Good afternoon, everybody. Thank you for joining us for another edition of Condo Insider that is put on by Hawaii Council of Community Associations. So happy to have you join us today. And today I am honored to have with me as my guest, Derek LaJoya, who is with Guardian Group. He has a big array of experiences. He was in the financial field and so he has a lot of experience with that. He's also now has gotten into more site management. And also with site management, he's also been involved with some condos that were also going under repairs. So helping to coordinate all of that kind of stuff. So what we're really going to talk to him about is because he does some site management. And I've always been asked about, you know, some condos are thinking about maybe transitioning to a site manager, but they're not sure. So they ask for what the difference are. So that's really what the show is going to be about today is like what do condos need to look at when they're thinking about transitioning from away from an onsite to an offsite and then the opposite. Cause I've heard that recently in the past couple of months, you know, that kind of topic coming up to my ears. So Derek, first off, what should a condo look at when they're looking to, maybe they have a, they're looking to go to an offsite manager. So they call it site managers, right? Right, yeah, sure. Yeah, no, great question. And it happens all the time. It goes back and forth.  That's why they call it site management company. You know, deferring, you know, basically going to a third party provider for those services. There are obviously advantages. One is, you know, you're contracting out basically all of that service. So there won't be disruption of services. A lot of times when you have an onsite resident manager, now you have to also deal with a lot of the HR, the labor, the labor part of that.  You really do look at more from an employee standpoint. Not to say site manager doesn't have that either, but there is that option of having a third party provider. But when they do also go to a site manager, most often or not, it's usually because maybe they don't need the manager there all the time. You know, one of the reasons why a lot of boards or owners like to have a resident manager, piece of mind. A lot of times maybe a lot of the activities doesn't happen during the day. Maybe it happens during the evening.  But I think one of the biggest things to consider when you're doing that is, does the association own a unit? When you have a resident manager, usually, you know, the association already owns the unit. So, you know, it is convenient for them to already have the resident manager. When they don't own the unit, now that becomes, you know, an added cost. You know, from your operating expenses, you got to rent out the unit for the resident manager. You know, their utilities, all of that have to be paid for. So from a cost standpoint, I feel like a lot of times, you know, most often just then the duties that are being acquired is the owner unit. Nowadays, right, it is expensive to rent those out. So that's probably something that all associations should consider if they want to go that route. So whether it's an onsite or even a site manager, I've had conversations with some that said, essentially you want them to do the same amount, same work. So you still have to detail out in either case, whichever way the condo is going to do, you still have to detail out a job description and what the expectations are. So that could, so with some people, I said that could be the starting point of creating your, also your employee manual, so to speak, right? It's really detailing out your job description and it should be detailed to the point of like, how do you want your grass to be cut? How low, you know? Or certain trees, everybody has their own interpretation of how they expect the tree to be trimmed. You know? Some just whack it and then let it grow back because it's less time consuming where others want it to be. You know, you can trim this little one every once in a while, you know?   And especially that gray paint just stains. Yeah, yeah.  So, but with a site management, you of course would also detail that out for the site people to maintain that property to that expectation, right? Yes. There's some, I said, take even pictures to include in your contract. So you have control of your expectations. So what if they went from like a site manager, they already tried the resident manager, they're kind of doing the site manager kind of a thing, but they're thinking about doing like security guards, like in the off hours, like evening time, you know, they have someone during the day and then in the evening time. And really, it all depends too on how much stuff is going on in the condo. Like is there a lot of household violations or disorderly conduct, that kind of stuff, right? But even again then, you would have to have your security guards trained on household and how to handle that, right? Totally, yeah, I think you hit it in the nail. One of the first things to do is really identify your needs or what is the priority of what you're trying to achieve in a property. So like if you want a site manager, even a resident manager, either one, and let's say, you know, town home associations, that's a great example, you know, you have a lot of landscaping, but there isn't ROI if you have a site manager, that can landscape, that can maintain a lot of those common areas because that's probably the biggest work that's being done on a day-to-day basis, you know, five days a week for however many hours you have him or her contracted out.  What is your immediate need? What is the biggest focus you guys want us to do? Because if it is in maintenance, then I would have to have a fit for that property. But for some associations, maybe they have already the landscaping contracted out, they have maintenance people contracted out. So we just provide administrative duties. And one of that is coming in a second, you know, walking around, interpreting the house rules, helping the property manager furnish violation letters and keeping track of those violations. And it's interesting, because as we come to, you know, as we discuss this more and more, I mean, everybody knows that property is age. So what ends up happening is needs are constantly changing as well. So with that, right, before when things are new, you just have to be pretty general with all the areas of, you know, condo management. Maybe you have all owners who, you know, really care about the property, they're not really renting it out. So there's maybe not a lot of violations or everybody's still playing good neighbor. Over time, you don't know what that ratio looks like. So that becomes a major issue. You know, we noticed it too, like, you know, pets are becoming more common, right? So maybe that becomes a major issue. But then, you know, then you start to decide, okay, you know what, this year maybe we want to focus on getting all the behaviors back in place and we need someone to really, you know, enforce the house rules. Or maybe over time, like you said, landscaping is just becoming a lot more of a bigger need. So that becomes a focus. So like you said, as the more you can detail out kind of what you expect, let's just say, even if it wasn't just a resident, let's say you had unlimited budget and you just said, okay, I'm going to contract out every facet of managing a property. So from maintenance to house rule enforcement, which is like security services, through maintenance, through handyman repairs, you could actually kind of get creative. Now you can decide, does it make sense as if he's about to contract these out or does one person exist that can do all of that? And let's say it's so hard to find a jack-of-all-trades. I think that's why we see a lot of turnover. Yeah. Some of it's great with landscaping, some of it's great with maintenance. Maybe they're great at that, but it'd be unrealistic to all to expect them to be great at house rule violations and typing out those letters when they're just out on the field all day, you know? And we can take a look at that from any industry, from construction to, I mean, any of the labor services industry, some one of these superintendents. But then you have some project managers that are really good at the paperwork, and that's to say, right? So I think that's something to, every association should really, basically when they're planning that out, how to be realistic. Yeah, I think, well, I'm sorry, go ahead. No, I just like be realistic. You know, I think when you lay it out, you could really find somebody that can fulfill all those duties in a 40-hour work week. Yeah, and with the workforce the way it is today, I mean, it's so different. And I think, like you said, it's hard to find someone that can do everything.  Some of them like to do landscaping, you know? But they may not be strong in maybe some kind of administrative things. So you may have to, you know, realign what the job description might be and the salary, because you might have to hire someone else to compensate for what that guy, but the workforce is really hard. So sometimes I think you have to work with what you have and get creative and, you know, do things based upon the person's strengths. Because I think they will last longer and that's what you want. You don't want the constant turnover. You really want that person and build upon their strengths. And they eventually, maybe they might be able to get a handle on that administrative part of it. Because come on, learning computer skills can take a little bit while, you know, even Microsoft, when they do an update, you're like, oh my God, what did they change now? You know, it takes a little while to get used to it, even though you're using it every day. So, I mean, that's where some condos have to kind of like realize that. And then one of the other things that I heard, and I heard this really a long, long time ago, and it's always stuck in my head, is when people come home from work, you know, they work during the day and they don't see anybody around. You know, and I said, well, you have to kind of realize that they've probably already been out doing stuff during the day when you're at work. So, you kind of can't really expect them to be visible 24 seven, you know, and then you have some other managers or site people that kind of, they know how to manage their time. They got to do some yard landscaping. So, they know that it's either the morning or late afternoon. They don't want to be out there in the hot sun getting dehydrated, you know. So, I really, so some associates need to also take that into consideration that, you know, some of them that they may do their jobs during certain times of the day, that makes it easier, even the employees, if they rather do certain things in the late afternoon because of the heat factor or some things early in the morning, they got to kind of like be a little semi-flexible, hear them out as for the reasons why, because they could be very valid reasons, like they're going to be shooting down a lot of things. You don't want to do it when there's going to be constant traffic, people going to work, coming home, don't want wet sidewalks, right? You know? So, what happens when like on, I guess for me, that big thing is like on a site manager, how often is the expectation of them to be there? And I would think the condo itself has to think about the future, okay? If you're going to switch to a site manager, do you have any repair projects in the looming? And how is that site manager going to be able to manage that when he's also has to manage other property, right? Yeah, so it's a great, yeah, you bring up a great point. So, same thing when we get a request for proposals, I ask a lot of questions. Is there an office? Because obviously we would have to know how to, for that work day to look like, office, do you have a support? What are the projects coming up? How many water leaks have you been having? Because that would give us expectation, how many after-hour calls? Because again, you hit it right on the nail. I think one of the things that aren't talked about a lot, which could be because it's across all industry is the burnout rate, you know? This is not an easy job. And a lot of times we're dealing with so many owners that it's not personal, it's just, they're there to, the owners have complaints. And so, a lot of managers, no matter, it's the general manager, resident manager, manager itself, even when we hire, we ask about that, like, angry tenants are going to come at you, give us situations, what is your tolerance for it?  So, you know, with that, right? Like those have to be addressed as well in order to have a long-term successful partnership or like a long-term successful like employee or a contractor if you're using a third party, if you want it to be long-term and sustainable and then you could work through it, there's gonna have to be a lot of working things, you know, between parties. And I think those have to get addressed. So, like you said, yeah, what are the projects coming down? Because if they didn't sign up for it, and all of a sudden you throw them all of those expectations, that's when there's a gap. I think when there's unrealistic expectation in two parties, and you and I know, like that's kind of a lot of times when this can happen. It's like- Yeah, I appreciate what you guys have. When he has no experience in how to even coordinate, you know, these people are coming outside, what do I do, you know, that can be really scary. And I've had some questions from some other condos, like, yeah, again, going back to workforce. I mean, the pool can be very, you know, very minimal. And like I had a conversation with one person, they were looking at these resumes, you know, one had past paralegal experience and another one had passed, his thing was boats, like, it's a red flag at the harbor, walking distance away at the time, you know. But, you know, they had no resident management type or even management type of experience. And I said, so what if he started them off without a manager title, and maybe put them into like a different kind of title and kind of ease him into that because he's gonna be into a big learning curve. Right. You know, and he bring in another site manager that can kind of mentor or guide them along, it might get additional costs, but you might not only need it for only, maybe a couple of months, you know, but maybe do a something specialist or something, you know, versus a manager, because, you know, someone coming from no experience and all of a sudden being a manager, that can be kind of a little hard. Right. To, you know, to kind of coordinate all of that stuff. You know, like, I remember on the main line, my niece was, I mean, she was only a teenager, she became a store manager and I'm like, what? Responsibility for keys and, you know, all this kind of stuff. I'm like, what? She's so nice to be like, what? So I was kind of like a little alarmed with that one. I go, oh, that's kind of scary. But just because you're hiring someone, this is all I'm actually mean, you have to give them a manager title, right? You can kind of give them an interim title and let them work into that, you know, and then also make sure you check with them. Like, we always check with Duncan Ark. He's a big condo labor attorney that we always refer to. And make sure your contracts are all in sync as well, right? So tell me about some of the bigger condos that have general manager. Oh, yeah.  If you become a general manager, you have staff that become specialists in those fields. But I always say too, I mean, you get general, every general manager should have at least done that work or know about that work. Because that's the only way you're gonna quality control it. So for example, if you're gonna head the different departments, you know, with like housekeeping, for example, how will you know if that's, because it's so subjective, how do you know if that's, you know, like a great quality? How do you know if their working schedule is accurate to the needs of the building? Are you over staff, under staff, landscaping? Do you at least have some idea of, you know, bougainvillias and hedgers, molars, and because you will be ordering equipment, putting in gas, how do you know they're not, you know, and then how do you make it like, you know, efficient, for example, for like, okay, do I need a two or three man crew to rotate around this property? Do I need to just outsource it at that point?  How do they patrol? How do they enforce rules? What are they looking for? How do they answer tenants?  So I think, you know, if I always say, if you wanna be a good general manager, and this is again, this, I think this is the general lesson anyway, as a leader, you wouldn't tell somebody to do something you couldn't do yourself. And that's just from a respect level anyway. And that's kind of always been the cornerstone also of guarding management. When I tell a lot of our managers, if you're trying to climb up in the industry, yes, don't, you know, you wanna humble yourself and can you clean? You know what it looks like. You know what, you know, can you, and that's the process of always learning and evolving. So everybody has to start somewhere. And I think it's like anything, if you're missing some fundamentals along that process, maybe that's when it might actually surface, that weakness will surface up in like the most, you know, stressful situation. And I've seen that quite a bit, you know, and my time even prior before that, you know, consulting some of these buildings and I'm picking on some of these buildings either interim or whatever they may be. You know, I look into operations and who I fit in there needs to be able to do every facet of the job or else how do you, like you said, if you're putting together duties and scope of work, I hope you know that what that looks like to yourself. Yeah. And then you don't see too many general managers that all of a sudden they graduate from college or whatever they may be. And all of a sudden they jump to general manager. I think they'd be overwhelmed and they won't succeed. I think a lot of them probably start from lower level work their way up, you know, whether it's F and B manager operations and they move into other departments from hotels. I mean, whatever that may be. They work from the ground up and then they really learn every facet of the operations. And I think that's what these DMs, you know, the ones that are, they for sure know how to. And it's the respect and the appreciation for the work, you know, because they've done it, they've been there. So they have a level of respect and dignity for that work that the other person is doing that they used to do way back when, you know. And like you said, there's different ways to clean. Like someone was complaining to me about the way a certain person mop the hallway. And you know, with that gray paint, how it has little grooves in it. They go, no, they're supposed to do it this way. I could bottom line it. Is it clean when they're done? Whichever way they do it, is it clean? Right, right. Because it was kind of, I mean, I heard it from both sides. Two different people, different times of the day. And I told them, I can mop my floor one way. You can mop it a different way. But at the end of the day, is it clean? Right, right. Four marks, that's the bottom line, you know. So, and you know, Security Guard too, when you're a general manager or even any manager that oversees all these different people, you have to understand like Security Guards, they're licensed individuals. So you need to know what the licensing requirements are. And even like an overview of what they need to do in order to get licensed. Right, as a general manager or any manager, if you're gonna hire people, you have to know what their scope is, especially when you're talking about licensed individuals, just like with contractors, you know, you have to know what that expectation is. You have to understand your own bylaws and declarations that's like a project don't require bonding, because you're gonna be the support team for your board. Right. So you have to also help the board in making sure they follow what they need to follow. Right. Permitting, yeah, permitting has its issues, but it's getting fixed.  And they've kind of improved some of their turn times that I've heard from other people. And these are like bigger contractors that have these projects, I said they've seen some changes. So good, you know, and that's really good to hear. We just have to be patient. Can't move the mountain overnight. So any other suggestions you have for condominiums for boards that are thinking of switching one way or another, you know?  And a lot of times that it's when they are looking for, you know, whether it's the resident manager or a state manager, and I do it as well in my hiring practices and continuation, right? It's one of the things that I wish to continue with them is what are they looking for? What is the candidate looking for? And I think that's something that's obviously when you're doing interviews, then you're doing, you know, you're trying to maybe recruit a potential candidate. A lot of times, you know, it's so easy to kind of go through the interview and the resume and you hear what they want to hear.  But at the end it's kind of like, you know, what are they trying to see? What do they want out of it? And do you see that it's a long term fit? So oftentimes, like, you know, you see a resume and like what we said, if the duties don't align with the expectation, how long will this candidate stay? Are they overqualified? Are they underqualified? You know, you have certain things that can make them stay for a long time. So no matter which they choose, like, you know, I know a lot of employees, they want to just learn, develop and grow and become better. And then do you have that in the budget to, you know, give them milestones and increases if they're performing well? So, you know, one of the things is like, you know, resident manager, you're basically putting a lot of investment in somebody already. If you're going to go to the resident manager route, I mean, they're going to move in, right? They're settled, they're there to stay, you know, and then, but how do you make that a three, four, five-year plan? Because if you're retaining somebody for four, five years, you're doing a pretty good job, you know? And then you've happened, right? Yeah, yeah. And so if you don't, but if it's a trial thing, then sure, go to site manager route, you know, that's a little bit easier to, you know, cut the relationship as opposed to if somebody's living on site. Yeah, yeah. And then you want to go with a third-party vendor to see how that may look like until, you know, you want to go to full-blown resident manager. And even if you own the unit, maybe you could rent it out for a year, just to keep some of those costs.  That's a good point to rent it. I mean, you know, but you already have a resident manager unit rent it out for a little while because that might help offset some certain things. I mean, that's a good point. You know, you could try that. I mean, trying is better than not trying at all. You can say you tried it. But again, sometimes you can't, if it doesn't work, I wouldn't like say, oh no, we tried it, it was horrible.  Like, what could you have done to make it better? You know, did you guys fail in having written documents for him to follow? You know, and things like that. And if you're going to hire someone to me is like when it comes to repairs, if they're willing to learn, you know, or even try, try to give them that opportunity because it just makes them feel that much better. You know, and you're helping for someone to learn the business that the condo can benefit from. No, like when, when I would always, a big advice, a big advice, our recommendation, I've made a lot of associations that need to be hired in part is there's no just things, a perfect candidate. We know, because we hire all the time, we're constantly recruiting, we're constantly interviewing.  It's not like somebody goes to school and say, I want to be a resident manager. There's really no pathway to it. It's really like a hands-on experience. You just stumble on it, you get lucky and you've got your way in. I see job description saying, I want a five-year minimum experience with an arm. Well, now you're limiting your pool. I mean, you have to get somewhat creative. We only have how many people here in Hawaii for a labor market. So what we do is we get creative. We look at a resume, we look at all the, maybe the little X factors, right? Like, okay, this person was in customer service all the references are great things. They show up on time, they're hardworking. They've progressed, they've stayed in organizations for a long time. So you know, they're committed. They're not just jumping all over the place. I could work with that. I could work with a lot of soft skills and true character. I think that's something that sometimes we overlook. I mean, we can look at something on a paper. They could be great on paper, but if character is not there, I'd rather have the person or character that I can groom and learn. And then from there, can I set up this person for success in the next three years, giving them training, putting them in a lot of classes that was going to benefit them. And if they succeed, give them more incentives to work harder, work better. And that's the increase in your salary or giving a bonus. And I think that is a big HR, more of an HR discipline than anything because whether it's in the kind of world or any other industry, every organization faces turnover. Turnover is very costly to any employer because of the training and the learning curve that was already set in place. And now you got to redo it all over again. So I think more than whether you get an on-site manager, resident manager, I think the real question is how do we keep this person for a long time and are we losing the right person that's gonna stay for a long time? I see more often than not, I see, even for us, I got staff that said, this is a great person, this person is great. I'm like, I don't think this person is gonna stay with us though. I don't know that they, this is just great for them. Yeah, but that's okay if we are very transparent about it and we also need that just for now, right? And so I think that's something that's overlooked it. It's almost nice knowing from the first like, hey, I'm looking for something now, but I really don't know. And we all know the job market's kind of really weird. And he may settle into it. He may like it, never had this job before because, but he's like iffy, but he applies and everybody likes him and he could be upset going, well, I'm not sure I wanna try it. You know, and he may be your guy, right? You'd be surprised, a lot of our most successful managers that have, we actually were able to place them to become resident managers that go back in our experience but they had all the other great that we knew. Cause you're gonna learn the kind of management side, the X's and O's, right? But you can't teach the other stuff sometimes. Like I said, the work ethic and the ability to learn quick. I mean, everybody's ability to learn is a wide range. So, and once you start to identify that and you start to really have a plan with your employee or your manager, I think no matter what, both sides are gonna be pretty happy with being committed. And again, that's just from like any industry you go in, right?  We're gonna put you in, once you get settled in after you've passed six month probation, maybe we'll give you a just increase, cause there is gonna be a negotiation back and forth. Somebody's gonna ask for 16, and say, you know what, we'll give you 57 to start. If you can make your six month and it's satisfactory, give you that 60. So it's constantly, like they have something to work for and you have something to measure. And a lot of it could just be proficiency. So, okay, in six months, you show me a proficiency and the governing document. And we can measure that through how many house rule violations have come through and how have you result that issue, how quickly. With the property manager may be able to look at it and say, you know what, you interpreted that correct or you did not interpret that correct. You're able to turn around really quick and issuing that letter. Same thing with maintenance things. They're like, okay, you know what, if you get proficient in getting bids, right? Like, how well are you in getting us standardized bids, putting in a report? I think those things are measurable and then that way you can start to, and also the employee is gonna feel a lot more motivated because they know they have something that's objectively able to chase. Because what is good, right? Good is always gonna be pretty relative. So, I think that's gonna be a big factor. I think right away, it was in the next, I don't know how many 10 years just because of the labor market. Okay, one last question. So how do you suggest your people that you hire, how do you suggest that they handle when a resident or it could be a board member that tells them how to do their job? All right, that was all the time. I know. I mean, this is where customer service has to come in first. Just say, okay, I hear you.   But also right before you get to the job, know your protocol, you know, who do you answer to? Property manager, board president, kind of like a trifecta, or your chain of command. Listen, bring it up to, you know, escalate it to the necessary parties that need to address that. You know, most certainly you have every resident manager, state manager, building manager, general manager, just like in any job, right? You need to know who you have to report to and then you got to know when to bring things up because probably that's not going to be your battle. It needs to be escalated to whoever is, you know, the higher up is, you know, the one that's supposed to be handling that situation. Yeah, and I think that's the hardest thing for a resident manager or a site person or even the landscaper guy that's coming to treat it.  That's kind of hard. Yeah, so I always say we have like default things, like for example, you know, somebody's saying that, oh, okay, now I understand, I'll bring it up to my community supervisor, I'll bring up the private manager and the board president and the board that, you know, that you saw this or you wanted me to, you know, focus on that first. I apologize, I just got directed to do this. This is the task that I've been directed and that I got to follow. But I will certainly bring up your picture to the board president because that's something that's probably going to be spoken about in board meetings. But same thing, if they don't know the answer to something, okay, let me write this down and let me get back to you through your research. If it's in a gray area, make sure you ask the private manager first and then you inform the board so that you're not going to make a decision or you're not going to inform the owner on something that's completely inaccurate that could make you look, you know, that could cost your job or give you a reprimand because I see that happen all the time too.  But, you know, as a manager, one of the most important key things to make sure of our life, you want to make sure that how you interpret it, what, we're just there to do the comment.   You're just being fair. You're going to do your job to the best of your ability.  And there's some owners, I told them, I said, well, you know, they're going, well, he's interrupting this. You spoke so beautiful and I go, let me ask you this question. And if it's pertain to landscaping, I said, is he changing something around? And I said, is he, maybe you should ask him a question like, is there something broken? Because there was one, I mean, there were things to about one area that they were kind of taken to the part. And I said, so if it's constantly wet, that area, to me, that's the red flag. And that's why they're doing something because there's a leak somewhere, you know, or they're trimming something because the rats will trim, climb the trees and jump from roof to roof. Or it'll scratch against the building and it's disruptive to that person where that wall is.  There's sometimes reasons why certain things are going to get done for certain reasons. And it's maintenance issues, preventive maintenance, you know, trying to figure things out. So I said, you guys have to be open to listening and listening to the why's and why it's being done. Because a lot of times there's a reason why. There is, yeah, it's interesting because we manage townhome associations and you know, honestly, the landscape and all of their pots and plants, it looks beautiful, but it starts to touch the eaves, starts to touch the roof. But in the house rules, right? It says there are limited common elements. So, you know, and that's why we always train our managers to read the rules and they're there for good cause. You know, it's to make sure you maintain the value. Like once they start to go through, you know, the fences and all that, that's more cost associated with repair later. So if they can kind of, you know, communicate that. I remember one area was, and that area, we ended up cutting it and that's where we figured out there was all the rats for congoing. So it was just trimmed down to bear, kind of get rid of them or get them under control at least. So, you know, where they're hiding and stuff like that. So we had told that the people that I told, they were fine with it. When you're solving that, you know, that's the goal of it. Right, right. Okay, Derek, so I think we're at the nearing of our show. I really, really thank you for spending the time with us and going through it. This was very helpful. And I think it'll give a lot of boards of insight on their decision-making, on their management, their onsite management for their properties. I really appreciate you joining me today. It was very informative. Oh, my pleasure. Thank you for having me. Okay. Thank you, Derek. And thank you everybody for joining us. Hope to see you guys again next week for another show.


Okay, we are ready to start again if you can just take a seat. It's my pleasure to introduce the next speaker, Brian Dietrich. He's one of our senior fellows in medical oncology. He's been with us in our urologic program now for more than a year. And I'm really pleased to say that Brian will be starting his job next year. I'm passing over the baton to Brian to help take care of our urologic oncology patients at the VA. So he's going to be talking on the overview of medical therapy for patients with kidney cancer in my introduction slide. I told you that the last decade has really evolved with therapies for kidney cancer. So Brian is going to briefly touch on the tyrosine kinase inhibitors, which is the bulk of treatments that we use for patients, both when they first have diagnosis with metastatic disease and subsequent therapy. And then that will follow by an immunotherapy talk that we'll have in the next session. So thank you, Brian. Thanks, Dr. Schoenevest. Can everyone hear me okay? So like Dr. Schoenevest said, I'm Brian Dietrich. I'm one of the third-year fellows. I've been here at Stanford for five years and lucky to have Dr. Schoenevest as my mentor. So hopefully she's taught me a few things I can pass on to everyone today. So we're going to be reviewing what types of drugs we use in advanced disease and kidney cancer. So I'll start just going over what these kind of drug classes are and then how these drugs actually work and some of the thought behind why we use these over things like conventional chemotherapy as is common practice in other disorders and cancers. And then it's a very evolving landscape actually on kind of which treatment options are the best. And I'll go through kind of some of how the risk stratification that we create for patients when they're first diagnosed and how that plays a role in how we think about what the best first treatment option is and then which treatment options we may use sequentially throughout their treatment course. And then each of these treatments has some anticipated side effects that our patients go through and I'll review, at least kind of an overview on how or which side effects are most commonly observed in each of these classes. So in 2017, the three largest groups of therapeutics that we have is the first are these VEG F inhibitors which are essentially blood vessel blocking drugs. And we have a number of these that have been approved through the FDA with some of the most recent ones, CaboXantinib and Lenvatinib in the last few years and some of the earlier ones with Su-10th or Su-Nitinib. Yeah, back at least within the last 10 to 15 years this landscape has been evolving. The rest of the talk will focus on these mTOR inhibitors that still have a role and are particularly kind of highlights when we may consider choosing this, particularly in the first line setting with Tim Serolimus based on some of these risk stratifications that we do. And then I'll briefly go over some of the immune therapies and how this is kind of changing the landscape of what we would consider for first line therapy and then there'll be a whole talk dedicated to those. So how do these drugs work? So I mentioned the VEGF inhibitors work by blocking blood vessels. So we've learned a lot more about the genomics of kidney cancer and one of the most frequent mutations that occurs is in this protein called VHL or von Hippel Lindau that we see in over half of advanced kidney cancers when we do sequencing of our tumors. So in the normal protein it actually works to break down or destroy some of these transcription factors called HIF, which when present they actually increase expression in another molecule called VEGF. So VEGF works basically by creating blood vessels. So if we think of a cancer cell these kind of start off as small tumors and normally they're able to get their kind of nutrients, their oxygen from the surrounding blood vessels but as these tumor cells start to get larger they have a higher need for access in order to pull in more nutrients and supplies in order to survive. So one of the things that happens is they upregulate these transcription factors or these HIF factors and this ends up leading to higher levels of this VEGF that essentially creates additional blood supply that the cancer feeds on. So one of the main targets is all of this class of medications that work on receptors that end up blocking the activity of this VEGF molecule and that's where basically by killing off the blood supply the tumor can't grow and survive and we take away one of the survival advantages to the disease. So over here on the right of this slide is kind of this next group are these mTOR inhibitors. So these work basically through a signaling pathway. So all of our cells basically work by responding to signals from the outside environment or signals from outside the cancer cell. So these can set down cascades that basically end up sending signals to the center or the nucleus of the cancer cell in order to basically tell these cells to divide, to survive. So there's all these complicated proteins that result in this interaction. So two drugs that we actually use, the virulimus and temsirulimus block part of this signaling that gives these cells their survival advantage. And the last group of drugs that we use are these newest immune therapies which are the new kids on the block. So we've known for a long time in kidney cancer that this is a very immune responsive disease and this goes back to some of the earlier trials that Dr. Shah will be talking about where we used to use high doses of cytokines in order to treat kidney cancer and even had durable responses in a number of patients. So we all have an immune system that's kind of floating around and we go through a process basically called tolerance as our immune system develops where our body recognizes us as us and anything else as foreign. So cancer cells, by definition, they're not our tissue. It's a foreign molecule that's kind of in our bodies. So one of the ways that these tumor cells kind of evade our own recognition of our immune system is through this interaction of a group of molecules and probably the most well known are these PD1, PDL1 molecules. And a lot of you may have seen commercials for a lot of these new therapeutics that try to exploit this pathway. So with this, if there's interaction between PDL1 on a cancer cell and PD1 which is on one of our immune cells called a T cell this basically down regulates the immune system or basically masks our immune system from being able to see cancer as it was designed to do. So we take advantage of this by giving an antibody that blocks that signal so then the immune system can actually go in and attack cancers and that's been the more cutting edge and more exciting treatment options that's come along in the last few years and is used not only in kidney cancer but has approval in a number of malignancies. So before I move any further, I'm just going to go over a few basic definitions of just some terms that we use in advanced disease. So I know our surgical colleagues had already talked about nephrectomy which is the surgical removal of the kidney that contains the tumor and there's a role even in the metastatic setting where we'll consider actually taking out the tumor even in patients that have disease that has already left the kidney and gone to other locations. In certain patients we'll also consider removing one of those kind of tumor seeds that's already in another organ which is something we call them metastatectomy and that's something that can be considered particularly if we're doing scans and we see one kind of tricky spot that might be growing but we see no other areas. Sometimes we'll talk to our surgeons to see can we consider actually removing one single metastatic site if everything else on the scan looks okay. Something that we call adjuvant therapy that I'll just briefly touch on today this is when we would give a systemic therapy after a surgery and there's been some studies that have looked at some of these drugs in kidney cancer and then the term metastatic is basically equivalent to what we would say is stage 4 disease. So this is when seeds of the cancer have already left the kidney and have ended up in other locations like the bone, the lung, brain, lymph nodes essentially anywhere in the body and then particularly we can't talk about oncology without looking at a lot of our clinical trials that drive the recommendations for the treatments that we have. So kind of the best trials that we have are what we call these randomized trials and this is basically where patients are randomized to one or another arm or one of several arms on a study. The randomization is to try to kind of separate all patient factors evenly between groups. So we're really looking mostly at the disease entity and have basically equal patient populations in each. And then each of these clinical trials occurs on different phases. So you may have heard of these phase 1, 2, and 3. Phase 1 studies, classically, are answering the question what's the best dose of the drug that prevents a lot of side effects. And then these move into what we call a phase 2 study which is looking is there actually efficacy or does these treatments actually work within a particular disease where we're trying to answer a question. And then the largest are the phase 3 studies which are trying to validate that question and kind of actually come up with a new standard frequently by comparing it to a current standard that's in practice. So treatment of the metastatic disease, this is a common scan that we see in our patients when they come to our urologic oncology clinic. They'll have a scan that shows frequently enlarged tumor as you can see here in the left kidney. And then they'll have areas elsewhere on their CT scan or PET scan that end up having a biopsy that shows basically this is a common finding of what we call clear cell kidney cancer that would confirm metastatic disease in this patient. So the landscape has kind of changed over the last 15 years or so and this is all of the drugs that we have available to treat advanced kidney cancer. And as you can imagine when we have all of these treatment options then it becomes the question on which of these treatment options is the best to recommend for our patients. So these go back to 2005 when the first of these small molecules, these tyrosine kinase inhibitors or these blood vessel blocking drugs were approved all the way to even last year in 2016 when we're still finding ways to exploit these blood vessel blockers through therapeutic options. So which drugs are the best to give first or which do we consider for our first line or upfront treatment? So this is kind of a table that shows all of these drugs and how we kind of sort of triage them into our clinics. So the first thing that I frequently do is actually just think about what's the risk when we see a new diagnosed patient. So there's a few basically algorithms that we can actually plug numbers into. This is one example from the group over at Memorial Sloan Kettering where you can actually look at a few prognostic factors of a patient's disease when they're first diagnosed. So in this they look at basically how long it takes in order to start a first systemic treatment. What are some of the lab values on the blood work looking at a marker of hemoglobin, of calcium, another protein that's commonly seen in cells called LDH and then just the physical performance status or how well a patient looks. So there's different variants of these prognostic scales that we look at and they can be useful in kind of predicting how aggressive we think a disease is just from the get go and do we think that based on some of these models a patient is statistically more likely to have a worse outcome compared to if these factors weren't present. And this is just one, there's many other models that will change some of these numbers. One that actually substitutes LDH to look at some other blood cell counts in your white blood cells and platelets. But this is just an example on how we might stratify a person that can be useful. One for how we determine treatment options as well as if we're thinking about clinical trials in the upfront setting. We're looking more frequently at using risk as part of that consideration. So a few questions to consider actually when we're choosing the first line drug. And this is something actually we tend to bring up in patients that I think can cause a lot of anxiety actually as a side effect is do we actually have to start a treatment even in the advanced disease right away? Do we have a little bit of time and can some patients actually safely be watched off of any treatment? Another consideration is with these tyrosine kinase inhibitors I had showed this slide that there's many different options. So which one of these is the best and is there actually an optimal TKI to use first over the others? And then currently in 2017 while we're coming out with all these new drugs, these new immune therapies, is there still a role for some of these older mTOR inhibitors for the frontline treatment? So this is an article that was actually published a little over a year ago in one of our oncology journals, The Lancets. And this is from Brian Rini who practices out of my old stomping ground in the Cleveland area looking at basically if we take patients that have asymptomatic disease meaning they were diagnosed based on a scan that was either done for surveillance or another indication and then had confirmation of metastatic disease if we actually watch them before doing treatment kind of what's the typical trajectory on how long they would actually need or could be watched before treatment would be indicated. So when we talk asymptomatic these are patients that basically walk into clinic and look extremely well. So some patients with advanced disease will have either pain symptoms. They can have tumor that's blocking structures that can be causing problems. They could have symptoms as far as cough or other shortness of breath if the disease is in the lung. So these are patients that wouldn't need treatment for any other reason. So what they did on this study is basically no treatment was started and they did repeat scans at set intervals usually about every three months just to see how fast these tumors are growing knowing that kidney cancer in general tends to be one of the slower growing cancers. So can we actually if we only have a one centimeter tumor spot if that's going to be slowly growing over a long period of time can we avoid some of the initial toxicities of treatment knowing that compared to when we're looking at earlier stages where we're trying to cure the disease all of our treatment options are mostly trying to control so if we can get a little bit more time just by watching and avoiding the treatment side effects until we really need them is one of the considerations of this study. So this is what we call a Kaplan-Meier curve that we'll be seeing a lot of throughout the rest of the talks through the day which basically plots patients on a clinical trial so everybody starts here at 100% and then whenever an event happens on study that causes basically a drop off on the curve so an event can be depending on what the endpoint we're looking at so if we're talking about progression free survival an endpoint that we look at that's looking at how long does it take for growth of the cancer to be seen overall survival is another endpoint that we look at meaning how long until there's actually a death of a patient on a clinical trial so these two curves are looking basically breaking down at these favorable versus unfavorable groups looking at some of those prognostic models that I had mentioned so clearly if you have more unfavorable features it takes less time before we would actually need to require a treatment if we're just doing surveillance so on average those patients it took about eight months before the clinician and the patient felt there was some indication to start therapy while on observation versus it could be actually much longer in the low risk group or the favorable group sometimes more towards the two years so this is something that particularly if we look at a scan in a patient it's completely asymptomatic we may consider even just watching and seeing where we're at in another three months to kind of see is there actually significant growth of disease just to kind of buy a little bit more time and avoid some of the toxicities of our treatments for a little while longer so getting to the treatments I'll talk about at least review the clinical trials on probably the two most common tyrosine kinase inhibitors that we use the first is Sunitinib or Sutent and then I'll review Votrienter, Pizopinib so all of these target not just VEGF or the VEGF receptor which is these blood vessel blocking drugs but they have a few other off targets as well so the dose that was approved through the FDA was this 50 milligrams once a day on this four week on two week off schedule although when we actually use this in practice we find a lot of patients actually have a harder time with this administration and there's actually good data and alternative dosing schedule where we give the drug for two weeks on one week off and at least from everything that we know about using it in that fashion it's felt to be equivalent so a lot of oncologists both here and throughout the country have a different dosing administration and we feel that that is equivalent to what was initially approved in 2006 so this is looking at the Kaplan-Meier curve from the initial Sutent study when they were comparing it to basically the only standard that we had available at the time which is Interferon so kind of a rule of thumb when you're looking at these Kaplan-Meier curves back in the room and you can put your thumb in between the curves that's usually a positive study and tells us that there's probably a good treatment effect between those so you can see when we compared it to one of our older treatments Interferon clearly patients that took Sutent ended up having control of their disease for a lot longer and then if you actually look at what the responses are when we kind of grade these CT scans on patients that are coming back so anybody that's either been on a clinical trial or known somebody that has been on a clinical trial knows they get scans fairly frequently sometimes even more often than we would generally do and that's to take measurements to kind of assess what the response is so part of those responses are what we call these complete response and that would be when we actually would see no evidence of cancer on a scan and then more commonly at least with these drugs we see at least some reduction of what we call partial response is what they're looking at and with Sutent clearly had more of a response compared to the older treatment with Interferon and then this is the follow-up where they looked at survival the curves are not as far apart you can see there's definitely separation compared to the old standard with Sutent compared to Interferon so in comparison another Tyrosine kinase inhibitor is Votrientropizopinib so this is another blood vessel blocking drug that inhibits all these VEGF receptors as we had talked about and generally the starting dose of this would be several pills a day or 800 milligrams and the drug actually you can have higher absorption actually if it's taken with food so a lot of these drugs we end up taking short from meals for that reason and this was actually approved in October of 2009 based on improvement in progression free or taking a longer time for your cancer to grow compared to placebo and this is a little bit of a fuzzy Kaplemeier looking at that compared to basically a placebo or a sugar pill Eusepizopinib led to significant tumor control for a much longer period of time and led to approval of this drug as a treatment option so these are two most commonly used Tyrosine kinase inhibitors so patients would come into clinic and it's always kind of a toss up on which drug we would pick and raise the question is one better than another so this is the compares study that actually enrolled a large number of patients over a thousand randomizing them to receive either Sutent or Pizopinib on this phase 3 clinical trial so the Sutent schedule ended up being that kind of approved 4 week on 2 week off rather than one of the other dosing recommendations and what we learned from this study is that the two drugs are essentially equivalent to each other so this on the left is looking at a human free survival or how long it takes the tumor to grow and you can appreciate these curves overlap meaning there's really no difference between Sutent versus Votrient as far as control they both seem to work or one is not worse than the other and this is actually overall survival or chances of dying on either of the treatment and again they're very similar between those one thing that I noticed is they actually gave patients just satisfaction scores and quality of life assessments meaning did one of these treatments tend to cause more side effects than the other so one thing that was noted is that there's definitely differences in some of the side effects between the two so Sutent overall tend to cause a little bit more fatigue or decreased energy again this is on that 4 week on 2 week off regimens so definitely we can see some modification of those side effects with different administration regimen and then Pizopinib can cause some other side effects but overall patients on the study seem to prefer to tolerate Pizopinib a little bit better but there's different ways that we can give Sutents as well yes Votrient or Pizopinib based on the study when they were just asking patients which of these they had done better and there was another study where they actually had given both drugs basically they gave one group Pizopinib first and then Sutent and then switched and then just actually asked them which one they preferred and Pizopinib was tended to be preferred even on that study but again Sutent like I said can be given a little bit differently so that can take away some of that more of the side effects that Sutent had so moving on to Toricella or Temsirilimus this is the one of those mTOR inhibitors or one of those drugs that interferes with that signaling pathway that causes cell growth and division so this is one of the only IV drugs I think the only IV drug that we use out of these agents and has been available based on the study comparing it to one of our old standards interferon so this got approval basically looking at patients with the worst risk features so basically those risk stratifications this would be patients that we would predict would have worse outcomes and they looked basically comparing the old standard of interferon to using this mTOR inhibitor Temsirilimus alone took the combination of them looking at survival as the primary endpoint so this is the Kaplan Bayer curve looking at each of those arms and you might be able to appreciate sorry the figure is a little bit fuzzy that this green line is the Temsirilimus arm and that one was basically showed a longer survival compared to either the combination or using the old standard interferon alone so based on this this led to FDA approval and this is one that though it's tending to fall more out of favor as new therapeutics are coming along it's still a consideration for this poor risk group based on those initial parameters so one of the newer kids on the block at least within the tyrosine kinase family is kabosantinib so this is a small molecule that hits not only veg f but some other targets as well which can cause a little bit more side effects than some of the other kind of more direct veg f inhibitors so this was improved in March of last year for patients that had basically disease growth after being treated with a tyrosine kinase inhibitor and this is basically the phase two study that compared this drug kabosantinib to one of the oral forms of the mTOR inhibitors which was kind of one of our go to drugs and for second line treatment before we had a lot of these immune therapies so kabosantinib basically led to longer control of the disease compared to the other oral mTOR inhibitors so this raised the question is yeah so this has a few other offset targets can we actually move this up earlier and this is a phase two study called kabosun where they actually tried to answer that question by comparing kabosantinib to sutent looking at disease control or progression free survival as the end point and they were looking at basically patients with worse risk so on those risk models looking at intermediate and poor risk with about 80% being intermediate risk and 20% being poor risk on this study so kabosun kind of confirmed that definitely there is some improved disease control with kabosantinib as compared to sutent and response rates were also a little bit more there were a few patients that actually had dropped off the sunitinib arm maybe a few more than the kabo which raised the question is there a better schedule that could make sutent a little bit more tolerated but at least based on the data that we have there may be some role for kabosantinib in the first line setting especially in those intermediate and poor risk group patients although this as of today is still approved only for the second line treatment or in patients that have progressed after a prior VEGF so this Kaplan-Meier curve is looking at what we call progression free survival so each of those lines is an event where on study the patient would have a scan that showed some tumor growth or progression so yeah that's when that's what each of those hashtags mean versus some of the other curves sometimes we'll look at overall survival which would be a patient death that would kind of mark those so it depends on kind of what the axis on the curve is looking at so those are kind of the treatments we've been using in the past years and now more recently we've been using immune therapy drugs and have had those available for the last two years or so in patients that had disease progression on a tyrosine kinase inhibitor and this was a press release actually from September of last month looking at combinations of immune therapies for patients that have had no prior treatment or looking at this in the first line setting so I had started this talk saying that kind of the treatments we choose are evolving so this is kind of an exciting update that was presented just at one of our European oncology conferences in September so we're anticipating that there's likely to be an updated FDA approval for this that will kind of adjust which treatments we think about and can actually add this as one of those options going forward and Sumit will likely be talking more about this in his talk so just a quick slide on treatment effects while I'm finishing up so each of these drugs has a unique kind of class of side effects anybody that's seen patients on these tyrosine kinase inhibitors probably knows that the blood pressure is one of the more common effects that we need and our patients come to clinic actually with diaries monitoring their blood pressure definitely we can see other changes particularly in the skin and in hair particularly vortirant can cause some whitening of the hair and then this hand foot syndrome is another common side effect that we see with any of these TKI's and then we do frequent monitoring of their blood work as well just looking for abnormalities in liver function tests and any other changes in blood counts that would be concerning with the mTOR inhibitors probably some of the more unique side effects is this pulmonary effect that we can see and depending on the studies somewhere between 1 and 5% of patients may have what we call a monitis which is just inflammation in the lung that can frequently just start presenting with cough or shortness of breath so that's something that we pay attention to that may require an adjustment in treatment and sometimes even stopping it and needing to treat with steroids if there's a lot of inflammation to bring that down and then Sumit will be talking more about the side effects of these immune type therapies which fatigue is probably the most common that we see but then since we're taking the brakes off the immune system we can get some of these immune reactions where our immune system can attack essentially any part of the body almost like an autoimmune type disorder so he'll be going into that more details during his talk so in summary our treatments consist of three large classes of drugs the blood vessel blocking veg F inhibitors the mTOR inhibitors that work on this cell proliferation and by slowing down that cell signaling and then these newer immune therapy drugs Pizopinib and Suthent as of today still remain first-line treatment options although that landscape is continuing to change as more drugs are studied and become available especially in combinations particularly for the porous group Timserolimus is still a consideration for upfront treatments again they're tending to fall out of favor here and then I had mentioned that Cabozantinib there's some data on use of that as kind of a first-line treatment option although we don't currently have an approval just yet for that and then for any patient that's progressed after one of these initial treatments treatment with either immune therapy basically a different veg F inhibitor or even combinations of these with veg F and mTOR are all reasonable options and then we expect that this is going to continue to evolve as more treatment options become available down the line any questions there so you talked a little bit about risk factors and you talked about how you assess risk factors or can you say a little more about how you define good intermediate so there's a few different algorithms that we look at I just put the Sloan Kettering as an example and it's all based on some of those presenting variables so a lot of those are lab abnormalities all of them tend to include how long it takes from diagnosis to when treatment is started so all of those just give us a little bit of sense on do we think that a patient is more likely to have a worse outcome earlier that can be suggested by some of those risk models hmm hmm yes hmm yeah so the FDA they review all of these large clinical trials and then determine based on that proven efficacy if they'll give approval for the drug based on the yeah how well the drug works and what the safety profile of it is to what extent does the firm and great determine treatment options so at least as far as grade yeah it wouldn't necessarily impact yeah which treatment that we think it does play a role kind of in the risk of the disease itself hmm but necessarily we wouldn't choose one treatment yeah just purely based on the grade there's some data looking at like the histologic subtypes that Dr. had talked about particularly there's some data looking at chromophobe and there's some phase 2 studies that may suggest possibly using mTORS may have a little bit of a signal or more benefit compared to the VEGF inhibitors so we take all of that in consideration yeah when we're doing those initial evaluations do you know if there's going to be a discussion about the efficacy of radiation versus immunotherapy yeah I don't think we have a scheduled balance out of radiation one of our topics for today but I can speak to it a little bit we don't use radiation we think about radiation more like surgery it's really a local treatment so if there's any one particular area that's bothersome radiation is used so typically it's used for either bone disease that may be painful it's used again you know as an individual site but really when we think about systemic treatments when there are multiple sites and wall radiation might not be an appropriate treatment any other questions yeah most of them that medicine lasted like somewhere around 8 to 10 months and then you start noticing a dip is that correct that would be about an average expected time span which is why it's important that we have new treatment options and expanding treatment options because eventually all of these treatments have a set failure rate so we're trying to learn not only other therapeutic targets but then can we combine these to get further efficacy and then depending on how the drug works if someone has a lot of cancer compared to someone who just a little bit if the side effects are more intense or not as bad yeah the burden of the disease shouldn't really affect the side effects on the drugs but kind of depending particularly sometimes we can see some immune flares so if there's a lot of disease burden then particularly that's something that we'll pay attention to which has kind of been a more unique phenomenon we've seen with some of these newer therapeutic drugs as opposed to the VEGF we generally some of the older oral drugs we don't see that same type of flair sometimes with those Thank you so much Brian and thank you all for your questions we're really glad you were engaged


The first energy drink dates back more than a half century. Doctor Enough launched in 1949. Now there are more than 100 brands. An industry now selling $50 billion of this stuff a year. They're popular on military bases, but some military leaders have questioned their safety based on data like this. The skyrocketing number of energy drink-related emergency room visits over recent years. But if you look at some of the reports, you see cases like this. 24-year-old guy who didn't feel well after drinking a can of energy drink and three bottles of vodka. Because energy drinks are often co-consumed with other substances, it's hard to tease out the culprit. Same problem with population studies. Sure, adolescents drinking energy drinks are at risk of a wide range of negative outcomes, but energy drink consumers are also more likely to drink soda and have other unhealthy habits, more likely to binge drink, take diet pills, and engage in other risky behaviors. So the only way to tease out the energy drink component is to put it to the test. One of the concerns that has been raised by public health advocates in terms of potential negative effects is increased blood pressure. But have people chug a can of Red Bull and 30 minutes later no significant change in blood pressure? Okay, but that was the little 8-ounce can? What about the 16-ounce big cans of Red Bull? 40 minutes later, no significant change there either. So concerns about energy drinks raising blood pressure were dismissed as overblown until the bomb dropped in 2014. Red Bull did indeed significantly raise blood pressure after all. The reason the earlier studies missed it is because the spike doesn't start peaking until like an hour after consumption. So if you just look at like 30 minutes after consumption, all seems fine, but the worst is yet to come.  Energy drinks are promoted as having beneficial effects, but this instead would suggest they're potentially harmful because of the extra cardiac workload and decreased brain blood flow velocity. Researchers subsequently looked at other brands. Here's Rockstar brand energy drink, significantly elevating blood pressure within just 30 minutes. Yeah, but wait a second. Is it just the caffeine? I mean, is there any difference in just drinking a cup of coffee? To figure that out, you'd have to compare the effects of an energy drink with just a plain drink with the exact same amount of caffeine, but there's never been such a study. Until now, a randomized double-lime controlled crossover study, in which young, healthy volunteers were randomized to drink two large cans of an energy drink or a controlled drink that had the sugar and the same amount of caffeine, but none of the other proprietary blend ingredients like taurine, quarantine, ginseng, guarana, all the other stuff they add. And it turns out it wasn't just the caffeine, significantly higher blood pressure on the energy drink than the exact same amount of caffeine in the control group. What's this higher QT interval thing, though? On NKG, it's the distance from the beginning of the downward Q wave to the end of the bump of the T wave. Okay, so who cares? QT prolongation, which is what the energy drink did, but not the caffeine, is a recognized marker of increased risk of fatal arrhythmias, fatal heart rhythms. That doesn't sound good. Okay, but by how much? Prolongation of the QT interval by more than 60 milliseconds is a marker for life-threatening arrhythmias. And the energy drink only prolonged it by about 10. But there have been drugs pulled from the market, profitable drugs bringing in billions of dollars because of a 5 to 10 millisecond prolongation. So we really need to start investigating some of these other ingredients in energy drinks. For example, in 2008, authorities found cocaine in Red Bull drinks. The Red Bull manufacturer insisted, however, that they were just adding the cocoa leaf or flavor and that all the active cocaine was removed. Given the global popularity of the multi-billion dollar energy drink industry, it's critical we figure out if there are any potential adverse effects. There are currently more than 500 energy drink products for sale on the market today. The most popular and most studied is Red Bull, a single can of which was found to bump blood pressure by 3 or 4 points within 90 minutes of consumption. What about all the other energy drinks? Studies show they similarly increased blood pressure 3 or 4 points on average. Oh, but come on, 3 or 4 points? What's the big deal? 20% higher risk of dying from a stroke is the big deal, and 12% higher risk of dying from a heart attack. Yeah, but that's if you have elevated blood pressure day in, day out. To see if Red Bull can increase your day-long average blood pressure, you'd have to put it to the test, a comparison. The effects of energy drink versus just caffeine supplementation on 24-hour blood pressure. The FDA imposes a limit on caffeine in soda, but the way energy drink manufacturers get around that is by claiming that their carbonated sugar water is not soda, but a natural dietary supplement. But Red Bull doesn't have any more caffeine than a cup of coffee. The question is, what are the effects of all the other proprietary ingredients they add to the energy drinks? So they gave people 4 of the small cans of Red Bull or 4 cups of coffee.  Same amount of caffeine, yet significantly higher average blood pressure by about 5 points over the coffee. So maybe it's the torene or some other combination of added ingredients in the energy drinks that makes them so harmful. Energy drinks may also impair artery function, one big can of monster energy drink and a significant drop in your artery's ability to relax normally within 90 minutes. The biggest risk, though, is likely the EKG changes that signal an increase in the risk of our hearts flipping into a fatal heart rhythm. And indeed, there are cases of young people suffering cardiac arrest after consuming like 7 or 8 cans in a row, or even just 3 cans back to back. Some people are just more susceptible. Yeah, there are a number of case reports highlighting multiple potentially fatal cardiac side effects from high energy drinks in the general population, but it's the families with a history of sudden cardiac death or fainting that education about the risks are even more critical as energy drinks may unmask a potentially life-threatening genetic condition such as LQTS, a long QT syndrome, which occurs in about 1 in 2,000 people. Yes, there are safety issues, but do the benefits outweigh the risks? Unfortunately, little evidence exists to support any beneficial effects. What about for athletes, though? That's who energy drinks were originally marketed for, and boy did that marketing work with 80% of college athletes reportedly drinking them. So does it help? You don't know until you put it to the test. And as you can see by the title, pre-exercise energy drink consumption does not appear to improve endurance, but it does seem to increase inflammation. 25-mile simulated road race, and they could not find any ergogenic potential, any athletic performance-enhancing potential of Red Bull above that of just straight sugar water and caffeine. In addition, the data indicate that Red Bull induced greater inflammatory-related responses than the just straight caffeinated sugar water or placebo. No apparent effect in resistance training, either, not just endurance sports. And those hoping energy drinks will help rev up their metabolism to lose weight, may be disappointed to learn you can get the same stimulatory effects with straight caffeine, or maybe they won't be disappointed. Black coffee or tea is way cheaper. No wonder there was no change in athletic performance, because unlike nitrate-rich vegetables, energy drinks don't change oxygen utilization or ratings of perceived exertion. But what they do is raise your resting blood pressure, so the opposite of vegetables like beets and greens, which both improve athletic performance and reduce blood pressure at the same time, whereas energy drinks appear to have no therapeutic benefit.


Healthy relationships are one of the best things in the world. They lift us up, challenge us, support us, and make us feel like we're superhuman. Nothing can get us down when we're in a good relationship, especially ones that are just beginning. But if you're in the beginning stages of getting to know someone, how can you tell if it really is healthy? Often we get so wrapped up in ourselves that we don't see when relationships are unhealthy. It might seem like a far away, it'll never happen to us thing, but unhealthy relationships are more common than you would think, and sometimes sneak up on you. If you suspect you might be in an unhealthy relationship, listen on and see if any of these match up to you and your bow. 1. You fight a lot. No, we don't mean arguing over who has to clean up after you've both cooked dinner. We're talking about yelling, threatening, and screaming at each other. If you two are getting into screaming matches over every little disagreement, you need to rethink why you two are together in the first place. 2. You hide things. And we don't mean candy or easter eggs, we mean things like texting other people, lying about where you were, or other dishonest actions. If your partner will get mad at you for texting your best friend forever, or going out with friends instead of staying home with them, you might just be in an unhealthy relationship. 3. This way or the highway. If your relationship always revolves around how the other person wants to do things, or how you want to do things, you're not in a good relationship. Partnerships involve being partners. This means you need to compromise, listen, and discuss before actions are taken. If it's always one person's way, you two need to sit down and sort it out before resentment and anger starts to breed. 4. You feel guilty. This one's a little harder to pin down. Your partner might not even be aware that you're feeling this way. Heck, you might not even be aware that you're feeling this way. If you get worried about taking time for yourself, or if you feel that you're not allowed to, address it with your partner. It might be a miscommunication, or it might be a clue that your relationship isn't as healthy as you think. 5. It's one-sided. So much of relationships is about sharing your burdens. When you're in a relationship, you get someone to lean on, talk about problems with, and help to deal with your struggles. And vice versa. You need to make sure you're available to be a support system for your partner, letting them lean on you when they need to. If the relationship is based on one person or the other, it's not a real relationship. It's just taking advantage of someone. 6. They put you down. We don't mean physically. We mean that they put down your hopes and don't support you and your dreams. You need someone just as brilliant as you are, someone who will help you achieve your goals, or at least cheer you along the way while you strive for them yourself.  Get out. Quick. 7. They refuse to do things that matter to you. If you've said three times that you hate when the dishes sit in the sink for days on end and your partner still doesn't change their slovenly ways, you need to get out. They clearly don't respect you as much as you respect them. If they did, they would listen to your concerns and make an effort to do the things that matter the most to you. 8. You're codependent. This one's a little trickier to identify.  Your relationship should be a happy addition to your life. 9. They make you feel insecure. Your significant other should make you feel like you're the greatest thing in the world. Why? Because you are.  And if your partner isn't respecting you, you need to leave them. They aren't healthy for you and you deserve better. If you feel insecure in any way, get yourself out. You're in an unhealthy relationship and you'll be much happier without them. 10. They're abusive. It seems obvious, but sometimes people in relationships can't see what's actually going on. They justify their partner's actions or take the blame on themselves. Don't. If your partner is verbally, physically, or sexually abusive, you need to get help and get out. If you aren't sure how or if you need help, talk to a counselor or doctor or someone else you trust. They'll be able to get you the resources you need to take care of yourself. 11.  This is a subtle sign of an unhealthy relationship, but should be a big red flag.  They want to be with their ideas. Find someone who loves you for you and then you'll know you're in a healthy relationship. 12. You're unhappy. The biggest sign of being in an unhealthy relationship is when you're unhappy. A relationship is meant to be a positive experience. You're supposed to look forward to seeing your partner, not dread or stress about fitting them into your schedule. Let the relationship go and you'll feel much happier. Trust us. No relationship is better than an unhealthy relationship. If you like this video, be sure to give it a thumbs up and as always, thanks for watching.


The company announced Lumiere. It's an AI video generator that it's calling a space-time diffusion model for realistic video generation. As far as text-to-image AI video generators go, pretty impressive, at least from what they've shown us. Does Lumiere feel like a leap forward? They have announced something, they've shown us videos, they've promised demos, but we cannot exactly get our hands on it. Google's Lumiere is supposedly doing, which again is contextualizing here is the scene, here is the subject in the scene, here's how that subject needs to get from A to B. So instead of it interpolating and trying to make the frames bleed and mesh and melt into each other, it's thinking about how those two interact. And that is revolutionary. Gavin, my co-host on AI for Humans, we pointed a little bit to the bleachers and said, we think in two to three years time, text-to-Hollywood level content is going to be possible. And I think we're on that trajectory still.


Appalachian Wireless is Appalachian Advantage. Unlimited text talk and two gigs of data for as low as $45 a month. Or if you like, get five lines on eight gigs of data for just $145 a month. See store for details. Better service, bigger savings. That's today's Appalachian Wireless and East Kentucky Network Company. In July, Ronald and Loretta Wright pleaded guilty to charges in the 2013 murder of Famer Halbert. With Ronald pleading guilty to murder, wanton endangerment and assault and Loretta pleading guilty to facilitation of murder. Today was sentencing day for the pair, but as Ronald Wright appeared before Judge Thomas Smith, he requested that his attorney, Jerry Patton, be relieved of his duties and that he be allowed to rescind his guilty plea. As a result, a hearing is now set for November 22nd to allow his new attorney, who has yet to be named, present evidence of why Ronald Wright should be allowed to rescind his guilty plea. Loretta Wright was sentenced to 15 years with five of those years to be probated. She was instructed to turn herself into the Floyd County Jail at 10 a.m. Monday morning. Family members of Famer Halbert say they were not able to get the closure they needed today. We came today, thought we was going to get a little justice. You know, I brought the boys to so they could be secure that they're going to prison, but it didn't happen today. No matter what they get, I'm not going to get enough justice.  Halbert's grandson, who was only six at the time of the murder, remembers very vividly the events that took place that night. They came to our house. At first, they were talking to a man more like it was honorable. Then Ronald asked to go to the bathroom, but instead of going to the bathroom, I noticed that he walked right past the bathroom, so I followed him. And as soon as I stepped on the wall, that was poking out and he grabbed the dry sheet off of the counter and he put it in my mouth and held me back and then he held me about six inches away from my grandpa and made me watch him and shoot him in the forehead. If Ronald Wright's original plea agreement is upheld, he will serve 25 years in prison. Reporting from Prestonsburg, I'm Sean Allen for EKB News.


Hello everyone, I am Mr. Sachin Rathod working in mechanical engineering department from WIT Solapur. Today we will see the concept of law of gearing. So the learning outcome of this session is at the end of this session students will able to understand the law of gearing introduction. The law of gearing states that the normal that is the common normal at the point of contact between a pair of teeth must always pass through the pitch point. So you can think about this whether is it necessary to check the law of gearing. The answer is as the law of gearing states the condition which must be fulfilled by the gear tooth profile to maintain the constant angular velocity ratio between the two gears. For example, if you are going to design the gear that is the machine gear at that time after the designing if you are getting the failure between the velocity ratio we are not getting the constant velocity ratio between the two meeting gear then at the end result it will give the separation of the tooth will occur. So that is not that one we are not getting the proper alignment between the two gear that is the proper machine we are not getting. So for that purpose we require to check the law of gearing while the designing. So we will see what is in my law of gearing. So first thing that we will check so I will draw the two teeth of the gear from which we are getting whether we are satisfying the law of gearing or not consider this is a one tooth and it is mating with the another tooth of the gear. So like this one complete gear tooth profile is there and another gear tooth profile is like this so just I have taken a two tooth of the gear both are mating about this point. So consider this is a O1 center point and this is a O2 center point O1 is a center point of the gear number one O2 is a center point of the gear number two both are mating at point A. So this is a meeting point when we are drawing tangent line this will give you common tangent and perpendicular to this is common normal this is a meeting point A. So our ultimate aim about this law of gearing we have to get the angular velocity ratio between the two gear is constant. So suppose this is a gear number one which is rotated by angular velocity omega one so this gear number two will rotate by the angular velocity omega two. So suppose this is a O1A is nothing but the radius of meeting point at A and O2A is the radius of second gear about the A point. So the velocity is perpendicular to the radius for that purpose we have to draw the velocity perpendicular to the O1A1 this is rotated in the anticlockwise direction. So draw the perpendicular line so it will give the velocity of OA so for the simplification purpose you will give the naming as A1 and A2 A1 is a meeting point of your radius O1A1 and this is the O2A2 so this will give you the velocity of VA1 similarly the O2A2 radius we have drawn the another velocity as VA2. So draw the perpendicular line to common normal we will give name as M this one is a perpendicular line that is N the perpendicular line makes the angle with O1A1 that is radius is alpha and the perpendicular line with the radius it makes an angle beta so as per the geometrical consideration we are getting the angle alpha1 or alpha VA1 velocity of O1A1 radius we are getting the VA1 makes an angle alpha and VA2 makes an angle beta with the common normal because common normal is perpendicular to common tangent and we have drawn O1A1 is a perpendicular line and it makes an angle alpha so by considering this geometry we are getting the alpha and beta angle with the common normal so this is a diagram for satisfying the law of Gearing. Now we will check how to verify the law of Gearing so first of all the condition is that for two gear remains in contact the velocity component of the velocity that is a VA1 and VA2 along the common normal should be 0 the resultant of this velocity should be 0 otherwise if the resultant of this velocity is not going to 0 then the separation of these two tooth will occurs for that purpose VA1 cos alpha minus VA2 cos of beta should be equal to 0 so if this condition satisfy then and then only the two tooth remains in contact therefore we are knowing velocity is nothing but radius into the angular velocity so for the first gear the radius is O1A1 into the angular velocity omega 1 into cos of alpha is equal to VA2 that is nothing but the O2A2 into omega 2 into cos of beta then O1A1 into omega 1 into cos of alpha by considering this triangle cos of alpha we are getting this triangle O1M A cos alpha is equal to O1 O1M divided by O1A1 O1M divided by O1A1 is equal to O2A2 into omega 2 into cos of beta is equal to O2N divided by O2A2 so this will get cancelled so we are getting omega 1 into O1M is equal to omega 2 into O2N so by considering this similar triangle O1M so if I joining this two center so along the common or we are getting the p point that is called as a p-point so by considering this triangle O1Mp and O2Np triangle O1Mp and triangle O2Np by the similar triangle rule we are getting O1M divided by O2N is equal to O1P divided by O2P therefore if you put the value O1M divided by O2N is equal to O1P by therefore omega 1 by omega 2 is equal to O2N by O1M is equal to O2P divided by O1P therefore we are getting omega 1 by omega 2 is equal to O2P by O1P so by referring this equation the angular velocity between gear number 1 and 2 is equal to the ratio of the distance between a center point of O1 and O2 that is nothing but the ratio of omega 1 by omega 2 is equal to O2P by O1P nothing but the O2P by O1P therefore the p-point must be your the fixed point if you are satisfied the law of gearing so for that purpose we are knowing the law of gearing so by this equation omega 1 by omega 2 is equal to O2P by O1P the p-point must be the fixed point if you want to check the law of gearing then the ratio of the angular velocity between the two gear must be the 0 according that we have to design the distance O2P by O1P these are my reference thank you