Alright, what's up internet? We are... How many days into death stranding So medyo ito na yung Kind of mid Mid game, I think or you know It's kind of like they've unlocked the basic stuff So you're kind of understood na Medyo alam mo na how to play And now they're like introducing upgrades To different game concepts For example Hindi na po rulakat na ngayon Like I'm building roads and things like that And I just drop off some stuff with this guy And we've connected him to the network So it's like Everything I've talked about feels like work But at the same time I'm kind of enjoying the work aspect of it Let me just remember what I was supposed to be doing Ano ko may parang I can go here There's like an express delivery here To Lake Nott City But I don't really need to do that I do need to go back to the collector Because I have some cargo for him Maybe I'll do that now Let me just check There's no cargo here I think I checked this last night Before I switched off for the night Let me check anyway We're done with the elders We don't need to pick up stuff for him Five stars na siya Same with craftsmen I don't really want to go to Lake Nott Right Top AGTV So you're asking pa na mag-overclock Usually Like the easiest way would be To use a program like MSI Afterburner Paganon, yes, you do need to run MSI Afterburner Every time na Look at that, 5,771 likes Because I helped contribute to our road I built that road So if you use something like MSI Afterburner You do need to I'll just try to Visit the junk dealer na din See if he needs anything So, yeah, you do need to run MSI Afterburner every time So usually pag start up ng windows Tatag mo na yan automatically Because you set the profiles Ano yung mga settings na Ano yung mga overclock settings mo So, yes Like who made this thing? It's like really out Or is it like just Looking for cargo Top Jazzwave Yes, it's true, you can also set The fan speed for In MSI Afterburner So actually, yes, a lot of people Just use it just for that May just stock settings Default speed ng GPU But they use MSI Afterburner To Change up their Their fan curves Stop computer I haven't been able to Find anything that these guys Need so they won't talk to me You need to usually bring some kind Of cargo And I keep scanning Usually, there's like one in the vicinity PM director Olai But I can bring this na man to Crater Lake I don't even know where Crater Lake is But Far be it for me to leave Cargo around I think that's why this game is bad for me Kasi Laman labas yung paka-OC ko Like even the Used items on the road Gusto ko sila-cunin, tas e-recycle Pasawa di lang sila-kakalat sa daan So it's not really a Alright, let's go to the collector din Ah, good for you Ako, directors ka tinto, pero nagbayad ako I mean, mas it's so bad na man Pero Like 250 bucks or something Pero Yeah, this was free Generator On that generator It was supposed to be free And then nagbago big lang yung epic Without any announcement So yung base game lang naging free So up revin dyan Rocky my brother is still out So it's just me This month again for the game streams And it's really more like a story game Even though there's a big online component Yeah, so a lot of people were kind of Iffy about this game Like when it first came out like two years ago I remember The reviews were like basically I don't know if you like this game Ako naman Like so far I've been enjoying it Even the slow part were like It's really like a walking simulator Yan yung Natandaan ko from one review Talaga described it as a walking simulator So far Yeah, so Epic games is actually around the holidays Parang sakto naman Is this mine? Nope, not mine I have a ladder here near the guy I'm supposed to go to Where's the collector? Straight ahead pa, okay Where is my ladder? Stop John Rubin o siya I know, I know, and I even have the Okay, there's my ladder I even have the extended range one now Yung instead of piling it with cargo It has like extra battery so you can go further It's really like real life It's like a This game is like a drive grab sim And at the same time yung Range anxiety na mga EV owners Kanundin ako sa Kanundin ako sa Sa where I think this one Kanundin ako when I'm riding around in these things Is the collector here? Where is the collector? Gosh darn it Ah no, back there Basically I put a ladder right On top of his house So siguro ito yun Oh yaya, there's my ladder Nobody has used my ladder I hate all of you May rope na, fine Don't use the rope Nobody appreciates my ladder Although to be true I was using this damn ladder I kept falling I don't know but Kusala na yung yung game ano e Kusala na yung yung game Parang tama naman yung pag-apak sa ladder I don't know why I kept falling off Alright, let's give you this The UI of this game is unnecessarily complicated But I don't know if um I don't know if that's because It was developed for consoles So medyo Yeah, delivery Any new missions for me?  I'm sorry bike It's always happened Always And bridge I mean there's never Bridges when you want Oh no I'm stuck in this ravine Actually I really hate visiting this collector guy Because this always happens to me That's the lui I don't want to give up the bike naman There was one time I got stuck Like I was just about to fall So I was on the bike And then I was about to fall And then I was about to fall And so I got off the bike And I'm still basically clinging to the Side of the cliff And I'm like Please don't fall, please don't fall Because I don't want to damage the cargo And in the end I did End up falling down So useless nandin yung pagdita ko Nung motorcycle It's not really the best advertisement for this game Now it's like The fun part is when you get stuck Falling off stuff Punch it Alright I did clear out these guys Last night So there Nobody left anymore Okay but yung nanyang pagkausiko Malabas na I'm gonna pick up some stuff Because you need this stuff too For building the highways And to be honest It's not very efficient If you get it from these guys But it's just like I'm There's a part of me I mean you know it's that video game part of you na Nandin siya sa higay Canang magpulutin It's automatic Parang sayang I'm in John for the 4070ti We can probably get it I mean the one that ASUS sent to us is I mean that one is for review So we do have to give it back But we can get you a 4070ti I mean just let us know the brand We can get it for you Okay it's miss mo inside the mule camp Alright Get that stuff One of three Two of three Where's three of three I'm sure the collector won't mind But it is not my fault Nakula You should read the game Make sure This game looks fun Did you just tune in At that part where I Drop in the ravine And I had to get my bike out Speed Hi You're supposed to accelerate So you could jump that one Now we have to find the way up again People need to build more bridges On that ravine Always man Always Alright there we go Feel bad for the bike ITX addict just wait for the next The next Epic game sale Nakalaman They'll have it As a freebie again I mean so far to be honest I am enjoying the gameplay Even though it's been derided As a walking simulator And stuff like that And a lot of it really does feel like work Build a highway You know you have to You're like a truck driver Ai ai shoot shoot Aww See who is the idiot To put the Ai Like I have lost track How many times That has happened to me See it's not my fault It's the game But I can't figure out where to Like I'm already on the ladder I just want to go down Now I gotta soothe the BB Believe me I get enough of this in real life No don't rate me one star That was not my fault That drop was not my fault That was the game I was already on the ladder I'm sorry I'm supposed to go down I don't know I don't know what happened Okay I'm sorry BB Yeah yeah That's my fault That's basically how I am in real life I just keep shaking the kid until he stops Great parenting Kainis na ngayon ladder na yung Tapagalit ko na ngayon leaching ladder na yung Dismantle ladder Since there's a rope anyway Man That's like the fourth time I swear to God That I've fallen off my own ladder In that spot daw That particular ladder Sorry cargo Is that my fault na partial lang No no I don't want complete order I mean we don't want to obsess over it Yeah no CD key videos For game streams Damn robot So this is like What you're seeing here is like The delivery of one of my robots made Apparently the cargo really got beat up What's up robot I do not go out of my way to Alright Upgraded the collector enough na Easily a full time member of the UCA Not just a Part time Waffle half in half out That's a good point niya magnaya Every time there's a bike in the game Pasok you CD key add The old CD key add Because the latest one wala na Wala na si Rocky the programmer on a bike Okay see I'm going to use this one Na ayah the boat I'm going to send this via boat Since I don't want to go there So and then there's going to be a boat Oh you missed the boat And then since I really got to go back to this other place I'll take this one Oh there's another one Dami Paano I just want to do the main mission na But at the same time Nandun na din Fine Do all of them I swear to God Every time I do something for this guy End up falling down his house Ya see this game is not good for me Lama naman sa lagi ang pakausi ko I like your place collector It's cool but Damn if I just keep Well now with the rope maybe I'll be better Alright so we got to go back to the Distro center Where my bike There my bike Okay that distro center in the In the distance Let's go there first Then we'll go back to the mule camp Then we'll go back here Oh look there Friendly porters there Stop friendly porters Where's the guy I wasn't going to run you over For real Jazzwave what are we going to sell It's hard to find I can't I can't recall if I've seen one on supplier list Pwede naman mga custom order Like if you want one We'll try to find one sa suppliers namin The drivers seem to have gotten better So But like if the question is When are we going to carry them regularly Pag medyo mas may interest From the consumer side So far kasi Wala pa masyado But definitely as a special Special order We can try to get I haven't seen a lot of them in the In the On the supplier list Yeah Intel should be good Especially they've started to Their elder elder Did it Destroyed ba to? Usable ba yan Still a lot about this game Okay this is the next one So this I'll take it na So we don't have to keep coming back and forth It's fine I'm happy with my extended range one But we might want to put Because the distribution center pa siya Hindi pa yung isa Lake not elder engineer Okay let's put this stuff See a lot of the game is just kind of figuring out What to do with the stuff that you find But this is for Should be disposed at the bottom of a crater lake At the bottom of a crater lake Cargo that has been contaminated by Kyrelium and subsequently abandoned Should be disposed at the bottom of a crater lake So it's not deliverable pa la Okay on the off chance like I don't know Do something with it Keep it in the Private locker and that Oh what's this Okay that's the thing I'm supposed to deliver Okay See a lot of the gameplay is just Figuring out Maki around your cargo Next row is my rig competition I'll have to ask the staff But we're open to it I think they had a good time With the previous one And there were some doozies If I remember correctly In the last one The last competition Okay so we're gonna hit the mule camp again To pick up something for the collector And then do the main mission Of going to the Distro hub So opening up another portion of the map So let's do that one first Wait lang Okay Kim director All right punch it Punch it Yay Where is my Ah there on the right From a different Different Pulse box All right pack it up Pack it up We need to Another Supposed to jump this pala Punch it Ah Sorry bike Okay this is for the collector And the collector Old guy Don't need the old guy Okay I'm laughing because I picked up cargo For the place we just came from So we gotta go back to that place Give the cargo Go back to the collector And then do the main mission So I'm laughing because my plan was to Being efficient Parang will just Will just From the collector will do the main mission akagad But then Inya may isa pang Yo don't fall Okay Ano mas keto safely Okay let's go back to this guy And then we will drop that stuff off That bridge very useful thank you All right just drop this thing off Go to the collector And then No this one don't do anything So I don't know So there's a connection level there in the lower right And every time you bring cargo for them it goes up slightly I don't know There's a mosquito guys Tried to get the mosquito But Means we need more spray So Once you get Any place up to five stars You get a special star Which goes on your uniform I don't know If that does anything to the game I mean you do Get more backstory of the game Pero I'm not sure if Collector elder Craftsman Craftsman Film director Lake nut city All right finally All right go back to the collector Then do the main mission So I don't know Is there any incentive Aside from the in game Lower Of getting five star Of getting all five stars But I'd like to I don't know feeling ko parang malam Mass effect na Oops sorry guys Okay where are we going In mass effect kasi if you Like if you fully upgrade Like when you're preparing for the big battle With the With the With the reapers Parang if you're able to Like the success of the final battle Rest a lot on how well you upgraded Your own forces I have no idea if it's something like that But Slowly but surely So yeah Like what incentive is to get everybody Five stars And I'm OC but I'm not like that OC But I try as much as possible To be honest to get Mostly five stars Okay na Where's the rope There's the rope Okay let's just deliver this thing And then get on to the Main quest Don't fall To be fair that rope is a lot more reliable Than my Than my ladder Alright deliver cargo Partial delivery lang possible I don't know where they kept it So the connection level will go up Just B Alright Story mission time Last night all I did was Last night all I did was Elder film director film director Ah see this one We are really going there so let's bring that This stuff too We can use that to upgrade Or to build another highway So what's unique about this game is that Other real players Real people contribute to the Structures in the game So I'm making highways but they're also Helping make The highways I make also appear in The other versions of the game The ones being played by other people So I mean that's the whole shtick right I mean it's a game about coming together And that Gameplay theme is Reflected in the gameplay mechanic na You know you're not in this alone And we're about to use one of the roads now Sup guys Okay I thought you were bad guys But I wasn't going to run you over Okay highway Jump Ah crikey I think I built this highway Alright see so my name yeah I built this highway Ah see last night wala pa tong bridge na to So somebody else made this highway Good job And that was it Medya malayo pa eh Where's the next Oh BTs? Oh it's BT time So happy na na Wait na Where's the next Road maker thingy Okay we gotta get up here actually Oh there there there's There's the next road thingy I do have some metals and stuff Just small stuff But always good to know where the next one is So that we know where we need to Bring stuff to This this this this Okay contribute a little bit Okay and I do take note How much stuff Like old school pen and paper Like how much stuff we need DC crystals 500 Just rounded up metals On one And ceramics Takes a lot to build a road guys One two Okay But that means the Road is down Ah we need to go there We need to go there Up there Oh and to be honest I'm not very prepared Like I only have one ladder Wasn't thinking this through na Sanain ako na puro Mga highways and stuff na dinadahanan Oh there's a rest spot And Somebody kindly left their bike In case we need it There's a bridge there Ouchie Oh here okay Oh there Thank you to whoever put that bridge Should go and like Oh not too bad Thought I need to Rough it up pero Thanks to that bridge Okay ba gaya And I think we've The scanning for cargo I think we've managed to Stop moniker I think we've managed to avoid the BT Ouch The BTs are like The boogie men The ghosts I mentioned in the title This game the graphics I'm not super impressed With the detail like up close But itong mga vistas na parang Ginga in the horizon And it's the mountains and stuff I mean like that Look at that view And then or itong ano That weather station Those are pretty good The up close details You're on the bike and stuff It's normal I mean I'm not blown away I mean this is a 4k But It does the vistas well Especially like I love these mountain scenes Oh there's some cargo What's that? Metals lang 100 La yun naman to go out of my way Okay let's deliver cargo I wish though The hotspot for these things Like you can collect them when you're on the bike You gotta get super close Time for us to stop Not raining anymore And here we are Omnis music Deliver requested cargo The graphic for the power exoskeleto Looks like You have inflatable balloons on your legs Yes it is I didn't drop that thing Should be in perfect order Yes it is Gotta thank that guy who Did that bridge What's this about special alloys Oh BCC Floating carrier What that Drowning Thanks man Okay Keep it up and we'll be finished Before you know it The weather station's forecast should be visible to everyone On the chiral network now Yourself included You can access them via your couplings Could be useful when plotting your routes You know I remember Playing the original dead space Maka takot nga siya Even then See that I made a mistake that was for the other place As this Timefall farm Construction safe house Say again, why not Let's do that one first We have the safe house Of it I need a PCC I already have a PCC Let's say floating carrier Thing With minimal effort If one's not enough for your needs You can hook it up to another And take two Just keep in mind that carriers require A steady supply of chiral crystals to operate Make sure you have enough to get where you need to go Okay that's good Why do I need all these special alloys What going on Okay let's leave you there And there Okay What I do with all these special alloys Ah Well how can I cause everything is so Okay wait lang Alright that's cool Okay wait Gotta adjust my cargo to bring that other stuff I don't know though Should I just Should I just float I just got rid of my That wasn't so smart I just got rid of my Man I just got rid of my Bike Why did I do that Sometimes Okay Can I load it onto the carrier Yes Alright alright Alright alright We can pick this up Okay Sam Find your way to the building site Use your math and compass if you don't Remember the way I'll contact you with additional instruction Why you always Okay it's just two Okay I need to Wow Way to make me feel more Like a pack mule Where's the site Man why did I get rid of my bike Ah there's a bike down there I can't remember correctly Oh my goodness How far away is this Okay that's in 200 meters And dude Alright let's just get the carrier First let's serve You got to go Sam First equip your PCC And select safe house Okay may do Fine Bridge no Safe house And then build I guess we want to build now Build Building When I first When I first played Dead Space Wala pang streaming I do remember the old one freaked me out Sooner rather than later It's that to me let's do it What's going on Complete structure special alloy One two three Special alloy Special alloy And chiralium crystal Why did you not give me the chiral crystals Dynamic ko po yung stash ko Ah so that's what I knew Like we were seeing different safe houses On the road Just na Is that an order Fine It's wild though that At least in this game we had the technology Where everything just gets magically built Or magically printed Why did I get rid of my bike Keep the show on the road Okay here's a cutscene from BB28's life Which we're still trying to figure out The last cutscene parang it was like Your dad, actually this is your dad And he's Running sort of like with a gun I think Like I bet the twist is The baby you're carrying is actually you So there's a lot of time jumping in this game That's not a spoiler I don't know I'm just like wildly speculating Apparently the BB28's Records are classified Alright so I was a dumbass And I cancelled the bike I don't even know how I managed to do that Okay but Let's get back on the road I do enjoy these Wide open At the mountains I mean you know It's not to like Come on Sam it's not like you're carrying anything Again I'm I don't quite know why They were so keen on using Norman Reedus For this one I mean not that I have anything against Norman Just like the characters he's a bit weird Or parang the way Parang reluctant hero type Parang di naman siya convincing for me To be fair maybe it's not Reedus' fault Yung story mentioned malabu Talagay Again this one is a spoiler alert Parang your mom Turns out to be The president of the US But the way the characters talk about it Parang It's like The president wants to see you But they all know that the president is your mom So I mean the way it's structured Parang it's supposed to be a big reveal Parang nagulat ka for the player But it just seems weird because Di naman natural the way the Other characters are talking about that relationship Oh yung there was an online generator pa Potec naman Why did I cancel that But there was I remember there was another I mean I can't make my own yes I can fabricate another one But it's kind of cheap And annoyed with myself I can um Ah okay thanks for that Takota 2k So it's like we wanted you for something else But then this is what we have Do I want to go up there? Why did you put a ladder there? Now I'm curious May it make sense maybe in another project Parang dito lang di siya ba Okay our bot Bot like Grabe yung Ah but the bot doesn't contribute to the Connection status The bot is cute though You can see the pop I feel the way it moves it's a her You can see her pop out I don't know there's something about the gate Or makes you think female Or why not Let's visit a timefall farmer And we'll go back for the other thing We said that's what we just did Yup that's what we just did Alright let's get the show on the road Are we walking? Walking at old school style Okay I'm done with that Pagbabana I'll get you later Pagbabana This one I do need because I think I'm out Like I don't have I forgot to make How are my boots? I always have extra boots though That one I'm proud to say Alright Okay we're hoofing it We're hoofing it How far? 1.5 clicks That's nothing man 1.5 clicks For Sam Porter bridges And this is the aspect of the open world That I liked it It's up to you to figure out How you wanna Approach Should I put a ladder there Should I put a Rope We reduced ourselves to animals Focused only on the here And now Okay okay no need to get Philosophic love me I'm just supposed to Just doing my job here Yeah but the graphics Oh okay Okay relax relax The graphics engine renders This kinda Very pretty Close up details Kind of standard Ano na siya for me but Then they do the music Sometimes you just want to take a walk Walks are actually very beneficial for you Until they play the music Ladder time Dinaman The sights you don't see if you just If you just Take your bike on the highway Hi Ochi, this is 4k One of the reasons why I bought Why I've spent a little extra For the director's cut Details are okay Not used to playing with 4k Only recently updated A monitor na kaya mag 4k Like I'm not blown away to be honest By the graphics detail Even on 4k But it's not I mean you know with the monitor And the resolution It does do these kinda Very open Scenes Ganda na pag-a-render na maga nito The in Like super Yung close details Maybe I should Maybe I should Get a bike At the next Oh other bad guys Is that a bad guy?   Usually if you've cleared out all of the They tell you na Parters can now Can now go through the area Didn't seem to be the case though The music has changed so I guess we're in the clear Alright All of the metals go into the back of the truck Biyan Anybody else? No What kind of farmers are it? How can there be allied farmers out here Where there are mules? Now the in-game lore is you can't Yaya Jazzwave Parang It's very clunky Hindi siya yung Hindi siya parang martial arts combat It's really kind of like I'm a porter and I'm a tough guy And like this is my fighting style Parang ganon And I mean I could have tased those guys basically But Satisfying ano yun Mas satisfying yung Back of the truck guys Back of the truck These trucks really fill up fast So All of these materials I'm just basically hoarding them for For the highways Alright Anything behind? Time to hack our resins Don't really care about resins Alright Let's go Let's go to our job Deliver stuff So where were we? Um I should be diligent and go get that stuff Alright Bulagon, leather Hardly hard Ay Where did the thing go? Where did the thing go? Hindi ba may parang chip? Ah, it's the chip downstairs What is going on? There's that chip Ah, I didn't need to go up pala Pick up Got the chip Chup Ceramics for it Okay, let's go there It's all just gravy Okay The truck Then the truck We will Drive it back to the weather station Time to remember Time to remember that it's the rain now Where's our destination? Oh, that one Sanay bang mules? Yes I just got an e-mail In-in-game e-mail Asking our bots for the best Yes, yes they are Don't knock them bots All of these bits and pieces We need it for the highways Parang walali ang magnaye I haven't really Look look to be honest Pero parang wala Man, that video Performance is way down I can really see you guys Prefer PC related stuff Although, Sandmark was kind enough To send over the stuff So we were I was also kind of curious to try it out But in general That Those kind of things Those kind of videos don't do super well Urban gadgets, Meron Thank you We had another Like lazy cable manager Was also asking about it We try I did drop that off Yes, I can It's clear to me how this Bunch of USB keys Connect everybody to Internet 2.0 Powered by ghost data But Here we are This game really Even story wise Kind of trippy Keeper to get on Amazon Story of our times It's hard for local distributors to compete With Amazon prices And that includes hardware, sugar But I like it When the mule start Chasing after me It's an interesting exploration of The rain that makes things age faster I don't know if the truck can I don't know if the truck can Hold it Hold all of that wheat That's why we need highways Anytime, guys Alright Let's head back to Let's head back to Oh, we can do this one It's like super easy And then pala It's over in Europe It's like so close It's just like Speaking of timefall Less than 500 meters out Hmm Thanks Let's try that Hmm How do we try it? Try it e-drop Oh That's how you use it Idiot How do I Ah, no But then I use chiral crystals Right Linolokok mo ko mamay I don't want to use my chiral crystals I need that stuff for the highway Right Oop oop Okay, it's a bit muddy Oop, it's a bit muddy Aw, thanks, BB I miss my bike Although for most of yesterday, I was Somebody just left it there For most of yesterday, I was Building highways and Being a truck driver and stuff So back to hoofing it Ano mind Oh, but they're scattered all over the place pala Ha, yop yun Wow, it's like really scattered all over the place There's like one up there Another one up there Wow, my goodness And another one over there Like how dedicated am I To this Endeavour Ah, highway Oh, yeah, I'm in time pool It's been a while since I had to worry about time pool I forget like the Damage to this stuff Are we at the sea now? Ah, this is the sea Mm-hmm All muddy and Okay, I'm getting kind of Distracted by Oh, look at the Kyro crystals How far? Technically not that far But I think I have extra boots Oh, on hour 13 na tayo Yeah, that's why You could just keep playing grab driver Mixed in with ghosts Thanks, buddy Oh, damang Kyro crystals in can All right, let's get the last bit And then let's head on in Then we'll go back to the Then we'll go back to the weather station To drop off now that cargo Let's drop a ladder Anong nandiyan na man e Daddy Okay, it's okay that The continuous ruin As long as you don't Drop the cargo, okay na man siya Now, time to get back to the time farm Oh, they're my footprint I've been here before Mosquito And time mosquito spray Terrible Let's see one now Timefall farm Okay, let's head back to the timefall farm first I still don't know why there were mules All right Let's deliver That way you can tell of us Can't keep it acting That goes on the truck It's very difficult, though, to Figure out What You can take Like, in addition To the truck Like, I bet this will, I know I bet I won't be able to use the truck But since I'm like I wanna See what other stuff we can See, weather station Sang na man All right Back to the weather station Online generator Let's charge up first There's one over there Is there one there? Charge you up truck Because you got a long way to go You have a long way to go Bye Jimi Rizo Thanks for stopping by Oh, I see another car The mules again Are they local porters? They don't seem to be Minding me Ah, there's the mule camp Should I just take out the mules now? Wait, there's a bridge Baka I should just, where's the nearest Where's the nearest Highway thingy Dito pa sa coast No, no, not that This one Truck, where's the truck damaged? Time fall All right, we're basically going in the same direction I'm not accelerating To conserve battery I don't know man I don't know if we can make it But I wanna see how far we can get with the mule truck And then we have to become the mule Damn these trucks are slow Everybody near I mean, I guess I could make a Generator Sayang naman Might as well get it Oh shoot, is the car moving Don't move, handbrake, handbrake Not to leave handbrakes in the future That ink line is pretty steep though It's the same The other station did then Okay, let's just get The truck on level ground And then I'll see if I can get that other cargo Here, here At least time fall stop It's always a pain Okay, we got a bunch of cargo for the We got a bunch of cargo for the Weather station I know, I know I think we might make it though Oh yeah, yeah, because there's a generator Up ahead, excellent Thanks mule truck Then we can use this also to get to the Alright Don't panic, don't panic Then we can use this Truck to get to the next To the next The Paver Return, return cargo Gotta get new boots too And look at all that bus cargo Don't do anything That's a whole bunch of stuff man We have to claim these things Alright Okay But now we have a truck Mi ba In case you're wondering Bog is vital to the work of our R&D division Deliver it safely and you might end up contributing To the creation of some new equipment For yourself Don't get me all excited Alright, so we gotta make our way back To the distribution center anyway I hope the truck Can hold all of this Kaya, kaya So I just wanna do like a straight run down here Pwede Like we just go straight down here Alright, let's do it Excited Keep the cargo intact he said Make sure it doesn't Explode he said It's just like a really steep Slowly lang, slowly He's mule trucks man That's pretty amazing Just a little bit Of where I wanted to But at the same time it's pretty good Unless, unless Unless I can't cross here Yun lang Okay, wait, wait, back it up That river looks pretty deep And I already sunk One motorcycle before I mean this is a truck But But I'm trying to be Cautious So if I go straight like this And I hit this bridge We should be good Power on through I kinda enjoy the Nobody telling you How to Go about things You kinda have to plan ahead a bit With the route and stuff Alright, alright Thank you to whoever Made this bridge You're awesome Alright, here we are And let's just make it back to The highway Okay, it's gonna be this one I can see the highway on the horizon And we still Still have enough gas in the tank Good job Alright, now we can offload Offload a bunch of stuff Basically toss everything Like the metals And Oh wow, we're gonna finish up the ceramics No, kawanti nalang Oh, ay, mayroon pa Ceramics, ceramics Kawanti nalang metals Alright, so we can actually go back And finish up this part of the highway Dami kong binigay Carl Crisels, we still need Oh, we need more Oh, mayroon pa dito Wait a minute Paan di na bigay Okay, let's give it first I donated so much, man Alright, let's check to make sure Stop, Anton What monitor? What monitor? Okay, Carl Crisels 60 nalang Sorry, ceramic 60 Metals 700 Sorry, not 831 Carl Crisels went up actually 831, what's my math of kanina? 950 Ah, sorry, what's this? 550 Ah, di atama naman, okay Well, awful by a little bit 531 5 Yeah, 550 Alright, we can bring that stuff Back from the other places Yes Alright, let's get out of time for Let's get back on the highway And you can scoot over to the distribution center Don't destroy the vog Vogs, whatever Yay And this is why we build highways Charge na, charge One ultra wide plus one regular monitor Versus two regular monitors Ah, I'd go with ultra wide You can use ultra wide for gaming and one regular And then Yeah, so one ultra wide and one regular versus two regular We had an ROG one Two years ago I mean like they send it to us for review That sounds pretty good actually Alright, finally in familiar territory Ha, I keep I keep I keep bringing home trucks Ah, look at this man I keep bringing home trucks Like the mule trucks Good day, good delivery No, jump wrap Important Well, take care of yourself Alright, I got a I think I'm being OC I don't want to keep cluttering up the Clutter up the The garage So we're gonna Put this outside Ah, yes, thank you, you're right Alright How many trucks have I stolen from these poor mules? Yes, yes, I agree I agree, I agree Don't worry Well, that's really a magnaya The ROG monitors are a bit pricey Actually, we have um Wait ha Just making sure I didn't leave anything Oh, there's nothing in the truck also Great Yeah, ROG Samsung a bit pricey But You get what you pay for Although Like we have an LG one now The price seems to me not bad For what you get So you really do have to research a bit kung ano yung Available And it is hard to find a good monitor On the cheap side So it's really kind of one of those things You just kind of have to bite the bullet on Alright, thanks so much for joining me guys If you notice, we've been streaming Like a lot lately Because Feb is a very short month And I'm kind of paranoid about Not meeting our Sponsor, so we're taking Kabag may time talaga I stream and so happens That's trending now, so that's what we're doing This week for sure, we're gonna have a video On the price watch video Like is it a good time to buy CPUs and GPUs Based on our tracking Of the largest retailers in the country For the past three months na ata And we have a bunch of other videos In the pipeline Actually a lot of it has been shot na And just needs to edit So yeah, that's it for me Thanks for joining me for another stream Have a good weekend What's left to the weekend


Starting a PhD position after years of being a student and worrying only about attending lectures during your homework and studying for your exams can be detrimental to your productivity. So I'm here to give you some time management tips for new academics. Number one and most important is create a schedule and stick to it. There's nobody who is going to hang over your shoulder until you need to work these eight hours a day. But you're an adult, you have a job, it's your responsibility to make sure your PhD is as successful as it can be. So create a schedule, stick to it, do your daily hours of work. You'll be happy that you did it. Number two, use pomodoros. Pomodoro technique is a very, very simple method of managing your time. You set a timer for 25 minutes or pick a different time if that works better for you. Experiment a little. Oh no, I have to send that email. Scroll it down, forget about it. Focus on the task that you've chosen to work on for these 25 minutes. Check all the things that you thought of and that you urgently had to do. It can wait for these 25 minutes. And you will have had a nice window of time where you can focus on things that you might not want to do otherwise. What I always enjoy doing is creating a reward system. So number three, a reward system can be as playful as you want it to be. I'm going to work 40 hours this week and I'm going to buy myself a chocolate sundae. There are even online services such as Habitica that help you manage your to-do lists and checklists and every single scheduled item that you have to do can be gamified. You can collect points, compare yourself to others in a similar position and in fact a lot of PhD students do do that to make their lives a bit easier and to feel a sense of community. If you want to make it a little bit more modern, you can also use a Kanban board. Create a big board on a poster. You can probably get an extra poster from the printing staff at your institution and just put some sticky notes on them to decide what belongs to which project, what you need to accomplish, what you're doing right now and the most important bit, what you've finished to make yourself feel good. Look at all these things you've done. It really does help and pushes you forward. If you're struggling with writing, then number five is writing tips. There are again many online services that may help you with this. A very popular website is writeordie.com where you can reward yourself for every, let's say 200 words you write.  Or perhaps if you don't write any words in 20 seconds, they'd start getting deleted. There's also a really nice website called For The Words where you get to gamify your writing process, fight monsters, be a part of an RPG community. Number six are browser extensions. Now I know we live in an era of the internet and you are watching this video on the internet, but sometimes you should really stay away from YouTube, Twitter, Facebook, Instagram and news portals. There are many browser extensions for your browser of choice that will block all these social media websites from you and at the same time allow you to browse papers and online resources and databases. Number seven, music. Now there's a lot of research that says that music does make you happier and makes it easier to work. However, when you're trying to focus on something and work on something mentally exhausting, research says that music doesn't help, it makes it harder to focus. So if you're dealing with something very stressful, feel free to turn that music on, but as soon as you get to an important part of your daily work, shut it off, focus, turn on a pomodoro and get on with work. And eight, and I think most important, is be comfortable. There are all these little things in your office that might bother you. Maybe it's the noise from the neighbouring offices. Close the door, perhaps invest in a pair of noise-canceling headphones. Maybe you don't feel all that comfortable with your desk. Ask around, maybe it can be lifted up or put down a little bit. Spend five minutes adjusting your chair so that you don't end up with back pain after a full day of work.  Maybe what works for me is I invested in a pair of fingerless gloves and an office blanket. So when my male colleagues lowered the temperature in the office, I still get to be comfortable and keep writing and keep working. So these were my eight tips for time management for new academics. I hope they help you and I hope you have a very productive time.


I would say I think it's difficult to pinpoint the biggest challenge if the whole process, the whole transport is consisting of a number of links in the chain and the whole chain has to be to its best to have the safe and secure transport. So maybe that is the biggest challenge actually to giving everything, every single bit of the chain to being at the best every time from the beginning where the customers have to give us the information on what they're sending to us, to the EDI exchange between the different parties and in the end also to the operational processes. In relation to what we benefit from these events like this one, I think there's two major benefits. One would of course be that we managed to get the same common view and common understanding on how things are developing a global model together. But the second one is of course also, it would always be inspirational for us to hear what our colleagues, stakeholders and so on do around the world. It inspires us to look at our things back home, we may adjust things, continuous improvement is an important part of our everyday life and we need to keep on finding them, what do you call it? It's the small things that helps us do that.


What's going on everybody got Kyle and Shawn here relating sports cards, and we are ripping 2023 definitive baseball Three box case break number nine. This one is pick your team stop Alexandros with the Brewers got shipe with the twins Charlie C has raised got Christie with the Guardians Edward P has the Rangers Evan L has Reds Tigers Marlins E and J with the D-backs James M has Dodgers Yankees Phillies Jeffrey H has Mets and Cardinals John F has Angels Joshua B has the Giants Lee G has Braves We got leeway H with the Nationals Mike K. Astros miles H has Red Sox A's Nixie Orioles Paul B with the Royals Paul B with the Padres as well Peter M with the Mariners and the Rockies Robert P with the Cubs Rylan P has the Blue Jays Scott F White Sox and Stephen H with the Pirates Ready good luck on this one guys again. We are still trying to fill up a select basketball and prism draft choice It's our next one to go. We are halfway on it 15 to go 15 to go. Thank you, um, Arturo grabbing a spot in Star Wars. I'm out of here Come on a little cardboard. All righty. Good luck guys. Have you been buying all the green to fives Victor? Good luck. Do some definitive box number one Good luck everybody See what we got Good Dolphins Eat First up we have a patch that's what are sorry 15. It's gonna be Salvador Peretz For the Royals there nice little number patch from the light blues 2 out of 15 Salvador Peretz Behind it we have this one's going to be for the Cardinals number to 30 game use mim of Nato Nato for the Cardinals there 18 out of 30 Mr. Aronato Yeah, thank you. Timothy grabbing two spots in the chrome black mixer We're not up to 30 There's forest boy, we got a zander bow guards on the jersey out of 25 that one is a red sock zander There we go red socks 17 out of 25 Can't believe they're still making them Rub it in 17 out of 25 on the zander There we go And to 50 this is gonna be rookie auto adley ruchman. Boom. There we go That is going to the Orioles Who has the os will mag that for you os? Is nick see there we go nick very nice hit there adley ruchman only rookie out of 50 Let's go nick Mag that up for you sir behind it. We have a donny baseball that one's going to be a relic out of 40 It's going to be game use on the bat relic go into the Yankees The Yankees Four out of 40 nice one there It's quite a box. Oh We've got for the diamond bags three out of 10 is rookie auto corbin carol. Oh, what a box For the rookies this one is going to the d-backs Who has then that is going to be a e and j E and j with the uh corbin carol that is number three out of 10 Oh mag that for you sir. What a start Goodness gracious Take it.  We got a uh gold frame auto that one is going to be bryce harper Eight out of 15 on the gold frame for the fillies That is quite a start man three sick cards all back to back Nice one there fillies on the harper to 15 And on the back is going to be dual auto. This one's going to the red socks It's going to be callia strimsky and carlton fisk There we go red socks got the uh zander now. We got the dual auto Nice one there fisk and your strimsky. I'll do it for box one Yeah, no victory. It's all over the place man for sure I mean gold to 15 any any tops gold is the 50. It's not the 10 So it is all over the place. I feel you we got a thick one on the back And two frames two frames two frames No, yeah, we've been hitting today for sure Malone been hitting today Start with the uh thick one That is going to be a helmet relative 50 of wandsoto Game used batting helmet relic there. That is national still on the wandsoto National soda This one there We got a redemption in here too two frames of redemption And another patch card to 30 is going to be ronald akunia Nice one there for the braves the mvp Ronald akunia on the patch Green to 25 is going to be oscar gonzalez working for the guardians On the green Hey, nothing wrong with that man. Nothing wrong with that Yeah, I don't know what was up with that coral. That's kind of weird talking about uh von biller redemption is oh, we got a uh definitive auto ultra patch collection of randia rosa reina There we go race Playoff randy I know uh, I know jaco liked that one. Oh, please don't patch collection randy Don't say his name. Hey, that's fair carl Happens to me There is a jersey auto that was gonna be a 40 palm oleder Put it down bat relic auto to 40 40 brew crew It's from there the hall moleder Sean liked that one We got a first gold frame is going to be flatamere guerrero jr. Number to 20 for the blue jays Nice one there jays the uh homerun derby chant five out of 20 the uh two color patch Nice, uh, vladdy And we have a second gold frame And it is going to be number three out of ten the big hurt Frank thomas there three out of ten for the um white socks Nutrigenics That's right You need it White socks to the night's hit there little frank thomas Not only are you gonna like it? That's what they tell me. I heard him in fluty. Yeah, there's a uh rpa there's going to be for the cubs chris Morel Nice one cubbies on the morel. I didn't know fluty sir color patch. I like those uh wrigglyville jerseys the blue Number to 50 nice one there cubbies And last box here guys box number three of definitive We'll get some flux basketball going next. We'll get on to basketball So we've got some work to do on um Select hobby and draft choice. We're at 15 to go on it 15 to go random team style Good luck on this one guys last box of definitive Start off. We have a matt chatman that one's gonna be for the blue jays on the two of five jersey I don't know if i've ever seen those red and uh white blue jays jerseys in person Nice one there matt chatman two of five Should be a big uh free agent signing this year And this one will be verlander number to 44 the astros on the game use jersey 18 of 40 just in verland. Yeah, it shouldn't be too long. It shouldn't be too long There's one for the yankee is going to be an anthony rizzo number to 30 jersey auto A little bit of a dirty patch there. I just saw something a little bit of a dirty uh game use patch Six out of 30 riz is for the mets number to 50 is going to be rookie auto bret baby The mets for baby another one for the yankees this time it's going to be bernie williams four out of 10 on the jersey auto Of course game used on the jersey Well bernie williams action there yankees again We have a uh definitive auto 25 25 robin yelts robin yelts there for the brewers brewers one of the last teams Hitting pretty decent here little robin yelts. I like that set the most too. They sign the biggest on those Kind of we have a um six of 30 for centenady going to be bernie larkin on the golf ring Hall of Famer for the reds six of 30 Come on bernie larkin Never know And on the back we got for the red socks. It's going to be a dual auto dustin padroia and jason verite That's a cool one there early 2000s red socks four out of 10 for the socks On the dual auto Hey, what's up scott scott, what up? How we doing? How we doing? Good morning? Where are you at scott? air tech and padroia to 10 Alrighty guys, and that will do it that will do it for a definitive um three box case number nine pick your team So let me do a quick hit recap Do a little bit of everything Verlander to 40 jersey we had matt chappen to five on the game used jersey ronald akuny to 30 Nato to 30 and salvi perez the 15 All game used jerseys Had base auto robin yacht to 25 There's bernie williams to 20 or sorry to 10 jersey auto Brett bated to 50 um rizzo 30 Morel rp 8 of 50 to 40 paul moleter got padroia and veritec dual auto to 10 had to 40 donnie baseball bow guards to 25 to 25 That's um oscar gonzalez and to 10 frank thomas Had our gold frames this one was the 20 vladig jr. Jersey auto barry larkin Dual auto was carleton fisk and yastremski had randy rosa rena on the ultra patch collection Auto and a 15 was bryce harper Then our mags we had a um onesoto bat relic or bat um batting Batting helmet relic we had to 10 corbin carol nice one there dvax and we had to 50 adley ruchman on the rookie auto Alrighty Alrighty that will do it for definitive. Give me just a moment here guys. We'll get going on flux


Welcome to MOOC course on Introduction to Proteogenomics. In last few lectures you have heard the technologies perspective, how technologies are evolving, in which way various technology platforms from the genomics and proteomics have contributed for the big data sciences. Today we have a clinician who is going to talk in a very different manner the kind of gap which we see from the clinicians perspective, what should be the questions right questions to be asked and the technologist who are generating data set. So, so far we have studied various diseases in context of big OMEX data, but today the speaker Dr. Sachin Jado will talk to us towards the patient based studies and being a researcher he is also providing the links between research and societal requirements. Our next speaker Dr. Sachin Jado, he is the chief of department of hematology, pediatric oncology and bone marrow transplant division at Fortis Hospital in Bangalore. Dr. Jado will provide the perspective of patients and society as they were and observe them closely every day. He will take us to a journey of how concept of cancer originated, what all limitations, clinicians and researchers faced during early times and how close are we now in terms of understanding various diseases. So, I hope today's talk will take you on a very different journey and eliminate you and challenge you with the thought process, how to design a right clinical study and which way OMEX sciences, OMEX technologies could at least try to fill the gap. So, let us welcome Dr. Sachin Jado for his talk on clinical considerations for OMEX first part. Do you even want to listen to a doctor because you are here for something else right? This is would you would you I mean you have to say yes, do you want to listen to a doctor? How many of you would rather be somewhere else just get over with this? I would assume it is a yes. I am assuming I will move on to the next question before the answer comes in. So, no seriously would you even want to listen to a doctor? How many of you are actually graduates and how many of you are in graduate studies? How many are actually in PhD? And how many are on clinical projects? So, I will tell you why I am asking this question because we have a couple of basic science research projects going on and the rule that I have created which is very uncomfortable for PhD students is before they start the project they will work in the ward for a week with us. Just like you would wish that the doctor comes to your lab so that you can have an intelligent conversation. I truly believe that for you to make effective scientific discoveries you need to understand the population which will ultimately benefit. And the first time we did this with the first batch of PhD students they were with us for a week it was a breast cancer project. They were in the OPD, they fell to the lump, they saw the lady crying, they went to the operation theater and then took that sample and for them it was you know then you have a face to that tissue. And then when they went back and they said you know amongst the four women that lady rapidly growing tumor the cells are growing in cell culture very rapidly.  And that is kind of what I am trying to do today I am a clinician like I said I do not understand what you do although I interact with researchers and try to do something sensible those are my conflicts of interest. And I belong to this department in Bangalore we are five doctors bunch of other clinical guys paraclinical people rest of our oncology colleagues and some administrative colleagues. What do we work for? Why do I do my job?  What do you think? What do you think? Sorry? First society come on here you are not thinking of society. Why do we do it? Why do it? For your satisfaction? Own satisfaction so let us see what we have here. So yeah you are right. So that is the first thing for personal goals. It really is because if it does not delight you you will not endure the gruel of coming at night and you know all of that not being there for social events etc. So of course usually it is personal goals and it is either I am working today to finish my experiment I have a medium term goal I have to finish my PhD postdoc is that right? I want to avoid conflict with my boss I just want to do this today all of us need to earn a livelihood as well very important some of us work for this reason I do that sometimes because I can comfortably say I am busy and and avoid some marriages right? I do not know if you can do that nobody questions me but then there is this other thing with sometimes we think of this sometimes all of us think you know what we have to do something something that will create an impact every once in a while and quite often when we are in this kind of situation we think because normally it is the usual rigmarole but then all of us think when we are outside our usual job that well we should do something new publish something create an impact and maybe impact lives trust me this is what we are going to focus on today I will essentially take you through a story of where clinical oncology was how much time it has taken us and how we are rapidly moving ahead in understanding what is actually happening to our patients so we look at the impact of your work on the lives of patients and these are patients that we deal with on a daily basis you may not encounter them but trust me it is important I will restrict to the kind of work that we do I do not understand solid tumors I do not understand cardiology we restrict ourselves to blood cancers and bone marrow transplantation for today's discussion so how did this whole concept of cancer originate right how did doctors in the past think that well I have five kinds of patients and this person has something else this person has a fever with lymph nodes this person has lymph nodes with no fever maybe this is something else maybe it is not an infection so how did this originate we can only go back to Egyptian mummies right we do not know anything beyond that these are very well preserved human bodies and tuberculosis have been discovered in Egyptian mummies tumors have been discovered so that is the oldest tissue specimen that we have but the oldest recorded case is about 1500 BC and at that time of course nobody knew it was cancer treatment no concept of treatment patients just got comfort care and died right and that description that we have 1500 the tumor whoever was the physician tried to chop off the tumor you can imagine no anesthesia right because they probably thought it is a lump and it is growing so let us just remove it we do not know what it is then theory started coming up after many more years and rather centuries so about a thousand years later Hippocrates the guy who guides our practice he first started writing a lot of things and he wrote about many many things and amongst that he also said that there is a reason why we fall sick and he felt that we have four fluids in the body and if these fluids are imbalanced then we get one sickness or the other if bile goes up this happens if that goes up that happens etc imbalance between the four fluids well he had his theory he really did not have the opportunity to test his theories right but he had his theory like Freud had his theories right and he thought it was imbalance and this theory of cancer actually went on for 1300 years there are four fluids imbalance in the fluid something happens but there were problems with this all of us know that it is not the quantitative increase or decrease in blood and phlegm etc it is something that is happening within that fluid that actually causes a problem and phlegm and bile they probably do not cause cancer but they are affected by cancer so if somebody has a liver tumor or a cholangio carcinoma then the flow of bile will be affected bile does not cause but you know Hippocrates did what he could do he did some I mean he tried to do biopsies but it was not allowed for religious purposes poor guy couldn't do anything but he had some theories which stood the test of time until somebody else came up with another theory and you know doesn't really work this was you know this was supported through the 17th century again problems I am not going to go into the details of these and then Muller said that no no no no it is not fluid these are cells and the problem is with the cells and you can see it is that late it is that late that people realize that is because of cells right it took so many years so the fluid phase if you can call it that endured for 2200 years until somebody figured out it's not the fluid it's the cells in between the fluids right and then you have this poetry by by Omar Khayyam I don't know if anybody has read Rubaiyat and he wrote long long ago that I am sick and tired of doctors and saints I talked to them they give me theories it's junk I go to meet them and I come out from the same door it's bogus right he was frustrated which was understood because nobody knew it and then more and more theories came up somebody thought chronic irritation which is correct in some patients etc and worker was amazing you know he thought that cancer comes from normal cells and irritation of the cell turns it malignant but he was overconfident his king had a laryngeal ulcer he thought this is benign we don't need to operate the king actually died of metastasis and this was probably one of the first doctors who was you know they actually said that he has committed medical malpractice but that's fine you know he had a theory he tried to follow it and he messed up whatever he was accused of malpractice as time went on people thought it's a cancer it spreads with the parasite but slowly people started showing that cancers metastasis not through the parasites but actually through the fluids in the body this is where the era of clinical expertise starts I mean it has been there from the beginning clinical expertise but until here people said okay there are cells and they spread but nothing much more can be done because you can't biopsy you really can't biopsy because it was not known it was not allowed so all that you could do is see what you can listen to what you can and feel what you can make your diagnosis find out is it a TB is it a cancer what is it is it an abscess what's happening and make your best judgment and treat until people started doing autopsy series they started cutting up dead bodies and what's happening so sequential patients having similar signs and symptoms let's do an autopsy let us look at the lymph node and the spleen under the microscope let us see what is happening still you are not allowed to touch and biopsy and living person so you can only do post humorous work and you can't really diagnose a patient who's standing in front of you until that fellow dies right but then there is recorded that about 30 40 years later biopsies were allowed again anesthesia was not common so you can imagine what happened and then you go ahead 25 odd years Dorothea Reed amazing lady brilliant gets a one year fellowship pathology fellowship in Johns Hopkins in that one year in the lymph node she finds some different cells and says hey this is different this is a different kind of lymphoma and that's a different kind of lymphoma and later on this was called Hodgkin and that was called non-Hodgkin lymphoma right brilliant lady but she was a lady so she was not given faculty position she gave birth to a child had to leave her hospital walk off just imagine how faster our knowledge would have grown had Dorothea Reed been allowed to stay on in Johns Hopkins and do more work on lymphomas it still takes 50 years for somebody to classify lymphomas 50 years and even then Rappaport can only divide lymphomas in three subsets he didn't really understand that there are 50 60 70 different kinds of lymphomas and at that time there was no concept that lymphocytes are T and B people just knew there are white cells lymphocytes that they can be divided was not known and when that was known 20 more years later the first proper classification came which was refined but until this point you can imagine 2001 is when I first passed my MBBS so until I passed my MBBS lymphoma diagnosis was based on how the cells look under the microscope that's it restricted to your sensory perception nothing inside is understood RNA DNA proteins everything that you have been hearing for the last 8 days 6 days 5 days was not known until 2001 the first WHO classification nothing it was only 8 years later that WHO said that you know what you can stay in bit different colors and the cells look different and maybe there are different cells and then divided lymphomas very well until then how is it how much is it spread what is happening it was all actually pretty vague to decide how to treat we had to see what is the age how much has it spread there were no better ways of differentiating different diseases because different diseases need different treatment different patients need different treatment but there was no way we didn't have a gene expression profiling until 2001 there was nothing clinically relevant right it was all very vague the way we would plan patient treatment until 2002 or so the first clinically relevant papers started coming out lot of basic science work had gone in until this paper came out and this was the first time somebody showed in what is apparently one lymphoma diffuse large visa lymphoma by gene expression profiling you can divide it into subtypes you can divide it into subtypes right clinically relevant remember and then WHO adapted this five six years later when they revised their classification etc and of course now 2006 actually early this year 2006 version of WHO classification came out and it's all about mutations it's all about mutations that the the subtypes are based on mutations you can imagine it's no more based on how it looks under the microscope it's based on your clinical genomics correct but even in that we have a problem so we'll come to that because there are multiple patients with a particular mutation who behave differently they may not respond to treatment some may respond beautifully to one cycle somebody may relapse within two months somebody may not relapse for 10 years with the same mutation so we don't really understand truly what is happening and our knowledge is growing so let's see where we have come all of us are aware of this yeah who reported it so somebody working on cancer proteogenomics needs to know this this happened 115 years after Warchov coined the term leukemia again somebody who was not a very high flying clinician sorry researcher discovered that in patients with chronic mylar leukemia one of the chromosome looks smaller than normal and this was again a landmark event because until now it was thought that chromosomes become small as a effect of disease chromosomes are affected by disease and they become small right but when novel and hunger food reported this right they realized that six seven patients of CML had small chromosome so is the disease making it small or the chromosome is chromosomal abnormality is creating the disease so this was the first time a definite gene signature was attributed to a cancer the first time a definite gene signature was attributed to cancer and as banding techniques evolved people realized it was a balanced translocation between chromosome 9 and 22 and this was the onset of the phase of our current understanding of etiology of cancer remember fluid phase parasite etc it's only here okay it's only here at this 1960 and this came as a letter to editor in science very low profile paper it's only at this point that we started understanding oh maybe it's the DNA which causes cancer right and then we move on but does this really help us in practice does it help to understand that yes this cancer is caused by this mutation do you think it helps yeah which disease how does it help okay so you can have a targeted therapy yeah that's that's the new aspirin so everybody's talking of targeted therapy you know everybody believed that we'll find mutations we'll target them and the cancer and and you know malignancy will go away etc etc but you know you're from pharmacology background and that is where genomics has failed us that is where genomics has failed us because cancer is a multigenic disorder it is not a monogenic disorder correct except some conditions one of them is acute bromelocytic leukemia AML acute myelo leukemia has various types the third type of AML is acute bromelocytic leukemia this is the mutation a balanced translocation of 15 17 and as knowledge grew it was understood that this is where the retinoic receptor is retinoic receptor and in Chinese traditional medicine Chinese traditional medicine not allopathy they would use various chemicals and they realized that if you put amongst various things if you put retinoic acid in a cell line then that leukemia cell differentiates into a normal cell it's no more a immature set it can differentiate and then clinical trials were conducted etc etc and we use this drug it's one of the best medicines like you said targeted mutation identified we understand the pathobiology give a chemical the chemical goes attacks it leukemia is practically cured in some patients others need more treatment then of course Philadelphia chromosome novel and hunger for people understood why this causes there is an upregulated tyrosine kinase what is this tyrosine kinase and then people started creating a rational drug design so I hope today you have learned that how researchers individually took almost 200 years to classify a disease like leukemia therefore we need collaborative efforts and a combined universal repository with all the data and information related to the patients for better understanding of disease and its behavior you also learned about the very first doctoral malpractice due to the lack of knowledge and understanding of a given disease which could be avoided if now we could work together looking at various type of information from the clinical perspective as well as molecular and omic data sets so Dr. Sachin Jadhav will continue his lecture and discussion about how now latest technology such as proteogenomics in hematology and BMT has really started impacting the patient care and he will give you some examples to convey his points and give you again a very thought provoking discussion about what best way we can do to bridge the gap between the data scientist as well as the clinicians thank you


Welkom te het op het ondersteek van het ondersteek in het private ondersteek. We gaan het ooit over het belangrijkste ondersteek van het medical ondersteek, het belangrijkste ondersteek van het strategie, het het ondersteek van het private ondersteek en het ondersteek, een kwikmeetje van het ondersteek van het typen en dan zal er ook een short introductie van het ondersteek zijn. Het is ooit wat het op het ondersteek om media, mode, meen, standaardigheid. maar ik wil iets doen wat anders, we gaan begin met de p-value dus waarom geef het like dit at al, waarom medical research, het handje is dat er meer te medicin is dan mere service delivery te zien patiënts op een dagelijks basis te diegnoos hem te manage hem is een belangrijk deel van wat we doen, maar one moet wat meer dan service delivery we moeten het oordeel van jouw practies te mentionen, het is heel belangrijk voor elke doktor om de uitkomst van die geschevene management protocols voor verschillende ziezes het is alleen wanneer je goed sit en rees jouw file die is een vorm van research dat je waar jouw succeses is en waar je mou proeven kan Lastly is the pure knowledge of statistics. Even if you do not embark on any kind of research, it's important to critically read the literature. To know statistics empowers you when you do read through a journal. You can critically evaluate the findings of any research. Much more important to do this than to merely read the conclusion and just look for statistically significant p-values. To be able to evaluate the research that was done so that you can make a decision whether you want to implement the findings of that research in your practice. So what is the role of private practice in medical research? While if your practice has been running for a while, you sit on an enormous amount of data locked in your files, in your cabinet, is the answer to many questions that are out there. Now think of the first world setting in which most of you practice. You have access to the best of medical care, the best investigations, the best treatments. Not always so in academia, specifically in more third world oriented countries. Where most of the research is done, there is no access to the variety of medication treatments investigations as they are in private practice. Yet that is where most of the research comes from. It comes from academia. It is important that we consider that we do research from a first world perspective. In a world where our patients are treated, there are a lot of questions that can be answered. And that brings me to the last point here. You know the questions. When you have a Brian's Saturday afternoon, there's a thought that keeps into your mind something that bothers you. Whilst you're seeing patients, you might have a certain practice that sees a lot of a certain type of patients and there's always lingering questions and you wish that you could get the answer and it might not always be in the literature that's already out there. Well, you might be able to provide the world of medicine with that answer. Again that data might be locked up in the files in your cabinet. So let's look at the different types of studies. We're going to talk about observational studies, trials, and then just mention two others. So the observational studies. Now I want to warn you, these different types, the classification system used here is not absolutely demarcated. Aspects of one study can creep into the design of another type of study. But usually we'll group them as such. Case series, case control series, cross sectional studies and cohort type trials. So what is a case series? Well that is a simple descriptive account of a characteristic. Some people also call this a clinical audit. So you'll choose a defined period of time, maybe during an epidemic. And you'll just describe what the patients had. What investigations you did, what the outcome was, what the results of various investigations were, etc. Now a quick word just about retrospective versus prospective. Don't get that mixed in with the classification system that is used here. Retrospective simply means that you are going to use data that was recorded not specifically for this trial. You made clinical notes on your patients. When you design your study now there's certain data points that you decide on. But it's not necessarily noted in the files. You simply have to go look through the files for that data points. The problem with the retrospective audit is that the data was never captured with a study in mind. A prospective study is where you decide I want to from today gather these data points. You then gather them. They might not be part of a study. But when you now do a case series looking back it is on prospectively collected data. You decided that on every patient these certain data points will be noted in the file. So when you now do a case series it's easy to go find that data. You don't have to go through a file and search for probability that that data might have been captured. So how does a case series help us? Well let's say for instance you just wanted to document all the cases of H1N1 that you saw in the last couple of years or perhaps during the time that there was the epidemic. You can identify all those patients and you can simply tell the world how they presented what their parameters were and what the various results of the investigations were that you found. What does it help us with? It helps us with future planning. Should something occur again? You can have this data available to help you plan the next treatments. The second observational type is case control studies. So here we start with usually the presence of an outcome. It might also be the absence but usually the presence of an outcome and we're going to look backwards. So say for instance you group all the patients that you have the same antibiotic to the same disease and you get responders and non-responders. Now we're going to compare the subjects with or without that outcome. So the responders and the non-responders of responders was your outcome. We look for risk factors and characteristics that might differ between the groups. That can help you in the future. You know now that if you have that characteristic it's probably going to be a responder. It is probably going to be a non-responder as an example. Next up is a cross-sectional study. In a cross-sectional study we have a particular observation and a particular point in time. A good example of this is a survey. You might design a survey that you hand out to your patients anonymously. You can look at their knowledge of a certain disease or just their opinion about something. It's an excellent example of a cross-sectional study. It can also be part of other study types. Lastly I just want to mention the word cohort or cohort study. What is a cohort? A cohort is a group of individuals with a common trait. Remain part of that group over an extended period. A good example would be all the framing him studies where that population was followed up over a long period of time and during that time certain traits, certain diseases developed and we can look at the prevalence of that. That group of patients will form a cohort. Next up is a clinical trial, an observational study. We didn't really intervene at all. We merely observed and noted and documented. In a clinical trial we have active intervention.  To do this we need controls so we need patients who receive the intervention and those that don't. Now there are different types, the patient can be his own control. In other words we will observe certain data points, we will do the intervention and then we will collect those same data points again. You can have external controls so everyone involved in your study gets the intervention and you are just going to compare them to another set of individuals that were not part of the study but were in some way comparable to your patient set and you will compare them. Then you get the gold standard date, randomized controlled trial where a certain group of similar patients will be entered and they will be randomly selected to receive the intervention or not the intervention and this can be blinded in various ways. Lastly there are two other types that I want to mention quickly, the meta analysis that is where we perhaps don't have enough data but if we accumulate a lot of trials that were done on the same subject we can improve the power of the statistical analysis and get a better answer. Lastly reviews where you critically look at everything that has been published on a certain topic and you bring it all together in a nice essay. Now introductory statistics, the p-value. I quickly want to mention software, we're going to talk about the role of dice we're going to talk about data types and the central limit theorem. First of all the software. Now most of you would have a computer at home or at work and some form of Microsoft Office is loaded onto the system. Most of you will be familiar with Microsoft Word but there is another piece of software there that most people never use it's called Microsoft Excel, it is a spreadsheet program. At home in your office is a computer right now which you can use as you go home now and do powerful statistical analysis on simply and easily.  Now it comes in two versions, one is for the Windows operating system and one for the Macintosh Apple operating system. I just want to warn you there's a slight difference between the two. The statistical analysis package is already built into the Windows one and it is excluded in the Apple version. In the Apple version you have to download a free piece of software from Statsoft and that will give you the same statistical analysis power as with the Windows version. I'm going to show you a short video now on how to get simple two groups, type in the data, press a few buttons and we'll get a p-value. Here we are now we're going to talk about the role of a dice. What it is all about is probability. The p- and p-value stands for probability. Here we have die number one and die number two might be a bit difficult to see but they are all the different combinations that you can get if you roll them. It is mutually exclusive and collectively exhaustive. In other words, all possibilities are listed here. I can throw a one and a one, a one and a two, a one and a three, etc. right till the end, a six and a six. There is no other possibility. The dice cannot land on a seven or one cannot have a zero. Let's total the number that is face up on these two dice. I can throw a one and a one and that will equal two. I can throw a one and a two and that will equal three. You'll see the totals listed there in the column under tot. Let's look at the frequency distribution of it. How many times or how many ways is there to throw a two? There is just one way to do that, a one and a one. How many ways is there to get a three? There are two ways. I can throw a one and a two or a two and a one. Then look at number seven. There are six possible ways of getting the number seven, totalling seven. Now, if I collect all of them as a hundred percent In other words, there is no other possibilities. I am listing there on the right hand side what the probability is.  Purely because there are more combinations making up seven than there are any other. It is very unlikely or the p-value for hitting a two or a twelve is very low. We see the 2.78%. I am using percentages here, but in statistics we don't use percentage. We use a value between zero and one. Zero means there is no probability and one means there is a 100% probability. 50% will be 0.5 and the p-value that we usually choose for statistical significance at 0.05 equates to a 5% chance. So p-value of less than 0.05 says there was a less than 5% chance of having found the results in my study and because the probability was so low, I call this statistically significant. Now look at this. I have represented the probabilities there of the various totals I can hit with my two dice by a little column chart. First of all note this the gaps between. That is because this is called discrete data. I cannot have a 7.5 or a 7.484529. It comes in discrete little packages, a 7, a 6, a 9. And therefore we leave these little gaps. If you quickly look at an article and you look at the columns, the charts, the figures, if someone designed them properly you should be able just to look at it and know well this was a discrete data. These columns should not touch. That would be a proper way of designing this little chart. Because it is discrete, because every value is contained within itself, we call the width of each of these, we give it a value of 1. Now dice is easy, it's 4, 5, 6, 7 and there is a difference between 1, between each of these. But it might also be something completely different whereby we have a few decimal points but that the data itself, the data points themselves are still discrete. We still going to have the gaps between them and we still see the width as 1. Now look at the height of those columns. That first, the middle one at 7 is 16.67. So if I were just to take the surface area, remember how to do the surface area of a rectangle, it's width times height. So if I look at the width of 1 and the height of 16.67, multiply the one with the other and I see that the area, the surface area of that little bar equals the probability.  I can equate surface area to probability. Now remember, if I total all of these up, they equate to 1. It includes all possibilities. There cannot be a 1, there cannot be a 13. It's impossible, everything is included here. So if I added up the surface area of all these little bars, they equal to 1 or 100%. So they are all in there. Important to note again, surface area of these little bars give me the probability or the p-value. I can now ask, if I throw a 12 and I chose 5% or 0.05 as statistically significant, I hit a 12, I can say my finding of throwing double 6s is statistically significant. Now let's quickly just mention data types. We have to bring it in some way. There are two ways to classify data types. Right at the bottom you'll see discrete and continuous. We've spoken about the discrete. You don't get a value of 7.5. But then you get continuous data types. In other words, let's say for instance, white cell count. Now you don't get a fraction of a white cell count but because we're really talking times 10 to the power 9 cells per liter, the sheer number is so large that we see this as a continuous data. Now another way to look at it is categorical versus numerical. Let's quickly categorical data. You get a nominal and ordinal type. Nominal is just things like appendicitis, UTI. There's no way to arrange these in some form of order. They're just different types of diseases. Or if you think about responders versus non-responders, that's a nominal categorical type. Ordinal is a bit different. I can put order to these. In a survey, I can ask patients how happy are you with a certain medication? Perhaps not the best of examples, but they can then rate it. 1 star, 2 star, 3 star, 4 star, 5 star. So there is some order to their choice. But if someone chooses 4 stars and someone chooses 2 stars, you cannot say that the person who chose 4 stars is twice as happy as the one who chose 2 stars. There's order to it, but there's no arithmetic to it. For that, we'll use numerical data types. Again, 2 different subtypes, interval and ratio.  Degrees Celsius would be an interval type. There is no absolute zero or true zero, I should say. So if it is 10 degrees Celsius outside and 20 degrees Celsius outside, I cannot say this twice as warm. For that, you'll have to use the Kelvin scale. The Kelvin scale has an absolute zero, minus 273 degrees Celsius. So for ratios, you must have a true zero. So here we have continuous data. Now contrast this, cast your mind back to the little bars we had. We said that they had a width of 1. They had a certain height and if I multiply those, I got the area of my little rectangle and that gave me the probability. But continuous data do not have those little gaps in between. So how would I now estimate the area under this curve? Well, integral calculus comes to our rescue. Now we're not going to do integral calculus. The software package actually does that for you. What I want to tie up in your mind now is that we are still going to use area to calculate probability because the sum total of all the area under the graph has to equal 1 if we include all possibilities. Good. Lastly, let's get to the central limit theorem. In order to do that, we have to discuss combinations. It's very easy to do in a software package. You'll see there it says equals common and a little brackets. It's just function in spreadsheet software so I can type equals common, and if we look at the first one there, 10 patients in two groups. I could type in equals common 10,2. If I hit enter, I'll get the answer there of 45. What does that mean? I took ten individuals and I made little groups of two. How many distinct different combinations can I make? Well, 45. Now if I choose Sam and Ingrid, or I chose Ingrid and Sam, that would be this exact same combination. If I viewed that as two different ones that would be called permutations. We're talking about combinations here. What is important to look at how rapidly things expand here? If I had ten patients and I had to choose at random four, how many of those random selections can I make and that they're completely different from each other? I can make 210 possible combinations. Now just think about this. Well, before you do, look if I had 100 patients and I randomly chose ten. Look at all the possible combinations that I could have made. Here comes the very important part. Think about it. Imagine there were 100 patients with a disease and only 100 patients on the whole earth. Only 100 patients had this very rare disease. I want to include some of them in a study and I only have enough time and resources and money to investigate ten of them. Out of those 100, I have to draw out of a hat ten of them at complete random. And remember that's exactly what you do. Even if you were to view UTIs. Now there are many millions of people on earth with a UTI but the ones that came to your practice in that specific time period that you chose is actually just at random. If someone else did it, if you chose a different time period you would have chosen a distinct different ten patients. Even if they just differed by one patient it would be a different patient set that is now involved in your study. Now back to this 110. We have this rare disease, there's only 100 and you chose ten at random. Look at all the different possible combinations that you could have chosen. And if you did research on those ten patients you would get, say for instance we're just comparing two sets with each other. Five in the one group, five in the other group. But you might as well have had one of those other ten 1.7 times ten to the power 13 combinations. You would have gotten another difference between your two groups. And if you had another of those ten in your another one of those 1.7 times ten to the power 13 ten patients selections in your study you would have had another difference. So you see your study that included your ten patients was just one of many many many possibilities. And this is what we have when we get to this well shaped bell curve. What this says is if you could take all those possible combinations 1.7 times ten to the power 13 of groups of ten then a group of five and a group of five and you compare them and you have a difference in a certain data point and you plot that and you plot that this is exactly what you are going to end up. This is exactly the same as the role of the dice. You could total between two and twelve that included all possibilities. Nothing was excluded and they all fall under the umbrella of 100% or one. Same exact thing happens here. Your study that you did falls some way on that curve at the top where it was most likely is that the vast majority of those 1.7 times ten to the power 13 possible studies that could have been done most of them would have a difference between the two patient groups right there up in the middle. And that is where the p-value comes from. If your difference was one of the rere differences you would fall at one of the two edges here and what we are simply going to do is draw a line there that is what the software does and then towards the sides the red here it is going to calculate using interval calculus the area under the curve and because the total area under the curve is 1.0 if your area is found to be less than 5% or 0.05 we would say your finding was statistically significant. Now we are just choosing 0.05 you might as well have chosen 0.01 many studies choose 0.01 but again it just means that if all possible studies could have been done and now we are just talking 110 can you imagine with 7 billion people on the face of the earth how many possible random selections you could have made to include in your patient set that you are investigating you are just one tiny tiny little speck your study is one tiny little speck now there are equations behind this graph so depending on how many patients you include there is various factors that go into this equation I won't show you the equation that estimates how this curve should look and in that way it can then put in your marker do the area under the curve and give you the p-value but how fantastic is that and this is called the central limit theorem is that if you include all possibilities the mean your mean that you found the mean difference between your two groups 5 patients 5 patients and your 10 patient study if you were to get the mean difference say the mean difference in white cell count of all the means all the means are plotted there remember there were many ways to throw the dice to get 7 so there will be many studies that will have a certain difference between the two groups so that is what is listed there the percentage of cases that would have had that difference so if the one you found is right there by the middle hump then obviously the area under the curve if it's on either side it's going to be much more than 0.05 so your finding was not statistically significant now I showed you how this worked in the software one thing look under the green data software it's going to give you two different kinds of p values it says two tail distribution and one tail distribution and the one day is 0.06 and the other one is 0.03 now obviously the bottom one is statistically significant if you chose 0.05 for your statistical significance but the other one is 0.06 now which one do you choose while you can't do it at this stage it is something that you have to do beforehand otherwise you are a scoopless researcher so it is about hypothesis before you start your test you have to ask yourself what the null hypothesis is and what the test hypothesis is null hypothesis is easy it says there is no difference between the two groups we are going to have two groups I am going to do the white cell count and the means of the two groups are going to be exactly the same the test hypothesis is important you are going to postulate and you are going to say one of three things most commonly you are going to say there is a difference between the two groups or you might say group two is going to have a value less than group one or group two has a value more than and that is very important if you look at the next slide there is a one tailed in this instance you can see we are looking at the right hand side of this bell curve so we are saying that our test group our group two is more than we are postulating our test hypothesis more than what the software then does is that it uses the one tailed test in other words I am going to group all the five percent on the one side and you can clearly see the red there representing five percent now this is not done correctly that is actually a bit more I think if you look at it more than five percent but for purposes of illustration it suggests that the red area there would represent five percent of the area under the curve now that green line is where the software works out your mean falls and if we then go to the right we look at the green area and we do the surface area of that it is less than this critical point where the red area starts your area under the curve is now less than five percent or 0.05 so your finding is statistically significant on the right hand side there you see that the green area is actually larger than the red area so your finding would be term statistically insignificant good so you have to say that before hand this is a one tail so the five percent red area falls into one part or if your test hypothesis was there is a difference I am not saying one is more than the other or less than the other I am just saying there is a difference that five percent would be spread on both sides two and a half percent on the one side two and a half percent on the other side and it uses a different equation to work out your little green area so final thoughts we all have questions in our daily practices we have a lot of data if our practices have been running for a while why not decide to use that data and answer some of the questions that you have you can send me a message there is my email address if you have any questions if you want to embark on this if you want to learn more finally my youtube channel there we have youtube.com we will find some more video lectures on various subjects but also on this important subject of clinical research