telling me there's a chance?
Still, there are a few optimists out there who know what Microsoft and the technology community are capable of. Underdogs have been known to upset giants before.
Ben Saren, Co-Founder and CEO of CitySquares thinks perserverance is the answer.
Microsoft is taking some hard swings at Google and its just a matter of time until they make contact. Their most dominant days may not be in their past, rather coming very shortly. This kind of competition is entirely necessary and is ultimately going to be a very good thing for search and its cottage industries. Seems to me that the battle drums in the search wars are growing louder and more intense.
Joshua Palau, vice president of the search engine marketing office at Razorfish (an interactive ad agency acquired by Microsoft in 2007) sees an opportunity ripe with potential for Microsoft now.
I think it now sets up MSFT to do what Yahoo failed at – combine search and display in an advertiser friendly way. With 30% search share and a boatload of impressions that can leverage BT, MSFT now becomes a more compelling option.
A wide sentiment is that Yahoo! has given up on search. According to Mark Kelly at Chair 10 Marketing, Yahoo! may have given up a long time ago, and getting rid of the dead weight might just be the ticket for Microsoft.
Yahoo stopped improving its pay-per-click platform, while Microsoft and Google have continued to improve. Advertisers need a stronger competitor to counter-balance Google's power, and Yahoo and Microsoft on their own weren't providing that. With this increased search traffic, Microsoft has a much better shot at competing effectively.
Rick Kahn, CEO of eZanga, thinks combining the technologies will inject fresh ideas into the search industry.
Well it's about time. By pairing up and using each other's technology, I believe Microsoft and Yahoo are going to have what it takes to slowly close the gap between their companies and Google. The old saying of 'Two heads are better than one' will be hard at work, as both Yahoo and Microsoft have some interesting technologies. I think by using Yahoo's system, but adding the new traffic available at Bing, it's going to be a winning combination for both companies. By putting them together there can be some interesting synergies created and new functionality that can benefit people searching as well as advertisers. I look forward to tracking the results of this deal over the upcoming months and years.
What is YOUR reaction to the Microsoft-Yahoo! deal? Continue the conversation by leaving a comment below.
Related reading
Five important updates to Google semantic search you might have missed
Google is constantly making tweaks and changes to semantic search. The vast majority go unannounced and unnoticed, but they can be an interesting indicator of Google's strategy, and it pays to keep an eye on them. Here are five recent updates you might have missed.
The 10 best Google Doodles of all time
Since 1998, Google has used its homepage to host an invariably inventive Doodle. We've picked 10 of Google's most memorable animations from the last two decades.
What we learned from SEO: The Movie
SEO: The Movie is a new documentary which explores the origin story of search and SEO, as told by several of its pioneers. It's a 40-minute snapshot of the search industry that is and was, with a glimpse into the future and what might become of SEO in the years to come. Here are some of the highlights.
Everything you need to know about visual search (so far)
Visual search is one of the most complex and fiercely competed sectors of our industry. Here's a review of the key players, and what their technology allows us to do.


text:
Dick's will cast wider 'Net with triple online sales
Dick's Sporting Goods Inc. is looking for a home run on the Internet.
With more consumers opting to purchase goods online these days, Dick's is joining other bricks-and-mortar retailers looking for ways to make Internet operations more efficient and boost sales.
CEO Edward Stack told industry analysts on Tuesday that the Findlay-based retailer aims to triple the percentage of sales that it generates from Internet shoppers by 2016. Online sales now account for 6 percent of the company's overall revenue, which was $5.84 billion last year.
"How (customers) buy, we don't care, as long as they buy from Dick's Sporting Goods," Stack told analysts gathered in New York for Goldman Sachs' 20th Annual Global Retailing Conference.
A significant part of the online push involves shipping more Dick's products to online purchasers from a nearby store, where possible, instead of from a centralized distribution center to speed deliveries.
Dick's, which has about 600 stores in 44 states, including 81 Golf Galaxy locations, two TrueRunner stores and one Field & Stream store, operates distribution centers in Smithton, Westmoreland County; Atlanta; Plainfield, Ind.; and Goodyear, Ariz.
The increased focus on the Internet is not surprising, given online retail growth. Annual sales ballooned from $63.6 billion in 2004 to $203.9 billion in 2011, according to data from Forrester Research Inc., which tracks online trends.
Total retail sales, including the online channel, grew just 23 percent during the same period, from $2.35 trillion to $2.88 trillion.
"Consumers have gotten more daring and are no longer afraid to shop online because they feel there's more security measures in place when they use their cards," said Audrey Guskey, a marketing professor at Duquesne University.
Online sales pioneer Amazon.com and other major retailers, such as Wal-Mart and JC Penney, have grown adept at selling online, said Guskey. She noted many retailers have made buying easier for frequent shoppers by saving their credit card numbers and often offering free shipping.
Dick's joins another locally based retailer, American Eagle Outfitters Inc., that recently announced plans to improve its online business.
Earlier this month, the chain retailer of trendy clothing for younger people said it will close a distribution center in Marshall in early to mid-2015 because it has no room to expand in order to accommodate American Eagle's growing volume of sales online, which is approaching 15 percent of sales.
Instead, American Eagle will build a larger, $160 million distribution center near Hazleton, Luzerne County, which can ship purchases more quickly.
"So if you're a retailer who doesn't recognize that consumers are increasingly buying online, you'll be behind," said Christopher Svezia, an analyst at Susquehanna Financial Group whose coverage includes Dick's.
As part of its online retail strategy, Dick's is developing a system with IBM that will enable it to ship more products to online purchasers directly from the nearest store. That provides Dick's with a better profit margin, Svezia said. Currently, Dick's ships online orders from one of its four distribution centers to a fulfillment company, which then ships the product to the consumer. The contract with that company runs out in 2017.
By the end of the year, Dick's will have a direct-ship capability at about 100 of its stores, Stack told investors.
The retailer is establishing a system by which customers could pick up their online purchases at a Dick's store, instead of waiting for the products to be shipped to them.
"Plus, if you can get the consumers in the store to pick up something or even return something, the likelihood is that shopper will buy something else," Svezia said.
In the quarter ended on Aug. 3, Dick's earnings jumped 57 percent to $84 million from $53.7 million a year earlier.
In addition to enhancing its online sales capabilities, Dick's is pursuing the outdoors adventurer with its Field & Stream store prototype, as well as remodeling dozens of store interiors to feature popular brands such as Nike. Online is now a big focus.
When one analyst asked the CEO how engaged Dick's was to the online channel, Stack quipped that the retailer was "not engaged to it; we're married to it."
Thomas Olson is a staff writerfor Trib Total Media.

subset: commoncrawl


text:
Fractal Design CORE 1100. Type: PC, Supported motherboard form factors: Micro-ATX,Mini-ITX, Colour of product: Black. Power supply location: Bottom, Supported power supply form factors: ATX. Front fans installed: 1x 120 mm, Front fans diameters supported: 120 mm, Side fans diameters supported: 120 mm. Supported hard disk drive sizes: 2.5,3.5". LED indicators: HDD, Power
Fractal Design Core 3500 is a wide body mid tower ATX case, also available in a Windowed side panel version, allowing users to show off their build. High-performance features include superior liquid cooling potential with support for up to two 240mm radiators or a 280mm radiator- A wide body mid tower case with bottom-mounted PSU, designed for exceptional airflow and cooling.- Brushed aluminum-look front panel with a sleek, three-dimensional textured finish- Superior water cooling support, supporting one 240/280mm radiator in the front and a 240mm radiator in the top- Featuring a 140mm rear exhaust fan for optimal cooling- Total 7 fan slots with two Silent Series R2 140mm fans included- Smart cable management with 22mm of space behind the motherboard plate and thick rubber grommets for clean installations- Supports extremely tall tower CPU coolers, up to 185mm in height- Featuring an integrated three-speed fan controller- Multiple easy-to-clean dust filters designed into the case to help maintain a dust free interior- Four vibration dampening hard drive trays for up to four 3.5" HDDs, all compatible with 2.5" drives- HDD trays split into two cages and strategically positioned with a large space in between to support all long graphics cards up to a maximum length of 430mm in the top four slots, and cards up to 295mm in length in the bottom three slots- Two additional SSD positions behind the motherboard plate


text:
of experience in all aspects of real estate development,
including the finance, development, construction and
management of real estate projects and enterprises. Before
forming The Cannon Company, he served as President
of Cousins Properties Inc. and CFO of the Sea Pines
Mr. Cannon earned a BA in Economics from the University of South Carolina and
an MBA from Harvard University Graduate School of Business. Present and
past affiliations include the Urban Land Institute, Financial Executives Institute,
the Harvard Club, Atlanta Country Club and Piedmont Driving Club.
770.431.9151 ext. 258
Dickson Cannon's experience includes acquisitions,
financing, development, brokerage, and commercial real estate
management. He joined The Richard Felker Company in 1987,
and then Colliers Cauble (formally Cauble Mortgage Company)
as a mortgage broker representing large life insurance companies
in 1990. In 1993, he formed Cannon Financial, Inc., specializing
in the sale of land and income-producing properties. The
Atlanta Commercial Board of Realtors named him a top five
land broker and a top twenty overall producer in Atlanta
in 1995. In 2001, he joined The Staubach Company as an investment
sales broker. The following year he formed Quest Realty Advisors,
LLC, where he pursued investment advisory services and personal
investment opportunities. He joined The Cannon Company in
development and acquisition areas in 2004.
Mr. Cannon earned his BA from the
University of South Carolina in 1987.
770.431.9151 ext. 224
Steve Dieckman has worked in real estate finance and
investment for 20 years. He joined The Cannon Company in 2004.
Prior to that, he owned Wesley Capital Investments, acquiring
and renovating Woodchase Village Apartments in Marietta,
Georgia, a 416-unit, tax-credit property, in a joint venture
with Atlanta developer Brencor. He also was a principal
at Watermarke Properties and Julian LeCraw & Company. Before
getting into the development business, he worked 10 years
in real estate finance and asset management at GE Capital,
and prior to that, was a mortgage broker with Portman Barry
and Johnstown Mortgage.
Mr. Dieckman earned his BBA from
Georgia State University.
770.431.9151 ext. 246
Wed like to welcome and acknowledge Patricia Greenwood of Patricia M. Greenwood, CPA, PC, as a consultant member of our team. Patricia comes to us on a part time basis; however, she is directly responsible for all accounting functions as well as assists in general office management.
Photo and Bio Coming
Home | About | Cannon
Company Projects | Cannon Company Team | Contact
© 2006, The Cannon Company, Atlanta, Georgia. Caswyck® is a trademark
of Cannon Advisory Partners, Inc.


text:
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text:
There were many things that the Voice in Ryou's head was fair about (though the Spirit tended to push the meaning of that word until it almost outstretched its definition, but he always managed to stay inside of the line somehow). Ryou, however, knew better than to trust him when he had a pair of dice. "Come on, Landlord," he said in a voice that was as smooth as as the flat of a sword, "let's play a game."
"No," Ryou answered immediately.
Of course, it wasn't as if the Voice was standing in front of him – that was impossible when they shared a single body. The Voice was purring at him from inside of his mind, in a part he couldn't quite reach no matter how long he tried to get to it. It was the host himself that held the die, and he rolled them in his palm. It was comfortable to fiddle with them, but it did not make him feel at all safe. When the Spirit wanted something, he would not back down just because Ryou said to.
"The power will be on your side this time," the Voice goaded.
"No," Ryou spat.
"Make your deal with the Devil and your payout will be more than you could pray for from a god."
The brown-eyed teenager closed his hand around the die and the edges bit into his skin. The sensation was grounding. "What, then," he asked but it didn't sound at all like a question.
"I will retire back into the Ring. I will never bother you or your friends again."
"You're a liar," Ryou accused.
A chuckle echoed in his head. "I have never lied about anything, Landlord."
Ryou pursed his lips and then huffed through his nose. No, perhaps the Voice didn't outright lie, but he did to the word "truth" exactly what he did to "fair". "And what will I wager?" he asked.
He didn't get a response.
"No," he said again and his tone was firmer than before, with his annoyance clearly showing through. His tolerance for the other was already so very low to begin with.
"Fine, fine," the Spirit chided. "I'll spoil the surprise." Ryou wasn't exactly holding his breath, but he was very close to snapping when the words just faded after that. He was not asking for much at all and even then, he was strung along like a toy! That actually described their relationship quite well, though Ryou Bakura had a strong bite when he needed it. Just as he was about to slam the two cubes onto the living room table, It spoke up again. "I want you to love Me."
That threw off any retort that Ryou had already planned and he went just as silent as the Spirit had a few seconds prior. "That's impossible," he finally managed to think up. "I can't just love you because you tell me to." And that was that; there was no debating it further.
Or he thought that, anyway. "Then you have nothing to lose," the Voice said, encouraging him. Ryou still didn't trust this at all. "I just want to hear you say you love Me if I win." The way the Spirit said that, it sent chills down Ryou's spine and sounded warning bells in his brain. No, that wasn't all this was. It couldn't be. He could trust this as much as he could trust a venomous wild snake to not bite him if he reached out for it. The words were said too easily, and they were said invitingly. Every part of this said that it was just a trap.
"Why?" the host asked. "Why do you want me to say that?" Instead of sounding angry he just sounded confused. Out of everything, why would the Spirit ask for love? The thought made him sick to his stomach.
"Because I am lonely," was the reply.
That sent Ryou reeling and he knew that was an outright lie. He couldn't prove it, but he knew and that made it even worse. If he could convict the other with evidence then he would go away and let the host win this battle. No, that tone of voice was not sincere. He would be gaining something from this, and he would never tell Ryou what it was until it was too late to fight back. That was the tone that was meant to be the bait that he took – no, bait was not the right word. The fish suspects nothing until it bites down, and that was never the case with the Spirit. With the Spirit, he would lure the fish into a false sense of security as he offered the bait to be eaten. He would even go so far as to pamper the fish with gifts after the bait was gone. He would shush the fish and assure it that it was perfectly safe for as long as it took. And just as the fish would begin to believe this, the Spirit would break its spine and render it helpless but very much alive. It was so much more complicated than simply baiting him. "I don't trust you," he said. It made him so disappointed with himself that his voice shook when the words left his mouth.
"I am not asking for your trust."
That answer was simple enough. The unease sloshed around more in his gut, and Ryou thought that rice was a very horrible thing to have to throw up. "But if you really hate the ones you call friends so much... I could take care of them for you."
That was undeniably a threat.
"Fine," he answered in defeat – but he kept his answer firm even so. "We will play a game, and if I win you will leave me – and them! – alone. If you win, I will tell you I love you and I don't have to mean a single word of it. And that's all I'm doing. Nothing more than that, do you understand me?" He didn't wait for an answer to that and honestly he didn't expect that there would have been one. "But you have to tell me what 'game' it is we're going to play."
"Of course," was the softer than silk answer. "We are going to play a nice game involving dice–"
"No," Ryou interrupted. "You know how to cheat with them and I've watched you." He was controlling his dice rolls just fine when he played the Game Master in Monster World (which was the last time Ryou had ever played his favorite game and this personal ban on it was a painful one).
His response earned another laugh. "Which is why you're going to be the one making the rolls."
Ryou frowned and spread his fingers to stare down at the die. "No loopholes," he whispered after nearly half a minute of silence that left his ears ringing. It wasn't a fact he was stating; it was a demand, even if it was less than forceful.
"No loopholes," the Voice agreed.
"So what is it, then? Highest roll? Lowest roll? Odds and evens? What about guessing the number?" Ryou thought that he really should have asked this before, but there had been more important things at the time – like making the contract. He knew that it was all tilted in the other's favor (as it always was), but that didn't mean it was impossible for him to come out the victor. And honestly, what would he be losing except a few minutes of his time and an exceptionally awkward moment that no one else would ever have to know about? If he won, though... the idea of it, of the other truly leaving him and his friends alone... it was like a distant sort of dream. He didn't plan on keeping his hopes too high because things never went that smoothly, but it made him giddy and excited without his consent anyway.
"Highest roll," the Voice replied. "I do enjoy greatness."
Ryou pursed his lips at that but he nodded to confirm. "Alright," he said, and his heart began to beat like he was getting up to run a race. His gut twisted with anxiety and he regretted already that he agreed. But he couldn't go back now and the Spirit really wouldn't have let him say otherwise. "This is my roll," he began. Then he jumped to add "You can't interfere with these." He didn't immediately make his move, but instead he worked to steady his breaths. One, two, three, that's it. Then he shook his hand and let the cubes drop to the table. They rolled with several loud clacks and then stilled. He felt a knot surge up into his throat and lodge there as he stared at the number markings. One was a two, and the other was just a one. He had only rolled a three, out of a possible twelve. He nearly called out that it didn't count, or that it was actually the other's roll he had been making and not his own. But he couldn't. He hated that in the end it boiled down to that he was an honest person and what's done was done. He weakly reached out to sweep them off of the table and he felt oddly detached. It wasn't the sort of detachment that came from being possessed, though. All the while the Voice said nothing – no snipes or mocking commentary and backhanded compliments. With a shaky breath Ryou steadied his hand and repeated the action a second time. The dice flew against the table and the sound was just jarring now.
One landed as a two and the other a three. A five. Both numbers were low, but Ryou truly felt humiliated that he had lost with nearly the worst roll possible. He wished over and over that he had switched who the rolls were for, that he had gone second instead of first.
The detachment hit him even harder and now he felt almost as if he were floating, half-asleep. "I lost," he murmured. Even still, the Spirit said nothing. Ryou attempted against to swallow but his throat was very tight. "I just have to tell you I love you?" he asked.
"Yes." The answer was short.
To tell someone he loved them when he did not was a violation of his morals and it made him angry that he was being forced into this. (Even though he had agreed.) That anger made him wonder if the other had actually influenced the roll, or even both of them! He certainly wouldn't rule it out.
"I love you," he managed out with difficulty, but he sounded either hurt or furious. Perhaps both. "There," he snapped after. "You got what you wanted. You can't do anything else."
He forced himself up to his feet and decided that he was going to go to his room and throw himself onto his bed. No, it wouldn't get him away from the problem, but it was something to do and he felt very childish just now.
The sensation of having the mattress press back up against him was a sobering experience and he took solace in that. The fact that saying what should have been a serious confession wasn't as bad as he had made it out to be in his head got to him. That ate away at his mind and he wanted none of it.
The Spirit treated him differently after that. He encouraged him in school (and that worried Ryou a lot) and many other places, and he complimented the host in general. Ryou had noticed that his presence seemed less overwhelming and more... considerate. He couldn't honestly use "considerate" to describe the other but that was the word that fit best. It certainly wasn't gentle, but it came awkwardly close. And the most important of all of it was that they talked. They talked about subjects that were so mundane it should have, in all rights, bored the other to death. …Or past death, if that was possible. They talked about religion, they tore apart the psychology behind that and the societies' behavior today. They talked about governments and kingdoms of the past. They talked about the weather. They talked about their favorite games and movies. They talked.
This went on for weeks. It went on for almost a month. During that month he was lured into other "games" where the wagers were the same. Each time Ryou had lost and he felt like he was growing to accept his fate instead of sitting there, numb or angry. The Spirit was always... especially... kind afterward. So kind that it made Ryou's heart ache because it was something he missed. He had purposely banned himself from being close in this way with anyone (because of the Spirit), and going without it had gotten to be easy, but now he had a fresh taste of it, and it was horrible. It was horrible and it was winning. It became hard to remember exactly how cruel and terrifying the other was in action. It faded into a fog that made it seem less intense and less real. It became hard to see the other a some Great Evil as he used to, because his words were so attractive and so easy to ingest. Ryou had grown to crave them.
He realized, after a time, what the Voice was doing. He realized that the Spirit was playing with his head (and his emotions). He realized that the Voice was trying to manipulate him, to make it so that Ryou would hesitate the next time he tried to side with his friends. That second of hesitation could be all it would take to change the outcome of the battle. He realized that he was being used again as a pawn, and, after a time, Ryou didn't care.
It turned out one could make another love them after all.


text:
PCR has evolved into one of the most promising tools for T. cruzi detection in the diagnosis and control of Chagas disease. However, general use of the technique is hampered by its complexity and the lack of standardization.
We here present the development and phase I evaluation of the T. cruzi OligoC-TesT, a simple and standardized dipstick format for detection of PCR amplified T. cruzi DNA. The specificity and sensitivity of the assay were evaluated on blood samples from 60 Chagas non-endemic and 48 endemic control persons and on biological samples from 33 patients, 7 reservoir animals, and 14 vectors collected in Chile.
Principal Findings
The lower detection limits of the T. cruzi OligoC-TesT were 1 pg and 1 to 10 fg of DNA from T. cruzi lineage I and II, respectively. The test showed a specificity of 100% (95% confidence interval [CI]: 96.6%–100%) on the control samples and a sensitivity of 93.9% (95% CI: 80.4%–98.3%), 100% (95% CI: 64.6%–100%), and 100% (95% CI: 78.5%–100%) on the human, rodent, and vector samples, respectively.
Author Summary
Chagas disease (American trypanosomiasis) is caused by the protozoan parasite Trypanosoma cruzi and represents a major public health problem in Latin America. Furthermore, growing human population movements extend the disease distribution to regions outside the South American continent. Accurate diagnosis is crucial in patient care and in preventing transmission through blood transfusion, organ transplantation, or vertical transmission from mother to child. Routine diagnosis of Trypanosoma cruzi infection generally is based on detection of the host's antibodies against the parasite. However, antibody detection tests are liable to specificity problems and are of limited use in assessing treatment outcome and congenital infections. The introduction of the polymerase chain reaction (PCR) to amplify specific DNA sequences opened promising diagnostic perspectives. Despite its reported high sensitivity and specificity, broad use of the PCR technique in diagnosis of Chagas disease is hampered by its complexity and the lack of any standardization. We here present the development and evaluation of the T. cruzi OligoC-TesT, a simple and standardized dipstick format for detection of PCR amplified T. cruzi DNA. The new tool is an important step towards simplified and standardized molecular diagnosis of Chagas disease.
Citation: Deborggraeve S, Coronado X, Solari A, Zulantay I, Apt W, Mertens P, et al. (2009) T. cruzi OligoC-TesT: A Simplified and Standardized Polymerase Chain Reaction Format for Diagnosis of Chagas Disease. PLoS Negl Trop Dis 3(6): e450. https://doi.org/10.1371/journal.pntd.0000450
Editor: Helton da Costa Santiago, National Institutes of Health, United States of America
Received: December 5, 2008; Accepted: May 1, 2009; Published: June 2, 2009
Copyright: © 2009 Deborggraeve et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This study received financial support from the Flemish Government in the framework of the Bilateral Scientific Collaboration Flanders-Chile 2006–2007. Salary support for SD was from the European Union's Sixth Framework Programme (priority INCO-DEV, project TRYLEIDIAG, contract 015379). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: P. Mertens, T. Laurent, and T. Leclipteux are employees of Coris BioConcept, a company involved in the development and provisioning of the OligoC-TesT. All other authors report no potential conflicts.
Accurate diagnosis of Chagas disease, the most important parasitic disease in the Americas [1], is challenging due to the latent character of the infection. Following a brief acute phase, infected individuals can progress to a lifelong chronic phase and about 30% will eventually develop the typical cardiac and intestinal complications that can be fatal [2]. Trypanosoma cruzi, the protozoan pathogenic agent, is naturally transmitted by blood sucking Triatominae bugs. Additional transmission routes include vertical transmission from mother to child, transfusion with infected blood and organ transplantation. Oral T. cruzi transmission by the consumption of contaminated food is linked to localized outbreaks of acute Chagas disease [3]. The T. cruzi species is genetically heterogeneous and has been classified in two major phylogenetic lineages, T. cruzi I and T. cruzi II, of which the latter is subdivided in 5 sublineages (IIa to IIe). T. cruzi I predominates in endemic countries north of the Amazon, whereas T. cruzi II is predominant throughout the Southern Cone countries of South America. T. cruzi I is associated with domestic and sylvatic transmission cycles, while IIa and IIc seem to be restricted to sylvatic cycles and IIb, IId and IIe to domestic cycles [4]. Both lineages are associated with cardiac lesions in human infection, but it seems that digestive tract lesions only occur in infection with T. cruzi II [5]. T. cruzi is closely related to T. rangeli that is apparently harmless to man but shares the same reservoir animals and vectors [6].
Acute infections, although rarely recognized because of the non-specific clinical manifestations, can be diagnosed by parasitological tests since the parasite load in the blood at that stage is generally high enough. Chronic infections, on the contrary, are associated with a very low parasite load in the blood and are therefore mainly diagnosed by means of antibody detection tests. However, antibody detection tests are liable to specificity problems due to cross-reaction with antibodies induced by other parasites, especially Leishmania and T. rangeli [7]. Hence, it is generally recommended that specimens are tested in two or three different immunodiagnostic tests, such as indirect immunofluorescence (IIF), indirect hemagglutination (IHA) and enzyme-linked immuno sorbent assays (ELISA). Furthermore, immunodiagnostic tests are less useful in testing the effectiveness of treatment and congenital infections. Xenodiagnosis is regularly used for parasite detection but results of this invasive test are only available after 1 to 3 months and the method shows generally low sensitivity with chronic infections [8]. Accurate tools to rapidly diagnose active infections, to assess treatment efficacy and to determine the impact of transmission control measures are needed. The introduction of the polymerase chain reaction (PCR) to amplify specific DNA sequences opened promising diagnostic perspectives. PCR has been used to detect T. cruzi in the blood of chronic chagasic patients [9], in congenital transmission [10], in patient follow-up after treatment [11] and in disease reactivation after heart transplantation [12]. Despite the reported high sensitivity and specificity, the PCR technique is restricted to high-level equipped laboratories. This is partly due to the laborious and time-consuming detection of the PCR products. Amplicons are generally detected by electrophoresis in agarose gel followed by U.V. illumination in the presence of the carcinogenic ethidium bromide. Quantitative real-time detection of PCR amplified T. cruzi DNA has been developed [13] and offers major advantages such as increased sensitivity, high-throughput analysis and single tube formats. However, the technique is complex and expensive. Besides the need for simplification of the DNA amplification assay, standardization is a crucial requirement for moving molecular tools towards patient diagnosis and disease control.
Oligochromatography (OligoC) provides a simple and rapid one-step dipstick format for detection of PCR products (Coris BioConcept, Gembloux, Belgium; Patent n° WO 2004/099438A1) [14]. After the PCR step, the detection step takes only 5 minutes and no other equipment than a water bath and pipette are needed. Controls for the PCR reaction and the chromatographic migration are incorporated in the assay. The technique has already been developed for diagnosis of human African trypanosomiasis [15], leishmaniasis [16], toxoplasmosis [17], schistosomiasis [18] and severe acute respiratory syndrome (SARS) [19], and high sensitivity and specificity were reported.
We here describe the development and phase I evaluation of a T. cruzi PCR-Oligochromatography test (T. cruzi OligoC-TesT), targeting a highly conserved satellite DNA sequence [20]. We assessed the diagnostic accuracy of the assay on a broad spectrum of biological samples from Chagas non-endemic and endemic control persons, infected children, adults, reservoir animals and vectors.
Experimental samples
T. cruzi Y (lineage IIb) epimastigotes were grown in glucose-lactalbumine-serum-hemoglobine (GLSH) medium [21] with 10% fetal calf serum at 26°C. At day 3 post-inoculation, parasites were counted in a Bürker counting chamber (Marienfeld, Germany). Tenfold dilution series of parasites ranging from 10,000 parasites/180 µl to 1 parasite/180 µl blood were made in human blood freshly taken on EDTA from a healthy volunteer. Non-spiked blood was used as negative control. Purified DNA from T. cruzi OPS21 Cl11, STC35R, IVV Cl3, X110/8, RN PCR 0 and VMV4, belonging to lineage I, IIa, IIb, IIc, IId and IIe, respectively, was obtained from the DNA reference bank at the Institute of Tropical Medicine Antwerp (ITMA), Belgium. DNA from 25 different Trypanosoma rangeli isolates (Table 1) and from Leishmania donovani, Trypanosoma brucei gambiense, Mycobacterium tuberculosis, Schistosoma mansoni and Plasmodium falciparum was obtained from other research groups. DNA concentrations were measured in the Nanodrop ND-1000 UV-Vis spectrophotometer (NanoDrop Technologies, Wilmington, USA) and the DNA was stored at −20°C.
Biological samples
Ethical clearance for the study was obtained from the ethics committee of the Faculty of Medicine, University of Chile, Santiago, Chile. Written informed consent was given by the patients or guardians and from non-diseased persons. Research on biological samples from animals was conducted adhering to the institution's guidelines for animal husbandry.
Blood samples from Chagas non-endemic and endemic controls.
DNA extracts from blood of 20 confirmed T. brucei gambiense infected persons from the Democratic Republic of the Congo (DRC), 20 confirmed L. donovani infected persons from Nepal and 20 confirmed P. falciparum infected persons from Zambia were obtained from the collection of the Department of Parasitology of the ITMA. Infections were confirmed by direct parasite detection in blood or tissue aspirates. Blood samples from 48 Chagas endemic control persons were obtained at the blood bank of the Clinical Hospital, University of Chile in 2004. Blood bank samples were classified as not infected with T. cruzi if negative in two different antibody detection tools (IIF and ELISA).
Blood samples from T. cruzi infected persons.
2 ml whole blood from 6 children (0–10 years old) and 27 adults (>18 years old) infected with T. cruzi were collected in Chile (region IV), between the years 2000 and 2004. The blood was mixed with an equal volume of 6 M guanidine-HCl and 0.2 M EDTA, and 200 µl was subjected to DNA extraction. Persons were considered as infected with T. cruzi if positive in kDNA PCR amplifying the minicircle variable region followed by Southern blot hybridization with a T. cruzi specific probe, as described by Zulantay et al. [22]. For 20 of the 27 adult Chagas disease patients, clinical, serological and xenodiagnosis data were available. Six patients showed normal electrocardiogram (ECG) results, 11 showed prolonged QTC syndrome and one showed sinus tachycardia, while for 2 patients no ECG was done. All 20 patients were positive in two independent immunodiagnostic tests (IIF and ELISA). All 20 patients were negative in xenodiagnosis but 5 showed a positive result when the kDNA PCR was performed on the xenodiagnosis specimens.
Biological samples from reservoir animals and vectors.
200 µl blood from 2 Octodon degus and 5 Abrothrix olivaceus rodents and the intestinal content from 14 Mepraia spinolai bugs were collected. All animals originated from Las Chinchillas National Reserve (Chile, region IV) and were classified as infected with T. cruzi based on positive results in kDNA PCR followed by Southern blot hybridization [22].
DNA extraction
DNA from T. cruzi Y culture was extracted with the QIAamp DNA mini kit (Qiagen, Hilden, Germany). Spiked blood and blood from the endemic control persons were extracted using the QIAamp DNA blood mini kit (Qiagen, Hilden, Germany). DNA from blood of patients and animals was extracted with the EZNA blood DNA kit (Omega Bioteck, Inc., Doraville, GA). Intestinal content of the vectors was mixed with 200 µl PBS, boiled for 10 minutes and centrifuged at 10,000 g. The supernatant was used as DNA template.
Primers and probes
An alignment of the internal control and target DNA, primers and probes sequences is presented in Figure 1. Primers, probes and internal control DNA were synthesized by Biomers.net (Ulm, Germany).
Alignment of the internal control (IC) DNA sequence and the T. cruzi OligoC-TesT DNA target sequence (T.c.) within the satellite DNA (consensus sequence of GenBank accession numbers AY519985 to AY520098). The forward primer Tc-Sat-F (1), the biotinylated (Biot) reverse primers Tc-Sat-R (2), the T. cruzi detection probe (3) and the IC detection probe (4) are shown.
103 sequences of the 195 bp T. cruzi satellite DNA (GenBank accession numbers AY519985 to AY520098) were aligned using the "DNA man" software (Lynnon Corporation, Quebec, Canada). The sense primer Tc-Sat-F 5′-CACTCTCTGTCAATGTCTGTTTGCGTG-3′ and anti-sense primer Tc-Sat-R 5′-GAAATTCCTCCAAGCAGCGGATA-3′ were designed targeting a conserved 81 bp sequence within the T. cruzi satellite DNA. The anti-sense primer Tc-Sat-R was biotinylated at the 5′ end.
Internal control DNA.
The internal control (IC) DNA sequence (81 bp) is identical to the T. cruzi target sequence except for a 20 bp central part. The IC central sequence was designed with the same length and the same GC content as the T. cruzi central sequence.
The T. cruzi detection probe (5′-TGGACACCAAACAACCC-3′) and the IC detection probe (5′-AGGGTCTACTGGGTTACCTG-3′) were designed to hybridize the T. cruzi and IC central sequences respectively. The detection probes were conjugated with gold particles using the procedure described in patent WO 2004/099438A1 [14]. The T. cruzi and IC migration control probes were synthesized with the reverse complement sequence of the respective detection probes.
PCR amplification
The 50 µl PCR reaction mixture was prepared by adding 2.5 µl sample DNA and 1 unit of Hot Star Taq polymerase (Qiagen, Hilden, Germany) to 47.3 µl of T. cruzi Ampli-Mix (Coris BioConcept, Gembloux, Belgium). This pre-made PCR mix contains all components to allow PCR amplification, the primers Tc-Sat-F and Tc-Sat-R and the IC DNA at a concentration of 10−18 M. The commonly used dTTP was replaced by dUTP to allow elimination of carry-over contamination with uracyl-DNA N-glycosilase. An initial denaturation step at 94°C for 15 minutes to activate the Hot Star Taq polymerase was followed by 40 cycles of 94°C for 20 seconds, 65°C for 20 seconds and 72°C for 20 seconds, and a final extension at 72°C for 1 minute. Amplification was carried out in 200 µl thin-wall PCR tubes (Abgene, Epsom, United Kingdom) in a T3 thermocycler 48 (Biometra, Göttingen, Germany).
The T. cruzi Oligo-Strip construction and principle is the same as the HAT-PCR-OC dipstick described by Deborggraeve et al. [15] but a migration control line was added to the test side. A schematic overview of the T. cruzi OligoC-TesT principle is presented in Figure 2. The IC line and the migration control lines determine whether the T. cruzi OligoC test is valid or invalid. An invisible migration control line indicates an invalid detection step, while an invalid PCR reaction is indicated by a negative IC line in combination with a negative test line. The latter may happen due to inhibitory factors in the extracted DNA. The assay is repeated when the control lines indicate failure of migration or of the PCR reaction. When a sample contains high concentrations of T. cruzi DNA, competition between the T. cruzi and the IC template DNA can result in an invisible IC control line but now combined with a strongly visible T. cruzi test line. In this case the test result is considered as a valid positive result.
Polymerase chain reaction (PCR) amplification of a sample containing T. cruzi DNA (1) is performed using a PCR mix containing single-stranded internal control (IC) template (2). The IC sequence is the same as the target sequence within the T. cruzi satellite DNA but with a specific internal sequence (dotted line). Both templates are amplified with the same primers of which the reverse primer is biotinylated (•). When the PCR and subsequent denaturation is completed, the PCR product solution contains single-stranded T. cruzi and IC DNA (3), and is mixed with an equal volume of migration buffer preheated at 55°C. The T. cruzi Oligo-Strip is dipped into the mixture and test results are read after 5 minutes migration at 55°C (4). During migration, the solution takes up the gold-labelled (○) detection probes. The T. cruzi detection probes (5) at the test side and the IC detection probes (6) at the control side hybridise with their respective amplicons. The biotinylated PCR products accumulate on the neutralite avidin lines at both sides of the dipstick and the T. cruzi and IC amplicons are visualized by their respective detection probes (7). In case of a negative sample, only the IC amplicon is present and visualized at the control side of the dipstick (8). The excess of detection probes migrate further and hybridise on the complementary probes coated at both sides of the dipstick as a control for migration (9).
Assay procedure.
After PCR amplification the PCR product is denaturated at 94°C for 30 seconds and transferred immediately to ice. Forty microliters are mixed with an equal volume of OligoStrip running buffer preheated at 55°C, followed by dipping the T. cruzi Oligo-Strip into the solution. Test results are read after 5 minutes qualitatively. Whenever a test line appears that is visible by naked eye, the test is considered positive. Once test results are read the Oligo-Strips should not be stored for future reading as background may appear after drying of the strip.
Analytical sensitivity
The detection limit of the T. cruzi OligoC-TesT was evaluated on three independent tenfold serial dilutions of T. cruzi strain Y DNA in water containing 0.1 mg/ml acetylated bovine serum albumin (BSA). The lower detection limit was consistently 1 fg DNA per assay (Figure 3A) which is about 1/200 of the DNA content of one parasite. The analytical sensitivity was also evaluated on DNA extracted from three independent blood sample series spiked with decreasing numbers of living T. cruzi epimastigotes. The assay was able to detect 1 parasite in a 180 µl blood sample (Figure 3B), while non-spiked control blood samples always remained negative.
The upper and lower line are the migration control and the T. cruzi test line respectively. A. Test results on a serial dilution of T. cruzi strain Y DNA in water containing 0.1 mg/ml acetylated bovine serum albumine (BSA). Dipsticks 1–10: 1 ng, 100 pg, 10 pg, 1 pg, 100 fg, 10 fg, 1 fg, 0.1 fg, 0.01 fg and 0 fg per assay. B. Test results on a serial dilution of T. cruzi epimastigotes in naïve human blood. Dipsticks 1–6: 10,000; 1,000; 100; 10; 1 and 0 parasites in 180 µl blood.
Analytical specificity
The analytical specificity of the assay was evaluated on tenfold serial dilutions of DNA from T. cruzi strains representative for the 6 different lineages and on DNA from relevant non target pathogens. The T. cruzi OligoC-TesT was able to detect 1 fg DNA of the strains X110/8 (lineage IIc), RN PCR O (IId) and VMV4 (IIe), 10 fg DNA of the strains STC 35R (IIa) and IVV Cl3 (IIb), and 1 pg DNA of the strain OPS21 (I). Negative test results were observed with 5 ng purified DNA per test of L. donovani, T. brucei gambiense, M. tuberculosis, S. mansoni and P. falciparum. To assess the level of T. rangeli detection by the T. cruzi OligoC-TesT, tenfold serial dilutions of purified DNA from 25 different T. rangeli isolates were tested (Table 1). Four T. rangeli isolates could be detected at a DNA concentration of 10 pg per assay, 13 at a DNA concentration of 100 pg or 1 ng, while 8 isolates remained negative when tested at 1 ng DNA per assay.
Specificity on Chagas non-endemic and endemic control blood samples
Negative results were observed when testing DNA extracts from blood of 20 T. brucei gambiense infected persons from DRC, 20 L. donovani infected persons from Nepal, 20 P. falciparum infected persons from Zambia, and 48 Chagas endemic control blood samples from Chile (Table 2). Hence, the specificity of the assay on 60 Chagas non-endemic and 48 endemic control blood samples was 100% with a 95% confidence interval [CI] scored by Wilson's method of 96.6% to 100% [23].
Sensitivity on T. cruzi infected patients, vectors and reservoir animals
The diagnostic accuracy of the T. cruzi OligoC-TesT was tested in 2007 on biological samples from 6 T. cruzi infected children and 27 infected adults, 2 infected O. degus rodents, 5 infected A. alivaceus rodents and 14 infected M. spinolai bugs (Table 2). All samples showed a positive test result except for 2 blood samples from children. Hence, the test showed a sensitivity of 66.7% (95% CI: 30%–90.3%), 100% (87.5%–100%), 100% (95% CI: 64.6%–100%) and 100% (95% CI: 78.5%–100%) on the specimens from infected children, adults, rodents and vectors, respectively. The two OligoC-TesT negative blood samples showed invalid results in two independent repetitions. Therefore, DNA was ethanol precipitated and washed as described elsewhere [15]. The purified DNA samples were retested in T. cruzi OligoC-TesT and valid negative test results were observed.
Antibody detection is routinely used for diagnosis of Chagas disease but suffers from specificity problems because of cross-reactivity with antibodies against other infectious agents such as Leishmania spp. and T. rangeli. Furthermore, immunodiagnosis is less useful in cure assessment after treatment and in diagnosis of congenital transmission. Xenodiagnosis is cumbersome, time consuming and invasive. Molecular detection of the parasite by the PCR technique is able to overcome most of these drawbacks since high sensitivity and specificity is combined with detection of DNA as surrogate for parasite detection. Despite the major advantages, PCR is still restricted to research applications and did not enter many diagnostic laboratories yet, which is mainly due to the complexity of the technique. Furthermore, the numerous in house diagnostic PCR assays and the neglect of any standardization hamper this promising technique to occupy a major position in clinical diagnosis. Next to patient management, PCR can play an important role as an accurate surrogate for parasite detection in epidemiological studies on reservoir animals and vectors.
In this study a molecular dipstick assay for simple, rapid and standardized detection of T. cruzi DNA was developed and evaluated. The T. cruzi OligoC-TesT consists of PCR amplification of a short sequence within the T. cruzi satellite DNA followed by a single step PCR product detection in dipstick format. The detection step is performed in 5 minutes and the only equipment needed is a pipette and water bath. The lower detection limits of the assay are 1 fg of purified T. cruzi strain Y DNA and 1 parasite in a 180 µl blood sample. This is similar to the detection limits of the primers Tcz1/Tcz2 and Diaz1/Diaz2 targeting the same 195 bp satellite DNA as reported by Moser et al. [24] and Diaz et al. [25], respectively. However, when we tested serial dilutions of DNA from T. cruzi strains representative for the 6 lineages we observed a 100 to 1000 times lower sensitivity on the T. cruzi strain of lineage I compared to the strains of lineage II. The lower sensitivity on T. cruzi lineage I is probably due to the lower copy number of the satellite repeats in lineage I as reported by Elias et al. [26]. This is confirmed by the fact that Diaz et al. also observed a lower sensitivity of their primers on DNA from T. cruzi I strains [25]. The test showed a positive signal when tested on purified DNA from T. rangeli. To assess the level of cross-reaction, serial dilution series of DNA of 25 different T. rangeli isolates were tested. Four of the 25 isolates could be detected at 10 pg DNA per test which is 10 times more than the required DNA of T. cruzi lineage I and 100 to 1000 times more than T. cruzi lineage II. Fourteen T. rangeli isolates required a higher amount of DNA to be detectable with the T. cruzi OligC-TesT and 8 remained negative at 1 ng DNA per assay. This is in contrast with Ochs et al. [27] and Virreira et al. [10] who reported no amplification of T. rangeli DNA by the Tcz1/Tcz2 primers. However, these authors used only one T. rangeli isolate and one DNA concentration. The observed cross-reaction with T. rangeli is not surprising since the satellite DNA has been described in T. rangeli. Breniere et al. [28] reported that the number of repeats of the 195 bp satellite DNA is far lower in T. rangeli than in T. cruzi, which might explain the higher detection threshold of the assay for T. rangeli. The variable T. rangeli detection levels are probably due to variable copy numbers of the satellite repeats within the T. rangeli population, as described for T. cruzi [26]. However, a parasitaemia of 10,000 T. rangeli parasites per ml of blood in human is unlikely since several studies reported no or very low T. rangeli multiplication in mammalian host cells [29],[30].
The specificity of the T. cruzi OligoC-TesT was estimated at 100% on blood samples from 60 Chagas non-endemic and 48 endemic control persons. Sensitivities of 93.9% on 33 infected patients and of 100% on 7 infected rodents and 14 infected vectors were observed. The high sensitivity on blood samples from adults is encouraging given the general low parasitaemia in the blood of such patients. However, we used a kDNA PCR followed by Southern blot as the main reference test instead of immunodiagnosis, that is currently the standard diagnostic technique for chronic Chagas disease. All 20 adult patients for which additional diagnostic test results were available showed positive immunodiagnostic test results but were negative in conventional xenodiagnosis, indicating the high sensitivity of PCR based parasite detection. Further evaluations are needed to estimate the diagnostic accuracy of the test on chronic Chagasic patients diagnosed on the basis of immunodiagnostic tools alone. The negative results on the two blood samples from children are unexpected since parasite loads are generally higher in children than in adults. The two samples showed initially invalid T. cruzi OligoC-TesT results, indicating inhibition of the PCR reaction. Therefore, the DNA was precipitated, washed and retested with the T. cruzi OligoC-TesT where after the tests became valid but negative. The DNA might have been lost during the multiple purification steps. The test showed high sensitivity on reservoir animals and vectors, which is promising regarding the coexistence of different T. cruzi lineages, including lineage I, at the collection site as reported by Rozas et al. [31].
In conclusion, the diagnostic accuracy on this diverse panel of biological samples indicates the potential of the T. cruzi OligoC-TesT. Further phase II and III evaluation studies are needed to assess the diagnostic sensitivity and specificity of the test on human target populations in different endemic regions. Persons with potentially cross-reacting diseases such as leishmaniasis should be included in the control group during future phase II evaluations. This new tool is a first step towards low-tech and user-friendly molecular diagnostics for T. cruzi detection. Besides the simplification, presentation of the T. cruzi OligoC-TesT as a self-containing kit with ready-to-use PCR mix and dipsticks offers excellent prospects for PCR standardization. Standardization of the PCR technique is crucial for its implementation as a reference parasite detection test for diagnosis and clinical studies. Chagas disease is routinely diagnosed by antibody detection but a simple and standardized PCR format can play an important role in situations were the use of immunodiagnosis is limited, such as congenital Chagas disease, patient follow-up after treatment and disease re-activation after organ transplantation. An additional potential niche for the T. cruzi OligoC-TesT may be patients with acute Chagas disease but negative test results in direct microscopy and patients with chronic Chagas disease but inconsistent or borderline immunodiagnostic test results. Isothermal amplification of the parasite's DNA through novel methods such as the loop mediated isothermal amplification (LAMP) [32] and the nucleic acid sequence based amplification (NASBA) [33] might further simplify the assay. Furthermore, standardized PCR formats to discriminate the 6 lineages of T. cruzi would be most welcome, since accurate lineage discrimination is important for disease and vector control programmes [34]. Additional standardization of the sampling procedures and DNA extraction is needed as well.
In conclusion, the T. cruzi OligoC-TesT represents a simplified and standardized PCR format for T. cruzi detection in biological samples. The innovative assay bears clear potential as a simplified molecular diagnostic tool for Chagas disease in midlevel-equipped laboratories.
Supporting Information
Checklist S1.
STARD Checklist
We kindly acknowledge Dr. C. Grevelding, Dr. F. Portaels, Dr. D. Mumba and Dr. U. D'Alessandro for providing DNA from Schistosoma mansoni, Mycobacterium tuberculosis, Trypanosoma brucei gambiense and Plasmodium falciparum respectively. We thank Dr. C. Barnabe, Dr. M. Llewellyn and Dr. H. Carrasco for providing T. rangeli DNA.
Author Contributions
Conceived and designed the experiments: S. Deborggraeve, A. Solari, J. Dujardin, P. Herdewijn, P. Büscher. Performed the experiments: S. Deborggraeve, X. Coronado, P. Mertens, T. Laurent, T. Stessens. Analyzed the data: S. Deborggraeve, A. Solari. Contributed reagents/materials/analysis tools: S. Deborggraeve, P. Mertens, T. Laurent, T. Leclipteux. Wrote the paper: S. Deborggraeve. Substantial revision of the manuscript: X. Coronado, A. Solari, I. Zulantay, W. Apt, P. Mertens, T. Laurent, T. Leclipteux, T. Stessens, J. Dujardin, P. Herdewijn, P. Büscher. Project co-ordination: A. Solari. Sample collection: I. Zulantay, W. Apt. Project co-ordinator: P. Büscher.
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- 11. Sánchez G, Coronado X, Zulantay I, Apt W, Gajardo M, et al. (2005) Monitoring the efficacy of specific treatment in chronic Chagas disease by polymerase chain reaction and flow cytometry analysis. Parasite 12: 353–357.G. SánchezX. CoronadoI. ZulantayW. AptM. Gajardo2005Monitoring the efficacy of specific treatment in chronic Chagas disease by polymerase chain reaction and flow cytometry analysis.Parasite12353357
- 12. Diez M, Favaloro L, Bertolotti A, Burgos JM, Vigliano C, et al. (2007) Usefulness of PCR strategies for early diagnosis of Chagas' disease reactivation and treatment follow-up in heart transplantation. Am J Transplant 7: 1633–1640.M. DiezL. FavaloroA. BertolottiJM BurgosC. Vigliano2007Usefulness of PCR strategies for early diagnosis of Chagas' disease reactivation and treatment follow-up in heart transplantation.Am J Transplant716331640
- 13. Piron M, Fisa R, Casamitjana N, López-Chejade P, Puig L, et al. (2007) Development of a real-time PCR assay for Trypanosoma cruzi detection in blood samples. Acta Trop 103: 195–200.M. PironR. FisaN. CasamitjanaP. López-ChejadeL. Puig2007Development of a real-time PCR assay for Trypanosoma cruzi detection in blood samples.Acta Trop103195200
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Renuart I, Mertens P, Leclipteux T (2004) One step oligochromatographic device and method of use. I. RenuartP. MertensT. Leclipteux2004One step oligochromatographic device and method of use.EU Patent WO2004/099438A1. 18 November 2004. EU Patent WO2004/099438A1. 18 November 2004.
- 15. Deborggraeve S, Claes F, Laurent T, Mertens P, Leclipteux T, et al. (2006) Molecular dipstick test for diagnosis of sleeping sickness. J Clin Microbiol 44: 2884–2889.S. DeborggraeveF. ClaesT. LaurentP. MertensT. Leclipteux2006Molecular dipstick test for diagnosis of sleeping sickness.J Clin Microbiol4428842889
- 16. Deborggraeve S, Laurent T, Espinosa D, Van der Auwera G, Mbuchi M, et al. (2008) A simplified and standardized polymerase chain reaction format for the diagnosis of leishmaniasis. J Infect Dis 198: 1565–1572.S. DeborggraeveT. LaurentD. EspinosaG. Van der AuweraM. Mbuchi2008A simplified and standardized polymerase chain reaction format for the diagnosis of leishmaniasis.J Infect Dis19815651572
- 17. Edvinsson B, Jalal S, Nord CE, Pedersen S, Evengard B (2004) DNA extraction and PCR assays for detection of Toxoplasma gondii. APMIS 112: 342–348.B. EdvinssonS. JalalCE NordS. PedersenB. Evengard2004DNA extraction and PCR assays for detection of Toxoplasma gondii.APMIS112342348
- 18. Akinwale OP, Laurent T, Mertens P, Leclipteux T, Rollinson D, et al. (2008) Detection of schistosomes polymerase chain reaction amplified DNA by oligochromatographic dipstick. Mol Biochem Parasitol 160: 167–170.OP AkinwaleT. LaurentP. MertensT. LeclipteuxD. Rollinson2008Detection of schistosomes polymerase chain reaction amplified DNA by oligochromatographic dipstick.Mol Biochem Parasitol160167170
- 19. Mertens P, Vijgen L, Olungu C, Degallaix S, Renuart I, et al. (2004) Detection of SARS-CoV by oligochromatography of RT-PCR amplicons [Abstract P1842]. Clin Microbiol Infect 10: (Suppl 3)526–527.P. MertensL. VijgenC. OlunguS. DegallaixI. Renuart2004Detection of SARS-CoV by oligochromatography of RT-PCR amplicons [Abstract P1842].Clin Microbiol Infect10(Suppl 3)526527
- 20. Sloof P, Bos JL, Konings AF, Menke HH, Borst P, et al. (1983) Characterization of satellite DNA in Trypanosoma brucei and Trypanosoma cruzi. J Mol Biol 167: 1–21.P. SloofJL BosAF KoningsHH MenkeP. Borst1983Characterization of satellite DNA in Trypanosoma brucei and Trypanosoma cruzi.J Mol Biol167121
- 21. Le Ray D (1978) Structures antigéniques de Trypanosoma brucei (Protozoa, Kinetoplastida). Ann Soc Belg Méd Trop 55: 129–311.D. Le Ray1978Structures antigéniques de Trypanosoma brucei (Protozoa, Kinetoplastida).Ann Soc Belg Méd Trop55129311
- 22. Zulantay I, Honores P, Solari A, Apt W, Ortiz S, et al. (2004) Use of polymerase chain reaction (PCR) and hybridization assays to detect Trypanosoma cruzi in chronic patients treated with itraconazole or allopurinol. Diagn Microbiol Infect Dis 48: 253–257.I. ZulantayP. HonoresA. SolariW. AptS. Ortiz2004Use of polymerase chain reaction (PCR) and hybridization assays to detect Trypanosoma cruzi in chronic patients treated with itraconazole or allopurinol.Diagn Microbiol Infect Dis48253257
- 23. Wilson EB (1927) Probable inference, the law of succession, and statistical inference. J Am Stat Assoc 22: 209–212.EB Wilson1927Probable inference, the law of succession, and statistical inference.J Am Stat Assoc22209212
- 24. Moser DR, Kirchhoff LV, Donelson JE (1989) Detection of Trypanosoma cruzi by DNA amplification using the polymerase chain reaction. J Clin Microbiol 27: 1477–1482.DR MoserLV KirchhoffJE Donelson1989Detection of Trypanosoma cruzi by DNA amplification using the polymerase chain reaction.J Clin Microbiol2714771482
- 25. Diaz C, Nussenzweig V, Gonzalez A (1992) An improved polymerase chain reaction assay to detect Trypanosoma cruzi in blood. Am J Trop Med Hyg 46: 616–623.C. DiazV. NussenzweigA. Gonzalez1992An improved polymerase chain reaction assay to detect Trypanosoma cruzi in blood.Am J Trop Med Hyg46616623
- 26. Elias MC, Vargas NS, Zingales B, Schenkman S (2003) Organization of satellite DNA in the genome of Trypanosoma cruzi. Mol Biochem Parasitol 129: 1–9.MC EliasNS VargasB. ZingalesS. Schenkman2003Organization of satellite DNA in the genome of Trypanosoma cruzi.Mol Biochem Parasitol12919
- 27. Ochs DE, Hnilica VS, Moser DR, Smith JH, Lirchhoff LV (1996) Postmortem diagnosis of autochthonous acute chagasic myocarditis by polymerase chain reaction amplification of a species specific DNA sequence of Trypanosoma cruzi. Am J Trop Med Hyg 54: 526–529.DE OchsVS HnilicaDR MoserJH SmithLV Lirchhoff1996Postmortem diagnosis of autochthonous acute chagasic myocarditis by polymerase chain reaction amplification of a species specific DNA sequence of Trypanosoma cruzi.Am J Trop Med Hyg54526529
- 28. Breniere SF, Bosseno MF, Barnabe C, Urdaneta-Morales S, Tibayrenc M (1993) Copy number differences in the 195 bp repeated satellite DNA from Trypanosoma cruzi and Trypanosoma rangeli: potential use for epidemiologic surveys. Mem Inst Oswaldo Cruz 88: 163–165.SF BreniereMF BossenoC. BarnabeS. Urdaneta-MoralesM. Tibayrenc1993Copy number differences in the 195 bp repeated satellite DNA from Trypanosoma cruzi and Trypanosoma rangeli: potential use for epidemiologic surveys.Mem Inst Oswaldo Cruz88163165
- 29. Osorio Y, Travi BL, Palma GI, Saravia NG (1995) Infectivity of Trypanosoma rangeli in a promoncytic mammalian cell line. J Parasitol 81: 687–693.Y. OsorioBL TraviGI PalmaNG Saravia1995Infectivity of Trypanosoma rangeli in a promoncytic mammalian cell line.J Parasitol81687693
- 30. Eger-Mangrich I, de Oliveira MA, Grisard EC, De Souza W (2001) Interaction of Trypanosoma rangeli Tejera, 1920 with different cell lines in vitro. Parasitol Res 87: 505–509.I. Eger-MangrichMA de OliveiraEC GrisardW. De Souza2001Interaction of Trypanosoma rangeli Tejera, 1920 with different cell lines in vitro.Parasitol Res87505509
- 31. Rozas M, Botto-Mahan C, Coronado X, Ortiz S, Cattan PE, et al. (2007) Coexistence of Trypanosoma cruzi genotypes in wild and peridomestic mammals in Chile. Am J Trop Med Hyg 77: 647–653.M. RozasC. Botto-MahanX. CoronadoS. OrtizPE Cattan2007Coexistence of Trypanosoma cruzi genotypes in wild and peridomestic mammals in Chile.Am J Trop Med Hyg77647653
- 32. Notomi T, Okayama H, Masubuchi H, Yonekawa T, Watanabe K, et al. (2000) Loop-mediated isothermal amplification of DNA. Nucleic Acids Res 28: E63.T. NotomiH. OkayamaH. MasubuchiT. YonekawaK. Watanabe2000Loop-mediated isothermal amplification of DNA.Nucleic Acids Res28E63
- 33. Chang AB, Fox JD (1999) NASBA and other transcription based amplification methods for research and diagnostic microbiology. Rev Med Microbiol 10: 185–196.AB ChangJD Fox1999NASBA and other transcription based amplification methods for research and diagnostic microbiology.Rev Med Microbiol10185196
- 34. Miles MA, Feliciangeli MD, de Arias AR (2003) American trypanosomiasis (Chagas' disease) and the role of molecular epidemiology in guiding control strategies. BMJ 326: 1444–1448.MA MilesMD FeliciangeliAR de Arias2003American trypanosomiasis (Chagas' disease) and the role of molecular epidemiology in guiding control strategies.BMJ32614441448


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Is North Dumpling Island Real or Made Up?
Is This Geeky Fact Real or Fake?
When geeks make millions of dollars from a genius invention, brilliant company idea, or other successful venture, one of the perks is that they can spend their millions on an awesome arsenal of items. And that's what Segway inventor Dean Kamen did, buying his own island in the Long Island Sound off the shore of Connecticut.
North Dumpling Island lies just 0.3 miles north of South Dumpling Island and is considered a part of New York state. After he was originally unable to build his own wind turbine on the island, Kamen joked about seceding from the US; he even created North Dumpling's own constitution, flag, national anthem, and navy (consisting of only one vessel).
So, what do you think? Is Kamen's Kingdom of North Dumpling real, or is the island an object of my imagination?
Is This Geeky Fact Real or Fake?
Is this geeky fact real or fake?


text: Falling Star by Solar Cloud published on 2012-03-10T14:35:23Z Looking for vocals to add to this Genre Psychedelic Rock Comment by Mr.T-Music Yeah ! I like this style ! 2013/12/31 08:13:25 +0000 Comment by Trinity Ward Great guitar work - love it! 2012/12/09 18:45:19 +0000 Comment by The Magic Onions Nice combination of sounds.... Great track 2012/08/26 17:26:01 +0000 Comment by Helloday Cool!!!! You are good!!! play HELLODAY =) 2012/08/21 13:01:26 +0000 Comment by Scott Shawn DeRocks Stick this in my dropbox for a chance to play on Spaceboy Radio! 2012/07/22 09:59:53 +0000 Comment by RyAn j. DiLLoN Nice jam... I can dig it. It reminds me of Neil Young. 2012/07/11 17:18:06 +0000 Comment by PictoMexico Hey sounds goood. Couldnt stop listening. give us a listen and see what you think, also like and add us on facebook. We would really appreciate the support http://www.facebook.com/#!/PictoMexico Keep it up, its awesome!!!! 2012/07/06 08:39:27 +0000 Comment by kliFF Studios nice track! 2012/07/05 19:38:32 +0000 Comment by Jaidog04 Dude I go on this site to find songs like this, u should add this to my new group http://soundcloud.com/groups/rock-pop-alternative-instrumental Amazing song mate 2012/06/26 13:14:32 +0000 Comment by Kelvyn Taylor Love this track, mix is understated & perfect 2012/06/24 16:53:47 +0000 Comment by Dragon Rose Superb guitars! Catchy melody! Great track!!! 2012/06/18 13:43:23 +0000 Comment by H2708 very nice track :) 2012/06/08 06:09:12 +0000 Comment by Xycon Good Job:) Love the Vibe from this 2012/05/15 02:11:07 +0000 Comment by The Bar Fines Very cool piece! Loved it! 2012/05/15 00:21:46 +0000 Comment by The Bar Fines Great guitar melody and tone! The whole song has a really nice feel that sets my imagination flying! 2012/05/15 00:19:59 +0000 Comment by GHel super 2012/05/14 16:48:54 +0000 Comment by Shirtless! nice fat guitar sounds 2012/05/10 20:29:57 +0000 Comment by Danny Joseph Like this alot! Awesome tune!! 2012/05/10 15:39:53 +0000 Comment by JazzCrisis Good stuff! Contemplative vibe...inspires thought. 2012/05/03 18:04:30 +0000 Comment by InTheDepthsOfTheOcean cool :) 2012/05/03 14:52:56 +0000 Comment by The Space Limit This is cool! Like it a lot! 2012/04/21 05:23:28 +0000 Comment by Simon Dwight Great guitars.. love the sound and the background instrumentation that allow for the lead solo(s). Nice piece of work. 2012/04/18 13:10:50 +0000 Comment by GreyMarket Dig it! 2012/04/17 20:00:18 +0000 Comment by Mitchell Frederick awesomenesss!!!!! keep it up man! :) check my tracks out when you get a chance too! 2012/04/05 13:24:53 +0000 Comment by DON DAVIDSIN KILLA TRACK G... CHECK OUT MY MUSIC.. ADD ME ON FACEBOOK...https://www.facebook.com/#!/Young.Don.G.P 2012/03/30 09:31:32 +0000 Comment by Kevin|Brand great track 2012/03/29 06:41:46 +0000 Comment by Johnny19 Nice sound. very cool sonic pallette 2012/03/25 22:53:52 +0000 Comment by The Sweet Disorder great stuff ;-) 2012/03/24 20:04:47 +0000 Comment by A Cromwell Very determined guitar riffs, great sense of direction. Really like this. Please give our song 'simple slip' a listen if you get time and keep up the good work! 2012/03/12 19:16:19 +0000 Comment by Rotary Phone it feels like surf rock meets oasis. very nice 2012/03/12 19:02:38 +0000


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In last month's (August) Ensign, Elder Bruce C. Hafen purports to put the Proclamation on the Family into its historical and cultural context.1 Hafen's view is that marriage as an institution is collapsing, and the family with it, because society has come to value the individual's interest at the expense of social interests, one of which is the support and privileging of stable heterosexual nuclear families. He views this as a cultural shift driven by legal changes in the last half decade, before which "laws maintained a workable balance between social interests and individual interests." In the 60s and 70s, however, the courts "began to interpret family laws in ways that gave individual interests a much higher priority than social interests, which knocked the legal and social system off balance." (52) Hafen picks out no-fault divorce laws, the availability of child custody and adoption to single people, abortion, and (as always) same-sex marriage as elements of this threat to the family, and mourns how far the family has fallen since the year 1960, to which he makes repeated and regretful reference, as his reference point for a happier time when families were stronger and we better enforced pro-social values.
But here are some other fun things going on in 1960: Read More
- "The Proclamation on the Family: Transcending the Cultural Confusion," Ensign August 2015, 50-55 [↩]


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Size: 6 months to 8
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An exquisite little outfit for Spring and beyond. Simple and sweet with a touch of Dutch in the tulip and heart motifs. Fitted style pink shirt has spring green ric rac stemmed tulips and hearts on the front and back. Choose from long or short sleeves.
Matching skirt is made from light weight tulip and heart print fabric and paired with a timeless floral print for the contrasting hem. Add a band of tulip print ribbon and it's perfect! Easy to wear with comfy elastic waist. Easy to care with machine washable cotton. Handcrafted with love in NYC.


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PASSIONATE campaigner for Blackheath and its people Mary Docker has died after a short battle with cancer at the age of 59.
Dubbed "Mrs Blackheath", she served the town as a Conservative councillor for eight years until losing the 2012 election when town hall Tories took a beating in the backlash against the national Government.
Although disappointed, it did not stop her working for Blackheath, and continued in her role as secretary of the Blackheath Business and Community Association, running the 15 CCTV cameras which protected the town.
Mrs Docker worked at the heart of the community with her market stall, Moonbeam Textiles, which was open house for residents to share their concerns and problems.
She ran Blackheath's annual Tree of Life to raise money for charities, was deputy leader of Sandwell's Tory group and served for a spell as chairman of the Halesowen and Rowley Regis Conservative Association.
Halesowen born and bred, she ran the Dean and Moon textile shop in Blackheath with husband John from 1990 until his death in 2001, after which she carried on with the market stall they had opened in 1997, and moved to Tividale.
The mother-of-two, who adored her two granddaughters, battled against multiple sclerosis for more than 30 years and after being taken ill at Christmas, was diagnosed with cancer just five weeks before her death on Sunday.
Daughter Bec said: "She was just such a kind, generous person. I used to call her the official do-gooder, because she wanted to help everyone."
A minute's silence was held at Tuesday's Sandwell Council meeting and tributes from Conservative colleagues flooded in.
Former Sandwell Tory group leader Ray Nock said: "She was not only a lovely woman, she was an excellent deputy leader of the Sandwell Conservative Party and she always put the people first."
Halesowen and Rowley Regis MP James Morris added: "It is difficult to sum up the enormous contribution that Mary made in Blackheath over so many years - as a councillor, with the Business and Community Association and through all her other community activities.
"She was a key source of help and advice for me after I was selected as the Conservative candidate in 2008 and throughout my time as Member of Parliament.
"I will miss her frank and helpful support greatly, but I know she would prefer to be remembered for all the help she gave to so many people and community groups in Blackheath and across Sandwell."
Independent Halesowen North Conservative councillor Karen Shakespeare said: "I still see Mary as Mrs Blackheath with the work she did for the town.
"She was really hard working - she was so passionate about Blackheath. So many people will have known her, and with her market stall as well, which she ran until last year."
Cllr Shakespeare added: "She will be desperately missed, I had a lot of time for her - she was a lovely lady."
Mrs Docker had stood unsuccessfully as an independent councillor for the town and it was Pedmore and Stourbridge East councillor Les Jones who persuaded her to stand for the Conservatives in 2004.
Fellow Halesowen North councillor Jeff Hill said: "She was absolutely dedicated to the people of Blackheath both when she was a councillor and before and after her time on the council.
"She was known by so many people, a friendly face to talk to at her stall in the market. She will be sorely missed by all of us."
Former Cradley Heath and Old Hill Tory councillor Liz Bowler and her husband Alan added: "She did work tirelessly and was very passionate about her work as a councillor. It is a really sad loss, really tragic."
Mrs Docker's funeral will be held at St Hubert's RC Church, Oldbury, on Tuesday April 29 at 11am followed by burial at Rowley Regis Cemetery.


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AGF Study, NO. 6: The Procurement and Branch Distribution of Officers
Army Ground Forces, when established on 9 March 1942, took over from the old chiefs of the combat arms the responsibility for the training of officer candidates. Since July 1941, when the officer candidate schools had started operation, the numbers of candidates to be admitted had been under the control of the War Department. No change in this arrangement was made with the establishment of Army Ground Forces; for
another year, until March 1943, control over the size of OCS operations remained with the War Department. Although Army Ground Forces took over the personnel functions formerly performed in the offices of the Chiefs of Infantry, Field Artillery, Cavalry, and Coast Artillery, specific exception was made of functions relating to the procurement of officer candidates.30 The War Department progressively stepped up OSC capacities to keep pace with expansion of the Troop Basis, for the new units in which officers were needed well in advance of activation. The OCS population, from slight beginnings in 1941, when only 1,389 officers were graduated, leaped upward in the spring of 1942 and virtually doubled every three months until the end of the year. (See Table II.) In all, 55,440 officers were graduated from the ground officer candidate schools during 1942. (See Table III.)
While the officer candidate schools were expanding, the rapid activations of 1942, outrunning the supply of inductees, left troop units with serious shortages of enlisted personnel.31 Procurement of officer candidates in the prescribed numbers was therefore difficult in the extreme. It was necessary to resort to several expedients -- including the recruitment of volunteer candidates from civilian life and the award of administrative commissions -- to keep the officer candidate schools filled. An AGF directive to the field, dated 4 September 1942, pointed out the urgency of the OCS program, cited the case of a company commander relieved for not filling his OCS quota, and urged commanders to use "salesmanship" in recruiting candidates.32
In procurement of officer candidates, Army Ground Forces was handicapped by the fact that its enlisted ranks represented a sub-average cross section of the population of the United States.33 Good men were kept from the Army by the recruiting methods used by the Navy and the Marine Corps. Within the Army, the classification system, emphasizing achievement in civilian vocations, tended to concentrate high-grade personnel in technical and noncombat branches. In addition, the classification system was modified in practice by special rulings to protect the quality of the Air Corps, which, under the "75 percent rule" and its successive equivalents, drew most of its inductees from the higher levels (by intelligence) of men available to the Army. Tens of thousands of high-calibre men were withheld from the Ground Forces by this means. For some branches, such as Antiaircraft, Field Artillery, and Engineers, in which mathematical knowledge was needed, it was especially difficult in 1942 for Ground Force units to meet officer candidate quotas.34 There was a marked tendency also for able-bodied officer candidates, after basic training in a combat arm, to elect officer candidate school in such branches as Quartermaster and Finance. This practice was stopped by an amendment to Army Regulations.35
The Army Ground Forces could not supply enough candidates to fill its own schools, despite repeated screenings of its units, the harmful effects of which are mentioned below. AGF schools were thrown open to candidates secured from all branches of the Army.36 Even this broadening of the base from which selections were to be made did not suffice. It became necessary, in the interests of expediency, to depart from the theory on which officer procurement had been based. As has been noted above, the prevailing Army policy was to secure new officers from the enlisted ranks of the Army, except for certain specialists appointed directly from civilian life, and to award commissions for general duty, including combat leadership, within a branch. Both these fundamentals were compromised in 1942.
The Volunteer Officer Candidate plan, inaugurated in March 1942, was an attempt to tap a large pool of potential officer material -- men deferred from military service.37 Under the VOC scheme, a man deferred for dependency might apply for officer training with the understanding that if not selected at the RTC to which he was sent for basic training or if not commissioned at OCS, he could return to civilian life and former draft status. By December 1942, 38,134 VOC's had been accepted in the Army as a whole; 27,000 were attending OCS.38 The program tapered off in 1943, when the need for officers declined, and disappeared late in that year when dependency ceased to confer draft exemption. The VOC program was a source of many officers who, but for the
exigencies of procurement that forced its adoption, might have remained outside the military service altogether or accepted commissions in one of the services whose officer procurement program was less restricted. The VOC's did much in 1942 to relieve the almost impossible burden of filling officer candidate schools, and without a lowering of quality.39
But going outside the Army for candidates did not entirely make good the shortage of officer material. It became necessary, in the summer of 1942, to make another breach in the established plan by redefining the qualifications for a commission. According to the original theory, every officer was qualified to be a combat leader; the mission of OC schools was defined accordingly: "to produce platoon commanders for units of the field forces";40 candidates judged lacking in leadership qualities were relieved from OCS. As the shortage of officers mounted, this practice seemed wasteful. Some 59,000 purely administrative positions in the Army at large had to be filled, none of which required combat leadership ability. To conserve some of the excellent material being squandered at officer schools under the restrictive view of fitness for commission, the War Department in June 1942 gave the OC schools a second mission: "to produce good administrators from those who lack combat leadership qualities." Only when a candidate was unfit for any type of commissioned duty was he to be relieved.41
This revision of procurement standards was not popular with the ground arms. The number of administrative positions in the arms was relatively not great. Double classification and complicated bookkeeping procedures reduced flexibility of assignment. In practice the restriction "commissioned for administrative duty only" was generally disregarded, officers being assigned to any duty for which they were needed.42 No figures are available on the number of men so commissioned in the Ground Forces. By February 1943, the crisis in procurement having passed, the original standards for commission were reinstated and candidates once more had to qualify as potential combat leaders.43
With pressure of the strongest kind being exerted to find candidates for officer training, it was inevitable that the system should break down at some point. Breakdown occurred at several points.
To find enough candidates in units it was necessary to deplete the sources of good noncommissioned officers. General Lear wrote to General McNair in October 1942: "We are scratching the bottom of the barrel now for officer candidates. We are decidedly short of the right material for noncommissioned officer leaders. We will pay dearly for this in battle."44
The quality of candidates declined as the enlisted sources were repeatedly picked over. Despite the desire of OC schools to graduate as many men as possible,. the percentage of candidates graduating fell steadily through 1942:45
|Percentage Graduating
|January 1942
|July 1942
|December 1942
|86.9 (Apr)
|94.5 (Mar)
|Coast Artillery
|Field Artillery
|80.3 (Feb)
|Tank Destroyer
|91.4 (Oct)
Academic failures, resulting chiefly from lack of proper educational background, rose at the Armored School from 3.2 percent in February to 14.8 percent in December, at the Coast Artillery School from 1.1 percent in July to 21.9 percent in December, and at the Infantry School from 1.8 percent in April to 17.3 percent in November.46
In October 1942 Dr. James Grafton Rogers, visiting officer candidate schools at the request of General Marshall, found them "notably troubled by poor quality."47 General Bull, commanding the Replacement and School Command, admitted that "emphasis on filling officer candidate quotas had influenced commanders in many instances to sacrifice quality for quantity."48 But General McNair defined the dilemma when he remarked to General Lear that "we must not set up arbitrary standards and ignore the fact that we must have officers."49
Numerous expedients, discussed in detail in Study No. 30 of this series (Training in the Schools of the Army Ground Forces), were adopted at the OC schools to combat or offset the poor quality of the available candidate material. Special tests were devised to screen out men sent to OCS merely to fill quotas; preparatory schools were established to give basic training to candidates brought in from other arms; and the policy was adopted of turning back weak candidates to repeat all or part of the course in the hope of salvaging as many men as possible. The result was unavoidably an adulterated product. By the end of 1942 the quality of recent OCS graduates had declined so far that The Inspector General suggested sweeping reforms in the selection and training of officer candidates. (See Study No. 30.) Army Ground Forces opposed the recommendations, feeling that the trouble lay not in the details of the selection system but in the reluctance of unit commanders to send key enlisted men to OCS and in the shortage of high-intelligence personnel which a year of preferential treatment of the Air Corps had brought about and which operation of the ASTP was now beginning to accentuate.50 (See Study No. 4, Mobilization of the Ground Army.)
The matter ceased to have practical significance for the procurement of officers in 1943. With passage from shortage to surplus, difficulty in finding enough qualified men to fill quotas disappeared. Quality could again be insisted on and high standards reasserted. The War Department, late in 1942, wrote a commentary on the problems of the year just past and a forecast of the year to come.51
While the reduction in officer candidate requirements will not operate to deny qualified applicants the opportunity to attend an officer candidate school, it will permit more careful selection, and will place officer candidate opportunities on a higher competitive basis. With a broad field from which to select a smaller number of candidates, commanders should give most careful attention to final selection to the end that the highest type of officer material available is selected.
The issue in 1942 had been numbers; it was expected that attention in 1943 could be concentrated on quality. This expectation proved to be incorrect. Numbers continued during 1943 to be central in officer procurement, but the question was no longer how to get enough candidates but how to avoid getting too many.
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Last updated 15 September 2005