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Mass Effect: Andromeda lead designer Ian Frazier on 'fulfilling the promise of Mass Effect 1'
By Wes Fenlon 2017-02-24T21:23:38.54Z
More on combat, the new planetary exploration, and how Andromeda compares to Dragon Age: Inquisition and The Witcher 3.
Andromeda is lead designer Ian Frazier's first Mass Effect game, but you wouldn't pick up on that by talking to him. He seems like he's been there all along when he talks about learning from the design of the first Mass Effect, or changing how we role-play conversations by removing the Paragon/Renegade system. He had tons to say about how Andromeda's new combat system allows for nuanced customization.
Mass Effect extravaganza
Check out our Mass Effect: Andromeda news hub for a collection of all things Andromeda, including our hands-on preview after three hours with the game.
After my recent hands-on with Mass Effect: Andromeda, I spoke to Frazier with a hundred questions running through my mind. What do you talk about when you've finally played a game five years in the making? A little bit of everything.
In our Q&A below, Frazier and I dug into the details of the new (seriously so much better) combat system, how characters will react to your dialogue choices, which Star Trek captain Ryder would be, and a ton more.
PC Gamer: I want to talk about what we've heard about the game so far, and what I've seen of it. In our newest issue of the magazine Mass Effect is the cover feature, and one of the things that stood out to me from our interview was this game, holistically, being less about the threat hanging over you, and more about the spirit of exploration, that sci-fi vibe that the first Mass Effect was really shooting for. In Andromeda you have this villain out there, the Archon. Can you talk about that balance—how much of this game is about that evil force, and how much is about going off and doing your own thing?
It's an interesting question. In general, with Mass Effect 1, you nailed it. In a lot of our internal documentation, our meetings early on, the big theme for the game was 'fulfill the promise of Mass Effect 1.' Take what was good about Mass Effect 1, and what it aspired to be, and go, well, it's been 10 years. What can we do to take that and deliver above and beyond what was even possible back then?
Lead designer Ian Frazier was previously the lead designer on fantasy RPG Kingdoms of Amalur: Reckoning.
In terms of the structure of the game, it is more open, and we do allow a lot more exploration. We didn't want to have you feeling, most of the time, 'DOOM IS AWAITING JUST OVER THE HILL, OH GOD!' We have some points that are like that. We want the stakes to be high. But we want that to be periodic beats along the plot, where it's like—'no really, man, go take care of that'—versus this constant, ever-present threat.
From a mechanical perspective we wanted you to explore, and craft, and see what's out there. And when the world's going to end in 20 minutes, you don't want to do that. We tried to have a mixture of short-term threats you need to deal with right now, and longer-term threats where you do get the sense that it's okay for me to go spend 20 hours exploring. [laughs]
If Ryder was a Star Trek captain, which one would be the closest analogue?
It's funny because there is no one answer. The idea of the tone system is very much for you to make that choice. If you choose casual, the bottom left option, very frequently, you're going to be kind of a Chris Pine Captain Kirk. If you choose the professional option on a regular basis, you're a mixture of Picard and, honestly, Shepard. If you choose the analytical option it's much more Picard-oriented with a bit of Spock mixed in. And if you choose the emotional option, it's a bit of Sisko, a bit of Kirk.
It's funny, because when we talk about things internally, it's like okay, is this the Picard option or the Spock option?
The flirt option is always Riker, by the way.
He does have sex with every alien.
If it's possible.
Your new enemies, the Kett: probably not romancable.
Talk about the ability progression through the game. As you put more points into them, do they just get stronger, charge faster, or is there more nuance to them?
Definitely more nuance. Some of it's just yes, +27% damage. But a lot of them are mechanically changing what's going to happen. As a simple example, there's an ability called biotic lance. One of the upgrades for that, I forget what the counter-option is but you can evolve it to do something, I think it's vastly improved headshot damage, or you can make it consume shields instead of having it cool down. So you really need to pay attention to your shields, because it's going to eat them every time you use it, but you can spam the heck out of it because you're not reliant on cooldown.
We have other things like that. Like incinerate, you can make it shoot two fireballs instead of one, or you can have one that's going to do something extra when it explodes. So you get more mechanical variance. Some of them are pretty substantial differences. It's really interesting to build different synergies as you create your character, especially if you include the squadmates.
As an example, I'm going to make the assault turret power from the tech tree and have that have an ability that primes enemies with cold, slowing enemies down and putting this chill cover on them. Then Cora, I'm going to make sure her biotic charge can happen a lot, the lowest possible cooldown, and make it a combo detonator. So I'm aiming Cora at whichever thing my turret has frozen. Cora, go blow that up. Cora, go blow that up. She's running around detonating those combos.
Especially if you combine yourself with the squad with potential constructs like the turret, it gets pretty crazy.
Can you plan your own synergies with your abilities? Like with lance, you can siphon your own shield to use it repeatedly. Is there an ability that offsets that, like recharging your shields quickly, or based on kills?
Exactly. So there's a combination of factors. In terms of just skills, let's set aside the other various bits and bobs of the game. With just skills, in that example, you could do a build—I've done this build—where you've got biotic charge as your main thing. You spec it heavily to regen your shields whenever you do it, and then take either nova or lance, both of them can be turned into things that thrive on shields. And you can do that, so you're ping-ponging between the thing that gives you shields and the thing that eats your shields. Just try to stay alive as you do that yo-yo.
How do all the different abilities play into the profile system?
It's kind of a complicated answer. At the beginning of the game you don't have any sense of class, but if you do choose to do character gen, you choose one of six backgrounds, or trainings, when the game starts. Now what that will do, is take certain abilities that are kind of higher level or specialized abilities, like charge or cloak that pretty significantly impact your gameplay. Normally we require you to invest several points in that tree before you can do it. If you want biotic charge, you have to have invested 9 points into something else on the biotic tree before you can get charge. But if you chose that background—there one where you are the guy that charges—then you have that available from the outset and you can immediately start spending points in it. So if you try the different backgrounds you'll see different things locked and unlocked in the trees.
But again, if you play long enough and invest in the right place, you can unlock anything. You can mix and match however you like.
Now the profile system is the way that we let you get a sense of identity, and get a bonus related to a particular playstyle. So the basic example is this. I start the game, I use the default background which is kind of the soldiery background, and I spend every point I ever get on every level-up on the combat tree. If you do that, you're going to unlock a soldier profile which you can equip, that gives you bonuses to playing as a person who's all about guns. Reduced weapon weight with your guns, ability to carry more guns, more effective with your guns. There's a killstreak bonus, more guys killed under a certain amount of time, you get escalating damage for that. It's all about the guns.
Let's say you did that, kept ranking up your soldier profile, it's giving all these benefits. Well, I want to try biotics. Purple stuff is cool. So you invest in some biotic abilities. Now you'll unlock a couple more profiles. You'll unlock one that's an adept profile, that gives you bonuses to using biotics. And a vanguard profile, which is a hybrid of combat and biotics.
The profile system is the way we let you get a sense of identity and a bonus related to a particular playstyle.
Now they'll be lower-level, because you haven't invested as much across those two trees, but you'll have access to them. So now I'll try this vanguard profile. You can only have one profile active at a time. So I can switch over to vanguard, and now every time I punch something I get shields back. Okay, but it's not giving as good bonuses to my guns, so maybe I want to stick with that. Oh, but the adept one makes it so that every time you do a biotic combo, it leaves little echo combos, mini explosions that ripple out from the main one. So maybe that's better for your playstyle, because you've totally specced to be Mr. Combo.
But you try it for awhile and eh, don't care for it. You switch your profile back, whenever you like, even in the middle of combat. But which profiles you have available is limited to what you've spent points in. You can't just do any profile unless you've spent the points to unlock that.
In the previous Mass Effect games you had more of a limit on how much experience was available, because they were more linear. In this one you can go out into the open world and kill stuff, so if I played this game for 250 hours, is there a point where I have the ability to spec into everything?
It would take a long time, but it is technically possible. We don't actually have a level cap, so you could keep going until you have straight-up run out of things to spend points on, which should be around level 123.
So if you played soldier for 40 hours and decide I'm tired of this, and want to shift to a completely different playstyle...
You have a couple options there. One is: 'You know I like a lot of this but I want to try something new,' you can invest in something else and use a profile to gradually shift yourself that direction. If you're like 'nope, I hate this, what have I done, I've wasted my 40 hours,' you can go down to the medbay in the Tempest, and you can spend some money to completely respec, get all your points refunded, and completely rebuild your character. Every time you do that the cost goes up, so you don't want to do it constantly, but you can do a complete nuke from orbit if you want.
Along the same lines of choice, a lot of hardcore PC D&D RPGs focus on 'you can play this game killing every single NPC and somehow still beat it.' Or you can go the other way and play totally pacifist and talk your way out of every situation. This game starts with a pretty typical run-and-gun mission, where you kill the aliens on sight, save your people. What's the balance there? How much of it is the combat game, how much am I going to be able to talk my way out of?
I'd say it's similar to the trilogy, the average of the three games previously. There are cases where you can get out of combat entirely through dialogue, but we certainly don't have a pacifist non-lethal approach to the game. It's not designed for that. Generally speaking, there's the talky bit, and there's the shooty bit, and sometimes they'll cross over, but for the most part they're separate aspects of the game that are interwoven over the course of the experience.
It seems like the shift between might be quicker, or more common, compared to like Mass Effect 2, where you have a mission sequence where you're fighting, then a whole hub section.
The other thing is we have some other elements. If you look at Mass Effect, especially 2 and 3, there's the shooting part, and the talking part. The end. Now we've got a more robust galaxy map experience, exploring space is kind of a richer part of the game all by itself. I wouldn't say full-blown platforming, but you do have the jump jet and the climbing, you can do these explorative bits just trying to get up to somewhere cool, either on foot or in the car. We have some light puzzle aspects. We have things like the crafting system. I think you'll just see more variation in what you do over the course of the game than you would've seen in Mass 3, simply because there are more mechanics.
In Mass Effect 2 there were time-sensitive missions where if you didn't get to it by a certain point, you couldn't do it anymore. In this one I had the experience of going back to the Tempest, and they're like 'I heard about this thing over here...' Are any of those time-sensitive, or are they all open forever?
So there's nothing that's explicitly time-sensitive, but there are two things that are kind of in that vein. One is, there's a handful of quests that if you finish the main story, are no longer accessible. But it's a pretty small percentage. But the vast majority of the game, including the loyalty missions, Mass Effect-2 style, you can do even after you finish the main story. Most parts are still open.
The other thing we have is we have quest content that gets unlocked in a time-based manner, like 'okay, you've been to three different planets, it's time for you to find something new.' But it's not that your whole crew died because that many missions have passed, it's just more content is available to you. We do it to not drown you.
Let's talk more about the character stuff. Changing paragon/renegade is a pretty big shift. 30 hours into the game, what is my character going to look like if I've been generally sticking to one style of personality?
What you'll find, we let you switch whenever you want, so even if you've been playing for 40 hours, always making jokes, you're like 'nope, I'm serious now, hitting the Picard button,' we'll let you do that. But the game is tracking under the hood how much you've chosen those different options, and we build a little psych profile for you based on that. Now it's not that everybody you walk up to is like 'you're that guy that's always joking!' But it may come up in conversation, and particularly specific things you've chosen over the course of the game, may come back to haunt you in either a good way or a bad way. Folks will remember certain decisions. Not in a more systemic way, but literally this one specific decision's going to get referenced back at this point later.
We don't have a thing where it's like 'you could tell him to back down but you can't because you haven't paragoned enough.'
The other thing we have, to let you keep track of what sort of character you've built. In the codex, the codex at its core works the same as the trilogy, but there's a section at the top called The Journey So Far. What that does is track your particular experience, what's been happening with your Ryder, what are the main story decisions you've made, what kind of relationships have you formed with your family, squadmates, and crew, and some other key characters, and finally your psych profile, which is tracking 'okay, you have only ever taken the casual option every single opportunity.' Or 'you take every single interrupt or narrative action the moment they're available. You're super impulsive, super casual.'
It'll give you that clear feedback on what you've chosen to be. But it's purely there so you understand what you've made. It's not feeding back into a system somewhere else. So there's no sense that 'if you want to get the golden gun, you're going to need to take the serious option every time.' We're trying to keep it open.
In the original games, if you weren't renegade enough or paragon enough there would be points where you couldn't influence conversations or characters. How does that work now?
We have deliberately removed that. We wanted you to feel like, at any time—there are things you can't say if the story doesn't give you a reason to say it, like you haven't done that thing or met that person, therefore you don't have this option—but only cases like that where it would be nonsensical for you to have that option. We don't have a thing where it's like 'you could tell him to back down but you can't because you haven't paragoned enough.' That concept doesn't exist.
Is there anything along those lines? Like in a Fallout game, say, you have 7 points in charm and you can charm this asshole instead of trying to kill him. Is there any equivalent to that?
No, there's no dialogue skills in that sense. It's purely: you can choose what you want to say, and sometimes the specific choice that you've made, not systemically, but the specific choice you've made might piss someone off or cause repercussions. But it's not that you had 15 points in bribery. It's that you chose to try to bribe someone who was not a smart person to try to bribe. [laughs]
How does that nuance feed into character relationships? That was a big thing too, how characters would respond to you if you were very paragon or very renegade. If I'm tossing jokes all the time, how does that affect romance options, for example?
I don't think we have any that are straight-up shut off, like oop, you made too many jokes, therefore this person will not smooch you. But you certainly will see reactivity, particularly with key characters, when you lean heavily towards certain options. Or even in the moment. There's at least a couple spots in the game where it's a very serious moment and you can make a joke in that moment. Do you really want to? is that the best idea? You can, and you'll get reactions like you'd expect to get when you make jokes in that situation.
In the beginning when we looked at the default character profiles, you talked about having different representation in there. How does that extend to the rest of the game in terms of depictions of romances, relationships between the player character and the aliens, between genders?
We learned a lot from Dragon Age: Inquisition in that respect. Something that I think that team did very well was having a variety of different kinds of romances. And I mean that both in the sense of different sexual orientations, but also in how they're portrayed.
You had everything from Josephine, the Disney princess romance, to the explicitly sexual Iron Bull, and some other ones like that. We've tried to do something similar. We have sort of a range of different options, in terms of the tone, the feeling of the romances you can pursue, and also there are ones that are more like flings, and ones that are more serious, and ones that are flings that could be serious depending on the choices you make. So we tried to have that mix, in conjunction with, of course, making sure that really everybody is represented to an extent. There are gay romances in the game, there are bisexual romances in the game, and so forth.
In our cover feature Bioware talked about more substantial sidequests, and they threw out Witcher 3 as a point of reference. What have you guys looked at since the Mass Effect trilogy came out, in terms of where RPGs have gone, that has played into this game at all? What you didn't or did want to do?
A lot of things. In terms of our own internal work, obviously we worked on Dragon Age for years, and we looked at how things went with Dragon Age. What was good, what was bad, what we could improve.
As far as the market goes, we played all the competitors, everything in the space. We played The Witcher, Fallout. We saw the things we liked and don't like. And just where the industry is right now. We try to use that to help guide us and what players are looking for and what we can do to make the best experience possible.
Where do you think the industry is right now?
For the RPG space, I think we are heading towards more quality over quantity. That doesn't mean you don't want to have quantity. You do. But I think particularly open world games were heading towards more and more and more filler-y, and I think there's a pushback on that now, rightly. People want more quality content. And they want quantity too! So you're always trying to find the right spot to peg that needle. So I think where we're looking, and where I imagine other games are looking right now, move the needle a bit in the direction of some more high quality rich content.
So Kadarra, the planet I'm on. I was just getting out into the open world. The thing I remember vividly about the first Mass Effect was the promise being amazing. The actual planets... pretty bland. Not that much fun to drive around. But the hub parts that you'd be on where awesome. There were just only four or five of them. How does this compare, having a more nuanced open world, having probably even more detailed hubs, I'm guessing. How many of those are we talking about that are going to be analogous to what we saw in Mass Effect 1?
I can't give numbers yet. I can tell you that, as far as other games we've looked at and so forth, what we looked at more in terms of how to build this than other open world games, is we actually did look at Mass Effect 1. We didn't want to feel like just another open world game. We tried to not even think of ourselves as an open world game. Open, yes. Explorative, yes. But not in that exact mold.
We instead looked at Mass Effect 1, examples like Novaria and said 'okay, if you built that now, and you could throw more time and money and energy at it than we could at the time, what would that look like?' Imagine a Novaria where you find a whole lot more than just driving from point A to point B, from the cool big hub to the other cool big hub.
And that's essentially what the game is. You go to these UNC spaces, or uncharted worlds, and you'll have something like Kadarra Port, the actual city portion which has a lot of rich content, you go out there, you're going to go to this piece, and this piece, and this piece, that are other interesting places to explore, with varying degrees of stories crisscrossing that world as you go from A to B.
And we try to orient them. You'll see this if you skim through the journal in your current savegame. We try to arrange that content in a way that the player can tell what's light and what's heavy. If you look in the journal, the first section is critical path, the main story. The next section is big plot threads that run throughout the game and go to many different places and involve, often, key characters like your squadmates, crew, family, that let you explore some of the bigger mysteries and stories of the game.
Those are a huge deal. Then you have the Helios assignments which are bigger, meatier story quests across the various worlds, that are usually self-contained. So this is just Kadarra stuff. Do these things on Kadarra. Not always, but usually. And then we have additional tasks, so if it's like, I want some XP and loot, and don't erally care about getting involved in a deep story right now, the additional tasks are thsoe things. So we have kind of a clear message to the player so you know, what kind of content do you want? Here it is, go do these things.
Are there planets, unlike Kadarra, where it's like one of those procedurally generated Mass Effect 1 planets with newer technology? Where you land on this uncharted planet, just drive around, find some aliens and stuff.
There is a spectrum, there's none that are fully procedural. We had used some procedural tools in the generation of our terrains and such, but everything at this point is actually hand-crafted. We at an earlier stage in development were looking at more fully procedural stuff. We spent a lot of time with it. We experimented with it. Weren't super happy with the results.
Just hard to keep it interesting?
It really is. I'm not going to say it's impossible. It's not. Who knows, maybe we'll go back to it someday. But with this game, we just got a lot better results in terms of the story we wanted to tell when we handcrafted the experience.
So are there lighter planets that are not as dense with people as this? Yeah. There are places where you can't breathe. But as far as the way we built it, they're all built with the same sort of methodology as Kadarra.
Gotcha. So there is going to be that mix where, here's a planet with a city or a spaceport, and then, here's a planet where it's just, go find an outpost or some mountains.
Absolutely, yes.
Let's talk a bit about the voicework and animation. When the game trailer came out a few months ago a lot of people were like 'the lip synching doesn't look so great!' It looks pretty good, from what I've seen—I think it's expressive in a different way from some other recent games. It feels a tiny bit more cartoony than some other facial systems. Can you talk about where you are on that stuff, how you incorporated motion capture, and how you did aliens?
The first thing probably worth mentioning is we're still actively working on it. Since that video, and even now, we're continuing to polish and work on the lip sync and facial performances. Even through the day one patch we're still working on this to be as good as it possibly can be and dumping more time into it.
We're continuing to polish and work on the lip sync and facial performance. Even through the day one patch.
But as far as how we did it, the big difference between this and all the previous Bioware games, including even Inquisition, is we used performance capture for a lot of our critical scenes. When you see some of the opening parts of the game, where your dad makes his rousing speech, that's not just hand animated by an animator. That's motion capture on the guy in the lab with little ping pong balls on his face, so facial expressions are carefully captured. So you get more of that rich emotion coming through, in addition to the lip syncing and the movements and so forth.
Previous Bioware games, up to and including Inquisition, have always been body capture, and that's all. The face was all done by hand. Now we have a lot more of that human element captured throughout a lot of our key scenes.
And what about the alien expressions?
Actual Salarians with ping pong balls. Actual Krogan with ping pong balls. No, those are all done by hand. But I'm actually really—I'm not sure how much you've gotten to talk to the aliens yet—but really proud of what we've done with the facial rigs. When you talk to a Salarian you'll see his funky irises closing inside. It's actually pretty biologically compelling. It's believable as a living thing.


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CAKE's most recent album, Showroom of Compassion, debuted at #1 on the Billboard Top 200 Album Chart and was touted as "deadpan brilliance" by the New Yorker. The band is currently at work on their ninth album due for release during 2021..
Tift Merritt
Tift Merritt is a Grammy-nominated songwriter who wanted to be a writer until her father taught her guitar chords and Percy Sledge songs. The New Yorker has called Tift Merritt "the bearer of a proud tradition of distaff country soul that reaches back to artists like Dusty Springfield and Bobbie Gentry." The Washington Post writes, "Tift Merritt is working in the tradition of Joni Mitchell, James Taylor and Leonard Cohen." Don Henley, with help from Mick Jagger, kicks of his album Cass County with a cover of her song Bramble Rose. With nearly twenty years of recording and touring under her belt, Tift is also a regular contributor to the Oxford American. Tift lives and writes in North Carolina with her young daughter..
Matthew Montfort
Award-winning guitarist and pioneer of the scalloped fretboard guitar, Matthew Montfort has over 40 years of experience in the music industry. He became involved in the movement for artist rights in the digital age early through his role as a class representative for independent musicians in the Napster court case.
He is the leader of the world fusion music ensemble Ancient Future and has released two solo CDs: Seven Serenades for Scalloped Fretboard Guitar and Sympathetic Serenade. Montfort is recognized as one of the world's 100 Greatest Acoustic Guitarists by DigitalDreamDoor.com, a curated "best of" site, along with such luminaries as Michael Hedges and Joni Mitchell. He is also known for his work on electric guitar, flamenco guitar, sitar, ukulele, charango, mandolin, and gamelan and has recorded with legendary world music figures such as tabla master Zakir Hussain. He has performed concerts worldwide including at the Festival Internacional de la Guitarra on the golden coast of Spain near Barcelona, the Mumbai Festival at the Gateway of India in Bombay, and live on national radio and TV shows such as the Echoes Living Room Concerts on Public Radio International, and the Rachel Maddow Show on MSNBC.
Montfort holds a B.A. in World Music and Composition and an M.A. in Artist and Media Technology from Antioch University. He has studied with the master musicians of many world music traditions, including spending three months in intensive study with vina master K.S. Subramanian in order to fully apply the South Indian gamaka (note-bending) techniques to the guitar. Montfort wrote the book Ancient Traditions – Future Possibilities: Rhythmic Training Through the Traditions of Africa, Bali, and India, which has been used by many musicians to improve their rhythm skills. Montfort teaches all styles of guitar, ukulele, bass, charango, sitar, and mandolin as well as music theory for all instruments and rhythm classes based on his book at his studio in San Rafael, California, and online via Skype. Additionally, he has taught masterclasses at many universities and music camps, and was on the faculty of Blue Bear School of Music in San Francisco for over two decades..
Maggie Vail
Maggie Vail started her career in 1994, when she was just 19 years old, at the preeminent independent label Kill Rock Stars. She oversaw the radio, publicity, and advertising departments for years, booked tours, and project managed releases. She also signed numerous groundbreaking bands, including Mika Miko, Erase Errata, Grass Widow and New Bloods. Rising from mail order to vice president by the end of her tenure, Maggie worked on literally hundreds of records by artists such as Bikini Kill, Elliott Smith, The Decemberists, Sleater-Kinney, Deerhoof, and Gossip in the 17 years she was with the label.
She joined the board of nonprofit CASH Music in 2007. CASH's mission is to empower artists to become sustainable in the digital age. To that end, they build free, open source digital tools and pair with them with educational resources for artists. Maggie left Kill Rock Stars in July of 2011 to move into a full time partnership with CASH founder Jesse von Doom as co-executive directors. Together they worked on projects with hundreds of artists and labels including Run The Jewels, De La Soul, Boyz II Men, TLC, The Lumineers, Mom & Pop, and Polyvinyl. When von Doom left in June 2017 she remained on as the sole executive director.
Maggie is the label manager of Bikini Kill Records, bass player of the band Hurry Up, DJ Magic Beans, and part of the all-women DJ troupe Strange Babes, who have a radio show on XRAY.fm. She was one of the organizers of the first Ladyfest in 2000. Maggie has also been in dozens of bands over the past 30 years, most notably Bangs from 1997-2003. Maggie is serving her second year as a governor with the Pacific Northwest Chapter of the Recording Academy (GRAMMYs®).
MUSIC COUNCIL
The ARA music council is a diverse group of artists and experts who help inform and guide the work of the Artist Rights Alliance.
Alex Delicata
Amy Reitnouer
Aaron Greenwald
Beth Nielsen Chapman
Blackie and the Rodeo Kings
Buddy Miller
Callie Khouri
Caroline Spence
Carter Little
Dan Knobler
Dan Navarro
Dan Neustadt
Donald Cohen
Duke Fakir
Dylan LeBlanc
Elizabeth Cook
Erin McKeown
Erin Olivia Anderson
Erin Rae
Ev Ehrlich
Faux Ferocious
Grant-Lee Phillips
Hampton Howerton
Hayes Carll
Joachim Cooder
Joel Grey
John Paul White
Jonathan Taplin
Judy Hood
Kate Tucker
Katelyn Silver Howard
Keb' Mo'
Laura Burhenn
Lera Lynn
Leroy Powell
Liz Leahy
Loudon Wainwright III
Mac McAnally
Marc Ribot
Mark Erelli
Marty Stuart
Mary Chapin Carpenter
Mary Gauthier
Michael Hausman
Michael John Mollo
Mikael Eldridge
Nick Howard
Neil Turkewitz
Patrick Carney
Rhett Miller
Rhiannon Giddens
Rodney Crowell
Ryan Norris
Shelly Colvin
St. Paul and the Broken Bones
T Bone Burnett
The Milk Carton Kids
Traci Thomas
Last summer, John Prine honored ARA by joining our fledgling Music Council. His participation honored all of us.
With his passing, we no longer have John's name on the Council rolls, a painful additional loss piled onto the enormous toll of heartbreak being felt around the world.
Throughout his career, John sought to help us better understand our shared humanity. That goal will guide our work.
And we will always strive to hold ourselves and this organization to the standards of decency, compassion, and artistry that he set.
Rest in Peace, John Prine.
© 2021 - Artist Rights Alliance. All Rights Reserved. Privacy Policy - Terms and Conditions

redpajama_set_name: RedPajamaCommonCrawl


text:
#Encrochat Scam Phones News: Thirteen people have been sentenced to a total of nearly 110 years
Commonly referred to as 'Encrochat', criminals use encrypted mobile devices to adopt and hide behind code names or 'handles'.
Messages recovered from an encrypted messaging service revealed the sheer volume of drugs that were being sourced and sold by separate and distinct criminal groups, as they effectively combined to become a formidable force operating as a drugs consortium bringing Class A and Class B drugs onto the streets of North Wales.
The investigation centred on Daniel Crossley, a resident of the Rhuddlan area, who sourced Cocaine and Cannabis, and facilitated supply to the Tommy Davies Organised Crime Group (OCG) in Flintshire.
Despite serving time in prison, Davies stayed in regular contact with members of his OCG.
Davies used both legitimate phones and devices which had been smuggled into prison.
He had trusted members of his OCG who managed the day to day running of the criminal network, including his mother Dawn Davies, brother Liam and Sophie Roberts.
Arrangements would be made so that either the drugs would be collected in Merseyside, where a North Wales courier would travel and meet in specific locations, or the Merseyside Courier (Robert Wood and on occasion Darren Nelson) travelled to north Wales and met for an exchange of cash and or drugs to take place.
Dawn and Sophie would receive almost daily instructions from Thomas Davies in relation to the collection of drug debts, management of finances and drug deliveries into Holywell.
Dawn Davies was assisted by Michael Munnelly, who acted as a debt collector on behalf of the OCG, and a network of individuals who would either sub deal or street deal in the Holywell area.
Darren Nelson, 32 of Whitfield Road Liverpool pleaded guilty to eight counts of conspiracy to supply Class A and B Drugs as well as Conspiracy to launder money. He was jailed for 15 years and 9 months.
Robert Wood, 58 of Stamfordham Drive Liverpool pleaded guilty to Conspiracy to supply, Conspiracy to launder money and Possession with intent to supply MDMA. He was sentenced to 9 years 11 months.
Thomas Davies 26, of Glan Y Don, Greenfield was jailed for 11 years 8 months for Conspiracy to supply Class A and B drugs.
Daniel Jerome Crossley, 36 of Frances Avenue Rhyl pleaded to Conspiracy to supply Class A and B drugs and received 10 years.
Dawn Davies 47, of Nant Y Coed Holywell was jailed for 9 years 6 months for conspiracy to supply Class A and B drugs.
Sophie Louise Roberts 26, of The Close, Greenfield was sentenced to 10 years 4 months for Conspiracy to supply Class A and B drugs.
Michael Munnelly, 39 of Pant y Wacco, Lloc was jailed for 8 years 3 months for Conspiracy to supply Class A drugs.
Thomas Aaron Wilson, 31 from Cilgant Yr Hen Ysgol, Greenfield received an 8 years 3 months sentence for Conspiracy to supply Class A and B drugs.
Dayle Owens, 31 of River view, New Brighton Rd, Bagillt was jailed for 8 years for Conspiracy to supply Class A and B drugs
Charlie McEvily 24, from Ffordd Pennant, Mostyn received 2 years 9 months for being concerned in the supply of Class A and B drugs and a further 6 months for a breach of a precious offence.
Matthew David Forrester 27, of Rhodfa Wenlo, Greenfield received 3 years 2 months for being concerned in the supply of Class A and B drugs
Peter Beecham, 38 from St Brides Rd, Egremont, Merseyside admitted Conspiracy to supply Class A drugs and was jailed for 5 years 3 months.
Liam Davies 22, Pen y Maes, Holywell was sentenced to 6 years 9 months for Conspiracy to supply Class A and B drugs.
Another defendant will be sentenced at a later date.
Speaking after sentencing, DS Tony Underhill of the Serious and Organised Crime Unit said: "Today's sentences are the result of a painstaking covert operation by a team of dedicated and hardworking officers, following information received from the National Crime Agency.
"The scale and sophistication of the operation run by these Organised Crime Gangs cannot be under emphasized, and the disruption of their business across our force region was a major victory in the war against drugs.
"We are, as ever indebted to the close working partnership we enjoy with our colleagues from Merseyside Police, and criminals should be under no illusion that we will continue to work across borders to bring them to justice.


Did you think energy tax credits were a thing of the past? Well, they're not over quite yet. Reinstated federal tax incentives cover qualifying central air conditioners and heat pumps placed into service by Dec. 31, 2013. The credits cover up to 10 percent of the cost of highly efficient A/Cs or heat pumps, with credits also covering qualifying heating equipment, water heaters, and other efficient HVAC-related appliances and products.
If you've been considering replacing your air conditioner, this may be the perfect summer to do it. It could be your last chance to save with a federal energy tax credit – and could be your most comfortable summer ever with today's well-engineered cooling systems. You're likely to start saving right away on utility bills as well.
To qualify, cooling equipment (air conditioners/heat pumps) must meet standards set by the Consortium for Energy Efficiency (CEE). The federal tax credit for A/Cs and heat pumps is capped at $300. Your local HVAC expert can help you determine which equipment qualifies. Also, be aware that the reinstated energy tax credits may cover qualified equipment purchase/installation from 2012.
Professional installation is just as important as system choice, because, among other things, your HVAC contractor must ensure that the duct system is adequate to handle the new equipment. He must have the experience/skill to retrofit, if needed, to ensure balanced airflow throughout your home.
Consult the experts at Ross & Witmer when you're in the market for a new air conditioning system. We've served the home comfort needs of Charlotte area residents for 68 years. Visit our website for valuable HVAC information or call us today.


Giacomo Puccini was descended from a long line of Italian musicians, and became one of the greatest of them himself. His father was a theorist and the director of the conservatory at Lucca. Unfortunately, he died when Puccini was only five years old. Puccini's first music lessons were taught by his uncle. During most of his childhood, Puccini seemed to be only modestly talented. However, his mother, who had some foresight, continually pushed him. By the time he was sixteen, Puccini was composing organ music for the church.
In 1880 he received a scholarship that allowed him to attend the Milan Conservatory. His most important teacher was Amilcare Ponchielli, an opera composer who wrote "La Gioconda." When Puccini graduated from the Conservatory, he entered his work "The Vampires" into an opera competition. The opera was based on a Slavic legend. He didn't win, but with Ponchielli's help the opera was produced in Milan and debuted on May 31, 1884. Its success prompted Giulio Ricordi, the publisher, to commission a second opera by Puccini. Puccini took a long time writing "Edgar," which was the opera's name, since during this time Puccini ran away with the wife of his old schoolmate. Edgar, at any rate, was not much of a success. Undaunted, Ricordi still continued to support Puccini and both Puccini and Ricordi worked on the next opera, "Manon Lescaut." This opera premiered on February 1st, 1893 at the Teatro Regio in Turin and was a great success.
Manon Lescaut made Puccini famous in Italy but his next work, "La Bohème" made him world-famous. However, his next product, Madama Butterfly, which premiered in Milan on February 17, 1904, was not a success. The audience reacted with boos and catcalls, but the opera was a success outside of Italy.
In 1906, during the French production of Madama Butterfly, Puccini received an invitation from New York's Metropolitan Opera to attend performances of his operas. He went the following year. When Puccini arrived in New York, he found that he was a celebrity. He was feted all over the city and took in some theater. One of the plays he saw was The Girl of the Golden West by David Belasco. This play became the basis for his next opera, La Fanciulla del West. The premier took place at the Metropolitan Opera and was one of the glittering events of the year. Arturo Toscanini conducted and Enrico Caruso sang the male lead. Though the work was enthusiastically embraced, it fell out of favor rather quickly and today is rarely performed.
Puccini remained in Italy during World War I and worked quietly on more operas. In 1921 he moved to Viareggio on the Adriatic Sea and began working on his last opera, "Turandot." It was still incomplete when he died. In 1923 he began to experience symptoms of what was throat cancer. The next year Puccini died of a heart attack. The work of finishing the final scenes of Turandot fell to Franco Alfano, a younger composer. Produced under Toscanini, "Turandot" premiered at La Scala in Milan on April 25, 1926.


text:
jest.unmock('Direction')

import Direction from 'Direction'

describe('Direction enum', () => {
  it('exists', () => {
    expect(Direction).toBeDefined()
  })
})

redpajama_set_name: RedPajamaGithub


We have a variety of tour packages available! A small group of 4 musicians plus a dancer is the most economical. However, we can also present a grand show of 10+ musicians and 4-5 dancers. We can also include Kathputli puppet show.
Born 17 April 1960 at household of Topan Ram Bheel, village Moolsagar near Jaisalmer region. He is an approved high grade artist of All India Radio. He learned folk and classical ragas from Akbar Khan a court musician who is founder of Ustad Arba Music Institute. Taga Ram Bheel is very talented and prominent player of Algoza (double vertical flutes), Morchang, and internationally known as Jew-sharp and also he play Ghara (an ordinary water pitcher). He has performed in France , UK , Spain , Germany , Italy , Sweden , Switzerland , Norway Denmark Croatia and Turkey.
Firoze Khan Manganiyar was born 10th February 1974 at the household of Sakar Khan, village Hamira Jaisalmer . He is an approved Dholak Player in France, Spain, Belgium, Germany, USA, Italy, Japan, UK and he has accompanied the International musicians orchestra and dancers.
Jalal Khan Manganiyar Was born on 13th October 1965 at the household of Sadak Khan, Kanoi village of Jaisalmer. He is a prominent and an approval singer of All India Radio as 'B' high Grade. He sings with a powerful and moving voice while playing Harmonium .He has performed in USA ,UK, Paris (France), Italy, Germany, Sweden, Morocco, Denmark, Norway, Australia for International Festivals of Music .


text:
February 2019 (Volume 28 Issue 2)
Steel demand in the developed world remains healthy
Demand continues to show resilience
Global steel demand is expected to rise 1.4 per cent this year to reach 1.681 billion tonnes, that is double the 0.7 per cent growth it forecast in April, according to Worldsteel
The World Steel Association has doubled its 2019 forecasts for global demand growth for the material used in everything from cars to construction, but warned that the outlook was clouded by trade tensions.
Steel demand is expected to rise 1.4 per cent this year to reach 1.681 billion tonnes, the body, commonly known as worldsteel, said at its annual general assembly in Tokyo. That is double the 0.7 per cent growth it forecast in April, last year.
Still, that would mark a slowdown from the 3.9 per cent growth in demand expected for 2018, to 1.658 billion tonnes, driven by the world's biggest consumer, China. In April, worldsteel said it expected 2018 demand to rise 1.8 per cent from last year.
The steel industry, worth about $900 billion a year, is seen as a gauge of world economic health. Worldsteel represents more than 160 steelmakers accounting for 85 per cent of global output.
Trade tensions between the US and China, along with capital outflows from countries including Indonesia, are clouding the world's economic outlook.
Commenting on the outlook, Al Remeithi, chairman of the worldsteel Economics Committee said, "In 2018, global steel demand continued to show resilience supported by the recovery in investment activities in developed economies and the improved performance of emerging economies. Demand for steel is expected to remain positive into 2019, growing at 1.4 per cent globally."
"Global steel demand faces uncertainty from tensions in the global economic environment," worldsteel said in its outlook.
While the strength of steel demand recovery seen in 2017 was carried over to 2018, risks have increased, according to Worldsteel. The association cited rising trade tensions and volatile currency movements as causes of increasing uncertainty, and added that `normalisation of monetary policies in the US and EU could also influence the currencies of emerging economies."
EYES ON CHINA
Steel use in China was expected to rise 6 per cent in 2018 to 781 million tonnes and be flat in 2019, the body said.
"China steel demand growth is expected to decelerate in the absence of stimulus measures," worldsteel said.
Consultancy CRU estimates that gross domestic product growth in China, which produces and consumes half the world's steel, could drop by up to 1 percentage point if Sino-US trade tensions hurt investor confidence.
With countries including Germany cutting economic growth projections and bearish sentiment increasing, "that will impact intentions on investment and will eventually lead to some downside risk for steel demand," said CRU analyst Wang Li in Beijing.
But Li said there was unlikely to be a sharp decline in China's steel demand.
"The Chinese government is trying to maintain sustainable growth in the economy," Li said.
China has been eliminating excess and outdated steel capacity, including more than 100 million tonnes of illegal induction furnaces in 2017, in a bid to pare its bloated steel sector.
In the first half of 2018, Chinese steel demand got a boost from a stimulus package aimed at real estate and the strong global economy. However, continued economic rebalancing efforts and toughening environmental regulations will lead to deceleration of steel demand toward in China at the end of 2019, Worldsteel predicted.
Both downside and upside risks exist for China, it said. Downside risks come from the ongoing trade friction with the US and a decelerating global economy. However, if the Chinese government decides to use stimulus measures to contain the potential slowdown of the Chinese economy in the face of a deteriorating economic environment, steel demand in 2019 will be boosted, it added.
China continued to close most of its outdated induction furnaces in 2017, a category which was not captured in official statistics. While nominal steel demand growth in China in 2018 is expected to reach 6.0 per cent, the dynamics of steel using sectors suggest growth of 2.0 per cent in real terms. Accordingly, real global growth in 2018 is 2.1 per cent.
GROWTH WILL MODERATE
Steel demand in developed economies is expected to increase by 1.2 per cent in 2019. Demand in the US for steel grew strongly in 2017, benefiting from strong consumer spending and business investment supported by tax and regulatory changes and fiscal stimulus, although growth in the construction sector moderated," the association said. Steel demand growth in 2019 is expected to slow as auto manufacturing and construction activity is expected to see modest growth in the US. The manufacturing sector, however, is expected to perform well thanks to the strength of the machinery and equipment sector.
At the same time, the developing world's steel demand recovery continues, but is facing challenges.
As India recovers from demonetisation and the goods and services tax (GST) implementation, India's steel demand is expected to move back to a higher growth track. Steel demand will be supported by improving investment and infrastructure programmes, although 'stressed government finances and corporate debt weighs on the outlook," for steel in India, said Worldsteel.
Sluggish construction activities and stock adjustments led to slow growth of steel demand in the Asean region in 2017 and 2018, but demand in the Asean region is expected to resume its growth momentum backed by infrastructure programmes in 2019 and onwards.
In the Gulf Cooperation Council (GCC) countries, reforms and a stronger oil market have led to an upward momentum in steel demand, but at a slow pace. The outlook for Iran has turned less favourable due to the reinstatement of sanctions by the US.
Global steel output surges, Mideast upbeat
Emirates Steel in refinance deal
Nucor to build $1.35bn plate mill in US Midwest
Iran plans to boost steel output to 25mtpa
Regional News Events Diary of Events Saudi Review Industry 4.0 Glass Steel Fabrication Turbines Statistics Tenders People


The National Association Against Police Brutality is building a network of affiliated service organizations in all 50 jurisdictions to collaborate with to reform our criminal justice system and end police brutality. NAAPB coordinates with local organizations to offer a wide range of services to victims and their families. NAAPB is seeking organizations that can assist in providing: basic necessities (food, clothing, shelter), spiritual/religious counseling, wellness counseling, community organizing, research and policy development, technology assistance. Our online platform receives misconduct complaints from citizens in all 50 states and refers their contact information to local service organizations for assistance. Each referral is reviewed by a law student or a trained volunteer for accurate contact information and then forwarded to the appropriate organization for assistance.


text:
'"John Ringham"' in Person
Rebellion from the North (1960 Television)
Age of Kings, An
Michael Hayes
Peter Dews
Third episode in a fifteen-part televised series comprising Shakespeare's history plays from Richard II to Richard III (the two tetralogies), effectively presenting a chronological history of British...
Red Rose and the White, The (1960 Television)
Ninth episode in a fifteen-part televised series comprising Shakespeare's history plays from Richard II to Richard III (the two tetralogies), effectively presenting a chronological history of British...
Fall of a Protector, The (1960 Television)
Tenth episode in a fifteen-part televised series comprising Shakespeare's history plays from Richard II to Richard III (the two tetralogies), effectively presenting a chronological history of British...
Rabble from Kent, The (1960 Television)
Eleventh episode in a fifteen-part televised series comprising Shakespeare's history plays from Richard II to Richard III (the two tetralogies), effectively presenting a chronological history of British...
Morning's War, The (1960 Television)
Episode twelve in a fifteen-part televised series comprising Shakespeare's history plays from Richard II to Richard III (the two tetralogies), effectively presenting a chronological history of British...
Sun in Splendour, The (1960 Television)
Episode thirteen in a fifteen-part televised series comprising Shakespeare's history plays from Richard II to Richard III (the two tetralogies), effectively presenting a chronological history of British...
Hollow Crown, The (1960 Television)
First episode in a fifteen-part televised series comprising Shakespeare's history plays from Richard II to Richard III (the two tetralogies), effectively presenting a chronological history of British...
New Conspiracy, The (1960 Television)
Fifth episode in a fifteen-part televised series comprising Shakespeare's history plays from Richard II to Richard III (the two tetralogies), effectively presenting a chronological history of British...
Uneasy Lies the Head (1960 Television)
Sixth episode in a fifteen-part televised series comprising Shakespeare's history plays from Richard II to Richard III (the two tetralogies), effectively presenting a chronological history of British...
Signs of War (1960 Television)
Seventh episode in a fifteen-part televised series comprising Shakespeare's history plays from Richard II to Richard III (the two tetralogies), effectively presenting a chronological history of British...
You are currently searching in Shakespeare. Search all the BUFVC's collections for '"John Ringham"' in All fields.


text:
DANNY CRATES
TV Presenter - Motivational Speaker - Event Host -Personal Performance Coach
Paralympic icon and world record holder Danny Crates is widely considered one of the greatest British disability athletes of all-time.
It is for his talents on the track that Danny gained recognition. A glittering 12yrs that saw him capture 400m bronze in the Sydney 2000 Paralympics. A medal that Danny was not content to settle for. He wanted Gold, and 4yrs later he achieved his dream, winning 800m Gold at the Athens 2004 Paralympics. Danny's Paralympic success was combined with numerous wins at European and World level.
The Essex-flyer received the prestigious honour of carrying the British Flag at the Opening Ceremony of the Beijing 2008 Paralympic Games as he led out the ParalympicsGB team.
Danny has also become a leading media personality, most notably when he played a lead-presenting role during Channel 4's BAFTA-winning coverage of the London 2012 Paralympic Games.
Danny hosted his own widely acclaimed BBC radio show as well as Ch4's coverage of the 2013 World Athletics in Lyon.
He has also published his autobiography "Danny Boy" which was chosen as the Evening Standard top Sports Book of the Year 2012. Danny has continued his career in the media, most recently working at the Rio 2016 Paralympic games and 2017 BDO World darts championships.
In 2015 Danny was a quarter finalist in Celebrity MasterChef.
Simply put, Danny is one of life's natural characters and will speak openly and from the heart.
Danny shares his experiences readily with others – from school children to corporate executives – engaging any audience with his easy-going nature and indefatigable optimism.
As a winner and achiever, Danny is an excellent speaker and motivator.
For more information or to check Danny's availability.


text:
Complementarity-determining regions (CDRs, komplementaritätsbestimmende Regionen) sind Teil der variablen Domänen von Immunglobulinen (Antikörper; hergestellt von B-Zellen) und T-Zell-Rezeptoren (hergestellt von T-Zellen). Jede B- oder T-Zelle produziert eine Sorte Proteinmolekül, das ein spezifisches Antigen, genauer ein spezifisches Epitop, z. B. auf in den Körper eindringenden Viren, Bakterien usw. erkennen kann. Die CDRs sind der variabelste Teil dieser Antikörper und T-Zell-Rezeptoren und somit die eigentliche Quelle der immensen Flexibilität der Immunabwehr.

Ein Satz (von sechs) CDRs bildet ein sogenanntes Paratop. Als variabelste Teile der Immunmoleküle sind CDRs unverzichtbar für das Hervorbringen der großen Vielfalt der von Lymphozyten erzeugten Antigen-bindenden Moleküle. Sie werden manchmal auch als hypervariable Regionen bezeichnet.

Lage und Struktur

Die Aminosäuresequenz einer Variabeldomäne eines Antikörpers (oder sonstigen Antigenrezeptors) enthält drei komplementaritätsbestimmende Regionen (CDR1, CDR2 und CDR3). Diese liegen in der Proteinsequenz (der linear vom N- zum C-Terminus, betrachteten Primärstruktur, also Aminosäuresequenz) nicht direkt nebeneinander. Antigenrezeptoren umfassen normalerweise zwei Variabeldomänen (auf zwei verschiedenen Proteinketten; der schweren und der leichten Kette).

Als Ergebnis hat jeder Antigenrezeptor sechs CDRs, die gemeinsam das Antigen binden können. Ein einzelner Antikörper hat zwei Antigenbindungsstellen, die zusammen zwölf CDRs tragen. Räumlich gesehen, gibt es drei CDR-Schleifen pro Variabeldomäne in Antikörpern. (Das pentamere IgM-Molekül hat daher sogar sechzig CDRs.)

Die CDRs werden auch als hypervariable Regionen des Immunglobulins und des T-Zell-Rezeptors bezeichnet, da sie die meiste Sequenzvariation aufweisen.  Diese Variation wird durch die Neuordnung (Rearrangement) der beteiligten Gene während der Lymphozytenentwicklung durch V(D)J-Rekombination verursacht.

Auf DNA-Ebene betrachtet, befinden sich CDR1 und CDR2 im Variabel-Segment (V) des Gens für die schwere bzw. leichte Kette. CDR3 umfasst einen Teil des V-Segments, das ganze Diversity-Segment (D, nur für Schwerkette) und das Joining Segment  (J). Als Ergebnis ist die Schwerketten-CDR3  ("HCDR3") die variabelste aller komplementaritätsbestimmenden Regionen.

Die (räumliche) Tertiärstruktur ist wichtig für die Analyse und zum Designen neuer Antikörper. Die dreidimensionale Struktur der (Nicht-H3) CDRs in Antikörpern wurde von der Forschergruppe des Cyrus Chothia († 2019)  geclustert und klassifiziert, was die gängigen Definitionen der CDR-Grenzen auf Aminosäuresequenz-Ebene nach Elvin A. Kabat verfeinerte. Neuere Bioinformatik-Ansätze zur Homologie-Modellierung ermöglichten das Herleiten der dreidimensionalen Struktur eines Antikörperproteins aus der Aminosäuresequenz. Dies geschieht durch Berechnungen basierend auf den sogenannten H3-Regeln, empirischen Regeln zur Konstruktion von CDR3-Modellen.

Siehe auch
Antikörper
Hypervariable Region
Nomenklatur der monoklonalen Antikörper

Einzelnachweise

Weblinks
PyIgClassify -- Server für Klassifikation von CDR-Konformationen

Protein
Antikörper
Immunologie

redpajama_set_name: RedPajamaWikipedia


Disponibles en 140/160 ou en 80/90 cm, les versions vont du lit mural au meuble lit qui se convertit en un sofa confortable une fois pli, sans oublier lincontournable armoire lit. Aujourd'hui ils sont principalement utiliss comme crou cage..
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National Eye Institute Research Today… Vision Tomorrow
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State of the Science Remarks—Vision Research
Dr. Santa Tumminia
Acting Director, National Eye Institute
UNIQUE PROPERTIES OF THE EYE DRIVE RESEARCH BREAKTHROUGHS
The vision community is excited to recognize the year 2020. As you know from your regular visits to the eye doctor, the goal is to maintain 20/20 vision. In 2020, the community is also anticipating the naming of a new NEI director. As NEI Director for nearly 20 years before leaving last July, Dr. Paul Sieving left a legacy that positioned NEI as a leader in neuroscience, regenerative medicine, genomics and gene therapy research, including his own gene replacement trial for an eye disease called retinoschisis.
Investments in vision research accelerate biomedical progress because eyes possess unique features. Eyes are accessible, enabling minimally invasive surgery and precise drug delivery. Eyes are relatively immune privileged, meaning many therapies can be administered without triggering an immune reaction. Furthermore, therapies can be administered in one eye, while the untreated eye serves as a baseline comparison to gauge the effect of the treatment—in science we call that the ideal internal control. For these reasons, the first FDA-approved gene therapy treats a form of childhood blindness caused by a mutation in a gene discovered at NEI. NEI is currently funding dozens of other promising gene-based therapies to treat eye disease. The field of gene therapy is once again being transformed, this time by a gene editing technology called CRISPR, which fixes specific misspellings in the patient's own DNA. Editas Medicine, a biotech company building on work by NEI researchers is conducting the first-in-human CRISPR trial to help patients with vision loss caused by a mutation in CEP290, another crucial gene in the eye, which was also discovered by NEI scientists.
First-in-human clinical trials represent the cutting edge of science progress. NEI just received FDA approval to begin the first-ever trial using tissue derived from patient-derived human induced pluripotent stem cells (hIPSCs), reprogrammed adult cells that can be converted into other cell types. In dry age-related macular degeneration (AMD), light-sensitive retina cells die leading to vision loss. Researchers made iPSCS from AMD patients and grew them into retina patches to transplant back into the patient. NEI is also leveraging a major AMD clinical trial to create a valuable scientific resource: a repository of stem cell lines generated from consenting AMD trial participants. The lines can be turned into any human cell type enabling new avenues for basic discovery and drug development. These lines are especially valuable because the basic research can be mapped to patients' deidentified clinical, imaging, and genomic data.
The NEI Audacious Goal Initiative (AGI) pioneers regenerative medicine in the retina to restore vision loss due to injury or degenerative disease. AGI has launched three key research consortia, to image individual cells in the eye as they respond to light, to identify factors that control cell regeneration in the visual system, and to develop animal models to test regenerative therapies. Furthermore, the NIH Regenerative Medicine Innovation Project, part of the 21st Century Cures Act, has funded 16 projects, one quarter of which are vision research. Finally, this fall, NEI will review submissions to the 3-D Retinal Organoid Challenge, a $1 million prize competition to develop functional mini-retinas in a dish for use in disease modeling, drug development and transplantation. In 2019, NEI created a new Office of Regenerative Medicine to catalyze collaboration and coordinate the extensive efforts in the field.
Artificial intelligence (AI) has revolutionized vision research and clinical care in recent years. NEI recently funded a clinical study that tested NGoggle, an easy-to-wear device that can assess vision loss by analyzing signals between the brain and eyes. This portable system based on AI and virtual reality can improve diagnostic testing for glaucoma, a leading cause of blindness in African Americans and Hispanics. The NEI Small Business program funds clinical studies developing AI and telemedicine imaging tools that can provide early detection and prompt diagnostics for glaucoma, diabetic retinopathy (DR), and retinopathy of prematurity (ROP), a significant cause of blindness for very low birthweight premature infants. Telemedicine provides new treatment options for rural and underserved communities. In January, FDA approved an algorithm developed by NEI researchers to diagnose ROP. In 2018, the FDA approved an AI diagnostic system, called IDx_DR partly built on NEI-supported research. IDx-DR analyzes retinal images to screen and detect DR, an important step in managing a disease that causes vision loss in over 30 million Americans.
NEW TARGETS AND NEW THERAPIES FOR IMPROVING EYESIGHT
Research advances in the past year have led to therapies to improve patient quality of the life and reduce vision loss. Dry eye can lead to pain and sensitivity to light, and disproportionately impacts post-menopausal women. Immune cells called neutrophils release a web-like material on the surface of the eye to trap bacteria outside of cells. However, in dry eye, this webbing can sometime induce an autoimmune reaction. An NEI clinical trial in dry eye patients demonstrated antibody eyedrops not only reduced biomarkers of inflammation but reduced corneal damage. Patients with elevated fluid pressure in their eyes are at risk for glaucoma; pressure creates mechanical strain on the sensitive nerve fibers exiting the eye, leading to neuron death and thus vision loss. Current treatments for glaucoma seek to increase fluid drainage to reduce eye pressure. New research demonstrated eye pressure and brain pressure are integrally connected. In animal models, altering brain pressure impacted fluid drainage in the eye.
The NEI Workgroup on AMD Pathobiology explores the disease from genes, to cells, to patients. While AMD genomics studies have revealed candidate disease-causing genes, a recent study used new single-cell sequencing to create a comprehensive human retinal atlas, and then used data analytics to identify culpable cell types. In addition to the retinal neurons, which are known to die in AMD, the analysis pointed to glia (neuron support cells) and blood vessels cells, providing potential new cell targets for therapy. As cells age, they eventually become senescent, losing their ability to divide and renew. Aged tissue that has accumulated senescent cells can attract inflammatory immune cells, which can lead to death of neurons. NEI researchers discovered that messengers derived from omega-3 fatty acids can target senescence genes in animal models of AMD and Alzheimer's Disease, restoring tissue structure and promoting repair and regeneration, pointing the way to new therapies for both diseases. Treatments for the wet form of AMD, as well as DR, target VEGF, a growth factor that promotes sprouting of abnormal blood vessels in the retina. VEGF therapies have slowed or even reversed vision loss in many patients, but for others, new drug targets may be needed. A new study in a model of DR identified Angptl4, a different signaling protein that also stimulates vessel growth. Dicer is an enzyme that cuts apart RNA messages to silence gene expression. Recent research has also demonstrated its role in controlling inflammation in dry AMD disease pathways. However, a recent study showed that absence of this enzyme led to both dry and wet forms of AMD, an unexpected link between the two forms. The team rescued mouse models of AMD by treating with an existing gene therapy to replace the missing enzyme, providing promise for a leading cause of blindness.
2020 VISION FOR THE FUTURE
This year, NEI launched our More Than Meets the Eye 2020 campaign to focus on healthy vision. We have increased outreach to patients and providers through our 65 partner organizations. One popular tool is a virtual reality app that allows users to visually experience the impacts of various visual impairment. In March, HHS released the 2030 evidenced-based preventive health objectives for the Healthy People Initiative. The Vision Topic, led by NEI, includes new objectives to understand the impacts of screen time on eye development, to increase surveillance of eye health at the state level, and to increase access to comprehensive vision services in community health centers.
Finally, NEI is engaging the community in strategic planning. The Anterior Segment Initiative (ASI) focuses on the ocular surface, where the eye interacts with the outside environment. In October, we solicited input to identify key research questions for ASI. Last fall, we launched the 2020 Vision for the Future strategic plan, under the auspices of our Advisory Council. We reached out to researchers, patients, providers, and other vision stakeholders through a Request for Information receiving 252 responses. One theme that emerged was to address unmet needs in Cortical Visual Impairment (CVI), a leading cause of pediatric blindness, often caused by stroke or trauma in utero affecting brain development. NEI is enlisting expertise to help identify and diagnose CVI, and to develop effective visual rehabilitation tailored to CVI. Unlike past plans which have been organized around our six core anatomical programs, this plan will be organized around seven cross-cutting areas of scientific emphasis: 1) Genes to Disease Mechanisms 2) Biology and Neuroscience of Vision 3) Immune System and Eye Health 4) Regenerative Medicine 5) Data Science 6) Individual Quality of Life, and 7) Public Health and Disparities Research. We have recruited panels of vision scientists, clinicians, patients, and experts from other fields to critically review scientific progress, needs, and opportunities to ensure the best vision for 2020 and beyond.
Santa Tumminia, Ph.D.
Santa Tumminia has served as Acting Director, NEI since July 2019. She was selected as the NEI Deputy Director in November 2018, where she provides executive leadership and scientific expertise on NEI policies and initiatives, strategic and organizational leadership, research oversight and priority setting, and financial management. She has expertise in a wide range of vision research issues and has provided leadership on NIH-wide programs in genetics and genomic medicine, behavioral science, angiogenesis, nanomedicine, translational science and rare diseases. In 2019, she also temporarily assumed the role of Acting NEI Scientific Director, managing the NEI Intramural Research Program.
Dr. Tumminia earned her Ph.D. in Biology from Rensselaer Polytechnic Institute in 1987. In her postdoctoral training, she examined the protein-nucleic acid interactions involved in ribosome assembly at the Roche Institute of Molecular Biology, Department of Biochemistry, Hoffman La-Roche, Inc. She then joined the NEI Laboratory of Mechanisms of Ocular Diseases, where she studied the mechanisms of cataract formation and tested the efficacy of anti-cataract agents as well as HIV-1 protease inhibitors. She also designed a mechanical stretch device to model the effects of glaucoma. She then transitioned to the Foundation Fighting Blindness, where she ultimately became Director of Grants and Awards overseeing the Foundation's entire research portfolio. In 2003, Dr. Tumminia was recruited back to NEI by NEI Director Paul Sieving, serving in various leadership capacities.
Key NEI accomplishments include designing and implementing the National Ophthalmic Disease Genotyping and Phenotyping Network or eyeGENE®, launched in 2006. This genomic medicine initiative for rare inherited eye disease is a public private partnership that bridges advances in ophthalmic disease gene identification to clinical care management and facilitates research and treatment efforts. Under her leadership, NEI developed international partnerships with scientists, eye health care providers, private industry, and 6,500 patients and family members. Dr. Tumminia has provided NEI leadership on stem cell policies and initiatives, recently building an NEI Office of Regenerative Medicine to catalyze collaboration. She was instrumental in the development and implementation of the NEI Audacious Goals Initiative in Regenerative Medicine. Other key initiatives include the Age-Related Macular Degeneration Integrative Biology Initiative, the Anterior Segment Initiative and establishing new offices in data science and population health.
Dr. Tumminia has received numerous awards including multiple NIH Director's Awards for the NIH-wide Strategic Plan Working Group, and for leading the eyeGENE® Initiative. In 2018, she received the NIH Director's Award in Mentoring. Her efforts led to increasing the number of female tenure-track investigators in the NEI intramural program, and she has also supported workplace diversity through the NEI's Diversity in Vision Research and Ophthalmology (DIVRO) training program.
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43 Rumors says Olympus is expected to announce the OM-D E-M10 Mark III by the end of August 2017. According to the site, the Micro Four Thirds camera will use a 16-MP sensor, be able to shoot 4K video , support UHS-II memory cards and have a touchscreen LCD.
Fuji Rumors says the Fujifilm X model has been scrapped. Supposedly, the APS-C body would be based on the X-T body and would have been the best of the X-series cameras for video. The site says the company brought the project along but eventually decided to drop it.
Nikon Rumors says it is now certain that the Nikon D850 will be the named of the replacement model for the Nikon D810. The site says the announcement could come within days. Or it might be longer. And it won't be the D820, which it said earlier.
Fuji Rumors has posted heavily watermarked images of what it claims is the upcoming Fujifilm X-E3. The site also listed a number of features that the camera allegedly will have.
Fuji Rumors says it isn't true that the Fujifilm X-T2S won't work with all X-series lenses. The sites a source, in which the site has "complete and blind trust" has assured the site that the body will be compatible with all X-series lenses. The site also said it has no update on the announcement of the body and that it could be either imminent or up to a year away.
Canon Rumors says Canon will announce two of its white-bodied lenses in 2018, although the focal length isn't known. These are the more expensive lenses that are targeted to professional photographers.
Canon Rumors says Canon will announce an f/1.4 85mm L lens at the end of August, as well as three other lenses. The site said the lenses won't be L optics but would be for the EF, EF-S or EF-M. What else would it be?
Canon Rumors says a replacement for the Canon EOS M10 will be announced at the end of August. The site is naming it the EOS M20, which might or might not be true, and says it probably will use a 24-MP APS-C CMOS sensor.


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Healthcare Innovators Celebrated at Imprivata HealthCon User Group
Creative thinking and teamwork drive adoption of Imprivata technology at UK and Ireland healthcare organisations with proven ROI and clinical excellence
These are all world-class case studies in how to apply technology to improve patient care in a highly creative and dynamic way."
— Ross Allen, VP, International, Imprivata
LONDON, UNITED KINGDOM, September 24, 2021 /EINPresswire.com/ — Imprivata®, the digital identity company for healthcare, has celebrated the achievements of customers from the UK and Ireland at its annual HealthCon user group meeting, this year a virtual, but no less glittering, event held on 22 September.
For each of the four Awards, there was an overall Winner as well as Special Commendations in the category, which reflected the strength and depth of nominations. The Proven ROI Award for the customer who has fully leveraged their Imprivata solutions, either by deploying effectively across their organisation, saving time, or realising the value of Imprivata solutions in their workflows, was won by The Queen Elizabeth Hospital King's Lynn NHS Foundation Trust, easily one of Imprivata's quickest and most successful Single Sign-On deployments, demonstrating a fast time to value. Imprivata applauded the Trust for its innovative integration of the Imprivata ConfirmID and WellSky Electronic Prescribing and Medicines Administration (EPMA) applications in the Pharmacy department. The project was a critical success factor in leveraging optimised secondary authentication when clinicians were e-charting, e-signing and e-witnessing patient medication.
Nigel Hall, Chief Digital & Information Officer at The Queen Elizabeth Hospital King's Lynn NHS Foundation Trust commented, "We are absolutely delighted to win this award. It is testament to the diligence and hard work of our project, implementation and wider support staff involved to make this a success.
"We are extremely proud of how we have applied Imprivata technology to deliver a highly secure medicines management methodology that keeps our patients safe whilst improving the digital experience for staff across the organisation."
Special commendations went to:
The Shrewsbury and Telford Hospital NHS Trust following the successful roll-out of Imprivata OneSign in the Emergency Department.
Cork University Maternity Hospital (CUMH) – in collaboration with the Office of the Chief Information Officer (OoCIO) of the Health Service Executive (HSE) in the Republic of Ireland and Cork University Hospital (CUH).
The Innovator Award for the Imprivata champion whose success story resonates innovation and achievement within their organisation, went to The Rotherham NHS Foundation Trust for their forward-thinking strategy, investing Digital Aspirant funding to extend the Imprivata OneSign solution across the whole organisation with 'tap and go'. The Trust has also completed a successful Proof of Concept with Welch Allyn medical devices. This will extend clinicians' digital identity through badge tag authentication to 150 connected medical devices that simultaneously interact with the Trust's Meditech electronic patient records system to reduce errors.
Kevin Grice, Programme Manager at The Rotherham NHS Foundation Trust commented, "We have worked tirelessly to create a connected health environment using digital technology from Imprivata. Winning this award is testament to our dynamic thinking and will spur us on to do bigger and better things in the future."
Bolton NHS Foundation Trust, this year, the team at Bolton NHS Trust was instrumental in guiding the development of Imprivata's new Virtual Smart Card solution.
Salisbury NHS Foundation Trust for their pioneering attitude to embracing Imprivata's beta developments.
The Early Adopter Award for the Imprivata customer that has contributed immensely to product roadmap initiatives, was presented to East Sussex Healthcare NHS Trust for the tremendous support provided by both clinical and IT stakeholders in pioneering a range of Imprivata technologies. Over the last year, the Trust has added Imprivata Mobile Device Access to the organisation's Zebra PDAs, introduced Imprivata OneSign with native tap into existing HP laptops, implemented new infection control keyboards, integrated Imprivata ConfirmID with Electronic Prescribing and Medicines Administration (EPMA) applications and deployed the Imprivata Virtual Smart Card.
Andy Bissenden, Associate Director of Digital at East Sussex Healthcare NHS Trust commented, "As a combined acute and community Trust serving a population of over half a million people, we have come to rely on Imprivata as one of the key systems that helps to create a secure IT estate across our large and complex health environment.
"Over the last 12 months we have tested and applied a variety of Imprivata applications in highly creative ways. It's fantastic that our hard work and leading-edge thinking when it comes to optimising workflows across our sites and services has been recognised with this award."
University Hospitals of Leicester NHS Trust, who has invested in the Imprivata GroundControl solution to improve iOS mobility workflows.
Swansea Bay University Health Board, early adopters of Imprivata and Hospital e-prescribing in NHS Wales.
The Clinical Excellence Award for the customer whose clinical team stands out as an exceptional proponent of Imprivata solutions, was given to South Tees Hospitals NHS Foundation Trust for the fantastic engagement with the clinical team pre and post their investment in Imprivata. Imprivata praises South Tees' energy and ongoing commitment to introducing Imprivata solutions. The Trust is currently implementing Imprivata OneSign and ConfirmID to accelerate access to and improve a range of clinical workflows.
County Durham and Darlington NHS Foundation Trust who saw first-hand the benefits of investing in Imprivata OneSign to complement the organisation's Cerner Electronic Patient Records (EPR) roll-out.
Midland Partnership NHS Foundation Trust – a comprehensive NHS Trust which provides community care, mental health and social care services, as well as a wide range of specialist services including care in more than 23 prisons across the country.
Ross Allen, VP, International at Imprivata concluded, "As the global pandemic continues to challenge healthcare organisations, we are amazed and inspired by the sheer dedication and professionalism of both IT and clinical teams everywhere. These are all world-class case studies in how to apply technology to improve patient care in a highly creative and dynamic way. Against such a backdrop, we not only celebrate the achievement of our very worthy winners, and their specially commended peers, but also acknowledge the rest of the healthcare sector that has given so much to keep all of us as safe as possible."
Andreina West
PR Artistry
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Millbrook: 4th Line Theatre presents "Bedtime Stories and Other Horrifying Tales" October 20-30
4th Line Theatre cannot wait to welcome audiences back to the historic Winslow farm to take part in their world premiere Halloween production, Bedtime Stories and Other Horrifying Tales, co-written by Kim Blackwell and Lindy Finlan. This creepy production is inspired by the images and creatures that fill children's nightmares, alongside a story of the devastating consequences of forbidden love. The show will be directed by Managing Artistic Director Kim Blackwell.
Set on a dark fall night in 1835, Bedtime Stories and Other Horrifying Tales, follows 10-year-old Samuel Deyell as he goes into the darkest night, in search of his missing mother. Samuel is joined on his quest by his two best friends. In the shadows, the children encounter the darkest secrets and most horrifying facets of Millbrook and Cavan. As the story unfolds, audiences will be taken throughout the Winslow farm to secret spaces never seen by audiences before.
COVID UPDATE:
This theatrical presentation will adhere to all provincial COVID mandates and guidelines for maximum audience numbers, physical distancing and mask wearing. Health checks will be done on all audience members and creative team members prior to each performance.
This production travels up and down dark paths and over uneven terrain for approximately 1 km. Trail difficulty level: moderate to high.
4th Line asks each patron to dress for the weather, wear appropriate, sturdy footwear and bring a flashlight to the performance. Masks and social distancing are required. The performances will run rain, snow or shine.
*Not suitable for people with mobility or health issues. Contains frightening scenes and mature content. PG.
CONCESSION BARN & BBQ
Our concession barn and picnic area opens at 6pm; drinks and snacks are available. We will also be running our BBQ from 6:00pm-6:45pm. Alcohol is not permitted on the Farm. For your convenience our Concession Barn accepts cash, debit, Visa and MasterCard.
Bedtime Stories and Other Horrifying Tales
When: Tuesday, October 20 – Sunday, October 25, 2020 at 7 p.m.; Tuesday, October 27 – Friday, October 30, 2020 at 7 p.m.
Where: The Winslow Farm (779 Zion Line, Millbrook)
Written by Kim Blackwell and Lindy Finlan. Directed by Kim Blackwell. Musical direction and original compositions by Justin Hiscox. Tickets available by calling 1-800-814-0055 or 705-932-4445, online www.4thlinetheatre.on.ca, by emailing boxoffice@4thlinetheatre.on.ca, or in person at 4th Line Theatre's box office (4 Tupper St., Millbrook).
<< Orillia: The Orillia Opera House reopens with live performances | Stage Door News | Toronto: Royal Alexandra Theatre to dim its marquee lights in honour of lighting designer Howell Binkley >>


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Because many lenders have changed their requirements it is important that the broker be knowledgeable in the changing regulations in the mortgage industry. MortgageMax has experience in helping individuals navigate through the paperwork. It is important that you understand your financial situation and clear up any troubling issues that can delay you getting qualified and MortgageMax can do that.


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