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    (Original post by Fission_Mailed)
    Nope, the only computer I own is a laptop. The family did have a desktop until last year, but they use laptops/tablets for everything now. It was a piece of crap anyway, the only thing potentially worth salvaging was the RAM but I literally have no idea where that is now, and RAM is cheap anyhow. I'll use my TV as a monitor, but because it's only 720p I'll still need a second monitor for proper HD, if not a 26" one.

    I was thinking of something along these lines: http://www.glhf.co.uk/high/14-glhf-i5-2400.html but I'm not averse to doing a bit of screwdriver work myself if it will save enough to significantly improve any components.
    I'll have a peruse to see what sort of rig I can come up with. I haven't had to work with a constrained budget in a while so it might take some thought. If you're going to be using a 26" monitor (will definetly be at least using 1920x1080, possibly 1920x1200) you may need to either think about spending more money on the rig (you'll need a fairly good GPU to run that kind of res at decent settings), sacrificing graphical quality or getting a smaller panel.

    I'm fairly up to date though as I'm currently in the process of building a new desktop myself. Ordered all the main hardware components over the last two days. Just got to try to source a TJ07 and a powder coater for a bit cheaper and work out what water parts I need.
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    (Original post by RollerBall)
    I'll have a peruse to see what sort of rig I can come up with. I haven't had to work with a constrained budget in a while so it might take some thought.

    I'm fairly up to date though as I'm currently in the process of building a new desktop myself. Ordered all the main hardware components over the last two days. Just got to try to source a TJ07 and a powder coater for a bit cheaper and work out what water parts I need.
    Cheers, appreciate it. I've started to look around, but there is just so much stuff to get through.


    Water cooling.:coma: What are you putting in this thing?
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    (Original post by Fission_Mailed)
    Cheers, appreciate it. I've started to look around, but there is just so much stuff to get through.


    Water cooling.:coma: What are you putting in this thing?
    In the post at the moment is a Crucial 128gb M4 SSD, i5 2500k, GTX 580, 8gb Corsair Vengeance 1600mhz CAS 9 and an Asrock Extreme4 Gen 3.

    I'm necroing my current pump (d5 vario/MCP655), current rad (MCR220 + fans) and PSU. Going to add a thick quad rad, change the CPU waterblock, order a GPU waterblock, order fittings (undecided on black compression fittings or nickel barbs), undecided on finish of the waterblocks nickel/plexi vs nickel/acetal. Water will be blue with tygon 3/8" ID tubing. Have to decide if I'm going all black, black /w highlight of blue or all blue on the sleeving. I still need to order a TJ07 with a few bits and peices and get it powder coated too.

    Once it's build I'll need to order a sheet of aluminium for the final finishing touchs I want to give it to. Think I need to replace my dremel disks as well. My bank balanace is really hating me at the moment.
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    (Original post by RollerBall)
    In the post at the moment is a Crucial 128gb M4 SSD, i5 2500k, GTX 580, 8gb Corsair Vengeance 1600mhz CAS 9 and an Asrock Extreme4 Gen 3.

    I'm necroing my current pump (d5 vario/MCP655), current rad (MCR220 + fans) and PSU. Going to add a thick quad rad, change the CPU waterblock, order a GPU waterblock, order fittings (undecided on black compression fittings or nickel barbs), undecided on finish of the waterblocks nickel/plexi vs nickel/acetal. Water will be blue with tygon 3/8" ID tubing. Have to decide if I'm going all black, black /w highlight of blue or all blue on the sleeving. I still need to order a TJ07 with a few bits and peices and get it powder coated too.

    Once it's build I'll need to order a sheet of aluminium for the final finishing touchs I want to give it to. Think I need to replace my dremel disks as well. My bank balanace is really hating me at the moment.
    :lolwut:

    I don't think I've still felt this clueless after reading something multiple times since revision times. I understand nothing technical about computers. :/
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    (Original post by Medicine Man)
    :lolwut:

    I don't think I've still felt this clueless after reading something multiple times since revision times. I understand nothing technical about computers. :/
    Rubbish person
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    Just discovered this guy, really beautiful music!

    Also, this is an awesome website for getting to grips with some tricky concepts, as much as I love wiki, I find some of the explanations on there are a little bit pants.
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    I got molested by a clown at work today . I was the only guy on tills so Ronald "The Rapist" McDonald chose me to come make friends with (prolly look a bit pervy if he tried hugging all the girls) but I'm scared of ****ing clowns.
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    (Original post by carcinoma)
    I never seem to be affected by things like this when I am actually at work. Its usually when I sit down and think about it that it hits me. What helps me is to talk about the person with colleagues. Hope your ok.
    They were well liked on the ward so we did talk about them. I'm alreet, it just took me aback a bit. It doesn't really help that it's me that has to wash the body etc.


    Really good shift today though, & glad for it.
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    (Original post by Fission_Mailed)
    :unimpressed: How about spreading some of that cash my way?
    I'm still crawling my way out of my overdraft!
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    (Original post by lekky)
    I'm still crawling my way out of my overdraft!
    :console: When do you head back to Glasgae?
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    does anyone know why digoxin is used in AF, yet in toxic doses causes arrythmia please?
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    (Original post by buzzcat)
    does anyone know why digoxin is used in AF, yet in toxic doses causes arrythmia please?
    how much detail are you looking for
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    (Original post by buzzcat)
    does anyone know why digoxin is used in AF, yet in toxic doses causes arrythmia please?
    I'm struggling to think of a single anti-arrhythmic that isn't also pro-arrhythmic.
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    (Original post by John Locke)
    how much detail are you looking for
    Thanks John, go as in depth as you want.

    I understand digi increases intracellular Ca indirectly, which increases the ionotrope and automaticity of the cell... good for CHF, but why is that useful in AF?
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    (Original post by Renal)
    I'm struggling to think of a single anti-arrhythmic that isn't also pro-arrhythmic.
    cool... sorry to be mindless and annoying, but..



    'but why?'
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    (Original post by RollerBall)
    I'll have a peruse to see what sort of rig I can come up with. I haven't had to work with a constrained budget in a while so it might take some thought. If you're going to be using a 26" monitor (will definetly be at least using 1920x1080, possibly 1920x1200) you may need to either think about spending more money on the rig (you'll need a fairly good GPU to run that kind of res at decent settings), sacrificing graphical quality or getting a smaller panel.

    I'm fairly up to date though as I'm currently in the process of building a new desktop myself. Ordered all the main hardware components over the last two days. Just got to try to source a TJ07 and a powder coater for a bit cheaper and work out what water parts I need.
    ooooo have fun, what are the specs? - and what games do you play RB??
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    (Original post by RollerBall)
    I'll have a peruse to see what sort of rig I can come up with. I haven't had to work with a constrained budget in a while so it might take some thought. If you're going to be using a 26" monitor (will definetly be at least using 1920x1080, possibly 1920x1200) you may need to either think about spending more money on the rig (you'll need a fairly good GPU to run that kind of res at decent settings), sacrificing graphical quality or getting a smaller panel.

    .
    Just saw your edit. My budget is moderately flexible, I could definitely spend more, and there's always scope to upgrade, no?
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    (Original post by buzzcat)
    cool... sorry to be mindless and annoying, but..



    'but why?'
    considering the complexity of cardiac electrophysiology and the level of coordination of the molecular and ionic events anything that causes a disruption (i.e. all of the antidysrhythmics e.g. by blocking channels/proteins) is going to knock even normal rhythms out of synch and thus be prodysrhythmic

    (Original post by buzzcat)
    Thanks John, go as in depth as you want.

    I understand digi increases intracellular Ca indirectly, which increases the ionotrope and automaticity of the cell... good for CHF, but why is that useful in AF?
    I'm not an expert or anything on cardiac physiology so i welcome anyone nipping in here to add what they know. I don't think the exact mechanisms are really that clear. At least part of their beneficial effects are due to an increase in vagal tone, although quite weather this is due to K+Na+ATPase inhibition is not clear anywhere i have read. This causes a vagally mediated negatively dronotropic effect which reduces the ventricular rate and thus allows more time for filling to occur and thus improves efficiency despite the continuing AF (of which i think the only clinical indication is rapid persistant AF as CGs aren't 1st line?). This is the basis for which they had previously had some use in terminating SVT although there are much better 'drugs' such as adenosine now! EDIT: not to forget increasing vagal tone also causes a reduction in sympathetic release via autonomic cross talk which also helps to reduce the atrial rate by removing some of the sympathetically mediated positive chronotropy (particularly at atria) and dromotropy (potentiating the parasympathic's AVN effect).

    The common story for its prodysrhythmic nature is a continuation of why it is used for it's inotropic benefit. The intracellular Na+ accumulation caused by over-inhibition of the ATPase is itself positively bathmotropic (i.e. reduced resting membrane potential) thus potentiates any of the other causes of dysrhythmia e.g. ischemia/sympathetic overdrive. The concurrent reduction of the gradient for NCX to act and thus accumulation of intracellular Ca++ is also pro-dysrhythmic at too high a level. This is at least part due to SERCA still hoovering up most of the extra intracellular Ca++ into the SER (it has eyes bigger than its stomach) and the tendency for this store to spontaneous discharge Ca++ when overloaded, particularly during early diastole. This leak of Ca++ stimulates NCX to electrogenically extrude this extra Ca++ and take up extracellular Na+ (recalling the 1:3 stochiometry) thus causing depolarisation (recalling too this is far from the correct point in the cardiac cycle!). If this is sufficient to reach the relative refactory/general threshold it can cayuse EAD/DAD respectively (mainly the latter by simple logic!). This is probably why digoxin overdose has a tendency to produce particular dysrhythmias such as ventricular bigeminy (from the DAD). This is all tightly interlinked e.g. ischemia also partly works via inducing intracellular Na+ accumulation and sympathetic overdrive causing Ca++ accumulation via L-type current carrying Ca++ channels (Cav1.1-1.4) alpha subunit phosphorylation and potentially (in a physiological sense) via increases SER 'leak' through RYR2 phosphorylation [activating](e.g. at ser-2809)/FKBP12.6 phosphorylation [inactivating] etc

    However this is all well and good and all of these play a (probably most significant) role but the rabbit hole goes deeper so to speak and lots of academics argue for other potential factors playing significant/partial roles. Unfortunately i don't have access to my remote access so i can't direct link you to any nice papers but can do tomorrow if you want. Examples of other things that may play a role in digoxins MOA/toxicity pathophysiology include; the signalosome around Na+K+ATPase, the effects on modulating a preexisting system in the body of endogenous glycosides (oubain-'like'), possible intracellular steroidal actions etc. If you want to evaluate your position on things like that there is much literature fun ahead of you .
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    (Original post by John Locke)
    hmmmmmm.
    very interesting stuff thanks for taking the time 'John', and I can see now why digoxin can be prodysrythmic(?) at toxic doses - however I'm still failing to make the deductive leap between increased ic Ca and vagal tone, perhaps it has something to do with the increased ionotrope and baroreceptor reflex?

    anyway thanks for that it's a bit clearer in my mind now... did you do your BSc in cardio by any chance? sounds QI
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    (Original post by buzzcat)
    very interesting stuff thanks for taking the time 'John', and I can see now why digoxin can be prodysrythmic(?) at toxic doses - however I'm still failing to make the deductive leap between increased ic Ca and vagal tone, perhaps it has something to do with the increased ionotrope and baroreceptor reflex?
    i like the baroreceptor idea! i think there may be a direct action on the vagal varicosities though which may or may not be due to the K+Na+ATPase effects of digoxin (e.g. it may be due to one of the other postulated mechanisms by which the glycosides act) but i'd have to look it up as its all speculation and its far from textbook (where it remains 'unknown')

    (Original post by buzzcat)
    anyway thanks for that it's a bit clearer in my mind now... did you do your BSc in cardio by any chance? sounds QI
    alas i am but a (going into) 2nd year so no i don't have any extreme myocardial physiology interest otherwise i would probably be able to offer you something a bit better than the bits and bobs i remember from last year! If you want it at that level i have a few bits and bobs but nothing that you wouldnt be able to find yourself i imagine!
 
 
 
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