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Fragments and Relocated Records
CA IDMS CA IDMS - Database CA IDMS - ADS
One of the most rigidly enforced rules within an IDMS database is that the dbkey of a record is assigned when a record is stored within the database and cannot change as long as that record resides on the database. A dbkey is composed of the number of the page on which a record is stored and a line index number that points the DBMS to information necessary to locate the record occurrence on the database page. This means that when the size of a record occurrence already existing on the database increases IDMS cannot simply move that record to another page if insufficient space exists on the current page since that movement would require a new dbkey to be assigned.
This article describes variable length fragments and relocated records which are structures used by IDMS to acquire the necessary space for these expanding record occurrences without changing a record's original dbkey. Performance implications of these constructs, ways to minimize their creation, and how IDMS attempts to eliminate their presence are also covered.
The type of record whose size is most likely to increase after it is stored on a database is one defined as variable length. Records are considered to be variable length when their element definitions include an OCCURS DEPENDING ON clause or the record occurrences are to be compressed. A variable length record (VLR) occurrence will increase in size when as a result of a MODIFY verb an additional reoccurring group is added to the record or changes to the record's data result in the compression algorithm providing a less effective level of compression.
When a record is defined as being variable length a Record Descriptor Word (RDW) is added to the data portion of the record and an additional pointer position is inserted at the end of the record's prefix. The RDW is used to contain the length of the entire data portion of the record occurrence and the additional pointer position is used to support an internal set known as the fragment chain.
When an existing VLR is to be expanded, and in some cases initially stored, and there is insufficient space to hold the entire record on the occurrence's target page the portion of the record that will not fit will be overflowed to another page within the area. The portion of the record that is on the original page is referred to as the record's 'root' while the overflowed piece of the record is referred to as a fragment and is assigned a record id of 4 (SR4). The root continues to be identified using the record's true record id and acts as the owner of that record's fragment chain with the SR4's being the fragment chain's members.
VLR Fragment Chain
When IDMS must access the fragmented VLR it will first read the page containing the root of the record as this is the portion of the record referenced by the record's dbkey. IDMS then recognizes that the entire record is not completely contained within the root portion of the record and will commence walking the fragment chain to reconstruct the record within storage. This reconstruction is transparent to the application but the need to read another page to get the record's fragment has a negative impact on the performance of the DBMS. It is possible that the fragment chain may link to multiple fragments, each on a different page. Each page containing a fragment for a VLR record occurrence can be considered to add 1 physical I/O to the amount of work performed by the DBMS to reconstruct the VLR.
Whenever a VLR is defined to a database it is very unlikely that fragmentation of some record occurrences can be completely avoided if the associated applications have the ability to increase the size of these records. However IDMS does provide some mechanisms that will allow a DBA to minimize the number of fragments that may appear within a database. The first thing to do is to insure the proper specification of the MINIMUM ROOT and MINIMUM FRAGMENT clauses on the VLR's RECORD statement within the schema.
MINIMUM ROOT IS RECORD LENGTH should be coded on the schema RECORD statement for all variable length records. This parameter tells the DBMS to insure that the page selected as the target page for a record occurrence has enough space to contain the entire record. Specifying any value other than RECORD LENGTH can result in SR4 fragments being created during the store of the VLR occurrence. In the same manner MINIMUM FRAGMENT IS RECORD LENGTH should always be coded. By coding this you are telling IDMS that whenever it must fragment a VLR during a MODIFY command it must find enough space on an overflow page for the entire fragment. Specification of any other value can result in multiple fragments being created if the database area is tight on space.
Finally, any area that contains a VLR should be defined to have a PAGE RESERVE on its AREA statement within the SEGMENT definition. By specifying a PAGE RESERVE the DBA is directing IDMS to stop adding new records to any page when the amount of free space remaining on that page reaches the specified value. That remaining space can then be used for the expansion of any VLR occurrence on that page which will prevent fragments from being created on a MODIFY command until that reserved space is exhausted.
Acknowledging the fact that VLR fragmentation can have a negative impact on a database's performance, IDMS does make an attempt to condense fragment chains when processing an area in an UPDATE mode. When a fragmented VLR is accessed and the area is in an UPDATE mode IDMS will check the free space on the root's page to see if any space has been made available. If space does exist IDMS will condense as much of the fragment chain as possible back to the original target page and will also condense any other fragments together if space allows on the pages on which fragments exist. Of course the best way to eliminate all fragments within an area is to perform an UNLOAD/RELOAD, DB-REORG, or REORG against that area with a subschema generated from a schema that had MINIMUM ROOT IS RECORD LENGTH specified for the record type.
Relocated Records
Relocated records are created by IDMS during the in-place expansion of a fixed length record or the control length of the root portion of a variable length record. This structure is necessary when such an expansion causes the record (or its control length) to no longer fit on its current page. When this situation is encountered the record occurrence is removed from its current page and replaced with an SR2 record. A new target database page is found for the data record using standard overflow algorithms but the data record is stored on the new page as a type 3 record (SR3) instead of using its original record type designation. The SR2 occurrence contains the relocated record's original record type and the dbkey of the new SR3 record.
When IDMS is directed to access a record at a specified dbkey one of the first things it does is verify the record id of the record on the database page to the type of record requested. If the record ids do not match, IDMS will check the record type on the database page to see if it is a 2 before returning an error status to the application program. If the record is an SR2, IDMS will check the record type indicator within the SR2 to see if it represents the type of record being requested. When the record id in the SR2 matches the requested type the dbkey of the associated SR3 in the SR2 is used to read the SR3 record occurrence. The data record in the SR3 is then returned to the application using its original record type designation.
The only time that SR2/SR3 records may be created for non-SQL defined databases is as a result of the execution of the RESTRUCTURE SEGMENT utility when the record prefix or data length of a record is being increased.
Expansion of records (rows) in an SQL-defined database occurs at various times but is always the result of the execution of a DDL statement. If the prefix portion of a record needs to be expanded due to the addition of a referential constraint an in-flight restructure is performed against the database during the execution of the SQL command which changes the SQL schema. If the expansion of a record will not fit during the in-flight restructure the necessary relocations occur and the required SR2/SR3 pairs created. If the definition of a table is changed by the addition of new columns no immediate restructure of the data is performed during the modification of the table's definition. However, as these database records are accessed in an update mode the DBMS will append the needed space to any occurrences that existed on the database prior to the change in the table's definition. If this expansion will not fit on the record occurrence's current page relocation occurs and the necessary SR2/SR3 records are created. This means that SR2/SR3 pairs may be created during normal application processing.
In the following example a record type 1024 was expanded and could not fit in the space available on its original page (1001). The record has been relocated to available space on page 1002 and an SR2/SR3 structure created to support the relocated record occurrence.
Relocated Record
Regardless of the type of IDMS database being used SR2/SR3 records will be removed from the database when a relocated record is accessed and its area is readied in an update mode and there is sufficient space on its original database page to hold the expanded record. In this case the SR2 will be removed from the original page and the record represented by the SR3 will be moved back to that page and re-assigned its original record id. The SR3 is then deleted from its overflow page.
Variable length fragments or relocated records provide transparency to application programs when the DBMS engine must locate sufficient space for a record by allowing the target record to retain its original dbkey. However this is accomplished through the cost of additional CPU and I/O operations and excessive numbers of these constructs can have a negative impact on an application's performance. DBAs should constantly monitor their database for an increase in these types of system records using the PRINT SPACE or IDMSDBAN utilities and be prepared to reduce their number of occurrences using the UNLOAD/RELOAD, DB-REORG, or REORG utilities.
Component: IDMS
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EU foreign policy chief expects deal on refugees this week
International (Forat) -The European Union (EU) is expected to reach a deal on refugee quotas this Tuesday on a ministerial level, and the EU leaders will discuss the agreement during the summit in Brussels on Wednesday, EU foreign policy chief Federica Mogherini said.
The European migrant crisis has become the main subject during the EU foreign policy chief's first official visit here.
"I hope that tomorrow the interior ministers will find an agreement," Mogherini told journalists at a press conference in Vilnius, BNS news agency reported.
"I think it will be extremely relevant, first of all, because our internal unity strengthens our external action," she added.
According to Mogherini, the migrant crisis is a "regional and global problem."
The EU seeks to agree on housing in 160,000 refugees. Lithuania has been asked to accept 1,105 refugees from Syria, Iraq and Eritrea over the next two years. The first refugees could be relocated to Lithuania from Italy as early as this year, the Baltic country's officials said.
"We are solid, solidary and rich, therefore, we should not feel burdened to share the responsibility within Europe in order to guarantee refugees' safety," Mogherini said.
The EU will soon be able to give "constructive news" to the world, she noted.
The Italian diplomat also stressed that she "appreciates the position of Lithuania of sharing responsibility and expressing solidarity."
Mogherini met with Lithuanian President Dalia Grybauskaite, Prime Minister Algirdas Butkevicius, and Minister of Foreign Affairs Linas Linkevicius.
"We welcome the European Commission's proposals to better manage the migration flows and ensure the prevention of further aggravations, we also look forward to the decisions by the interior ministers council," Butkevicius said after the meeting.
Linkevicius expressed solidarity with EU member states in response to migration challenges and addressing the causes of migration. Lithuania has already made the decision on its share of refugee burden, he underlined.
"Special attention should be devoted to address the causes of migration. We must maintain solidarity in the EU in order to overcome the crisis," Linkevicius was quoted as saying in the ministry's statement.
The EU's Eastern Partnership issues, including the current situation in Ukraine and the EU's support to this country, were also discussed during meetings.
"Europe needs unity today as never before," President Grybauskaite echoed Mogherini's insights in the statement.
Meanwhile, the Lithuanian leader repeatedly expressed her negative stance concerning the EU's permanent mandatory refugees' quota mechanism.
In her words, sharing refugees alone would not solve the problem in substance, hence, decisions were needed as to how to ensure EU's external border security and to effectively manage migration flows./End/

redpajama_set_name: RedPajamaCommonCrawl


We so love catering events for Picture This Production Services and Stage…they always have great lighting and sound effects on the movie stage. At this holiday party we got to enjoy the live blues music as we passes savory hors d'oeuvres and bartended fine Northwest Wines and Microbrews to their clients and employees.
Chef assembled on-site for freshness, our Bay Shrimp Cocktails in Mini-Cosmo glasses are drizzled with our own Vanilla Bean Citronette for a refreshing Caribbean flavor!
The small plate cooked on-site by Chef Nick, was our Cocoa and Black Pepper crusted Hanger Steak served medium rare on a Red Garnet Yam Mash with a Beef Demi Glace!


Located in a quiet residential cul-de-sac, 6 Priors Walk is a wonderful opportunity for purchasers looking for a bungalow in the lovely village of Coldingham. The spacious accommodation comprises: Vestibule, Hallway, Sitting Room, Dining Room, Kitchen, Utility Room, Conservatory, three bedrooms and bathroom. There is also an integral garage. Outside space includes garden ground on all sides of the bungalow, with a short driveway from the roadside to the garage. The property benefits from modern double glazing throughout, plentiful storage cupboard space and has electric storage heating. In need of some general upgrading, 6 Priors Walk is priced accordingly and a high level of interest from buyers is anticipated, so early viewing is very much recommended.


You can choose from two services, minor and major. One is simply more extensive than the other. On top of your service you'll also receive UK and European Roadside Assistance, a tyre rotation and repair and a wash and vacuum clean. For just £35 extra, we'll also MOT your car.
All prices quoted include parts, labour and VAT on vehicles up to and including 2500cc.


In this post, we will give you information about our shooting set, camera, how many pictures we shoot, how we shoot, and what kind of computer/software set up we use in order to effectively capture our clients' menu. If you like our models on Sketchfab and love food as we do, you should keep reading.
As hardware manufacturers enable content developers to push limits, we hear more and more uses of virtual and augmented reality technologies in our daily lives. On the content creation side of the business, 3D artists are working on creating CGI (computer generated imagery) to create scenarios for virtual and augmented reality applications. But designing models on computers isn't the only solution; by using photogrammetry or 3d scanners we can convert any real life object to a CGI 3D models, which enables us to work on a virtual and augmented reality development environment.
After taking 360 pictures around the objects, you can create point cloud data with textures than build a mesh using related software to create 3D model.
Until recently, 3D scanners have been mainly used for industrial and professional applications like scanning an architectural site or creating digital models for film. The technology is becoming more advanced and accurate than ever, but at the same time, it is also becoming much cheaper.
At Kabaq.io, we create 3D models of food by using photogrammetry technology and present them in augmented and virtual reality environments. To get best quality models, everyday we test different scenarios with different food items in different shooting sets with different cameras.
We use dart targets and full markers on our turntable to make the conversion process easier.
We use a powerful computer solution to make the process faster but you can easily use your daily computer and create amazing scans.
We use anything from a $300 to a $3,000 camera and we will try to show the differences with an example below.
Lighting: The most important piece is in photogrammetry, is the lighting.
Focus: Sharp pictures will convert into sharp 3D models. Setting your focus on the model is the key when shooting small items. That's when an expensive lens comes in handy.
Pictures: Don't forget to take pictures all around the item.
Add your pictures to your project on Agisoft and Align your cameras. At this point you should see a low quality model of your item surrounded with your pictures.
Once you build Dense Cloud your model should look more realistic.
Next step would be building a mesh to match those dense point cloud data and create little triangles. You can zoom in to see the details.
Last step is to build a texture around the item.
Voila and you have your first photoscan, upload it to Sketchfab with a touch of a button through Agisoft.
We performed the test with a special Hotdog from Schaller's Stube Sauage Bar in New York. We shot the same hotdog 4 times to compare the effects of picture quantity and quality (I wish we used a direct light source while shooting under the bread but still these models give you an idea about the test).
Using a Samsung S7 we shot 109 pictures on the continuous turntable.
We shot a video using a Samsung S7 of the hotdog and extracted the images from the video with Adobe After Effects. Why did we do this? We are trying ease the ways of smoothing and fast scanning for entry level scans.
Using Agisoft Pro and following basic process; Align Pictures, Build Dense Cloud, Build Mesh, Build Texture functions. You can use Autodesk Remake or similar applications to start testing on photogrammetry.
Please let me know what you think of the quality of the scans from each shooting.
Thank you, Alper! Seems like food photogrammetry is possible for all– does this inspire you to document your meals more? Be inspired from KabaQ and leave a comment or question below!
Great to see the side-by-side quality comparisons. Very informative. Thanks.
Great question.. did you ever get an answer?
Tools like Photoscan allow you to capture a model in multiple steps or 'chunks', and then merge them together into one object. Alternatively, you could 'suspend' an object using metal wire or sticks and edit them out of the final scan.


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HomeFantasyTwin Magicians Of The 999th Generation
Twin Magicians Of The 999th Generation
By: Sokiiro Updated just nowFantasy
Chapters: 124 views: 2.4K
Light NovelFutureCyberpunkWastelandSystemUpgradehard-working protagonist
As the remaining bloodline of the most unmatched lineage of magicians, Magi and Cian thrive and hide in the current society by becoming hired by all sorts of people for money. With overbearing power, came an extreme caution towards their own actions. However, whenever they move, they wear their mask to hide their identities, becoming known to all by the name, 'Twin Magicians.'
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Twin Magicians Of The 999th Generation The Make Believe Hero
"Argh!"Slamming his fist against the white wall of the hospital, he held back as he expressed his frustration, waiting outside the surgery room now that they have began. They were all at the hospital, waiting for the news about both the tournament as they hoped for Kira's recovery. Saeko had fallen asleep into Vincent's arms as she cried the whole time and Teresa had already gone home to check on the children. It has been an hour, and with his frustration being left unchecked, Cian was beginning to think of radical ways to win the tournament despite him not being on it anymore.Rather, he just wanted to fight, to fight Asa Narasu and make her regret doing this. "...""Cian. Don't."Just as Cian stood with a gloomy face, Vincent immediately stopped him with a word. "They're not stopping here, aren't they? This will not stop until we win or eliminate them all. If they're going to play dirty, doesn't that mean we have the right to do just that?"Cian said those words with a clear t
Twin Magicians Of The 999th Generation Next In Line
"O, the wind that follows, become my spear, strike true!"Lifting his hand as he aimed it at Red, Bahamut conjured multiple wind spears that materialized above him, launching themselves one by one toward Red.Red would only conjure his windshield once more, repeating the process of creating one larger spear to counterattack. "——Tch." Bahamut clicked his tongue, pushing himself out of the way as he dodged an attack once more. Red had always only come up with a ranged counterattack if he had attacked from a distance, however, even if he did also close the distance and tried to force Red into close combat, his light magic was too fast to dodge. Blinking would do nothing and turn around would only make his back open.The battle duration was an hour, and it had been 30 minutes since their battle started, making this the first battle of the tournament to ever last."What's wrong? You've run out of ideas?" Red scoffed as he was trying to provoke Bahamut. Bahamut himself was aware of it,
Twin Magicians Of The 999th Generation The Strongest Weakest Contestant
With Kurumi winning the following match, the audience cheered as Kurumi made her dramatic exit, lifting her fist as she was teleported out of the arena.Everyone imitated her as her name was cheered on, becoming something of an idol for the masses. For the audience to finally witness the use of multiple elements, it was like watching a hero be born from the fights.Perhaps, she wasn't one, but for the masses that saw her determination to win even against an invisible obstacle, she overcame it."Whoa! The matches are getting interesting! I can't believe that the past ones are being overshadowed by the following ones! Are we going to finally get a winner from another organization?! Will the Red Trackers make their way into the finals?!"Those questions were said by the host to hype the audience and answered by mixed people as they were divided. Some were in disbelief, and some believed that they could win.This was but entertainment for them after all, but for those fighting, it was a
Twin Magicians Of The 999th Generation Ice Cold and Hot Fire
"With the Red Trackers being down to two members, will they be able to last until the very end of this tournament!?"After Kira's delivery to the hospital, the tournament kept on going. Sabrine remained seated among the audience as her right eye glowed, seemingly wearing digital contacts as she kept her eye still. The host announced the continuation of the matches as if nothing happened."Kira was transferred to a hospital. The others are already there. I'm sure she'll be fine. You guys must focus on your fights."Sabrine muttered to herself, her voice only hearing her voice as the audience began to cheer louder and louder."I know. Kira lowered her guard. There are many things that we don't know yet. They have the advantage in terms of information, but I have no intentions of letting up."Magi's voice spoke into the earpiece Sabrine had on her ear. It was illegal to have real-time communication with the outside world before their match, however, Magi was able to slip in a device tha
Twin Magicians Of The 999th Generation A Painful Decision
At the colosseum, the tension in the air had caused the people to silence themselves as they waited for the countdown of the start of the fight. It seemed like the fight would be decided on who would make the first move, and just as the audience broke into a cold sweat, the host brings his raised hand down."FIGHT!"The barriers were lifted and the restrictions were gone just as both of them were. Kira began to run toward her right and Asa also did the same thing, causing them to become trapped at a stalemate as they both rotated at the same time. However, Kira stopped at the spot where Asa was before, claiming the space she had teleported in.At first, the audience and the host were unsure of the reasons for their action, yet soon they would notice it."Huh?! It's been 5 seconds in and no one has activated their ability nor used their Grants!"The host himself announced as time went on, surprisingly in which both are aggressive fighters, becoming passive towards each other."They'
Twin Magicians Of The 999th Generation The Next Match
Before the day had ended, Cian left Ruriko's house at a late hour, giving his farewells to both Ruriko and Mia before he left. Cian felt that Ruriko became more open and genuine with him as they talked, making him feel a bit satisfied besides the fact that he was able to get the weapon without doing anything special.He went home shortly as Magi greeted him at the entrance of the headquarters despite it being past midnight. He was waiting there, leaning against the door of the headquarters, his arms crossed and his eyes looking dead straight at Cian as he walked near."..."Cian stopped right before him, yet Magi didn't greet him. It was but a short moment of silence as each of them looked at the other.As seconds passed, Cian slowly lost his composure, becoming impatient as he stomped. Perhaps Magi was asleep with his eyes open, but he was sure that he is conscious. "Oi! I'm here. What's the silent treatment for?" Cian exclaimed. "——You smell like her now. That Ruriko woman." Magi
Twin Magicians Of The 999th Generation The Past That Haunts
*** "Ugh... A-Achoo!"Immediately sitting up, Cian sneezed as he rubbed his eyes open. He remembered losing consciousness at the bath as his eyes widened, frantically looking at his body."H-Huh? I have clothes..." Cian was already wearing the clothes he had, seemingly cleaned and rather bathed in a sweet fragrance. He scanned the room that he was in and saw a desk beside the bed. There was a note placed, and just as he was about to take it, he would notice someone move from the other side of the bed.It was Mia, it seems like she had fallen asleep in a chair. Although Cian didn't know the reason why she was there, he would stand up and put a blanket to cover her up, letting her comfortably sleep."Geez. What the hell just happened though?"Just as he took the note and opened it, he was able to notice that it was dark from outside the window. It was already night. He remembered going here after lunch."I must have passed out for hours..."He was calm for some reason, looking at Mia
Twin Magicians Of The 999th Generation All Reasons Aside
"Was it really okay sending him on his own?" Kira had her doubts about such an idea, but with Magi having authority over his brother, she couldn't attest to it.Magi knew that he was the only one that could even get in contact with Ruriko without a problem. Besides, it was Kurumi who had made the others agree."We've been there before. Although I could have gone with him there, Cian himself insisted to go alone." Kurumi crossed her arms, her weird position on the chair catching everyone's attention as she straddled it as it was turned around.There were five people in the training room of the Red Trackers. Kira, Vincent, Magi, Kurumi, and Saeko. Violet was still working on certain things like Magi's Grant as they continued to constantly look for a match on the Grant's data. Sabrine was at Teresa's place, sent by Magi to assist her after the number of their customers skyrocketed."Who knows? Maybe he wants to fool around as well. I mean, he's a man so he definitely has some needs as w
Interesting books of the same period
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124 chapters
Prologue: The Twins
Twin Magicians Of The 999th Generation/Sokiiro
"Shit——"Running across the field, his breath ran short. "——I'm out of minimum magic required to use this damn thing!"He was running across a field that was riddled with metal junk that was scattered everywhere. He was being fired from behind by multiple people that chased him down, barely dodging them and hiding behind a large satellite disc.It looked like an abandoned farm, with its crops withering just recently. The masked man wielded two pistols, however, he was unable to use them as the screen that was integrated into them blinked red. [Warning: Minimum Mana requirement is not met. Disabling function.]He holstered it into what seems to be a futuristic belt, vanishing into digital particles upon contact.It was useless to him now, but fighting unarmed against guns would be something blown out of proportion for him. It was just straight-up impossible. "...Ngh. Those bastards..."He cursed them, yet he wasn't just about to lose his wits and hopes yet. Why? Because he was n
The Masked Brothers
In the bustling city of Newyark, situated between the dissolved borders of the Unique and Elemental Magistry, there was a market that thrived in selling technology and goods alike. "Can I buy this... part for sixty CCs? It looks like it was passed down for centuries now!"Offering to buy a part that had looked like junk on a nearby stall, the presumptuous red-haired man passed by with bags on hand. It was Cian who was wandering around the said market."——What do you mean by that?! We've been only able to get that because we had a direct source! If you're not going to buy it for 180 CCs, then get outta here!"Yet, that offer was far beyond acceptable by the vendor, pushing him away as the vendor tried to call customers in."Che! You won't last long in this market if you keep that attitude!"Cian walked away from the vendor while harboring a grudge, verbally retaliating. The paper bags that he was carrying was filled with food and vegetables that he had picked and bought in the marke
"We have a job."Hanging up, Magi placed down the traditional phone before speaking to Cian. Cian had just finished breakfast, and the first thing that comes to greet their day was a job to be done. It was convenient as they needed a job to earn quick money as they held nothing at the moment. Cian had thought of taking over their financials but Magi would refuse and beat him up as he thinks that Cian would use it for fooling around. "What's the job?"Cian asked as he finished up, wearing a coat again that was identical to the previous one. He had a closet full of it. "I don't know. He told us to meet him up at the shop. Could be something that shouldn't be said through the line, anyone could be eavesdropping after all."Magi answered with certainty that it was the reason, and just like Cian, Magi had suited to prepare to seek out their job.Magi would open his closet as well, but there were a lot of stones and important-looking junk parts that were stashed in it as if they were
Central Park was filled with distinct people with distinct appearances. Despite it being a public landmark for everyone to take a stroll on and hang around, it was a notorious place for illegal transactions. "Why would they want to meet us at night...?"Wondering by himself, Magi stayed hidden behind the trees as he waited for Cian's call from their intercom.Before they headed here, Shanti, their employer, and the broker had sent a message through the handheld computer. It was a file containing details about a certain organization that was beginning to work itself up in the ranks of the underground organizations. There were currently only three major organizations in the underground. Black Skull, Viper's Venom, and Pandemonium.Violet Hex would be the recent organization that was able to fill up the slot of the third largest and major organization. It was rumored that they had ten fighters that were more than compatible with their Grants and that, they were capable of clearing
Crossfire Amidst Evil
"Jack'ole Tern at your service, blah."Posing his feet widely apart and his tongue out while pulling down on his face, the man who arrived showed nothing but a crazed face. His hair was a weird variant of a mohawk, but with only three spikes, the back of his head was shaved. Behind him was a gang that wore green headbands to imply that they were from the organization Viper's Venom."——Looks like you didn't learn your lesson last time."From the smoke caused by the explosion, Violet and Bahamut would come out unscathed, protected by the barrier Violet had set before. Magi and Cian were also inside it, but Magi had already cast an inner barrier only for the two of them if the barrier were not enough. Both of them had also begun to wear their masks as other people appeared. It wouldn't be wise to reveal themselves too easily."My! Explosions never do the trick, eh? They always raise a flag that it doesn't work somehow."Jack'ole would take one step forward as he proceeded with his id
Caught In The Aftermath
"Cough... Cough——"Everything was covered by smoke. The concrete ground has shattered, and the fountain that was once there had crumpled into nothing but a pile of degrees with water leaking around it. The twin was able to be shielded from the massive explosion, caught by Bahamut who withstood the blast with his barrier and his body. He exhausted his magic from protecting the two, granting Violet's last wish. He knew that Violet was reminded of the twin brothers she had before, who were killed by a man from an unknown organization and wanted to exact revenge by looking for him. It was the sole reason she became a member, only to die before she could ever exact her revenge. "——Bahamut! You're injured!"Cian would be the first to notice Bahamut's state. His mouth and nose were bleeding, and his skin was pale. They were symptoms of Mana Deprivation that could lead to paralyzation, or worse, death. "Geez. You guys act like her brothers..."Bahamut would only smile at them, confusing
The Philosopher's Deal
In the technological era of Areia, Technological Magistry has been the leading city after its advancement to the skies. With many people working premium jobs and living in such comfort, only those who are rich in both wealth and ideas can climb and be one of the elevated society. Technological Mages were inventors that had aspires to make a world where the Talentless are not oppressed by those with power but rather seen as an equal.They were formerly only a group that favored the Talentless, but now it was but a mixed race of mages and normal humans, bound together by their technology. The Talentless were what they called those who were unfortunate enough to be born without magic. They were discriminated against in the older era, but now they were considered to be equal by most as they were the ones who invented the innovative technology that forever changed mankind. However, regardless of the massive changes, the history of the Two Great Magicians remained. They were the Two G
Keeping Them Under Wraps
Even in the world of a post-apocalyptic society, there were still governments that formed themselves to create a sense of unity. With other cities embracing anarchy, there were still cities that had been guarded not only by Sentient Guards due to their trade but by also human forces that tried to track down the roots of crime to prevent them. They had no specific names but people of the underworld had called them Dogs, as they would sniff out the crimes and criminals alike out of their den.Small organizations were caught by them, but when it comes to large organizations, they become powerless due to their ability to blend and hide their trade.It was truly a contrast in power, however, the police were not a force to reckon with as they wielded special authority with not only Grants but with Magic as most of them wielded Unique Magics capable of catching criminals off guard.They were the highest form of security next to Sentient Guards, but as long as one steers away from them, it
Rising From The Rubble
With the memories left in the burning embers of the past wars between the rising underground organizations, Violet Ghaani, became an orphan in Newyark after her parents were killed in a battle. It was but a reckless war that involved taking away innocent lives, ending up as but an ongoing occurrence. The Police were incapable of tracking down these large organizations whose tracks were everywhere, and despite the Sentient Guards being recent, were incapable of tracking the culprits down as well. Wars between underground organizations were hard to track down, as most of the time they would happen in areas far from the city, a place far from the police's jurisdiction.Regardless, there were infamous people with bounties placed on their heads, dead or alive.Violet was one of those, a rookie with the lowest bounty starting with 100,000 CCs, and Bahamut being thrice as that. They were considered criminals that had committed endangerment and destruction, making their bounty smaller as
With Better Insight
Three days later, Bahamut was now able to be released from the hospital. "Ah, sir. It's all been paid."The nurse would dismiss their payment with a swipe, canceling the transfer."——Huh? That's weird. We haven't given you a single coin yet."Leaning towards the registry of the hospital, Cian was confused as to how did such a thing happen. He still had the bill that summed up all of the expenses, pertaining to almost 10,000 CCs. It should have been required when paying someone's bill, but to think that someone was able to pay it regardless was unusual."There was a tall man with tattoos all over his arms that came here just yesterday and paid the amount due under the name Bahamut. It's all paid, sir."The nurse behind the registry was somehow stressing out that it was paid and that there shouldn't be any problems as she looked at Cian. It was obvious that something was up."A tall man with tattoos...?"Cian would only walk back slowly as Magi arrived with Bahamut in a wheelchair.


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Able to use read and understand resistant measurements using DMM.
The Build Inspector will oversee all Quality activities within the Bio cleanroom, responsible for the verification of flight hardware to Drawing in line with Work Instruction, Processes and Procedures. This will includes the raising and control of Non-conformance reports against complaints..
Working in a Bio class 7 Cleanroom.


text:
30 Infections in the compromised host
The human body has a complex system of protective mechanisms to prevent infection. This involves both the adaptive (cellular and humoral) immune system and the innate defence system (e.g. skin, mucous membranes). (These have been described in detail in Chapters 910 and 11.) So far, we have concentrated on the common and serious infections occurring in people whose protective mechanisms are largely intact. In these circumstances, the interactions between host and parasite are such that the parasite has to use all its guile to survive and invade the host, and the healthy host is able to combat such an invasion. The focus of this chapter involves the infections that arise when the host defences are compromised, resulting in the host–parasite equation being weighted heavily in favour of the parasite.
The compromised host
Compromised hosts are people with one or more defects in their body's natural defences against microbial invaders. Consequently they are much more liable to suffer from severe and life-threatening infections. Modern medicine has effective methods for treating many types of cancers, is improving organ transplantation techniques and has developed technology that enables people with otherwise fatal diseases to lead prolonged and productive lives. A consequence of these achievements, however, is an increasing number of compromised people prone to infection. In addition, viral infections including HIV and HTLV result in a compromised immune system referred to as AIDS and adult T-cell leukaemia/lymphoma (ATLL), respectively.
The host can be compromised in many different ways
Compromise can take a variety of forms, falling into two main groups:
• defects, accidental or intentional, in the body's innate defence mechanisms
• deficiencies in the adaptive immune response.
These disorders of the immune system can be further subclassified as 'primary' or 'secondary' (Table 30.1):
• Primary immunodeficiency is inherited or occurs by exposure in utero to environmental factors or by other unknown mechanisms. It is rare, and varies in severity depending upon the type of defect.
• Secondary or acquired immunodeficiency is due to an underlying disease state (Table 30.2) or occurs as a result of treatment for a disease.
Table 30.1 Factors that make a host compromised
Factors affecting innate systems
Complement deficiencies, phagocyte cell deficiencies
Burns, trauma, major surgery, catheterization, foreign bodies (e.g. shunts, prostheses), obstruction
Factors affecting adaptive systems
T-cell defects, B-cell deficiencies, severe combined immunodeficiency
Malnutrition, infectious diseases, neoplasia, irradiation, chemotherapy, splenectomy
Table 30.2 Infections that cause immunosuppression
Mycobacterium tuberculosis
Mycobacterium leprae
Congenital rubella
Epstein–Barr virus
HIV-1, HIV-2
HTLV-1
Brucella spp.
Primary defects of innate immunity include congenital defects in phagocytic cells or complement synthesis
Congenital defects in phagocytic cells confer susceptibility to infection, and of these perhaps the best known is chronic granulomatous disease (Fig. 30.1), in which an inherited failure to synthesize cytochrome b245 leads to a failure to produce reactive oxygen intermediates during phagocytosis. As a result, the neutrophils cannot kill invading pathogens.
Figure 30.1 Bilateral draining lymph nodes in an 18-month-old boy with chronic granulomatous disease. Abscesses caused by Staphylococcus aureus had developed in both groins and had to be surgically drained.
(Courtesy of A.R. Hayward.)
The central role of complement in the innate defence mechanisms is undisputed, and inability to generate classical C3 convertase (see Ch. 10) through congenital defects in the synthesis of the early components, particularly C4 and C2, is associated with a high frequency of extracellular infections.
Secondary defects of innate defences include disruption of the body's mechanical barriers
A variety of factors can disrupt the mechanical non-specific barriers to infection. For example, burns, traumatic injury and major surgery destroy the continuity of the skin and may leave poorly vascularized tissue near the body surface, providing a relatively defenceless site for microbes to colonize and invade. In health, the mucosal barriers of the respiratory and alimentary tract are vital to prevent infection. Damage sustained, for example, through endoscopy, surgery or radiotherapy, provides easy access for infecting organisms. Devices such as intravascular and urinary catheters, or procedures such as lumbar puncture or bone marrow aspiration, allow organisms to bypass the normal defences and enter normally sterile parts of the body. Foreign bodies such as prostheses, e.g. hip joints or heart valves, and cerebrospinal fluid (CSF) shunts alter the local non-specific host responses and provide surfaces that microbes can colonize more readily than the natural equivalents.
The adage 'obstruction leads to infection' is a valuable reminder that the defences of many body systems work partly through the clearance of undesirable materials, e.g. by urine flow, ciliary action in the respiratory tract, and peristalsis in the gut. Interference with these mechanisms as a result of pathologic obstruction, central nervous system dysfunction or surgical intervention tends to result in infection.
Primary adaptive immunodeficiency results from defects in the primary differentiation environment or in cell differentiation
The major congenital abnormalities arising in the adaptive immune system are depicted in Figure 30.2. A defect in the stromal microenvironment in which lymphocytes differentiate may lead to failure to produce B cells (Bruton-type agammaglobulinaemia) or T cells (DiGeorge syndrome).
Figure 30.2 The major primary cellular immunodeficiencies. The deficiency states (shown in purple boxes) derive either from defects in the primary differentiation environment (bone marrow or thymus) or during cell differentiation (shown as dashed arrows derived from the differentiation state indicated).
Differentiation pathways themselves may also be affected. For example, a non-functional recombinase enzyme will prevent the recombination of gene fragments that form the B-cell antibody or the T-cell receptor variable regions for antigen recognition, with a resulting severe combined immunodeficiency (SCID).
The most common form of congenital antibody deficiency – common variable immunodeficiency – is characterized by recurrent pyogenic infections and is probably heterogeneous. Although the number of immature B cells in the marrow tends to be normal, the peripheral B cells are either low in number or in some cases absent. Where present, they are unable to differentiate into plasma cells in some cases or to secrete antibody in others.
Transient hypogammaglobulinaemia of infancy, characterized by recurrent respiratory infections, is associated with a low serum IgG concentration, which often normalizes abruptly by 3–4 years of age (Fig. 30.3).
Figure 30.3 Serum immunoglobulin concentrations in a boy with transient hypogammaglobulinaemia compared with the range of normal controls. The patient developed mild paralytic polio when immunized at 4 months of age with live attenuated (Sabin) vaccine.
Immunoglobulin deficiency occurs naturally in human infants as the maternal serum IgG concentration decays. It is a serious problem in very premature babies as, depending on the gestational age, maternal IgG may not have crossed the placental barrier.
Causes of secondary adaptive immunodeficiency include malnutrition, infections, neoplasia, splenectomy and certain medical treatments
Worldwide, malnutrition is common and the most important cause of acquired immunodeficiency. The major form, protein–energy malnutrition (PEM) presents as a wide range of disorders, with kwashiorkor and marasmus at the two poles. It results in:
• drastic effects on the structure of the lymphoid organs (Fig. 30.4)
• gross reductions in the synthesis of complement components
• sluggish chemotactic responses of phagocytes
• lowered concentrations of secretory and mucosal IgA
• reduced affinity of IgG
• in particular, a serious deficit in circulating T-cell numbers (Fig. 30.5), leading to inadequate cell-mediated responses.
Infections themselves are often immunosuppressive (see Table 30.2), and none is more so than HIV infection, which gives rise to AIDS (see Ch. 21). Neoplasia of the lymphoid system frequently induces a state of reduced immunoreactivity, and splenectomy, for whatever reason, results in impaired humoral responses.
Figure 30.4 Thymic histology in normal children and children with protein–energy malnutrition (PEM). (A) Normal thymus showing a cortex and medullary zones. (B) Acute involution in PEM characterized by lobular atrophy, loss of distinction between cortex and medulla, depletion of lymphocytes and enlarged Hassall's corpuscles. C, cortex; CT, connective tissue; H, Hassall's corpuscle; L, lobule; M, medulla.
(Courtesy of R.K. Chandra.)
Figure 30.5 The proportion of T cells is decreased in malnourished patients compared with healthy controls. B-cell counts are usually unaltered, and lymphocytes lacking T- and B-cell markers are increased.
Treatment of disease can also cause immunosuppression. For example:
• Cytotoxic agents such as cyclophosphamide and azathioprine cause leukopenia or deranged T- and B-cell function.
• Corticosteroids reduce the number of circulating lymphocytes, monocytes and eosinophils and suppress leukocyte accumulation at sites of inflammation.
• Radiotherapy adversely affects the proliferation of lymphoid cells.
Therefore a patient receiving treatment for neoplastic disease will be immunocompromised as a result of both the disease and the treatment.
It is important to recognize immunodeficiencies and to understand which procedures are likely to compromise the natural defences of a patient. Due to improvements in medical technology, many immune defects, particularly immunosuppression resulting from radiotherapy or cytotoxic drugs, are transient, and patients who survive the period of immunosuppression have a good chance of a complete recovery.
Microbes that infect the compromised host
Immunocompromised people can become infected with any pathogen able to infect immunocompetent individuals as well as those opportunist pathogens that do not cause disease in a healthy person. They may be lethal when the host defences are lowered. Different types of defect predispose to infection with different pathogens depending upon the critical mechanisms operating in the defence against each microorganism (Fig. 30.6). Here, we will concentrate mainly on the opportunist infections and refer to other chapters for information about other pathogens.
Figure 30.6 Ecthyma gangrenosum in a child with Pseudomonas septicaemia associated with immunodeficiency.
(Courtesy of H. Tubbs.)
Infections of the host with deficient innate immunity due to physical factors
Burn wound infections
Burns damage the body's mechanical barriers, neutrophil function and immune responses
Burn wounds are sterile immediately after the burn is inflicted, but inevitably become colonized within hours with a mixed bacterial flora. Burn injuries cause direct damage to the mechanical barriers of the body and abnormalities in neutrophil function and immune responses. In addition, there is a major physiologic derangement with loss of fluids and electrolytes. The burn provides a highly nutritious surface for organisms to colonize, and the incidence of serious infection varies with the size and depth of the burn and the age of the patient. Topical antimicrobial therapy should prevent infection of burns of < 30% of the total body area, but larger burns are always colonized. Non-invasive infection is confined to the eschar, which is the non-viable skin debris on the surface of deep burns. It is characterized by rapid separation of the eschar from the underlying tissue and a heavy exudate of purulent material from the burn wound. The systemic symptoms are usually relatively mild. However, organisms can invade from heavily colonized burn eschars into viable tissue beneath and rapidly destroy the tissue, converting partial-thickness burns into full skin-thickness destruction. From here, it is a small step to invasion of the lymphatics and thence to the bloodstream or direct invasion of blood vessels, and to septicaemia. Septicaemia in patients with burns is often polymicrobial.
The major pathogens in burns are aerobic and facultatively anaerobic bacteria and fungi
The most important pathogens in burn wounds are:
• Pseudomonas aeruginosa and other Gram-negative rods
• Staphylococcus aureus
• Streptococcus pyogenes
• other streptococci
• enterococci.
Candida spp. and Aspergillus together account for about 5% of infections. Anaerobes are rare in burn wound infections. Herpesvirus infections have been reported and are most likely due to reactivation at a damaged skin site.
P. aeruginosa is a devastating Gram-negative pathogen of burned patients
P. aeruginosa is an opportunist Gram-negative rod that has a long and infamous association with burn infections. It grows well in the moist environment of a burn wound, producing a foul, green-pigmented discharge and necrosis. Invasion is common, and the characteristic skin lesions (ecthyma gangrenosum) that are pathognomonic of P. aeruginosa septicaemia may appear on non-burned areas (see Fig. 30.6). Host factors predisposing to infection include:
• abnormalities in the antibacterial activities of neutrophils
• deficiencies in serum opsonins.
Added to these are the virulence factors of the organism, which include the production of elastase, protease and exotoxin. This combination makes P. aeruginosa the most devastating Gram-negative pathogen of burned patients. Treatment is difficult because of the organism's innate resistance to many antibacterial agents. A combination of aminoglycoside, usually gentamicin or tobramycin, with one of the beta-lactams such as azlocillin, ceftazidime or imipenem is usually favoured, but several units have reported strains resistant to these agents.
It is virtually impossible to prevent colonization. Prevention of infection depends largely on inhibiting the multiplication of organisms colonizing the burn by applying topical agents such as silver nitrate.
Staph. aureus is the foremost pathogen of burn wounds
The most important predisposing factor to Staph. aureus infection in burns patients appears to be an abnormality of the antibacterial function of neutrophils. Infections follow a more insidious course than streptococcal infections (see below), and it may be several days before the full-blown infection is apparent. The organism is capable of destroying granulation tissue, invading and causing septicaemia. Staph. aureus infections of skin are discussed in detail in Chapter 26. Treatment with antistaphylococcal agents such as cloxacillin or nafcillin (or a glycopeptide if methicillin-resistant Staph. aureus is isolated) should be administered if there is evidence of invasive infection. Every effort should be made to prevent the spread of staphylococci from patient to patient. Although transmissible by both air-borne and contact routes, the contact route is by far the more important.
The high transmissibility of Strep. pyogenes makes it the scourge of burns wards
Strep. pyogenes (group A strep) infections of skin and soft tissue are discussed in some detail in Chapter 23. Strep. pyogenes was the most common cause of burn wound infection in the pre-antibiotic era and is still to be feared in burns wards. The infection usually occurs within the first few days of injury and is characterized by a rapid deterioration in the state of the burn wound and invasion of neighbouring healthy tissue. The patient may become severely toxic and will die within hours unless treated appropriately. Strep. pyogenes rarely infects healthy granulation tissue, but freshly grafted wounds may become infected, resulting in destruction of the graft. Every effort should be made to prevent spread. Penicillin is the drug of choice for treatment, and erythromycin or vancomycin can be used for penicillin-allergic patients.
Beta-haemolytic streptococci of other Lancefield groups (notably groups C and G) and enterococci are also important pathogens of burn wounds.
Traumatic injury and surgical wound infections
Both accidental and intentional trauma destroy the integrity of the body surface and leave it liable to infection. Accidental injury may result in microbes being introduced deep into the wound. The species involved will depend upon the nature of the wound, as discussed in Chapter 26.
Staph. aureus is the most important cause of surgical wound infection
Staph. aureus surgical wound infection (see Ch. 36) may be acquired during surgery or postoperatively and may originate from the patient or from another patient or staff member. The wound is less well defended than normal tissue; it may have a damaged blood supply and there may be foreign bodies such as sutures. Classic studies of wound infections have shown that far fewer staphylococci are needed to initiate infection around a suture than in normal healthy skin. Wound infections can be severe and the organisms can invade the bloodstream, with consequent seeding of other sites such as the heart valves, causing endocarditis (see Ch. 29) or bones, causing osteomyelitis (see Ch. 26), thereby further compromising the patient.
Catheter-associated infection of the urinary tract is common
Urinary catheters disrupt the normal host defences of the urinary tract and allow organisms easy access to the bladder. Such catheter-associated infection of the urinary tract is especially common if catheters are left in place for > 48 h (see Ch. 20). The organisms involved are usually Gram-negative rods from the patient's own faecal or periurethral flora, but cross-infection also occurs (see Ch. 36).
Staphylococci are the most common cause of intravenous and peritoneal dialysis catheter infections
Intravenous and peritoneal dialysis catheters breach the integrity of the skin barrier and allow organisms from the skin flora of the patient or hands of the carer easy access to deeper sites. Staphylococci are the most common cause of infection, but coryneforms, Gram-negative rods andCandida are also implicated.
Coagulase-negative staphylococci, particularly Staph. epidermidis, account for more than 50% of the infections (Table 30.3). These opportunists are members of the normal skin flora and for many years were considered to be harmless. However, they have a particular propensity for colonizing plastic and can therefore seed sites adjacent to plastic devices and thence cause invasive infections. Their virulence factors are not well understood, but their ability to produce an adhesive slime material and grow as biofilms on plastic surfaces is likely to be important. Infections are characteristically more insidious in onset than those caused by the more virulent Staph. aureus, and recognition is hampered by the difficulty in distinguishing the infecting strain from the normal flora. Treatment is also difficult because many Staph. epidermidis carry multiple antibiotic resistances, and agents such as a glycopeptide (vancomycin or teicoplanin) and rifampicin may be required (see Ch. 33). Whenever possible, the plastic device should be removed.
Table 30.3 Percentage of infections caused by Staph. epidermidis in patients with plastic devices in situ
Infection of:
Infections caused by Staph. epidermidis (%)
Prosthetic heart valve
Early (< 2 months postoperatively)
Late (> 2 months postoperatively)
Prosthetic hip
Cerebrospinal fluid shunt
Peritoneal dialysis related
Intravascular catheters
Data from Gemmell and McCartney.
Infections of plastic devices in situ
The technical developments in plastics and other synthetic materials have enabled many advances in medicine and surgery, but in the process have produced further ways of introducing infectious agents. Staph. epidermidis is an important cause of infection of cardiac pacemakers, vascular grafts and CSF shunts.
Staph. epidermidis is the most common cause of prosthetic valve and joint infections
Patients with prosthetic heart valves or prosthetic joints are compromised by:
• the surgery to implant the prosthesis
• the continued presence of a foreign body.
Staph. epidermidis is again the most common pathogen, gaining access either during surgery or from a subsequent bacteraemia originating from, for example, an intravascular line infection. Endocarditis associated with prosthetic heart valves is discussed in Chapter 29.
The most common complication of joint replacement is loosening of the prosthesis, while infection is the second most common complication and is much more likely to lead to permanent failure of the procedure. The difficulties of treatment have been outlined above, but there is understandably great reluctance to remove a prosthetic device, even though it is sometimes the only way to eradicate an infection.
Infections due to compromised clearance mechanisms
Stasis predisposes to infection, and in health the body functions to prevent stasis. In the respiratory tract, damage to the ciliary escalator predisposes the lungs to invasion, particularly in patients with cystic fibrosis, who are infected with Staph. aureus and Haemophilus influenzae and later with P. aeruginosa (see Ch. 19).
Obstruction and interruption of normal urine flow allows Gram-negative organisms from the periurethral flora to ascend the urethra and to establish themselves in the bladder. Septicaemia is an important complication of urinary tract infection superimposed on obstruction.
Infections associated with secondary adaptive immunodeficiency
The underlying immunodeficiency state determines the nature and severity of any associated infection, and in some cases infection is the presenting clinical feature in a patient with an immunologic deficit. However, septicaemia and related infectious complications of immunodeficiency are most commonly encountered in patients hospitalized for chemotherapy for malignant diseases or organ transplantation. In these patients, infection continues to be a major cause of morbidity and mortality (Table 30.4). Increasingly, these infections are iatrogenic and caused by opportunist pathogens acquired in hospital.
Table 30.4 Examples of opportunistic pathogens in immunocompromised hosts
Gram-positive
Coagulase-negative staphylococci
Streptococci
Listeria spp.
Nocardia asteroides
Mycobacterium avium-intracellulare
Gram-negative
Enterobacteriaceae
Legionella spp.
Bacteroides spp.
Candida spp.
Aspergillus spp.
Cryptococcus neoformans
Histoplasma capsulatum
Pneumocystis jiroveciia
Strongyloides stercoralis
Herpesviruses, e.g. HSV, CMV, VZV, EBV, HHV-6, HHV-7, HHV-8
Hepatitis Cb
Polyomaviruses, e.g. BKV, JCV
Adenoviruses
HIVb
a Formerly P. carinii. BKV, BK virus; JCV, JC virus; CMV, cytomegalovirus; EBV, Epstein–Barr virus; HHV, human herpesvirus; HSV, herpes simplex virus; VZV, varicella-zoster virus.
b HIV and HCV have been transmitted via organ transplantation and unscreened blood.
Haematologic malignancy and bone marrow transplant infections
A lack of circulating neutrophils following bone marrow failure predisposes to infection
Susceptibility to infection of patients with leukaemia is primarily due to the lack of circulating neutrophils that inevitably follows bone marrow failure. Septicaemia may be the presenting feature, but is much more common when the patient has been exposed to chemotherapy to induce a remission of the disease (remission-induction chemotherapy). Neutropenia, defined as a count of < 0.5 × 109 neutrophils/L, may persist for a few days to several weeks. Similarly, prolonged periods of neutropenia occur after bone marrow transplantation.
The length of time over which the patient is neutropenic influences the nature of any associated infection and the frequency with which it occurs. For example, fungal infections are much more common in patients who are neutropenic for more than 21 days. Although Gram-negative rods such as Escherichia coli and P. aeruginosa from the bowel flora have in the past been the most common cause of septicaemia in neutropenic patients, Gram-positive organisms such as staphylococci, streptococci and enterococci are also important. Staph. epidermidis septicaemia associated with intravascular catheters (see above) is common. Infections caused by fungi are also increasing, partly because more patients are surviving the early neutropenic period with the aid of modern antibacterial agents and granulocyte transfusions. Viruses such as CMV infections are an important feature of bone marrow transplantation and are associated with graft-versus-host disease as well as immunosuppressive therapy. In addition, adenovirus, EBV and BK virus infections may be seen, especially in allogeneic bone marrow transplant recipients.
Solid organ transplant infections
Most infections occur within 3–4 months of transplantation
Suppression of a patient's cell-mediated immunity is necessary to prevent rejection of a grafted organ, and the cytotoxic regimens used usually suppress humoral immunity to some extent as well. In addition, high doses of corticosteroids to suppress inflammatory responses are required. The combination of these factors results in a severely compromised host, and those that have an effect on infection in recipients of solid organ transplants include:
• the underlying medical condition of the patient
• the patient's previous immune status
• the type of organ transplant
• the immunosuppressive regimen
• the exposure of the patient to pathogens.
The organisms that cause the most common and most severe infections are shown in Table 30.4. Some of the viral infections are latent and reactivate when cell-mediated surveillance is suppressed.
From 3 to 4 months after transplantation, the risk of infection is reduced, but remains for as long as the patient is immunosuppressed.
HIV infection leading to AIDS
The clinical definition of AIDS includes the presence of one or more opportunistic infections
People with AIDS are often infected concomitantly with multiple pathogens, which they fail to eradicate despite prolonged, appropriate and aggressive antimicrobial chemotherapy. Most of the pathogens involved are intracellular microbes that require an intact cell-mediated immune response for effective defence. As the HIV-infected individual progresses to AIDS (see Ch. 21), organisms that are usually controlled by cell-mediated immunity are able to reactivate to cause disseminated infections not seen in the immunologically normal individual. Improved immune surveillance as a result of antiretroviral therapy has reduced the incidence of infections that are the hallmark of AIDS including Candida, Kaposi's sarcoma and other opportunist pathogens described in more detail below.
Many of the pathogens that cause infections in the immunocompromised host (Table 30.4) are described elsewhere in this book.
Other important opportunist pathogens
Candida is the most common fungal pathogen in compromised patients
This yeast is an opportunist pathogen in a variety of patients and in various body sites. It is the cause of:
• vaginal and oral thrush (see Ch. 21)
• skin infections (see Ch. 26)
• endocarditis, particularly in intravenous drug users (see Ch. 29).
Candida manifests itself in different ways depending upon the nature of the underlying compromise:
• Chronic mucocutaneous candidiasis. This is rare and is a persistent but non-invasive infection of mucous membranes, hair, skin and nails in patients, often children, with a specific T-cell defect rendering them anergic to Candida (Fig. 30.7). It may require repeated or long-term treatment with azole antifungal drugs. Diminished sensitivity to these agents may occur after repeated use.
• Oropharyngeal and oesophageal candidiasis. This is seen in a variety of compromised patients, including HIV-infected individuals (Fig. 30.8), people with ill-fitting dentures, diabetes mellitus or on antibiotics or corticosteroids. Oropharyngeal candidiasis generally responds to treatment with antifungal mouthwashes (nystatin or an azole compound). Those cases which do not respond can be treated with fluconazole. Oesophageal candidiasis requires systemic therapy.
• Gastrointestinal candidiasis. This is seen in patients who have undergone major gastric or abdominal surgery and in those with neoplastic disease. The organism can pass through the intestinal wall and spread from a gastrointestinal focus. Antemortem diagnosis is difficult, and as many as 25% of patients do not have any symptoms in the early stages of disease. If there is dissemination from the gut, blood cultures may become positive and Candida antigens may be detectable in the serum. A high index of suspicion is required to initiate antifungal therapy early in these patients, but disseminated disease is often fatal.
• Disseminated candidiasis. This is probably acquired via the gastrointestinal tract, but also arises from intravascular catheter-related infections. Patients with lymphoma and leukaemia are most at risk. Blood-borne spread to almost any organ can occur. Infections of the eye (endophthalmitis;Fig. 30.9) and the skin (nodular skin lesions; see Ch. 26) are important because they provide diagnostic clues, and without these the non-specific symptoms of fever and septic shock make early diagnosis difficult. Immunocompromised patients are often given antifungal therapy 'blindly' if they have a fever and fail to respond to broad-spectrum antibacterial agents (Fig. 30.10).
Figure 30.7 Chronic mucocutaneous candidiasis in a child with impaired T-cell response to antigens.
Figure 30.8 Candida oesophagitis. Endoscopic view showing extensive areas of whitish exudate.
(Courtesy of I. Chesner.)
Figure 30.9 Candida endophthalmitis. Fundal photograph showing areas of white exudate.
(Courtesy of A.M. Geddes.)
Figure 30.10 Neutropenic patients succumb very rapidly to infections, and decisions to treat have to be made on an empiric basis. This figure shows one example of such a decision-making tree. GVHD, graft-versus-host disease.
(Adapted from: Rogers.)
Cryptococcus neoformans infection is most common in people with impaired cell-mediated immunity
C. neoformans is an opportunistic yeast with a worldwide distribution. It can cause infection in the immunocompetent host, but infection is seen more frequently in people with impaired cell-mediated immunity. The onset of disease may be slow and usually results in lung infection or meningoencephalitis; occasionally other sites such as skin, bone and joints are involved (see Ch. 26).
C. neoformans can be demonstrated in the CSF and is characterized by its large polysaccharide capsule (see Fig. 24.6). Rapid identification can be made by antigen detection in a latex agglutination test using specific antibody-coated latex particles. Treatment involves a combination of amphotericin and flucytosine (see Ch. 33) and can be monitored by detecting a fall in CSF antigen concentration. The prognosis depends largely upon the patient's underlying disease; in the severely immunocompromised, mortality is approximately 50%. In patients with AIDS it is almost impossible to eradicate the organism even with intensive treatment. Fluconazole can be given as post-treatment prophylaxis.
Disseminated Histoplasma capsulatum infection may occur years after exposure in immunocompromised patients
This is a highly infectious fungus that causes an acute but benign pulmonary infection in healthy people, but can produce chronic progressive disseminated disease in the compromised host. The organism is endemic only in tropical parts of the world and notably in the so-called 'histoplasmosis belt' of the central USA, particularly in the Ohio and Mississippi river valleys. The natural habitat of the organism is the soil. It is transmitted by the air-borne route and the fungal spores are deposited in the alveoli, from whence the fungus spreads via the lymphatics to the regional lymph nodes. As disseminated disease may occur many years after the initial exposure in immunocompromised patients it may present in patients who have long since left endemic areas. The infection may occur in HIV-infected individuals who have visited such regions.
Cultures of blood, bone marrow, sputum and CSF may yield Histoplasma, but biopsy and histologic examination of bone marrow, liver or lymph nodes is often required to make the diagnosis (Fig. 30.11). Approximately 50% of cases of progressive disease in the immunocompromised are successfully treated with amphotericin. Itraconazole can be given for post-treatment prophylaxis.
Figure 30.11 Histologic section of the lung showing yeast forms of Histoplasma capsulatum. Methenamine silver stain.
(Courtesy of T.F. Sellers, Jr.)
African histoplasmosis, caused by Histoplasma duboisii, is found in Equatorial Africa. Patients may present with localized cutaneous or disseminated disease.
Invasive aspergillosis has a very high mortality rate in the compromised patient
The role of Aspergillus spp. in diseases of the lung has been outlined in Chapter 19, but this fungus is now increasingly reported as a cause of invasive disease in compromised patients, usually in profoundly neutropenic patients or those receiving high-dose corticosteroids (Fig. 30.12). LikeHistoplasma, aspergilli are found in soil, but have a worldwide distribution. Infection is spread by the air-borne route, and the lung is the site of invasion in almost every case. Dissemination to other sites, particularly the central nervous system (Fig. 30.13) and heart, occurs in about 25% of compromised individuals with lung infection. Diagnosis involves microscopy, culture, antigen detection and PCR on bronchoalveolar lavage specimens. Lung biopsy may be required to make a tissue diagnosis.
Figure 30.12 Chest radiograph showing invasive aspergillosis in the right lung of a patient with acute myeloblastic leukaemia.
(Courtesy of C. Kibbler.)
Figure 30.13 Numerous septate hyphae invading a blood vessel wall in cerebral aspergillosis. (Periodic acid-Schiff stain.)
(Courtesy of W.E. Farrar.)
Invasive aspergillosis has a high fatality rate in the compromised patient. Prophylactic antifungal agents such as caspofungin, posaconazole and voriconazole, early diagnosis and institution of treatment using an intravenous lipid formulation of amphotericin B known as liposomal amphotericin B complexes or AmBisome (see Ch. 33), together with a reduction in corticosteroid and cytotoxic therapy wherever possible, appear to improve the prognosis. Outbreaks of hospital-acquired infection have been reported (see Ch. 36), especially in relation to recent building work.
Pneumocystis jirovecii (formerly P. carinii) only causes symptomatic disease in people with deficient cellular immunity
P. jirovecii is an atypical fungus which appears to be widespread; a large proportion of the population has antibodies to the organism, but it only causes symptomatic disease in people whose cellular immune mechanisms are deficient. There is therefore a high incidence of P. jiroveciipneumonia in patients receiving immunosuppressive therapy to prevent transplant rejection and in people with HIV. It is very rare to find Pneumocystis infection in any other site in the body, but the reason for this is unknown.
Diagnosis is not easy and requires a high index of suspicion. The symptoms are non-specific and can mimic a variety of other infectious and non-infectious respiratory diseases. In addition, unlike the other fungi described above, the organism cannot be isolated in expectorated sputum using conventional culture methods, and invasive techniques such as bronchoalveolar lavage or open lung biopsy are required. In samples obtained by these techniques, the organism can be demonstrated by silver or immunofluorescent stains (Fig. 30.14). DNA amplification by the polymerase chain reaction improves the sensitivity of the diagnostic tests.
Figure 30.14 Darkly staining cysts of Pneumocystis jirovecii in an open lung biopsy from an AIDS patient with pneumonia. (Grocott silver stain.)
(Courtesy of M. Turner-Warwick.)
Treatment is with high dose co-trimoxazole (trimethoprim- sulfamethoxazole). Pentamidine is an alternative (see Ch. 33). Adjunctive corticosteroid therapy is given in moderate to severe infections in HIV co-infected individuals. Co-trimoxazole is used prophylactically.
Nocardia asteroides is an uncommon opportunist pathogen with a worldwide distribution
The family Actinomycetes, relatives of the mycobacteria, but resembling fungi in that they form branching filaments, contain two pathogenic genera, Actinomyces and Nocardia. N. asteroides infections have been reported in the immunocompromised, especially in renal transplant patients. The lung is usually the primary site, but infection can spread to the skin, kidney or central nervous system (Fig. 30.15). As with Aspergillus, hospital outbreaks of nocardiosis have been described.
Figure 30.15 Pulmonary nocardiosis. Chest radiograph showing a large rounded lesion in the right lower zone with multiple cavities.
Nocardia can be isolated on routine laboratory media, but is often slow to grow and is consequently easily overgrown by commensal flora. Therefore the laboratory staff should be informed if nocardiosis is suspected clinically, so that appropriate media are inoculated. The organism is a Gram-negative branching rod and weakly acid fast (Fig. 30.16).
Figure 30.16 Nocardia asteroides in sputum. (A) Acid-fast stain. (Courtesy of T.F. Sellers, Jr.) (B) Gram's stain.
(Courtesy of H.P. Holley.)
Sulphonamides or co-trimoxazole are the drugs of choice, but treatment can be difficult and various other regimens involving tetracycline, aminoglycosides or imipenem have been described.
Mycobacterium avium-intracellulare disease is often a terminal event in AIDS
Although mycobacterial infections are well documented in immunosuppressed patients, the association between AIDS and mycobacteria includes disseminated infection with Mycobacterium tuberculosis and Mycobacterium avium-intracellulare (Mycobacterium avium complex or MAC). These organisms can be isolated from blood cultures from patients with AIDS. M. tuberculosis has been described in detail in Chapter 19. M. avium-intracellulare belongs to the so-called 'atypical' mycobacteria or mycobacteria other than tuberculosis (MOTT). It resembles M. tuberculosisin that it is slow-growing, but it is resistant to the conventional antituberculosis drugs. Multidrug therapy with combinations such as clofazimine or rifamycin derivatives together with macrolides such as azithromycin or clarithromycin, quinolones, isoniazid, ethambutol, cycloserine or pyrazinamide have been recommended.
Protozoa and helminths
Cryptosporidium and Isospora belli infections cause severe diarrhea in AIDS
Cryptosporidium (Fig. 30.17) is a protozoan parasite that causes human disease, and is well known to veterinarians as an animal pathogen. It causes significant but self-limiting diarrhea in healthy normal people (see Ch. 22), but severe and chronic diarrhea in people with AIDS. Highly active antiretroviral therapy in individuals with AIDS infected with Cryptosporidium has been reported to improve the diarrhea symptoms. Paromomycin reduces oocyst output but does not clear infection. Nitazoxanide is effective in HIV-negative patients but is only partially active in those co-infected with HIV. Isospora belli (Fig. 30.18) is a parasite very similar to Cryptosporidium and also produces severe diarrhea in people with AIDS. Unlike Cryptosporidium, however, it is susceptible to co-trimoxazole.
Figure 30.17 Numerous organisms in the brush border of the intestine in cryptosporidiosis.
(Courtesy of J. Newman.)
Figure 30.18 Human coccidiosis, with a single Isospora belli organism within an epithelial cell and a chronic inflammatory reaction in the lamina propria.
(Courtesy of G.N. Griffin.)
Cyclospora cayetanensis, also related to Cryptosporidium, likewise produces prolonged and severe diarrhea in immunosuppressed individuals. Co-trimoxazole treatment is effective. Ciprofloxacin is partially effective.
Infections with microsporidia also cause diarrhea in people with AIDS and other immunosuppressed patients. Enterocytozoon bieneusi is the most common cause, although Encephalitozoon intestinalis also occurs. Albendazole treatment is effective against Encephalitozoon intestinalis but has disappointing activity against Enterocytozoon bieneusi. Where feasible, immune reconstitution is the mainstay of treatment.
Immunosuppression may lead to reactivation of dormant Strongyloides stercoralis
Strongyloides stercoralis is a parasitic roundworm that remains dormant for years following initial infection, but may be reactivated to produce massive autoinfection in the immunosuppressed patient. Although rare in the UK and most of the USA, it should be borne in mind in patients who have lived in endemic areas such as the tropics and southern USA, even if this was many years before their immunosuppression. Human T-cell lymphotropic virus type 1 (HTLV-1) infection is associated with disseminated strongyloidiasis due to the modified immune response to this enteric helminth. The lungs, liver and brain are the most common organs affected.
Certain virus infections are both more common and more severe in compromised patients, and regular surveillance is critical
The virus infections that are more common or more severe in the compromised patient (see Table 30.4) have been described in detail elsewhere in this book. Many of these represent reactivation of latent infections. Pre-transplantation baseline serology is carried out to determine both the donor and recipient status for a number of virus infections, including HIV, hepatitis B and C, CMV, EBV and HSV.
Suppression of specific virus infections using antiviral agents is part of the management of the recipient in conjunction with regular virological surveillance post-transplantation using viral genome or antigen detection methods.
As part of a pre-emptive treatment strategy, blood samples are collected for early detection of viraemia or antigenaemia which precedes disease. For example, transplant donors and recipients are screened for CMV IgG. CMV causes a broad spectrum of clinical disease in this setting, including pneumonitis, oesophagitis, colitis, hepatitis and encephalitis. If there is a transplant mismatch, i.e. the donor is CMV IgG positive and the recipient CMV IgG negative, the infection may be acquired from the donor organ or bone marrow. If possible, transplant centres try to avoid this situation, as the risk of a primary CMV infection in the first month post-transplantation is extremely high, as is the morbidity and mortality. In this case, CMV DNA monitoring is carried out on blood samples on a regular basis post-transplantation to detect early infection and start antiviral therapy as soon as possible. Some centres offer antiviral therapy in the immediate post-transplant period in this clinical setting to delay the onset of infection to a time when the recipient is less immunosuppressed. CMV IgG positive recipients are at risk of reactivation or reinfection and will also be monitored regularly post-transplantation. A primary CMV infection is usually detected around 4 weeks, compared with reactivation at around 6–8 weeks, post-transplantation, respectively.
Antiviral prophylaxis for HSV reactivation that may occur in the immediate post-transplantation period is often given to bone marrow transplant recipients for prolonged periods post-transplantation. Aciclovir is given at a low dose and is effective in preventing HSV and VZV reactivation. Virus surveillance is therefore not carried out, but if a breakthrough infection occurs it is important to collect material from the lesions for virus isolation or genome sequence analysis to determine the antiviral susceptibility. Herpetic lesions can be persistent and involve the lips, oesophagus and other parts of the gastrointestinal tract, and may cause a pneumonitis, hepatitis or encephalitis.
Herpes zoster, a reactivation of VZV infection, may occur within a few months post-transplantation, affecting the skin dermatome supplied by the involved nerve. Sometimes the distribution may be multidermatomal and dissemination can occur to other sites.
HHV-6 and HHV-7 infection, reinfection or reactivation has been reported in transplant recipients, in particular with neurologic conditions including encephalitis. HHV-8 has been associated with the development of Kaposi's sarcoma (KS) in individuals with AIDS as well as classic and endemic KS in HIV-uninfected individuals.
EBV infection can lead to tumour development
EBV infection has been associated with the development of Hodgkin's disease, non-Hodgkin's lymphomas in individuals with HIV infection, post-transplantation lymphoproliferative disease and smooth-muscle tumours in immunosuppressed children. EBV-associated post-transplant lymphoproliferative disorder (PTLD) has a broad spectrum of clinical syndromes ranging from infectious mononucleosis to malignancies containing clonal chromosomal abnormalities with a high mortality rate, especially with the monoclonal tumours. The risk factors recognized for PTLD development in solid organ transplant recipients include post-transplantation primary EBV infection, mismatched donor and recipient CMV status, CMV disease, and intensity and type of immunosuppressive therapy. With respect to EBV infection, EBV-susceptible recipients have a 10–76-fold higher risk of PTLD compared with recipients with previous EBV exposure.
As the two peaks of primary EBV infection are in children and adolescents, the incidence of PTLD is higher in paediatric transplant recipients. In addition, without an effective cytotoxic T-cell response due to post-transplant immunosuppression to prevent graft rejection, the EBV-infected B lymphocytes may proliferate in an uncontrolled fashion. This results in B-cell hyperplasia with CD20-positive lymphocytes that ranges from polyclonal and benign to developing a monoclonal or oligoclonal B-cell lymphoma. The prevalence of PTLD in paediatric liver transplant recipients ranges from 4% to 14%, depending on the immunosuppressive regimen. Retrospective studies have shown that up to 50% of paediatric transplant recipients with primary EBV infections are at risk of developing PTLD. The infection may be acquired in the community or, in the transplant setting, from the donor organ or blood products. The natural history of EBV infection and pathophysiology of post-transplant EBV-driven lymphoproliferation is not well understood.
Diagnostic criteria for EBV-associated PTLD have been developed. However, in the absence of randomized, placebo-controlled trials, there is little information on the efficacy of specific treatment protocols. The treatment of PTLD includes reducing immunosuppression to allow a better host response to control the infection, although there is a risk of rejecting the graft, using rituximab, an anti-CD20 monoclonal antibody that targets the B cells with the EBV receptor, and chemotherapy. Treatment of post-transplant lymphomas by adoptive transfer of EBV-specific cytotoxic T lymphocytes has been reported.
Respiratory virus infections
Immunocompromised patients, especially transplant recipients, are at increased risk of pneumonia and death if they develop respiratory tract infections with viruses such as RSV, influenza, parainfluenza and adenoviruses. Preventive measures include influenza immunization, prophylaxis with palivizumab, an RSV-specific monoclonal antibody that is used in specific clinical settings, and early diagnosis of an upper respiratory tract infection using sensitive tests such as viral genome detection. There are some specific antiviral treatments that include oseltamivir for influenza and ribavirin for RSV infections.
Adenovirus infection has a high mortality rate
Primary and reactivated adenovirus infections can result in disseminated disease in immunocompromised hosts, in particular paediatric and adult bone marrow transplant recipients. Hepatitis and pneumonia are most frequently reported. Again, adenovirus surveillance is often carried out in centres by collecting blood samples post-transplantation which are tested for adenovirus DNA in order to detect early viraemia. Where adenovirus viraemia is detected, management options include reducing immunosuppression and treating with an antiviral agent such as ribavirin or cidofovir. However, there are few reports of successful outcomes in patients with disseminated infections.
Hepatitis B and C infection in transplant recipients
Hepatitis B virus infection has an immunopathologic pathogenesis, with jaundice occurring after cytotoxic T cells have lysed the hepatitis B surface-antigen-bearing hepatocytes. The virus is integrated in the hepatocytes after acute hepatitis B. Bone marrow transplant recipients with evidence of previous, not current, hepatitis B infection are likely to suffer a hepatitis B reactivation post-transplantation. They will be asymptomatic as they are immunosuppressed and will not mount a cytotoxic T-cell response until they have engrafted. It is at this stage they will become symptomatic, develop jaundice and the morbidity and mortality can be high. Antiviral prophylaxis with antiviral agents such as lamivudine or tenofovir is given to prevent reactivation, together with HBV DNA monitoring. Antiviral treatment will be given pre- and post-transplant if a transplant recipient has a current HBV infection, i.e. is hepatitis B surface antigen positive.
The most common reason for liver transplantation in the USA and Europe is hepatitis C-related end-stage liver disease. HCV reinfection of the graft post-transplantation is common and within 5 years nearly one-third of these transplant recipients may develop cirrhosis and subsequently suffer liver decompensation and lose their graft.
Hepatitis C virus infection is also associated with veno-occlusive disease in bone marrow transplant recipients. Venous congestion occurs in the liver due to a non-specific vasculitis and results in liver necrosis. Multiorgan failure can be precipitated due to increased capillary permeability throughout the body.
Polyomaviruses can cause haemorrhagic cystitis and progressive multifocal leukoencephalopathy
BK or JC viruses are polyomaviruses acquired via the respiratory tract that lie latent in the kidney, and may be detected in the urine of bone marrow transplant recipients (see Ch. 20). BK viruria is associated with haemorrhagic cystitis.
JC virus can reactivate and disseminate to cause central nervous system infections such as progressive multifocal leucoencephalopathy (PML) in individuals with AIDS. However, since the advent of highly active antiretroviral therapy resulting in higher CD4 counts and suppressed HIV load, PML is seen less often.
• A compromised person is one whose normal defences against infection are defective. Immunodeficiencies may involve the innate or adaptive immune systems and may be primary or secondary.
• Compromised patients can be infected with any of the pathogens capable of infecting immunocompetent individuals. In addition, they suffer many infections caused by opportunist pathogens. The type of infection is related to the nature of the compromise.
• Effective antimicrobial therapy is often difficult to achieve in the absence of a functional immune response, even when the pathogen is susceptible to the drug in vitro.
• Important bacterial opportunists include P. aeruginosa, especially in neutropenic patients and those with major burns, and Staph. epidermidis in patients with plastic devices in situ. In AIDS, the predominant bacterial opportunists are intracellular pathogens benefiting from the lack of cell-mediated immunity.
• AIDS, and neutropenia (particularly following cytotoxic therapy), predispose to fungal infections (e.g. Candida, Aspergillus and Cryptococcus) especially when the patient has received previous antibacterial therapy.
• Viral infections are more common and severe in immunodeficient patients than in immunocompetent patients, particularly reactivation of latent infections (e.g. herpes simplex virus, CMV, JC virus).


The Center for Media Freedom and Responsibility (CMFR) is administering the search for the 2nd Sandra Burton Nieman Fellowship sponsored by the Ninoy and Cory Aquino Foundation (NCAF).
As in the program's first year, CMFR will be in charge of the selection process. CMFR will receive applications starting February 20, 2012 (Monday). Deadline for applications will be March 10, 2012 (Saturday). The application form may be downloaded from the link provided below.
Sandra Burton was the Hong Kong bureau chief of TIME magazine who accompanied then opposition leader former Senator Benigno Aquino Jr. on his flight home to Manila on August 21, 1983. The senator was killed on the tarmac upon his arrival. Ms. Burton reported on the assassination and the political turmoil triggered by the death of the opposition leader as well as the events that led to the fall of the Marcos dictatorship in February 1986. She continued to report on the democratic transition and the presidency of Mrs. Corazon Aquino, developing strong ties with many Filipino journalists working during that period.
Ms. Burton passed away on February 27, 2004 in Bali where she lived after retiring from journalism. She left a scholarship fund to the NCAF to support the study of Filipino journalists in the US.
The Nieman Foundation selects about 12 US and 12 foreign journalists for Nieman Fellowships each year. Only full-time journalists (including freelancers) with at least five years' experience are qualified. Those journalists working for the news or editorial departments of newspapers, wire services, radio, television, web sites, online publications or magazines of general public interest may apply. Photojournalists, editorial cartoonists, columnists and broadcast producers are also eligible. Public relations practitioners and those who write in or for organizations whose primary business is not the media are not eligible.
Fellows are expected to do academic work at Harvard for two semesters, during which time they may not do professional work and should have obtained clearance from their employers, if applicable.
Philippine Daily Inquirer senior editor and columnist John Nery became the first recipient of the Sandra Burton-Nieman Fellowship for Filipino Journalists.
CMFR is inviting you to apply for the fellowship.
1. Download the application form (PDF).
2. Print the form and fill it out using a pen (please print clearly).
Materials must be sent no later than or postmarked by March 10, 2012 (Saturday).
Should you have any questions about the Sandra-Burton Nieman Fellowship for Filipino Journalists, you may email CMFR at staff@cmfr-phil.org. You may also call the following CMFR numbers +63 2 894-1326/894-1314/840-0889 (attention Bryant Macale). Details regarding the Nieman Foundation for Journalism at Harvard are available here.
This is lifted from www.cmfr-phil.org.


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