Difference between revisions of "938: T-Cells"

Explain xkcd: It's 'cause you're dumb.
Jump to: navigation, search
m (rv)
Line 1: Line 1:
βˆ’
{{comic
+
crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap 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βˆ’
| number    = 938
 
βˆ’
| date      = August 15, 2011
 
βˆ’
| title    = T-Cells
 
βˆ’
| image    = t cells.png
 
βˆ’
| titletext = 'We're not sure how to wipe out the chimeral T-cells after they've destroyed the cancer. Though I do have this vial of smallpox ...'
 
βˆ’
}}
 
βˆ’
 
 
βˆ’
==Explanation==
 
βˆ’
 
 
βˆ’
This is a cancer- and leukemia-related comic. Two characters are having a discussion about a new trial ([https://www.nejm.org/doi/full/10.1056/NEJMoa1103849 Porter et al. NEJM 2011]) in cancer treatment. A trial is done to test a proposed treatment on a select group of patients before approval for the wider patient group.
 
βˆ’
 
 
βˆ’
In this case, the two characters are talking about a trial in which immune cells are taken out of the patient's body and genetically modified. The modified cells are able to both attack the cancer cells and replicate very quickly. However, to make these genetic changes inside the cells, they used {{w|HIV}} as the vehicle to introduce these new genes as it is specialized in invading and modifying immune cells.  HIV is good for this because HIV attacks your T-cells and slowly kills off your immune system. If HIV was used as a {{w|vector (molecular biology)|vector}} to introduce a trait into your T-cells it could express a trait to hunt tumors and since it is already good at changing your T-cells it would be well-suited to this task.
 
βˆ’
 
 
βˆ’
Basically, this treatment seems to replace one terrible disease with another terrible disease. As the title text says, they don't know how to get rid of the modified T-cells after they remove the cancer. And the last part of the title text is a joke, in which the doctor suggests yet another disease, {{w|smallpox}}, to inject into the patient's body.  This is similar to the song {{w|There Was an Old Lady Who Swallowed a Fly}} in which a little old lady who swallowed a fly where each time she puts some other animal in her body to get rid of the last one and eventually she dies.  This is akin to that as you have cancer so you put super-strong T-cells modified by HIV to get rid of them but then you have Leukocytosis so you get smallpox to kill those, and so on.
 
βˆ’
 
 
βˆ’
Cueball possibly could have guessed this because he is familiar with biology according to this comic and one of the most common diseases that attacks T-cells would be HIV.
 
βˆ’
 
 
βˆ’
Although highly expensive (because it currently requires customized set of alterations for each individual cancer), over the next few years subsequent clinical trials revealed the power of these super-strong T-cells (called Chimeric Antigen Receptor T-cells, or CAR T-cells for short) to cure previously uncurable cancers.  For example, in 75 children with previously untreatable leukemia, 4 in 5 had no detectable cancer three months after treatment with CAR T-cells ([https://www.nejm.org/doi/full/10.1056/NEJMoa1709866 Maude et al. NEJM 2013]). More and more different kinds of CAR T-cells are becoming FDA approved to treat a growing number of cancers. Seven years after this cartoon, the American Society of Clinical Oncology chose CAR T-cells as the [https://www.cancer.net/blog/2018-01/car-t-cell-immunotherapy-2018-advance-year 2018 Advance of the Year].
 
βˆ’
 
 
βˆ’
==Transcript==
 
βˆ’
:[Two people are standing facing each other, having a conversation. One is holding a laptop.]
 
βˆ’
:Cueball (with laptop): What's the deal with this leukemia trial? <nowiki>{{Citation: Nejm, Aug 10, 2011}}</nowiki>
 
βˆ’
:Friend: Gotta wait and see.
 
βˆ’
:Friend: Helping the immune system attack tumors has been a longtime research target.
 
βˆ’
:Friend: Lots of promising leads. Often they don't pan out.
 
βˆ’
 
 
βˆ’
:Cueball: What'd these guys do?
 
βˆ’
:Friend: They took some of the patient's T-cells and patched their genes so they'd attack the cancer. That hasn't been enough in the past but their patch also added code to get the T-cells to replicate wildly and persist in the body.
 
βˆ’
 
 
βˆ’
:Cueball: Which worked, but created its own set of problems?
 
βˆ’
:Friend: How'd you guess? But I think the craziest part is the way they insert the patched genes.
 
βˆ’
:Cueball: How?
 
βˆ’
:Friend: Well, think - What specializes in invading and modifying T-cells?
 
βˆ’
:Cueball: Seriously?
 
βˆ’
:Friend: Yup. Must've been a fun conversation.
 
βˆ’
 
 
βˆ’
:[The last panel is set in a doctors office. A patient is sitting on the observation bed talking to their doctor.]
 
βˆ’
:Patient: Ok, so I have blood cells growing out of control, so you're going to give me different blood cells that ''also'' grow out of control?
 
βˆ’
:Doctor: Yes, but it's ok, because we've treated ''this'' blood with HIV!
 
βˆ’
:Patient: Are you sure you're a doctor?
 
βˆ’
:Doctor: Almost definitely.
 
βˆ’
 
 
βˆ’
{{comic discussion}}
 
βˆ’
[[Category:Comics featuring Cueball]]
 
βˆ’
[[Category:Cancer]]
 
βˆ’
[[Category:Biology]]
 
βˆ’
[[Category:Multiple Cueballs]]
 
βˆ’
[[Category:Medicine]]
 

Revision as of 17:33, 11 May 2022

crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap 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crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap 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crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap crap