And you're very welcome back and you two together there you see a heartbreak with Roseanne Cash and Bruce Springsteen and before that Mary Coughlin and Double Cross. Joining me in the studio tonight as promised I've got Connie McGrenahan and we're going to be reviewing the Paper Palace by Miranda Coiley Heller and you're very welcome. Connie? I'm sort of I can see you. I thought you would have called me Miranda. So Connie the Paper Palace I asked you now for a choice for the book club this and you recommended this and the Paper Palace could you just give us a little bit about what is about. Okay I actually took some notes a lot of notes so the book actually centres around the main characters Elle and she's probably about my vintage in her early 50s and her family and the narrative for the book actually jumps between the present and past. The present section actually just focuses on two days but it feels a lot longer. Elle has been brought up in a very non-conventional manner with a mother who is a very unorthodox view of marriage and has been married a number of times as was her father.  So the backdrop for the story is in Cape Cod and it's Paper Palace which is described as a ramshackle of a holiday village which was built by her grandfather and it comes across as being somewhat like a commune. There's so many of them in it so at the beginning of the novel right at the start so I'm not giving anything away we encounter Elle who is having what you might call a brief encounter of her own. She's left her husband and family and friends playing games indoors and in the sitting room was she and her childhood friend Jonas are outside playing their own private game. She and Jonas share very private and scandalous secret from from their youth and this changed their friendship forever and the guilt of this secret has kept them apart and but she feels that Jonas is her true love and she's now married married in English journalist Pete and they have three children the story essentially goes over the past number of years of how she met Peter and how they came to where they are in their lives now and the paths they choose the chapters that are in here now center around whether I was going to choose her last love long last love Jonas or is she gonna choose her husband Peter and that is really the main premise of the story I suppose. And I suppose Jonas and Peter she loves both of them in different ways and Peter is such a really nice guy and it's not that she's on happy in her marriage she has a very solid marriage and two kids and she's very happy but there's this this connection with Jonas that she can't really get out of her system. Yeah I think Peter represents the stability that she didn't have growing up because her father was so weak and he had no backbone he had a number of girlfriends a number of different wives and he always chose them over her he never chose her and that was always a grievance with her and then I suppose Peter and her own mother was very unorthodox and very caustic you know she clearly loved her but didn't give her any affection so I think that Peter was so stable and the way he you know the way he treated his children she got great joy out of that you know as opposed to how she was brought up. And as you said the relationship really is between Jonas and L and Peter but there are other relationships too the relationship with their mother and her father. She seemed to have a very as you said an unstable background and you felt sorry for her she was just pushed from tiller to post and her mother and father they always put their their love or their partner before their children which I'm sure was very sad. Yes she was used to have to go and stay with her father weekends the mother essentially couldn't wait to get rid of her and her sister and sent them off on buses and trains when they were no age and then this particular time the father's new wife Joanne didn't like them so they didn't even stay with the father they ended up staying with Joanne's parents you know and that's what we were saying there was such a huge cast of characters it kind of got a bit confusing because there was so much bed hopping going on and at one point you didn't know who who was who it was quite you know you get mixed up very easy and then there was a relationship between herself and her elder sister Anna which I thought was very well portrayed because Anna was the elder sister and in their early years they didn't get on that bill but then as as they grew and matured their relationship became much stronger and Anna was she was forced to go to boarding school because what was it her mother's new husband Leo whose son Conrad hit her or something so she didn't like Conrad so she got turfed off to boarding school and then Conrad got her bedroom and then of course Conrad is another kettle of fish a nasty piece of work is a yes yes he was he was absolutely horrible and like Elle was told about abuse when she was young how her mother had been abused and how the mother's mother her grandmother was aware of this and actually caught caught some of it and caught the man in the act of doing it to his daughter and she slapped her daughter and the women were very much for the men you know they weren't for their children that was her grandmother I can't remember what her name was but then her mother Wallace you know was you know it was it was like marry it was like adultery was just you know commonplace she says you don't put up with a unhappy marriage she says you just change it like you do a suit and she says you don't be sad or she says sad people are much more interesting anyway you know so get over it kind of thing it was tough the way the way the book is structured Connie it goes like as it all happens within 24 hours but you get the flashbacks over 50 years did you find that that worked well I did I did I liked it you see I like the book overall I found the book very interesting and I did like that I like it when things you know like a pendulum I enjoy that to see how we got where we are and and as well you didn't know the ending you know the way sometimes at the start when it goes like that you might know the ending but in this case we didn't know the ending you know they sometimes it tells you the ending at the start but no I enjoyed it I like to see the path I like to see you know where we've got to you know and no I enjoyed that enjoyed it yeah and some some people have described it as a page turner now I have to admit that at the beginning I found all the characters just very confusing and it took me it seemed to be 50 or 60 pages before I got into the book and then I thought yes this is a really good story and you know it's very very curious to see how it was going to go did you find out or was that just me no not because as I said to you before we went on there I've read it now a couple of times because I did read it a while back and then I reread it for another occasion and I rekind of skimmed through it again and I found that I was finally understanding who the people were do you remember Dixon who was a family friend and he was in the apartment with a girl there was a lot of there was a lot of reference sexual references and a lot of that going on and I wasn't mad about that do you know what I mean she was very explicit the writers very very explicit in her writing but you know as I say I didn't like that but no I just know there's so many characters oh yeah yeah because Dixon was the one I kept thinking who's Dixon you know and I think it took me to my third go to realize he was just mom's family friend because she married him why is he here again you know there was just so many of them and you remember the car the grandparents and then there was a young fellow there feeding mice to the snake like it was odd there was a certain oddness to that too I sort of thought that maybe there wasn't a need for all those sort of minor characters you know that's at the beginning but and I said that just put me off at the beginning but once I got into the book then I certainly thought that it was it was it was a really really good book and I suppose it would not fit it across as something like 50 she is of gray or something that it is it is quite explicit and it is but it's so sad yeah like it's desperately desperately sad like you're talking about abuse and you're talking about children you know seeing their parents being unfaithful seeing not not being loved you know they weren't loved and then of course it happened to L herself you know when she couldn't tell anybody she wasn't able to tell anybody and that secret you know went went through her with throughout her life you know she wasn't able to tell her sister she wasn't now Jonas was aware of it and of course that's a huge part of the book as well what happened there you know and I suppose that at the end of the story and again was talked about that in a minute she's just going to have to choose between Jonas and and Peter and I suppose Jonas knows her secret so if she chooses Jonas she's going to have to live with that secret it's going to be more open or talked about but you there's that there's another little twist as well there's another little twist before you come to the end she actually goes back and she meets up with Conrad sister Rosemary okay and this is in the present tense her husband Peter's called to Memphis away from Cape Cape Cod so that's where Conrad and Leo were from so she goes back to Memphis and meets up with Conrad sister Rosemary and what Rosemary tells her pits a whole new if she'd heard that 50 years ago right she might not have felt the guilt that she felt throughout her whole life Rosemary revealed something so it changes everything and we were going to have your sister orla orla Carolyn here today unfortunately she couldn't make it but she did give you a synopsis of what she did very brief yes very brief orla said to me orla wasn't keen she says that I would give this book five out of ten she's for me it was too descriptive vivid descriptions are okay from time to time but I felt the book was filled with too many unnecessary descriptions of natures of nature characters are not very likable particularly the mother who showed little affection for her children and she felt that the book she come with a warning as it could be triggering for some people it was quite sexually explicit some nice characters and everyone enjoys a love story but I won't say what she says because she gives it away then but she's I won't say what she gives a she kind of gives away the ending there but that was orla wasn't that keen you know and I I felt in her right like there was a certain amount I kind of called it grimy do you know what I mean she was so vivid in her descriptions and it was all sort of like there was grease splattered like Peter was smoking heavily heavily and coughing and fried an egg and they splattered grease on a shirt and she was talking about the fish in the pond a blinger feet and where was all the dead skin going there was there was this sort of griminess to it you know you kind of likened it there to craw dad's yes I thought craw dad's was more beautiful you know where this it was I did love it as well the descriptions but they were kind of like they were like sort of wild and dirty sort of do you get me yeah you know she was on about the ants and the turtles and she kind of focused on all these you know things that were grimy and like talking about the thread bear towels and the paper palace and her mother's old nightgown frayed you know you get this description of a little wee bit gray rather than blue you know your picture cape cod yes and you think of it as blue and yellow even I seen it as gray you know and it was the ending is quite controversial we're just talking about it before we went on air Connie and she's going to choose between one of the other were you surprised by the ending or did you enjoy the ending of some people didn't enjoy yourself do you know what Jean I nearly missed it I nearly missed it so she gives sort of Peter a choice about doing something and he very very very insignificant what seems very insignificant and he get he replies and essentially that kind of paved the way for the ending and it came just about two seconds later and I sort of went oh what happened there and I had to go back and I was under no doubt as to what happened where all it was ringing me and saying what happened there at the end you know what who has she chosen so I says well I think she's chosen and like of course I went and googled and looked and talk about this ending was huge everybody was talking about this ending you know I felt I I understood the end and I would like to have gone on another wee bit I would like to have seen how her choice impacted but you didn't you know it just ended so out of ten or the city was five I was very very tight so what about yourself see I would give it eight yeah I would give it eight because I enjoyed it I enjoyed it and I thought what I enjoyed the most about it was I thought it was interesting you know I looked forward to opening the book and reading it you know it wasn't boring you know and I think I would give it a seven and a half to me and I the reason why I wouldn't give it higher is because it took me a while to get into it but I would definitely recommend people to read it oh I would yeah yeah it's and as I said it was it was well there's been that book of choice when it came out and it was a New York Times number one bestseller so it's well worth the read great talking point yes yeah yes great talking point great book for that so many thanks for coming out this very very cool night coming and hopefully Orla and yourself will join us in the new year for another book we'll get out to make her husband now and let him take me I show for a wait thanks a million cheers to you now good boy keep your house on pet why we're playing dinner at the North Pole remember so we need to wear our big warm coats inside when it comes to food or heat many families will face impossible choice


In our normal day-to-day life, the minimum amount of work that you can do is zero. If you just lie around doing nothing, you do zero work. That's the least you can do, right? But in physics, you can do even less work. That's right. You can do work less than zero in physics. Let's find out how. Now in a previous video, we saw how to calculate work. It's calculated as force acting on an object, multiplied by the displacement of that object. This means that to do work in physics, you need to push or pull on something. And while pushing or pulling, you have to make it move. This is how we do work in physics. Now here's the thing. This work done can be both positive and negative, okay? So let's quickly find out when it's positive and when it's negative. To do that, let's make some space. So let me write this in short form. We'll just write as w equals f into s. f is the force. S is the displacement. And let me get rid of this. Excellent. Now if the force and displacement happen to be in the same direction, that's when we say work done is positive. It's a positive number. On the other hand, if the force and the displacement happen to be in the opposite direction, and we'll look at some examples, then we'll say work done is negative. This is when work done becomes smaller than zero because a negative number is smaller than zero. So let's look at some examples. Suppose a lady is pushing on a grocery cart and makes it move, then she is doing work on it because she's pushing on it and she's making it move. Now is that work positive or negative? Well let's see. If you look at the direction of the force, she's pushing it to the right. And look at what direction that cart is moving. It is moving in the same direction to the right itself. So here the force and the displacement are in the same direction and therefore here she's doing positive work on that cart. So the work done over here is positive. On the other hand, imagine an uncontrollable car that is being stopped by Superman. Now let's think about the work done by Superman on the car. Let's see if this is positive or negative. Okay, let's look at it one more time. So here's our Superman and here's the uncontrollable car. The moment Superman starts pushing on it to try and stop it, he puts a force on it. What direction is Superman pushing on this car? Well from here you can kind of see he's trying to slow down that car. It's pushing on it towards the right, okay? But what direction is that car moving? Well, the car is moving to the left. As it's being stopped, notice the car is moving to the left. So notice the force on the car is to the right, but it's being displaced to the left. So the force and displacement are in the opposite direction. So over here Superman did negative work on the car. Now here's where it sounds a little weird. If you look at some people who might be just standing and watching this show, they did absolutely nothing. So they did zero work. That Superman who saved the day did negative, less than zero work, which means Superman strictly speaking did less work than these people. How does that make any sense? You may ask. Well, that's how it is. It's mostly because work done in physics can mean very different things compared to work done in our day-to-day life. Okay, you try one. When you play catch and a ball is thrown and you catch that ball, in that case you are doing work on that ball because you are putting a force on that ball and the ball is moving. Can you think about this, whether the work done by you on that ball, is it a positive work or a negative work? Go ahead, pause the video and think about this. Here, let me show you one more time. So here's the ball and you catch it. All right, let's see. So as the ball comes towards you, the moment you make contact with the ball, you start pushing that ball. Now in what direction are you pushing? Look at where your hand is placed. You're pushing that ball towards the left, isn't it? That's what you're doing. But in what direction is the ball moving? Both the ball and your hand are moving back, right? They are moving back as you stop that ball. Which means, notice, the force on that ball is to the left and the ball moved to the right so the force and displacement are in the opposite direction, which means while catching that ball, you did negative work on that ball. Okay, you can try another one. Imagine we take a ball and we throw it up. Let's say we throw it up and consider the upward motion of the ball. Now, during this time, gravity is putting a force on that ball, right? So can you think about the work done by gravity during the upward motion of the ball? Do you think it's positive work or negative work? Again, have a look at it one more time. We're throwing the ball up. Just concentrate on the upward motion of the ball. Again, pause the video and think about this. All right, let's see. So what direction is the force of gravity acting? Well, gravity always acts downwards, right? So the force of gravity is downward but the ball is moving up. So notice that the force and the displacement are in the opposite direction. That means during this motion, gravity is doing negative work on that ball. The force is due to gravity, right? So gravity is doing work. So gravity is doing negative work during the upward motion of the ball. On the contrary, what would happen if you were to throw a ball down or if you were to drop a ball? Well, if you were to drop a ball, I'm now pretty sure you can agree. Again, the gravitational force would be downwards because gravity always acts downwards. And notice now, the displacement is also downwards. So when a ball is falling down, this time, gravity is doing positive work on that ball. Now, before we wrap up, you may be wondering, why is it defined this way? What's going on? Well, to get some insights, that's because when the force and the displacement are in the same direction, objects tend to speed up. And when the force and displacement are in the opposite direction, objects tends to slow down. So they have opposite effects. To give an example, when the ball was falling down, the force was in the same direction as that of the displacement. The ball speeds up. When you drop things, they become faster and faster as they go down, right? On the other hand, when we threw the ball up and the force of gravity is in the opposite direction of the motion, what happens to that ball? It slows down, isn't it? So notice here, this has opposite effect of this. And to denote that, we call this work as positive when the speed tends to increase. And we call this work as negative when the speed tends to decrease. But as of now, don't worry too much about this because we'll get more clarity on this once we start connecting work and energy. Then we'll start making more sense, okay? So what did we learn in this video? We saw that when the force and displacement are in the same direction, we call the work as positive. In the opposite direction, we call the work as negative.


Great, can you all hear me? Great, thank you very much, Dr. Srinivas, for the introduction.  We spend a lot of our time speaking with other physicians about how to advance the field. But I think I speak on behalf of all our colleagues when I say that we get the most satisfaction from being with you, the patients. So it is quite an honor to be here with you all today. I also wanted to thank Dr. Diedrich for that great setup for this portion of the talk as well. As Dr. Diedrich was saying, we have made considerable advancements in the field of not only kidney cancer, but also cancer in general over the last several decades. And I actually first wanted to start off with the book recommendation, because I feel that no one actually better chronicles this germany that we've been on over the last several decades better than Siddhartha Mukherjee in his book, The Emperor of All Malades. Many of you may have actually read this book before. But it's a Pulitzer Prize-winning book, which is subtitled A Biography on Cancer. And Mukherjee talks about the evolution that has taken place over the last several decades. And for those of you who may not have the attention span to read a 300-page book, there's actually a PBS series on it, so you can just watch it on TV as I did. And so Mukherjee actually talks about the four pillars of cancer treatment. So I was going to go into those in a little bit more detail. So just to give you a historical perspective of where the field has evolved. So we know back in the day in the 1800s, we actually first started off with surgery, being the first pillar of cancer therapy. So if you ask a surgeon how to take care of a cancer, he or she will say, let's just cut it out. And that actually is very effective in early stage treatments. However, we know that the role of surgery is somewhat limited in advanced cancer. So then in the early 1900s, we actually saw the evolution of what we call radiation therapy. Radiation therapy was invented shortly after we discovered x-rays. And the thought was that x-rays actually cause breaks in the strands of DNA of rapidly replicating cancer cells. So the thought is if we could prevent that from happening, we would prevent cancer cells from replicating. And in the 1900s, it was thought that radiation therapy would be the cure for all cancer treatment. And while that's not quite the case, we do know that it is still very effective. The effectiveness in kidney cancer is still yet to be seen, however. In the 1940s then, we actually saw the introduction of what we call chemo therapy, as you all know today. So something that you may not have known is that chemo therapy actually derived initially from nitrogen mustard gas. That was a tool that was used in World War II as poisonous gas. And when soldiers came back from the war, physicians and scientists actually noticed that their white blood cell counts and the red blood cell counts were severely depressed. So they actually had what we call bone marrow suppression. So a few scientists got together and thought, hey, maybe this is a good idea of a way to treat actually blood cancers. So now it was actually being used in the 1940s as a treatment for leukemia and lymphoma. And then in the last decade, we saw this explosion of what we call targeted therapy, as Dr. Dietrich was just talking about. So targeted therapies is basically an evolution of where we come because our improved understanding of the molecular underpinnings of kidney cancer. So we know, as Dr. Dietrich said, that the protein VEGF, or vascular endothelial growth factor, plays a very important role in kidney cancer. So targeting this pathway and blocking its ability to exist in tumor cells limits the ability of this kidney cancer to grow and divide. Similarly, the mTOR pathway, which is another very important protein and pathway that is involved in the survival of kidney cancer, we know that by blocking this pathway, we have drugs, as Dr. Dietrich had talked about, temserolimus and everolimus that are very effective in kidney cancer. So in the last 10 years, we've seen this explosion of drugs in kidney cancer. So we as oncologists are very optimistic about where the field is going. And now all these drugs are now FDA approved, which is very exciting. So in the last four or five years, however, there's been a lot of buzz in the oncology world, and there's been a fifth pillar that's been added to the cancer treatment paradigm. And you probably guessed that's immunotherapy, as you're probably all well aware. In fact, the director of clinical immunology at Johns Hopkins was quoted as saying, I have such confidence in the potential of immunotherapy that I think the years from 2010 to 2015 will be looked at historically as the time that immunotherapy became the fifth pillar of cancer treatment. So certainly a very exciting time in the field, and I think a lot of people will see this as potentially the golden age of oncology. So how do we define immunotherapy? So I define immunotherapy as harnessing the power of the immune system to fight cancer. And a lot of people will think that this is something that has just began in the last two or three years. But the origins of immunotherapy were actually much farther back than what you may have imagined. It actually dates back to this year in 1891 with this gentleman, Dr. William Coley. So Dr. Coley was a specialist on oncology who specialized in this type of cancer, which is soft tissue sarcoma. And so Dr. Coley actually kept meticulous records of all his patients that he was seeing with sarcoma. And what he noted one day was an outstanding revelation. He actually noticed that patients with sarcoma who were infected with this bacteria streptococcus pylogenies, which manifested as a facial rash or erycypolis, actually lived longer than patients who did not have the infection, which was a very interesting observation at the time. So Dr. Coley did what any illogical person in the 1800s would do, and he started injecting people with syptococcus pylogenies. And what he actually called this, Coley's toxins. And the thought at that time was that maybe these toxins are actually killing the cancer. And lo and behold, he actually saw several responses. So he started injecting patients with bacterial strains, and he started seeing tumors regress or get smaller, which is very interesting. The bad side is that people started dying of syptococcus pylogenies infection, so it wasn't the most effective treatment. But this is kind of the story of how immunotherapy was born. So since that time, now we have a lot more mature data that shows that there is a relationship between the immune system and cancer. And some of the most compelling data comes from patients who have undergone kidney transplant. So when you undergo a kidney transplant, you take certain medications that we call that immunosuppress the body. So there are immunosuppression drugs that keep the immune system at bay so you don't reject your transplanted organ. And so when these patients who have a weak immune system, we know that they have a high susceptibility to developing cancers. So you can see here that the patients with a weak immune system have a 20-fold increase of developing skin cancer, non-Hodgkin's lymphoma, leukemias, ovarian cancer, breast cancer, and it's mattering of the other oncologic problems. So the thought is that if you have a weak immune system, you're more susceptible to getting cancer. So then the thought was that the corollary should also be true. If you have a strong immune system, you should be able to either prevent cancer or eliminate it. So more science came on over the next several years, and one of our first drugs in this modern day of immunotherapy was actually not so modern. It was in the 1970s, and we had a drug called IL-2. So IL-2 works by stimulating T cells or immune cells that you have in your body, causing them to release molecules called cytokines, which wake up a dormant immune system. And this treatment, even in the 1970s, turned out to be extremely effective. So these are patients with metastatic kidney cancer. And as Dr. Dietrich was saying, this is a Kaplan-Meier plot, basically a survival plot. So the higher the line, the better. And you can see here that there were 20 patients out of about 200 who had a complete response, what we call a CR. So they were effectively cured of their disease. So we say one in 10 patients who received this IL-2 therapy was effectively cured. And this is in the advanced setting, so patients with metastatic disease. So this is quite impressive. Here is a CT scan of a patient who has first diagnosed with metastatic kidney cancer to their liver, as you can see by the shaded out region in the liver there. And you can see even 20 years later, this is a scan of a patient who had IL-2 therapy back in the 70s. 20 years later, no evidence of recurrence in the liver. So quite impressive. The problem with IL-2 therapy is that it's extremely toxic, similar to what we were talking about with the bacterial treatments that Dr. Coley was giving patients. These patients often land you in the intensive care unit. So it's very difficult to give patients. And I would say in general, we only give this maybe once or twice a year at Stanford, very, very rarely, because it is so toxic. But this started to give us reason for hope that the field of immunotherapy may be very promising. So as you probably see now, the field of cancer immunotherapy is really a buzz. You've seen this not only in the scientific community, but also in the popular press. So you've seen this on the cover of Newsweek, it's on the cover of Time Magazine, and it was made actually very popular by Jimmy Carter, who was diagnosed with metastatic melanoma, who had disease, both had gone to his liver as well as to his brain. He got a medication with a type of immunotherapy, and he has now rendered disease-free two or three years after starting treatment, which is quite remarkable. So there is a lot of promise in this type of therapy. So November 23, 2015 was a very important day in kidney cancer, because this was the day that the FDA approved its first immunotherapy drug in kidney cancer. And as Dr. Dietrich explained, that was nevolamab or op-divo. And some of you may have seen the commercials on TV with the slogan of a chance to live longer. And that's somewhat debatable, in general, it is a very good drug for kidney cancer, and it is moving the field forward. So how does nevolamab actually work? So I'm gonna take you back to immunology 101, and I'll start off with an example of when you get the cold or the flu. You don't take any medications, you don't even see your doctor most of the time. You take some chicken noodle soup and everything is better within one to two weeks, right? But why is that? So what's actually happening within your body? So your immune system is certainly at work. So your body has these T cells, or these immune cells that are floating around your body, they're essentially your first line of defense system. And you also have what's called these antigen presenting cells. And these antigen presenting cells are looking for foreign particles all throughout the body to bring them to the T cells, to activate the T cells, so that way it's programmed to kill whatever it's looking for. So your body does exactly that with the flu. So your body's able to recognize that there are particles of the flu virus within your body, and you have these dendritic cells or antigen presenting cells bring that particle of the flu to the T cells, activate them, and now you have a robust immune response fighting the flu. So then the next logical question is, why isn't this working cancer? Well, it turns out that cancer is extremely smart. So cancer has developed these escape mechanisms to evade the immune system. So what cancer does is that it holds up this white flag.  And so what this white flag called scientifically on tumor cells is called PD-L1. And so this is something that you may have heard of as well on the news as well. So PD-L1 is this white flag that tells the tumor when it engages with an immune cell, don't eat me. And how Novolamab works then is this antibody that blocks this interaction between PD-L1 and PD-1, which is found on the immune cell, and thus effectively lowers that white flag.  And then you allow the immune cell to gobble up that tumor cell, that makes sense. So this has been a very effective way of combating kidney cancer and many other cancers in general. So that's how it works in theory, but then does this actually work in humans. So there have been many clinical trials looking at this drug. And the registration trial, which actually showed that there was benefit of Novolamab compared to other targeted therapies, was this trial called the Checkmate 25 trial, that randomized patients who have been previously treated for kidney cancer with different therapies like Su-10 or Presopenib. And these patients were then randomized to either get Novolamab, which is the immunotherapy, or Evrolimus, or Affinitor, as you may know it. And you can see here on this overall survival plot that the patients in the blue arm, which is Novolamab, is significantly better than the patients who got the Affinitor, or the Tyrosine Kinase inhibitor, or the targeted therapy. And you can see here, the p-value, it was, it's a good question, it was significant here actually. The progression-free survival was not seen in the initial trial, but the overall survival was significant. I don't have the p-value here, but it was significant less than .05 though. And if we look at the response rates, we do see that the Novolamab group did have a higher response rate, meaning the patients who either got a complete response, which is very rare to see, only 1% of patients, or at least a partial response, which is more than 20% reduction of their tumor. And we can see that that happened in 25% of patients compared to only 5% of patients with everolimus. While that's great, we would love to see this number improve however. So right now, only one in four patients are responding to Novolamab monotherapy, meaning if you only received that one drug. So what are the side effects of immunotherapy? So the side effects that's noted in this clinical trial are that, well, for one, patients, 20% of patients had what we call a grade three or a grade four side effect. So these are more severe side effects. So at least one side effect that was pretty severe. So that is somewhat toxic, is one in five patients. The most common side effects seen were fatigue, as well as rash, pneumonitis, or inflammation of the lung, which may have been manifest with a cough, an anemia, or lowering of your red blood cell counts. In general, we think of the ituses when we think of the immune-related side effects, because as Dr. Dietrich was saying, most of the side effects are related to what we call autoimmunity, because we're essentially taking the brakes off the immune system. So we're letting the immune system go rampant, and what can happen is that the immune system can start attacking itself. So these are all the different side effects that can happen because of immunotherapy. So if you have your immune system attacking the colon, it's called colitis, and that can show as diarrhea. If you have inflammation of the lung, we call that pneumonitis, and that can present as coughing or shortness of breath. Patients can also get rash, as we talked about, arthritis or pain in the joints, and quite a few other different side effects that you can see here on this chart. So then I want to talk a little bit about how long do you treat for? So this has actually been a little bit controversial because of this concept of what we call pseudo-progression. Pseudo-progression, as opposed to regular disease progression, is an immune-related phenomenon. So what we know in disease progression, in this regular, old-fashioned disease progression, if you put you on a clinical trial and we get a CT scan eight weeks later, if things grow, we assume that's because the tumor itself has grown, so we typically take you off the clinical trial. However, what we've noticed in immunotherapy is that at the eight-week mark, sometimes the tumors look bigger on the scans, but that's not necessarily because of actually tumor growth, it could be because of immune cell infiltration. So you have immune cells infiltrating the tumor so it looks bigger on the CT scan, but if you give it more time and allow the immune system to do its job, you actually see that these tumors start to shrink over time. So this was data that was presented last year that looked at patients who have actually previously progressed on the trial that we just discussed about, the Checkmate 25 trial of patients who got either Everolimus or patients who got Nevolamab, and these patients were actually continued on treatment despite progression. And this is what we call a waterfall plot. So in 150 patients, they actually treated beyond progression and here you can see each of these lines represents a new patient. If the bar goes up, that means their tumor got bigger. If the bar goes down, that means their tumor got smaller. And what you can see is patients who have already shown progression on a CT scan, if you get a CT scan at least eight weeks, if not later, what you can see is that 20% of these patients actually have a response of greater than 30% reduction in their tumors. So nowadays we say that if we can treat for longer, the better. So in general, we try to treat for six months as long as you're tolerating the side effects okay because there's a chance that you could respond later even though your initial scan showed growth. So then the question becomes where does the field go from here? How do we improve upon that 25% response rate? Well so I'll go back to this slide and I'll say that remember when I talked about cancer waving that white flag, well it turns out that it's a lot more complicated than that. There are multiple white flags unfortunately. So the thought is that if we use combinations of different mechanisms of how the tumors evade the immune system, potentially we can get a more robust response. So the field right now is going towards what we call combination trials. So if one is good, is two better? That's the big question that we're answering right now. So Stanford was actually involved in a clinical trial using two immunotherapy agents called one is nevolumab and the other one is called epilumamab. And these drugs work by blocking two different immune pathways that are essentially releasing the brakes off the immune system in two different mechanisms. So we know that the CTLA pathway and the PD1 pathway are both pathways that tumors use to evade the immune system. So we're actually now using drugs to affect both pathways. So this was done in the checkmate 214 trial. So in this trial patients, these are treatment naive patients meaning that they've never seen any other type of treatment for their advanced kidney cancer. And they were stratified by risk and Dr. Gidrick had previously talked about good risk versus poor risk. And essentially this is the risk stratification is based on a series of both clinical parameters as well as laboratory parameters looking at things like your hemoglobin, your calcium levels, your LDH, which is a marker of inflammation in the body.  So patients in this trial were actually randomized to two different arms. The first arm received combination immunotherapy with the two drugs that we talked about, nivolumab and ipulumumab. The RMB received a suitent alone. And you can see here, and this is actually hot off the press. This is actually not even published. This is a picture off of a Twitter slide that I saw. So, and it shows that the overall response rate was quite impressive in the intermediate and poor risk patients. And that's important to know because this was not seen in the good risk patients. So the intermediate and poor risk patients, you can see that there was a overall response rate of 42% in the combination arm, versus 27% in the targeted therapy alone arm. And you can see here that there was a 9% complete response rate, almost 10% of patients were having complete responses to the combination immunotherapy treatments, which is quite impressive. And here is the preliminary overall survival curve, which has also been shown to be statistically significant. And it shows that there is a significant improvement in overall survival with the two drugs as opposed to the one drug. And importantly, the two immunotherapy drugs. So as Dr. Dijik was saying, this trial was actually halted early because it was shown that there was a significant improvement on one arm over the other. So they stopped the trial saying that everyone should potentially be getting this treatment. So this may be the new way going forward, potentially in the next several years for this treatment of newly diagnosed metastatic kidney cancer. I will say that these drugs can be, that the toxicity was essentially combinatorial in terms of the side effects that each of these drugs actually delivered. So that's one thing to consider. We don't have all the data. I didn't have all the data in front of me to present to you some of the side effect profiles, but we know that the addition of two drugs can be very, very toxic though as well. So something to watch out for when that data actually gets released. So I wanna talk a little bit about immunotherapy trials here at Stanford. So we know that there's a lot of different ways that we can actually modulate the immune system. We can augment it either by inhibiting an inhibitor, meaning that some of these checkpoints that we talked about, the PD1, CTLA4, we can effectively take the breaks off their immune system to allow the immune system to be more effective. Or the converse is on the right side or the left side of your slide, that you can see that these are all activating receptors. So these actually boost the immune system. So we have a trial now that takes advantage of two of these combinations, the PD1. So we're taking the breaks off the immune system and also using a antibody against CD27, which it works as an agonist and activating the immune system on the other side of it. So we have one that's gonna take off the breaks off the immune system and one that's gonna activate the immune system. And this is a trial of two drugs called, with nivolumab, with a drug called varlumumab, which is an anti-CD27 molecule. And what we know is that in mice, this is actually very effective. These are survival plots in mice and we can do a great job curing mice with a combination of these two different immunotherapies. Now the question is, how are we doing in humans? And this is evolving and we still don't have a whole lot of data yet because it is a phase one, phase two trial. So we're still very early in the clinical trial, but they have published a little bit of evidence that shows that this may be effective. So this is a patient who had metastatic kidney cancer, who's had prior lines of treatment. And you can see that even after one dose of varlumumab, you start to see a small regression of one of the patient's lung nodules. So of course you have to take this with a grain of salt because this is only one patient, but the data is starting to come out to see if this is gonna be more effective. So part of moving the field forward here at Stanford is that we try to get patients on clinical trials so we can see if these drugs are indeed effective because the science is in general very promising. We also have clinical trials that are based on recent data that show that the adenosine pathway is yet another way that tumors evade the immune system. And this likely represents a mechanism of resistance for PD1 therapy. So when drugs like nivolumab are no longer effective, the question is why aren't they effective? And it's probably because these tumors develop secondary mechanisms to evade the immune system. And one of these is the adenosine pathway. So adenosine is actually secreted by these small molecules on tumors called CD73. And when adenosine binds to an immune cell, the T cell at the A2A receptor, it essentially renders the immune cell ineffective. So it's very similar to that checkpoint inhibitor that I talked about earlier. And what we know is that we're now working with a company called Corvus Pharmaceuticals which has built a small molecule to block that receptor that I talked about, the A2A receptor, essentially denying the ability for adenosine to interact with the T cell and therefore leaving it effective and able to kill cancer. So the data still is very naive and we're still getting more and more data is still in the phase one phase right now. But we know that in kidney cancer, it looks relatively promising. So we see that in small numbers, and that's the caveat here, that 60% of patients responded when they were given this drug alone and 100% of patients responded when they got the drug plus another immunotherapy called Atizaluzumab, which is another PDL1 inhibitor. But if you'll note there that there are only 10 patients there. So it's very, very early to say if there's really any signal or not. Dr. Fan has actually started another trial looking at what we call a Glutaminase inhibitor. So Glutaminase inhibitors work by targeting the metabolic pathway of these cancers. And this is actually an interest that many patients come to us with because there's a lot of these popular press information out there about the way sugar affects cancer metabolism. Well, this is actually a Glutaminase inhibitor which inhibits glutamine, which is a sugar metabolite, from getting into the cell. And essentially, this drug is starving the cancer cell and it's being used in combination with immunotherapy to be a potential another promising target for kidney cancer. And finally, I just wanted to speak about kind of where the field is going in general. So those are some of the clinical trials that we have at Stanford. But in general, in the entire field of immuno-oncology right now, a lot of the therapy is going towards combined trials and not just necessarily to immunotherapy drugs, but a lot of combination trials looking at the use of immunotherapy plus other standard treatments, such as the targeted therapy that we talked about. So if you'll see here, these are all very large phase three trials that are undergoing right now, looking at, many of them are looking at immunotherapy, such as Avilumab or Pembroluzumab, in combination with a targeted agent like Sutent or Exitinib. And I think in general, we feel that this may be the way going forward, is that they'll probably have some combination is which treatment will eventually win out. So just to conclude here, we made enormous progress for advanced kidney cancer in the last decades. We have a number of new treatments that are now FDA approved. Cancer and the immune system have a very close relationship, as you have seen through the data. Immunotherapy, such as checkpoint inhibitors, are promising in a subset of patients. And the next steps include combination trials, vaccine studies, and biomarkers to predict who will respond to treatment, which is something that Dr. Fan will be talking about here soon. Thank you all. Any questions? Yes, go ahead. I have a question about something you talked about at the beginning about testing for a weak immune system. Two-part question, how do you test for it? And number two, is it a genetic kind of thing that children should or adult children or some should be tested if they find that we have one? It's a good question. So the slide that I showed earlier wasn't necessarily testing patients randomly for a weak immune system. We were actually inducing in a weak immune system on them because they had a kidney transplant. So what we do is we give them drugs like steroids, for instance, that weaken the immune system so that their body doesn't reject the donated organ. So we were actually giving them a weak immune system. In general, I would say that it's a good question about testing patients' immune system. The biomarker that we look right now to see if tumors are amenable to what we call immunotherapy is a marker called PDL1. And I would say that right now it's prognostic, meaning that we could tell if you're going to do well or not in general with kidney cancer. But we can't predict whether you're going to respond to treatment that hasn't correlated to treatment responses yet. Can you tell the difference whether it's pseudo-progression or it is a real progression? Yeah, it's a terrific question. The question is how do you know if this is truly pseudo-progression or real progression? And I think right now there's, technically there's two ways. One way is that you can technically, if you had a strong suspicion, biopsies the tumor. And if you get back a bunch of inflammatory cells, that may be one way to answer it. Oftentimes we do this clinically though. What we do is we get another scan, potentially four to eight weeks later, to see if there's regression of that tumor. If the tumor continues to grow, we assume that it's real tumor growth. Yeah, it's a great question. Yeah, it's a great question. So the question is about CAR T therapy. So CAR T therapy is chimeric antigen receptor T cells. And what we do is actually is pretty interesting. So this therapy works by taking your white blood cells and extracting them from your body through a process called leukophoresis. And then we take those cells and transfect them with a virus that is able to what we call up-regulate a receptor or a target that hones in on a certain cancer target that you have an interest in. So for instance, in prostate cancer, it can be a PSA. In lymphoma, it can be a target called CD19. The question is how to do this effectively in kidney cancer? And which receptor would you actually want on to serve as a target for kidney cancer? So this has actually been looked at and they have done preclinical models of CAR T cells looking at CA9, which is a target found on kidney cancer. Well, I have to say that they haven't seen any responses or it hasn't been as quite as effective yet in kidney cancer even in the preclinical models. So it's still at the very early stages for shallow tumors in general. It is FDA-approved now in leukemia and a certain type of leukemia. And it looks very promising in certain types of lymphoma. And there was recent data showing that it can be promising even in glioblastoma and multiforme, a type of brain cancer. But in general, I think the field of CAR T cell for solid cancers is probably still a couple of years away, at least a few years away. Okay, thank you so much, Sumit.


Hey guys, this is Mary Lee Johnson here with the 21 Convention 2014. Greg Swan, you just had your 2014 talk. It was so good and so incredible, and I say that for a couple of people, but for his I really mean it. It was really, really good. I wanted to ask you first before I ask you about this talk. Other people might not have seen it. I'd love for you to elaborate on Mr. Maybe. I wrote a book called Father's Day earlier this year, and I talk about three different kinds of fathers in that book. Mr. Married is the ideal father, the father who's going to have the group photo with their children, their grandchildren, maybe three or four great grandchildren. Everybody's happy to be a part of that family. They're all still together. That's the ideal family from my point of view. The other two fathers in the book are Mr. Maybe and Mr. Divorced, and in the current marital circumstance, a father that we used to know, who used to be fairly common, Mr. Stick It Out, really doesn't have a chance that if you're Mr.  You're going to lose access to your children. Your life is going to turn into a desperate miserable thing. You may recover from it. I certainly did. I'm happily married for the second time, but I want a lottery ticket, and I don't recommend this as a strategy to think, well, if I screw this up, I can marry somebody just as good. No, chances are you won't. Therefore, my argument to men is do step up, live up to your promises, establish yourself as the moral leader of your family, and follow through. Become Mr. Married, because this is how Mr. Married leads his family, is by leading them, by being the moral leader for his wife, for his children, and for himself. And taking your moral responsibility as a man, as a husband, and a father seriously makes perfect sense to me. And I comment this having been Mr. Maybe more than once through one marriage that I destroyed and destroyed a family, but also through my second marriage, through a substantial part of my second marriage, but frankly, every romantic relationship I've ever had in my life. I was Mr. Ghanabi, I was Mr. Driven, I was Mr. Mann with the plan while we were courting, and as soon as things settled down into a committed relationship, then I started to withdraw and started to let things go, let things slide, and when that happens, Mrs. Maybe gets more and more afraid, because she's not getting what she bargained for, and she's not sure how she's going to weather this calm, it's not really a storm, this calm of indifference or seeming indifference, this withdrawal, this distance, this lassitude.  And when you were talking about being a moral leader, you're not talking about living up to religious ideals. Not necessarily. If you are religious, I don't object to that. I don't tell people what to think or what to do or how to choose. I was talking to Jolly about this, I don't know if I should mention him or not, but the photographer for the 21 convention is a Sikh by tradition and by preference, but not necessarily by religious belief. But he admires the Sikh philosophy and he upholds it to the extent that it makes sense to him. There are a whole lot of religious people who are religious in that way. They may or not not necessarily be terribly theistic, but they grew up in a family tradition, a religious tradition, and they continue to honor it. Having a serious committed moral philosophy of any nature is preferable to not having one or to being haphazard, catch-a-catch-can or making excuses for your moral failures. I really don't care what your moral philosophy is. I care about how serious you are about it. I don't care what you believe. I care what you choose to do. And if your behavior is exemplary, then it doesn't matter how you got there.  That's such a hard thing because I know that you're an atheist by choice, but you don't present that to anyone. You don't try and convert anyone. And I don't argue with people about it either. The obnoxious atheist is just another kind of religious zealot as far as I'm concerned. I do not care for that behavior. I think that's bad behavior. I would never presume to tell somebody else what to think because, frankly, I'm not going to bear the consequences of your choices. You're going to choose for whatever reason you choose, whatever choice you make is fine with me because I'm not going to suffer the consequences one way or another. But I'm certainly not going to take responsibility for the choice.  You can blame God or you can blame your parents or you can blame your wife.  I'll tell you what I think. I'll tell you what I do and I will defend my positions. When I think it necessary to defend a position, I will defend it to the best I'm able, but I will never tell anybody what to do. I don't should people is the way I say it. I will talk about what I think is intelligent, the strategies that make sense to me, but I don't should people. You're responsible for shooting yourself. That's, it's, it's just so refreshing to hear something like that where somebody doesn't come from a stance of this is what I believe and then this is what's right and this is the only thing that's right. Right. You're wrong. I'm right. And that's the way it is. I don't believe that. I certainly don't let anybody say that to me. And I in the book, Charlie's Delight, which I talked about in my talk today, I didn't really talk so much about the book as just as compared with the content of the book. I'm lost. I spoke for an hour and it wears me out. This is Dr. Doug McGuff was talking about what happens to your brain under stress and so you should watch that video. Oh, it's gonna be I will tell you, since you mentioned this, that my strategy in giving my talk today, in addition to everything else I was doing was that I was mentioning every other speech that I thought was worthwhile because I think they're worthwhile and because I think you should see them, but also because I want my video to be processed first. And by mentioning all these other speeches that I can build interest in all these other speeches and hopefully I'll get my video produced first. I don't remember where I was going. No, refreshing refreshing not to should people. I don't remember how I got there where I was going. So that's great.  This has been barely Johnson with the 21 convention here with Greg Swan. And you heard it first, his video will come out first. You will see that before any other video. Well, I hope that I hope that's the case. But if it's not I will not resent it in any way at all. I admire the 21 convention beyond all measure. I admire what Anthony Johnson's done. I admire you personally. I am very impressed with you and Anthony for the commitment that you've made to each other. And I really like to see the way that you work together this weekend to make this come off so well. I like to see you involved in doing videos for the 21 convention. I mean, obviously, you're a delight to look at, but you're also very intelligent and and really a wonderful person to know even if you only know Merrily through these videos, you're getting to know her and she's for women watching if there are 10 or 15% women watching the videos maybe more watching Merrily's videos. Merrily is a moral exemplar. She's a good example for women to live up to. And so I'm honored to know you. I admire you know and I'm honored to know you. So bless you. Thank you for your time and your attention. Thanks. Bye guys.


Why do narcissists want to get married? If you are such a problem for them Why would they want to marry you in the first place? Why would they log themselves into a situation where they are stuck with you? You might think that a narcissist wouldn't want marriage They're always looking for the next big thing They need narcissistic supply. They don't like intimacy or being vulnerable They prefer superficial things. They also hate your emotions They hate any vulnerability that you display to them They're not good with anything that involves any form of longevity So why would they gravitate towards marriage? Why would they choose something that seems to contradict everything that they want? There are reasons why a narcissist would want to get married Even though it may not it may not be right for them The narcissist has a false image That they want to display to people and marriage fits in well with that image They want to look normal Which is why they can often be so obsessed with getting married and having a family Because it's all about how other people see them Narcissists have a fear of abandonment. They are terrified that you may leave them They cannot deal with rejection But marriage makes them feel more secure They use marriage and children to trap their targets So that you can't get away so easily They like things that are documented Because then they feel like you legally belong to them As though you're their property Narcissists also want marriage Because it's a part of their grandiose fantasy It's a display to other people That they are desirable and attractive That they are special and important Which then makes the narcissist feel better about themselves Even when they want children That's still a part of the image They view the child as a fashion accessory and as an extension of themselves It's just something that complements their image It's something that makes them look good And they want children because they know it's what they're expected to do They know that society expects us to get married and have children Narcissists want to look normal They want to be socially acceptable people But while marriage may fulfill some of the narcissist needs It causes a big problem for the other person Because many people don't want to get married for those reasons And if they knew that's why someone was marrying them They probably wouldn't want to get married Because they're not marrying you for you They're marrying you for themselves But they don't reveal their true motivations to you Which is why when you marry a narcissist It's only a matter of time until difficulties begin to surface Because they didn't marry you for you They never intended to be committed with you They never intended to cooperate or compromise with you They weren't looking for any like-mindedness They had no intentions of being reciprocal with you Because right from the start It was all about how it could benefit them It was never about sharing anything with you Which is why so many difficulties begin to surface after you've married a narcissist Getting through a marriage with a narcissist can be very difficult But what's more difficult is divorcing a narcissist They don't like it when you try to leave them You are much better off if they leave you and move on with someone else At least then they're more likely to leave you alone Because if you try to leave the narcissist They will feel like they're in a fight for their lives They will hold on to you for dear life Divorcing a narcissist can be very difficult It will affect any children that are involved It will cost a lot of money And the court system doesn't even recognize these types of personalities Which is why you are so much better off If the narcissist leaves and finds someone else Even if your marriage with a narcissist does come to an end They will often want to get married again Because they're very insecure So they use marriage to trap and control their targets They also love the attention it gets them from other people But no matter how many marriages they have It will always lack intimacy and warmth There will never be any empathy There will never be any empathy for the person they're with It will always repeat itself Because narcissists are just not meant to get married Thank you for watching I hope this video resonates with you Please like, comment, share and subscribe If you would like to donate My PayPal link is in the video description Coaching inquiries You can email me at coaching at NARC Survivor to Coady UK


Hi and welcome to the session, I am Arsha and I am going to help you solve this problem of your book which says, check whether 7 plus 3x is a factor of 3x cube plus 7x. So before solving this problem, let us first learn what does remainder theorem say. With the help of this theorem, we will check whether 7 plus 3x is a factor of 3x cube plus 7x or not. So this theorem says if px is any polynomial of degree greater than or equal to 1, then when px is divided by x minus a, where a is any real number, then remainder is equal to p at a. So this theorem is a clear idea that we will be using in this problem to solve it. So let us now start with the solution and let us denote 3x cube plus 7x by px. Here we have to check whether 7 plus 3x which is the linear polynomial, a factor of px. So first we will find the 0 of 7 plus 3x, 0 of 7 plus 3x is minus 7 upon 3, since to find the 0 of any linear polynomial, we equate it to 0 and upon doing so we get x is equal to minus 7 upon 3. Now by remainder theorem, 7 plus 3x is a factor of px if p at minus 7 upon 3 is equal to 0. So what we will do is, we find the value of the polynomial px at minus 7 upon 3. So we have 3 times of minus 7 upon 3 whole cube plus 7 into minus 7 upon 3, which is further equal to 3 minus 7 whole cube is minus 343 and 3 whole cube is 27 plus 7 into minus 7 is minus 49 and the denominator we have 3. 3 is the common factor in the numerator and denominator, so on cancelling we have 3 1s 3 9s are 27, therefore minus 343 upon 9 plus minus 49 upon 3 which is further equal to minus 490 upon 9, since on taking LCM of 9 and 3 we have 9 and when 9 is divided by 9 we get 1, so multiplying the numerator minus 343 by 1 gives minus 343, then we have plus 9 and on dividing 9 by 3 we get 3, therefore multiplying the numerator minus 79 by 3 and hence on solving we get minus 490 upon 9 which is not equal to 0. So this implies that p at minus 7 upon 3 is not equal to 0. This shows that 7 plus 3x is not a factor of px, as the remainder is not 0, 7 plus 3x is not a factor of x cube plus 7x, no since the remainder is not 0 is our answer. This completes the solution, remember the remainder theorem while you doing these types of problem and also be careful with the calculations, so hope you enjoyed this session, take care and have a good day.


Okay, so Malcolm in the middle. It's a classic American sitcom from the early 2000s. It's a really good solid show, and I just watched all of it in quarantine. So over the past month, I went through seven seasons, 151 episodes, and at the end, they really dropped the ball, but no one ever really talks about how it dropped the ball. So, um, yeah, I'm just gonna rant about that for a few minutes. This is the introduction song. It's not very good, but it's not too long. Okay, so basically, the premise of the show, if you haven't seen it, is like, there's this lower-middle class American family, and they have four kids at the beginning, but as the series goes on, they get a fifth one in there. I'm sorry, the camera's a little too close. I can't really do my hand motions the way I normally do, and the main character is this one named Malcolm, who is the middle child. He has an oldest brother, or two older brothers, yeah, whatever, you get the point. They're all boys, and they're all crazy troublemakers. They're constantly making trouble. They're constantly breaking stuff, causing issues with their parents, getting in fights with each other, horribly abusing each other as well, and that's where a lot of the humor comes from most of the time. Sorry, you can see my laundry sitting on the floor there. And Malcolm is also a genius, though.  There are multiple points throughout the show where he gets into a relationship with a girl or almost gets into a relationship with a girl, and she leaves after like 20 minutes as soon as she gets to know him a little better, because even though they think he's cute and smart and funny and all that, he becomes kind of shitty when you're around him too long. And that continues throughout the show, so that's where a lot of good jokes come from. And anyways, what I'm getting at here is that in the final episode, Malcolm is about to go off to college at Harvard, and they finally found a way to pay for it and all that, and he's offered a dream job where he'd make a lot of money, and his mom refuses for him.  Why'd you do that? And apparently she has already planned out his life for him, and she is demanding that he go to Harvard and do all that, do well, get educated and work super hard and suffer a bunch like he hasn't already, and then eventually he needs to become president of the United States so that he can make life better for poor people like them. And while I get what she's saying about the leaders of the U.S. being just a bunch of rich douchebags that don't really care about people like them, I totally get what she's saying, and the show does have plenty of moments like that that reflects that attitude where they just get screwed over by the system, and it kind of leaves out how a lot of their problems are self-inflicted. There's an episode where a couple of them leave a couch on some railroad tracks which causes a chemical spill and it infects most of their town, and so they have to spend a couple nights in a school gymnasium while the government cleans everything up.  And more than that, when it's shown that Malcolm's mom feels, has these super high expectations for him, which are a burden by the way, high expectations from your parents are a burden more than anything else, and she has all this weight that she's thrown on his shoulders and she's running his life for him and not letting him do things on his own, but it's portrayed as heartwarming, and that really is at odds with the tone of not only the rest of the episode, but the show as a whole. The show as a whole is about the kids in the family growing up, because, I mean, think about it, and this is something that isn't super uncommon in sitcoms, but it's uncommon in other types of media where the kids actually start out as kids and as time goes on they grow up and get older.  It's not heartwarming. And so where most sitcoms I feel, most sitcoms that I've watched have had pretty solid endings because it's much easier to write an ending to a sitcom than it is for serious dramas because with those, you have to wrap up actual storylines, whereas with sitcoms, it's just kind of a feel-good send-off to characters that you've known and loved for a while, and, yeah, this one, it went for the feel-good thing, and it just didn't work. You know, it didn't work as feel-good. It didn't work as humor. It didn't work as dark humor. It just felt like, oh, okay, Lois is still going to be overbearing and running her kids' lives and cause them issues in the future and not allow them to follow their dreams, and we can see throughout the show as well that her mother was a crazy person and so that's partially why she wound up the way she did, and I think you just know going forward that when any of the boys have kids, their kids are going to be fucked up, too, so it's just perpetuating this terrible cycle, and so, yeah, yeah, the ending of Malcolm in the Middle, they really dropped the ball and it was a little more depressing than they probably intended it to be, and that's about all I have to say about this.  Bye.


Hey y'all, welcome to what Chelsea eats. Thank you so much for joining me today I just wanted to come quickly and talk to you about a workshop that I'm thinking about having I Sent out an email last week and got a huge response But I figured I should come and do a video just to see what you That may not be on my email list or miss the email think about me doing a workshop to help you shrink fibroids and to heal other Reproductive issues naturally It was my final program because as I was praying at the end of last year What I should be doing for 2023 I felt the Lord speak to my heart that I would only run the 90-day program One time in 2023 and that was January as I continued to pray about what I should do going forward I quickly realized that the 90-day program is no more so For those of you who have been wondering I have officially retired the 90-day walk to fiber a freedom group coaching program I know it's sad Because I know there was a lot of you looking forward to that group But since then I launched another private program for the alumni of the 90-day program Which is not available to the public yet I am planning to launch Two new programs closer to the third quarter of this year a number of you have been Reaching out to me seeking support and after much prayer and conversations The idea of doing a workshop a workshop came to the forefront You know, I'll be honest though. I did not think it would be possible to simplify what I've taught over three months into a workshop that can happen in a day But the more we thought about it. I think we came up with a solution That could work. So I'm very excited about that the details of the workshop are still being sorted out But before I move ahead with setting a date, I Want to know that there is enough interest in this kind of event This workshop will be done a bit differently than any other program that I have ever offered in the past It will be live with time and space to write your responses to ask questions You will get a workbook a time to write your responses as we go along and so much more. I Won't cover everything you would have gotten in the 90-day program However, you will walk away with everything you need to get moving With adopting this lifestyle as your new way of life You will be equipped with the knowledge and the resources needed to detox and nourish your body so that you can shrink fibroids and heal other reproductive issues naturally if attending a workshop like this interests you please comment below in The comment section below You can also click the link in the description box to sign up and get notified when information comes available for the workshop Now the date that I'm looking at is probably the last week of July So kind of keep that in your mind as well If I get enough interest then we can move forward with finalizing the details So that you can register and prepare to make those Dates available for yourself Thank you, and I'm looking forward to hearing from you all lots of love. Take care


TFNN, headline, news update. Welcome folks, we're at the Dow Industries. They just nailed it at the end. It was red when I started the show at three o'clock, green at 355, guess what, 359 went back to red. Not big, but nailed it down a little. Dow down 53, Nasdaq off 15, S&Ps up four and a half gold. Gold contract up $17.60, traded 18.74 an ounce. We had silver up 28 cents, $23.63 an ounce, light sweet crude off a buck 24, $90.82 a barrel, notes and bonds. The 10-year note up 66, 125.30, the 30 year up 11 at 150.03 and King Dollar. King Dollar down 219.06 at 95.770, Euro 113, yen 150 and a half and the British pound 135 to one US dollar. We get up and we take a look at the S&Ps folks, what you have, you get a good bounce going, bottom line, no volume, you get a contraction of volume on the way up. Today we only did 77 million inside the spy. Yesterday was light volume loss, so it was 88, so you're 10 million shy. That's what happens when you get counter trend bounces. I do expect that the bottom line is that we can get up to the top of this range, which is at 457. That's another 10 bucks higher than where we are. NDX 100, showing how weak it is. NDX also, you know, bottom line, 56 million shares. We did 55 yesterday. You're going into 101 and the real, the kickin' with the NDX 100 is that will it be able to make the 366? We're at 356, you know, the high before that was 370, so this is gonna get intriguing as it gets up into that area as it has any juice whatsoever. Gold, gold contract out here, had an inside day, did 133,000 contracts. As I said earlier, what gold had done is 100% move for the move. And so most times what you do there, you're gonna move sideways, you're back down a little, it's gonna build cause to get over the 1882. You know, we hit the 1881, 60, and you hit that with volume. That's how you wanna go into a swing, folks. If you go into the swing with volume, which we did, your probability gets much higher that you're gonna blow it away. That being said, I expect you're gonna have to move sideways for a little time here because the move and gold once it breaks this baby is basically 2,500. It's 2,250 and 2,500, you know, and I expect we're gonna get there. Just gonna take a little time. Have a great night, folks. Have a safe night. Come back and visit Tommy tomorrow morning, kicks us off 9 o'clock in the morning, great show. Have a great one, folks. Have a safe one.