Hello Learners! I am Chai Nicaroy from the Discipline of English, Krishnakanta Handik State Open University. Welcome to the second part of the video lecture on the topic, industrialism and its impact. In the first part, we have dealt with the concept of industrialism and discussed some of the aspects of the pre-industrial times. We have also learned about the various inventions that were responsible for bringing about the industrial revolution. In this video, we shall try to focus on the industrial revolution with reference to England. For a long time, it was believed that Britain provided the world with the model for industrialization and set a trend that the rest of the world followed. However, present-day historians and social scientists have taken a newer look into the idea and challenged the superiority of England as the path-breaking industrial empire. With regard to the industrial revolution in England, it may be noted that between the 1780s and 1850s, there occurred a great transformation in the industry and economy of England. And this is the period of the first industrial revolution in England. The term industrial revolution was first used by the socialist philosopher and writer Frederick Engels in 1845. John Stuart Mill also used the term in his Principles of Political Economy as early as 1848. The term was used by the English philosopher and economist Arnold Toinby in order to signify the changes that took place in British industrial development between 1760 and 1820s. The industrial revolution refers to a period of remarkable economic and industrial growth in the cotton and iron industries, in coal mining, in the building of roads and canals throughout England and in foreign trade. There were many factors responsible for Britain's lead in industrial and economic growth. For example, new inventions in industry were made in England because of the scientific temperament patronized by the English monarchy. The country was naturally rich in supplies of coal and iron, the essential materials for the new industries. Among the European countries, Britain was the first to apply machine to manufacture. During this time, the British politics was relatively stable in England. Wales and Scotland unified under a single monarchy. This led to cross-border taxes being minimized, which further added the advantage of a common law, a single currency and a large market. Though the land enclosures of the 16th century and the use of machinery in farming led to an agricultural revolution, it also rendered many small-time farmers landless, adding to unemployment and migration of the rural poor into nearby towns. This large-scale migration also provided ample and cheap labour force. The population in most of the towns in England grew many-fold. London gained significance as the principal source of loans for international trade too. The city gradually became the hub of trade and many companies functioning in America, Asia, Africa and the West Indies, set up offices in London. England was also helped by a good network through rivers, indented coastline with good transportation and market outreach. All these factors aided the upsurge of the industrial revolution in England and set the stage for far-reaching changes in the social and economic front. With regard to the spinning and weaving industries, it may be noted that with abundant raw material and ready market, it was not difficult for Britain to gain supremacy in the world textile industry. Though the textile industry made rapid strides in England, it caused untold misery to its workers, mostly women and children who were made to toil ceaselessly and in very bad working conditions. Several inventions paved the way for this remarkable progress made by Britain in the field of textiles as already discussed. Among them, the most remarkable ones were John Key's The Flying Shuttle Loom, James Hargreaves The Spinning Jenny, Richard Orkwright's The Water Frame, Samuel Cromtoms The Mule and Edmund Cartwright's The Power Loom. Though the textile industry made rapid strides in England, it caused untold misery to its workers, mostly women and children who were made to toil ceaselessly and in very bad working conditions. Naturally, rich in resources of coal, iron, timber, copper, lead and tin, the Industrial Revolution brought a great boom in the metallurgical industry also. The discovery of coal greatly revolutionized the iron industry, as iron came to be used to make household furniture, machines, water pipes and so on. Later, steam power replaced water power and brought about further progress in the iron as well as textile industry. Another advantage for England was that most of the iron fields were located near its ports so that the products could be easily shifted to overseas markets. Consequently, there was a growth in the shipping trade as well as in shipbuilding. In 1769, James Watt patented his invention, the steam engine. Watt's steam engine came to be largely used in coal mines, iron furnaces and the textile industries. In the 1770s, John Wilkinson, known as Iron Mad Wilkinson, made the first iron chairs, wets for breweries and distilleries and water pipes. The increase in the use of machines also necessitated better means of transport and communication. Thus, a revolution was also brought about in road and river transport and subsequently in railways. Rich landowners with mines and queries on their lands initiated the process of canal making in order to transport goods and connect the loads to big market cities. The first canal called the Worsley Canal was built in 1761. From the 1760s to the 1850s, a period known as the period of canal mania, over 4,000 miles of canals were built along with the making of canals. Road conditions were also vastly improved and many new roads were constructed. Thus, in this video, we have got an idea of the remarkable inventions in the textile industry, development of transportation, coal, iron etc. Apart from getting an overview of the growth of industrialism in England. I hope this video will help you in understanding industrial revolution in the context of England. In the third part of this video series, we shall discuss the impact of industrial revolution and try to relate it with the rise of the working class. Thank you.


Today Professor Josh Rebair will discuss about biomarkers in more detail and also different phases of biomarker detection. Till then continue talking about the importance of statistics for the biomarker discovery program. Usually biomarker discovery programs are very challenging because to have a real biomarker which could work globally, one need to do large number of samples analysis. One need to do many ways of data analysis to ensure that a given protein or a given candidate biomolecule could really cater the needs of detection or the therapeutic significance in the clinics. So biomarker discovery programs usually depends on a big team which involves clinicians, technologists, statisticians and many people who are together trying to make meaningful and reproducible data and a sense out of these experiments. I hope today's lecture will give you more insight and integrity detail about how to do biomarker discovery based research. So let us welcome Dr. Josh Rebair for today's lecture. So now we are going to talk a little bit more specifically about biomarkers. So I won't go through this part a lot because we kind of did this. So we talked about why you would do it. You want to monitor disease. You might want to monitor whether therapeutics are working properly. You might be able to use the markers to predict toxicity of drugs or efficacy of drugs. We talked about the use of a screen for disease to early detection or even acute diagnosis. Patient shows up in the hospital with crushing sub-sternal pressure in their chest and you want to know is this patient, do they just eat some bad food or do they actually have an ongoing heart attack? And a blood test would be very useful in that setting and there are a couple of blood tests but they're still not fast enough. You might need a test to look for infectious disease. Yesterday if you went to the symposium you heard about the need for a blood test for tuberculosis. This is an illness that infects a third of the population on our planet and it's one of the top ten killers of all people and yet it's very difficult to diagnose. And then to personalize treatment of therapy, again biomarkers may be helpful for that. So all of these are reasons why you'd want biomarkers. So this is sort of a different way of saying what I've told you earlier. This is based on a publication from the Early Detection Research Network at the National Cancer Institute in the U.S. This basically outlines if you're going to develop an early detection marker the phases that you should go through. First you should do exploratory studies. This is the kind of observed difference study I told you about earlier. Then you need to do a clinical assay and validation so you need to establish that the assay can detect the disease. Then they would say do a retrospective longitudinal study so you look, these may be old samples but you're looking at samples collected over a period of time to ask, you know, does the marker change when the patient goes from no disease to disease? So that's phase three. Phase four would be to do a prospective study, we talked about that earlier, collect samples going forward starting today and asking does the marker actually identify those people who are ill? And then cancer control would be to implement the use of that marker in a large scale screening population. So I'm going to walk through about six or seven rules for biomarkers and then let's see if we can understand them all. So the first goal, and I told you about this earlier, is to define your goal clearly. So what is it that you want to do? Why are you making a marker? What do you hope that it will help you accomplish? So let's diverge now and talk a little bit about the statistics of biomarkers. Okay so this is obvious, right? You have a population of people, some of the people have the disease and some people don't, right? That's true of any population anywhere. You got some people in that population that have it and some people that don't, right? For the moment now let's assume that this is absolute truth. This is truth with Roman characters. This is the absolute answer. And then now we also have a test. This is our biomarker right here and our test is designed to predict these two features. The test can either have a positive result or it can have a negative result. Basically we want the positive result to tell us when the disease is present and the negative result to tell us when the disease is absent. But as you know nothing is ever perfect. So let's look at the possible cases. The first mathematical thing we know is that A plus B plus C plus D are all the people in the study population. So this box here is everybody in our study. So first we've got this group over here. So we call those the true positives. True positives means the test was positive and they actually had the disease. So the test got it right. That's as it should be, right? Okay the second group is this group down here and those are what we would call the true negatives. In this case the test was negative and these people also did not have the disease. So once again the test was correct. So this box here and that box there that's when the test is working well. It does what it's supposed to do, right? So that group of people is A, this group of people is D. Okay so what about this? That's a false positive, right? What's a false positive? Okay I've got a lot of answers over here. Okay yeah but the test is positive, right? The test says they have it but they don't really have it. So why do we care? Why do we care? Is it bad to be false positive? So they might get inappropriate treatment? What else? Right, right so you're going to particularly if it's a disease like cancer there's a lot of emotional anguish to thinking that you're a cancer patient when you don't really have cancer, right? Right and then in some cases it's also you put them through needless testing to see if they have a disease and that can be either or both expensive and tiring for patients, right? So the consequences of false positives are as you all point out emotional angst, expensive testing and it reduces the success of a treatment regimen. This has to do with when you're actually testing your drugs. If the marker said that they had the disease but they didn't have the disease and your drug won't cure those people and so you'll get inappropriate results. Okay and then this group down here we call those false negatives. The test was negative but in fact they really have the disease. So what's the consequence of a false negative? Right, you miss the disease. The patient is ill, you told them you know what you're perfectly healthy. Go about your life, don't worry about it and then six months later they have the disease. Right, so this is the misdiagnosis. It's a missed opportunity for intervention. It is by far the most common cause for malpractice lawsuits in the U.S. The misdiagnosis of cancer is the biggest cause of huge lawsuits in the U.S. And so you don't want to be wrong about this. The consequences of a false negative are big. So rule number two of biomarkers is understand the consequences of being wrong. You need to know why it's important to have a good biomarker. Okay, so now how do we calculate the probability of disease? Well you take, right, so this is the disease and these are the people that have the disease. So what's the probability of disease mathematically here? Right, right, so A and C divided by everybody, right? So that is the probability of disease. So in your population this will tell you how often the disease occurs. Okay, now the next thing we want to talk about is sensitivity. Okay, sensitivity we define as a positive test in the presence of disease. That's sensitivity. And in this case mathematically it's A over A plus C. So you're saying the denominator is everybody with disease and A is just the people who the test were positive for. The closer that A is to A plus C, right? That means the smaller the negative, the false negatives, the better the test, right? So that's called sensitivity. Finding disease when it is present. I make all my students memorize this because people often forget this stuff. So this is a good measurement of how good the test is at finding it when it's there. Okay, specificity is something different. Specificity is ruling out the disease when it's not present, okay? So, that's sensitivity. Oh yeah, okay, yeah, so this is specificity. We're looking at the false, we're taking the people who are truly negative, divided by all the people who are negative. So how well can you count on the test to be negative when in fact there is no disease, right? In other words, how low are the false positives, right? And so we measure it by D over B plus D and that's the equation here. So it's ruling out disease when it's absent, okay? Let's do a little quiz question. If you're gonna design a test to be screen for cancer, which is more important. Sensitivity or specificity, I'm hearing vaguely sensitivity, right? That, and why is that? Well, I just told you that the biggest cause of malpractice lawsuits is the misdiagnosis of cancer. You don't wanna be wrong if you tell someone that they're cancer-free and they're not cancer-free. So in the case of cancer detection, sensitivity is probably the most important thing. You're willing to tolerate some false positives, if you have to, to make sure that you don't miss anybody. Okay, now let's talk about a different circumstance. Imagine someone going to a doctor, they're coughing up blood, they have weight loss, they have night sweats, right? And the doctor appropriately suspects that they might have tuberculosis, right? Those would be common symptoms. So which is more important here? Sensitivity or specificity? Hey, why? Raise your hand so I know who to, okay, right, for the TV.   That's not the question anymore. The sickness is already a given. What you wanna know is, is it TB or not, right? You already suspect it's TB, and here what you're relying on is the test to be very specific to say yes, it really is TB and not some other, you know, some other illness. Okay, so now I'm gonna show you a little bit about, it turns out sensitivity and specificity in many cases work against each other. Because typically what happens is you have a test for a particular molecule or a typical biomarker. You set a threshold value, and you say if it's above this value, I'm gonna say it's positive. If it's below this value, I'm gonna say it's negative, right? And the challenge is that as you elevate or decrease that number, you will alter both the sensitivity and the specificity, and oftentimes in opposing ways. So I will tell you right now that these are data for a test for diabetes, and the idea behind this test was that they were gonna measure blood sugar after a meal. It turns out this is a bad test for diabetes, and no one uses it, okay? You'll see why in a minute. But it is a useful test to look at this because it does illustrate the concept a little bit, okay? So these are the blood sugars after eating a meal ranging from 70 milligrams per deciliter up to 200 milligrams per deciliter. And here, if you use this value as the cutoff, in other words, if you say that if you're above 100, you have diabetes, then this will be your sensitivity, and that will be your specificity, okay? So let's look at this example here. So at 80, if you use 80 as your cutoff, you're gonna be 97% sensitive, right? But you're gonna be only 25% specific. So one goes up, the other goes down. So what that means is that you're gonna identify 97% of the actual diabetics. The test will be positive in the presence of disease 97% of the time. But almost three quarters of the people that test is disease free will also have diabetes. So you won't be very specific. I mean, we'll also test positive. So three quarters of people who have no disease will test as if they had to be a huge amount of false positives, right? Okay, by comparison, let's say, well, okay, that was too lenient. Let's, that allowed too many people in. Let's set a more strict number. Let's say it's 160, all right? So now the sensitivity is 47%, but the specificity is 99%. Okay, so what that means is that if you make a negative call, if you say that they don't have diabetes, you're gonna be almost always right. 99% of the time, you're gonna be correct. But you're gonna miss half the diabetics. You're gonna miss, so you're gonna have a lot of false negatives. And so that's just to show you that sensitivity and specificity often work against each other. Of course, sensitivity and specificity are both values that specifically refer to the test itself. That, when you go to the doctor, that's not what you care about. You don't care how good the test is, what do you care about? What's happening to me? Tell me about me, I don't wanna know about your test. I wanna know what, how am I doing, right? And so there are two statistical terms we use to describe what's happening to me, all right? The first one is the positive predictive value. Okay, so what do I mean by the positive predictive value? The positive predictive value is if the test is positive, what's the chance that I have the disease? So the test says I have it, do I really have it, right? And so to mathematically calculate that, that's shown here. It's basically taking all the people who actually have the disease, divided by all the people who are tested as having the disease. And that is the predictive value of the positive test, right? And that matters a lot to patients. Sometimes this other value matters even more. This is what we call the negative predictive value. So it, you had a test, we did a test for, for cancer or we did a test for birth defects in your child. How sure are we that you don't have cancer or you don't have, your child doesn't have birth defects, right? So what, how confident is a negative value in telling you that you are disease free? And that is defined as taking all the people who are truly negative, divided by all the people who are tested as negative. So positive predictive value and negative predictive value, this is what doctors care about, this is what patients care about. What's happening to me? How am I doing? Okay, so we're ready to do a little quiz now. Okay, so this is a quiz for in this case, a test called Reward Amnesia. The disease is occurs in one in a thousand people. It's a pretty common disease. The sensitivity of our test is 99% and the specificity is 95%, okay? We test a random individual for the disease. What's the chance that he actually has the disease? Okay, got it. Sensitivity 95, 99, specificity, specificity is, is 95. So how many people think that there's an 80 to 90% chance that he has the disease? Okay, got one of those. How many people think it's 60 to 80% chance that he actually has the disease? How about 40 to 60? I'm going to assume you got it all wrong if you didn't get it. 20 to 40%, I got one 20 for 40. So far, okay, how about 10 to 20? How about 0 to 10? Got a few of those? The rest of you all think that it's 90 to 100. How many think it's 90 to 100? Okay, got a few 90 to 100s. All right, all right, it's about 2%. Yeah, it's about 2%, right? Because remember, what affects you here is the incidence of the disease. It's very low and that is, it turns out that this is an important thing to remember about these statistics. And let me go back a second and point that out. Remember that sensitivity and specificity were down in these columns here, right? Those terms do not depend on the population. It doesn't matter how often the disease occurs for them. They strictly measure the value of the test on whatever specific population they're being tested on. But positive predictive value and negative predictive value, they depend on how often the disease occurs. And I'm gonna walk you through that in a minute, but it's really important to remember that. When you hear somebody boast about the positive predictive value of a test, the first thing you need to ask was, what population did you test? How prevalent was the disease in that population? Okay, so let's walk through that. So this has to do with what's called Bayesian calculations, which includes looking not only at the probability, but also at what's called the prior probability. Which is when you begin your test, what was the likelihood to start with? And we're gonna use as an example the prostate specific antigen test. It's a very common test used to detect prostate cancer. It has a sensitivity of around 70% and a specificity of 90%. That's one of the best values you'll see anywhere. That's a pretty typical marker. When people, when I told you before, but people publish 99% and 99%, you don't believe it. Numbers like this, that's kind of what you'd expect from a pretty good marker. So now we're gonna ask the question, how does incidence or prevalence affect the positive predictive value of a test? We're gonna consider three different populations. We're gonna consider all men, in which case the incidence of prostate cancer is 35 cases in 100,000. We're gonna consider men who are over 75. In which case the prevalence of the disease goes up to 500 per 100,000. And then we're gonna consider men who already have a clinically suspicious nodule. A doctor did an exam and found a mass. So that in that case, there's about a 50% chance that they have cancer. Okay, so three different populations, these are the incidents. Remember I told you the probability of disease, A plus C over A plus, C plus D, that's what these numbers are, right here. Okay, so let's look at the first case. In this case, we're looking at the clinical nodule, a 50% likelihood to start that this person has cancer, right? So notice that I have that this number here and that number there add up to 50,000, right? So 50,000, remember I said that out of 100,000 men, 50,000 had it. So 50,000 have it and 50,000 don't. So that's appropriate, right? Remember I said that it has a 70% sensitivity. So that means of this number here, 70% or 35,000 are positive. And remember I said that it had a 90% specificity. So of this number, 45,000 don't have it, right? So these numbers all add up to these numbers here. And believe me, so now do the math. If you do the math, the positive predictive value is 88%. So even though you already have a suspected mass, and even though this test has a 70% specificity and a 95% sensitivity, the predictive value is still not 100%, it's still about 88%. Now let's look at a very different population. We'll go to the other end of the spectrum. Let's look for men who, all men, 35 men in 100,000 that have a disease. So now let's do the math again. The population that has a disease is 35. The population that doesn't is everybody else, right? Out of 100,000, still we have a 70% specific sensitivity here. And here we still have a 90% specificity. Look at how good that test is. 0.2%, so the take-home message here is that, depending on the population, the positive predictive value changes dramatically. We didn't change these numbers at all. Those numbers stayed the same throughout the whole discussion. The only thing that we changed was how often the disease occurs. And if the disease is rare, then the predictive value of the test drops quite a bit. This is one of the reasons why, at least in the US, we don't recommend that young men do treadmill tests for heart disease. Because the treadmill test was designed for older men, where it has good predictive value. But when the incidence of the disease drops like it does here, then the predictive value drops precipitously. And then the risk of a false positive becomes much higher. And then this is just to show you the more general circumstance of 500 and 100,000. So this is not far from the 1 in 1,000 we looked at in that quiz question. And again, here the test is around 3.4%. So it all has to do with the population you're dealing with. Okay, so I sat through a lecture in my institute where someone was boasting about his test that he had developed. And this is the clinical study he did, 450 cases and 150 controls. So the prevalence in this population is what? So the prevalence is very high, right? Because your three quarters of the people in your study have the disease. Three quarters of them have it, right? So he had this positive test and he said that his predictive value was 75%, right? And I looked at the numbers here and it turns out that if he had zero, if the tests were equally split between positive and negative, right? He would have, like half the time it's positive and half the time it's negative, he would have still had a predictive value of 75%. So he had to do nothing. The test had zero predictive value in a sense, and it would still have given him a positive predictive value of 75%. So it's pretty lame presentation. Okay, so rule number three, choose your population carefully, right? All right, so if you're gonna do an early biomarker study, then make sure you pick people who have early stage disease. Because that's when you want to get the disease. Will it apply, if the test will apply to people with different stages of disease, if it could be confounded by people with different diseases, maybe they have other things that could alter their CEA levels or have nonmalignant GI disease. And just remember that sometimes it's more important to separate disease A from B than disease A from normal. So imagine if you're in a clinic and someone walks into your clinic and they have abdominal pain. They tell you that they've had abdominal pain for months and they've been losing weight, right? In that case, you're not necessarily interested in distinguishing colon cancer from healthy people. You might be more interested in distinguishing colon cancer from inflammatory bowel disease. You know the patient's ill. They've been suffering from GI symptoms for months. So you know there's something wrong. You're not separating normal from cancer. You're separating cancer from other GI diseases. And so always remember that if you're gonna do a study to find a biomarker, you should use a population of maybe people with non-cancer GI diseases from cancer diseases. You need to make sure you don't extrapolate inappropriately. If you develop a test that's good in one population, it might not work in another population if, for example, their kidneys don't work as well in older people. If it's something that's excreted by the kidneys, the test may work in a 20-year-old, it may not work in a 60-year-old. Diseases on stomach cancer, for example, don't extrapolate to the USA. The risk factors for stomach cancer are much higher there. That population is different. And of course, patients in the hospital are different from healthy people. Okay, and then this is something that we talked about a little bit earlier already. This is what I call the fallacy of statistical significance. And so we kind of covered that already just because there's a good p-value between A and B doesn't mean that they're good biomarkers. You should be using sensitivity and specificity, not p-values. And that's really shown on this thing here, which we've already covered, so I'm going to skip that. All right, so focus on sensitive and specificity markers and not on statistical significance. All right, that's fair. So now I want to mention a little bit the, and we're coming to the end here, the omics trap.  That's what we all do these days. And you often hear this statement from people in the omics studies. I'm not going to look for a biomarker, I'm going to look for a pattern. I'm going to look for a signature. They might be doing it on DNA microarrays or protein arrays. But you have to remember that a pattern is really multiple parallel tests. They're doing a bunch of different molecular and statistical studies. And by doing multiple tests, they increase your sensitivity because each test has a chance of being positive. But they reduce your specificity because you have a higher now rate of false positives, right? So if you're going to do multiple parallel tests or look for patterns, my biggest advice is to get a statistician. Because you're going to need more careful statistics. And this class is not prepared, we're not going to do those statistics here. You just need to be aware that when you get to that stage, it's time to engage somebody. So we have two tests. Imagine that this test, they have two tests for the same illness. And they're testing for a positive. And they both have a positive predictive value of 95%. So imagine test A is positive and it has a probability that it's going to be positive is 5%. Test B might be positive, so it's chance to, chance alone is 5%. If you do both A and B, now, if you require them both to be positive, now your test is getting more stringent because the chance of a false positive is much lower now. But if you accept either one, now the chance is much higher because you now have to add the two effects together. Okay, so this is even, imagine if you do this with multiple tests. So now you have a whole series of tests. I'm going to just go. So now each of these is going to have a different positive predictive value. They're going to have all kinds of different due to random chances. And if you add them all up, the numbers get to be outrageous. So again, the take home message is get a biostatistician. So here's the example that I like to remind people of when they're doing multiple testing. And this is a lot like what you would see in an ohmic study. So if I asked every one of you to take out a coin and flip it and mark down whether you got a heads or a tails, what do you think the likelihood is that the result on the coin would predict the gender of the individual who flipped the coin? Right? Nothing, right? Okay, now let me change that. Let's say that I gave you each 10,000 coins to flip. And you went one by one and flipped every coin and you marked down heads or tails. What's the chance that among those 10,000 flips that one of them, maybe the 5,635th of them would correlate with sex of the individual? There's a chance, right? Might not be perfect, but among those 10,000 tries, maybe one of them by chance alone would align, maybe not perfectly, but it would align with the gender of the individual. And you would say, aha, I found a biomarker, if you flip a coin 5,635 times, that one will predict the sex of the individual, but you'd be wrong. So how would you prove that you'd be wrong? You repeat the study. You do it a second time, 10,000, right? And now the 5,630 doesn't work anymore. Now it's the 123rd, right? It's just random chance, some of them will happen to work. And that is what we do with ohmic studies. We test 10,000 things. We get one that works and we say, aha, I found a biomarker. But you tried 10,000 times. So you have to adjust for that by doing some kind of false discovery adjustment. So that's kind of what I did here. So imagine if people did all these studies, right? You have to keep the number of the population small. This is especially a problem when the size of your population is small relative to the number of variables you're trying. If you have a study of 100 individuals, 50 cases and 50 controls, but you're testing 10,000 variables, you have this risk of what's called overfitting. And then that's why if you repeat the study doing a completely different population. All right, so I kind of went through this. All right.  OK, the last couple of things I'm going to mention is where do you get your samples? Make sure that the sample that you use is relevant for the use of the test. So imagine if you're going to do a biomarker on early disease detection, right? We said that you're really going to be testing a healthy population. Healthy people are not going to be interested in giving you biopsies, nor would it be appropriate to put them through that risk, right? If you're going to take a test for healthy people, it should be a simple test. You're in maybe blood. It's got to be something that you can measure easily, maybe saliva. You can't rely on doing biopsies. On the other hand, if they already have cancer, then of course they might be willing to do that. You have to look at whether the sample will be stable. If it's a biomarker in blood, will it be stable in blood? Remember I told you about Paul Temst in the study where he could tell the difference between the tubes? Well, what it turns out is that one of the tube types was inhibiting a protease, and the other one was not. And what was causing the difference was proteolysis in the sample. So in that case, the material was not stable. So you need to know that what you're measuring is stable in your samples. You need to know if it changes in body states. If that molecule goes up and down after a meal, if it goes up and down with a sleep cycle, again, that's something that you have to consider. And then of course, if you're measuring samples from a tumor, you need to look at where you're taking your biopsy from. So rule number six is the willingness of an individual to partner with some of his liver is directly proportional to the gravity of his diagnosis. People do not give up parts of themselves easily. They only do so when they're really sick. So it's good to remember that. OK, part of biomarkers is knowing how to prepare your samples. How are you going to preserve it? That could dramatically affect outcome. I already gave you the example with Paul Temst. Is the instrument robust and reliable? Is it going to give you the same answer every time you measure it? Is the chemistry robust? Well, if you ship this sample to a hospital far away, will they get the same answer that your hospital gets here? And then of course, what controls are you going to use? So these are just some of the general things to think about. So will sample preparation affect the reading? Are you handling the samples properly? Are you going to freeze them? And then of course, you need to know if there are natural variations of the biomarker you're testing from person to person. Because if there's a lot of natural variation even among normals, that's going to make it more difficult to use that as a biomarker. And then there's this question of abundance of the biomarker. Is there enough of it in the sample that you can measure it? Is it likely to, will you be able to detect it when you want to detect it? So in the case of early biomarkers, early detection biomarkers, is there going to be enough there in an early specimen from people with early disease that you can actually detect it? So the marker may be very good at picking up cancer, but it may be too weak to be able to pick it in early disease. That was the case with the CA125 that I mentioned earlier. It was a good marker for distinguishing ovarian cancer. It's just not abundant enough in early disease to pick it up. Developing a robust, reliable test is half the game. Just because you found a molecule that looks good doesn't mean that you've got a biomarker. What you need now is to develop it into an actual diagnostic test. And then the last thing I'm going to mention is this one, which is that your markers are likely to be more believable if they relate to the biology of the disease. And I think a couple of you have already mentioned that. But just keep that in mind that if you want the marker to make sense, look for markers that fit with what you think is going on the disease. If it's sort of a random molecule, it'll be a lot harder to validate it. So I will stop there. All right, so by now you are quite familiar with the importance of studying biomarkers. And you've also seen the challenges of performing the experiment to discover new biomarkers. And I must say that you notice very, very challenging journey. And that's why actual clinical translation of biomarkers is not easy and not very successful either. There are a lot of candidate proteins have been discovered which have potential for the biomarkers, especially for early detection of disease or prognostic values or even therapeutic values. However, many of the biomarkers are not easily translable to the clinics. The reason that you need to do a lot of validation to ensure that from the discovery work what the biomarkers have been identified, they really fit the purpose of the clinical assays. And they are able to serve the utility for the large patient populations. Therefore, the biomarker discovery program, even if it is performed on the small number of samples, you need to now scale up to the really large number of samples to do the validation that these proteins are actually showing the kind of expression pattern which you have discovered from the initial workflow. You've also learned the need to have a good team involving clinicians who can give you the right samples to test your hypothesis, the right type of technology platforms where you can execute these experiments and then involve the scientists who are good in doing the big data analysis who can now make reproducible and sense of your data without compromising on the data quality. So these are the considerations which are very crucial and I must say that despite all the odds, despite all the challenges, these are the many biomarkers which are now getting translated to the clinics, they're getting approved by the US FDA and there are some such stories, especially the OVA 1 and OVA 4 and so the other protein which are now coming to the markets giving you the motivation that if you do these kind of discovery workflow properly, probably eventually it may be translatable to the clinics. Thank you very much.


Welcome to rehash on the internet. We're all news is old news. We bring you the best and worst of what's happening today Hi, everyone, my name is Dr. V and welcome to Thanks so much to drag TV who provided our intro if you'd like to be awesome like him link in the description Or where you can provide an intro in exchange for a meaningful spotlight at the end of any of our episodes Alright, so we've got a couple of news to have whatever's that we're gonna try to buzz to really quickly But I'm gonna be a nice guy because I was mean to you yesterday and you're gonna get to go first with your stories today We just just one hand and we're back and forth promise Okay, you hear that freedom family. I get to go first. So in today's video.  Refused to save her child from a car because she didn't want to mess it up And you had a news to talk about yeah, I'm actually surprised you aren't covering it But I wanted to talk about a Nazi making a surprise appearance in a Donald Trump campaign at I Don't really want to be the Donald Trump. I'm not Donald Trump guy. Okay. I'm just saying hey Man last and final story is a woman who says thanks Obama because she got caught Counterfeiting Jesus, Tennessee.  So you I'm gonna let you have the first story All right, let's go. So Jimmy Fallon the host of the tonight show Unfortunately had a minor incident When he was in his off time. He was at his home His wife had recently purchased a nice little rug a braided rug and he was like for his head now for the for the kitchen floor Oh, that kind of yes, it's another Donald Trump, right?  I'm actually worried. Oh, so he kept going in the ring And it completely ripped his finger off except where the skin was holding it Ouch, you can tell that neither one of us is married right now because we keep pointing to our right hand Talking about this Whatever so the gist of the story is it's pretty insane though So for the most part he had to go to the hospital They said they wouldn't do it so they had to go to a micro surgeon where they then took a vein out of this Just like a really short surgeon Maybe maybe it's like a tiny surgeon would like tiny tools that like does tiny surgery that would make a cute Sorry moving on anyway, he walked in with cowboy boots. He was a really nice guy He says and he removed the vein from his foot put it into his finger and now his finger is healing pretty well Nice, but I feel pretty bad for the guy. So hopefully he recovers pretty Speaking of feeling bad. I feel bad for this kid. The Singapore Times is reporting on a mother who decided You know if I save my kid, it's gonna ruin my car That was actually decent segue. Anyway, this is personally for me despicable I have never been a parent. However, I've been a doggy parent Which is nowhere near the same thing I'm not saying it is but I am saying that if I am if I would be willing to do something as a doggy parent I would expect any self-respecting parent parent to do well I wouldn't consider that person a self-respecting parent Probably not no but come hell or high water I would definitely you know break into the vehicle be it for a pet or even my child Even if you had to scratch up your pretty new BMW, of course, this is a material thing. There's plenty of glass in the world There's only one of your offspring unless you have two or unless you have two or three or four or five or seven So my question of the freedom family is at what point would you say it's not worth saving somebody now? As far as who the person is I don't know make somebody up your uncle Steve the one who talks to himself at Thanksgiving or Christmas or whatever At what point would you decide? You know, it's not worth it For me personally the chances of death for me have to be 75% or greater for me to not be like Let us know in the comment section down below And then that was it was my story so you go next. All right. I said I'm surprised you didn't cover it Here we go. Nazi makes a surprise appearance and Donald Trump campaign ad So I actually saw this one and decided not to cover it because I don't want to be the Donald Trump guy And not only that but you know this show airs all over the world not just in the US though It's I guess kind of you know, the US presidential elections kind of world news But it's kind of not Anyway, I'm hoping for this to be a more of a global show, but Oh Yes, yes on a on hashtag Make America great again, but wasn't that it? Yeah, um There was a campaign or there was a campaign like thing. Yeah, and one of the elements was Nazi soldiers marching into Donald Trump's face with hashtag make America great again And this is all superimposed over the American flag. Now. This is either a Someone on his team who's performing the most awesome troll of all time. Yeah, or be a massive Blunder on their part and I am awaiting Them to say that it was symbolic of how evil forces bow down to great men or just I think they're gonna try to save this Somehow by spinning it, but it was a massive blunder Anything else to add? No, I mean I apart from so you kind of just made me cover it, didn't you? I just wanted to say something and maybe the fact that you would cover it would like make you the Donald Trump guy Is that you keep talking exactly? Yeah, you fire. Oh and now the most important of all news Comments for our previous videos. Let's go. I'll drive us there Oh Comments first comment comes from heroic gaming who says Hashtag rehash I asked this before but do you think freedom will ever give us fan funding? Yes, as soon as it is available to the network as a whole we will turn it on Unfortunately because the network is based in a country that has not been allowed to happen We can't turn it on for everybody because we're based here But as soon as YouTube gives around to it, we will do that. So put some pressure on now. Yeah So coming over to comes from Sykes TV. Oh Is this you know not really I wanted to cover the comment because my personal channel is real psyched for those of you That don't know who we're viewing the video Sykes is my last name. Oh, so I really liked it Sykes TV says never give up your dreams. Indeed. I do agree Whatever get your dreams up. Yeah, that's pretty much it comment number three comes from Captain wrapped rex who says why does my Say unverified May 2015 unverified means that we've made our list, but we haven't checked it twice So that's why that almost that was like a Santa Claus reference. Yeah, well, it's a Santa Claus reference And that just means that you know, we have the numbers we're just we haven't double-checked them yet And then comment number four comes from GG gamers who says What's with the red lines at the bottom of the screen ps? I Made you guys in I said intro cool. Thank you Okay, the red lines at the bottom of the screen It's an experimental feature that we're playing around with it's topic switcher bar if you get bored with the topic Just click the next red line. It should work with the old player and the new We're kind of playing with it We don't know if it's gonna be a permanent fixture if you like it let us know in the comment section down below And we will continue to use it, but now we go talk about Yeah, today's channel spotlight we're talking about drag TV now I will be honest drag TV is not my kind of channel Like this is not necessarily something that I would subscribe to though He's got a lot of elements that I could see why other people would right As far as his channel trailer goes it's a it's only like 54 seconds long I think it makes a decent case for why to subscribe, but I think it could be better Right, so I mean he has playlists. He had the basic necessities to avoid a normal YouTube content creator has but I feel like I'm a Broken record. I see a lot of people using white and the text or their thumbnails now white is good to an extent It's like I use white in some light thumbnails, but if you just there's a color is behind it That's gonna make white hard to read that bad idea And he's got some really strong ideas with his thumbnails some things I like some things I don't like and really as The main things and we covered some of this yesterday, but the main things that I would say is trying to Make sure if you have text make it minimal make it as large as possible because when it's scaled down to Mobile size or when it's scaled down to the smallest size that people are going to see it You don't want it to be a jumbled mess. Yeah, like he has a video here called everything wrong with Prince Royce back it up That's the perfect thumbnail I mean the background it makes it easy to see the white text Disagree do you really because he's got people in the thumbnail, but you can't see their faces All right, so it for me personally, you know, if you're going to include faces make sure you're able to see them Just me personally He's but he does have some like he all of the vines that he releases his own vines He puts together in compilations Those thumbnails are very strong. I like that. I do agree with that one And but it's one of those things that honestly Without actually sitting down to him and having a discussion I couldn't describe so I'm gonna stop talking and He's still yeah on a scale of one to ten. I would rate this channel birthday cake No, because birthday cake, okay Because it's something that you can definitely overindulge on you probably you know I can see how people would get lost in this channel like a birthday cake.  I like Oreos Thank you so much to everyone who's provided us an intro. I believe this is episode 28 of this show Let us know in the comment section down below what you want us to do for episode number 100. Also, don't forget to subscribe down below and Also, there should be like a little eye somewhere above Zach's head if you want to check out my previous episode So yeah, anyways till next time don't forget to like subscribe and do all those things that make us love our jobs Also be awesome to yourself and amazing to each other. See you guys later. Bye freedom family


we lose our dogs, you know, it's everything. It's all we've got. We have no other place to go. Lori and Richard paid cash for this fixer-upper five years ago, then took out a loan for repairs. With their expenses mounting, they decided to refinance their mortgage, but that's when their problems really began. The day that we went to sign the papers actually, they said something about, which I didn't understand, about raising us three points from the previous loan. But at the time we were sitting right there ready to sign the papers, pen in hand when he said it to us, which I signed the papers. I thought that was the thing to do. It was a little ignorant. Now Rich and Lori have a lawyer and are fighting off foreclosure. Their case is just one example of a bad situation that could have been avoided. The Federal Reserve Bank of Philadelphia wants you to see their story and the stories of others like them so that you might avoid becoming another victim. Hi. I'm Dr. Marvin Smith of the Federal Reserve Bank of Philadelphia. It seems that every week we hear heartbreaking stories of people who've lost their homes through foreclosure. Congress and federal regulators have worked over three decades to increase the availability of credit, particularly for mortgages and underserved communities. And they've also increased rules to protect consumers from unscrupulous lenders and brokers. But no amount of regulation can substitute for being an informed borrower to help you, your family, friends and neighbors. We've created this video so that you can avoid the mistakes others have made. They all found out the hard way that when you borrow money, using your home as collateral, it can be very painful. Particularly if you don't really understand all the loan terms. You'll want to listen carefully to these stories. This is where it all begun. With the ceiling, having that done, and then these railings was included and this steel door. Veronica owned her home, but she needed some simple repairs that should have cost a few thousand dollars. What she got was debt close to forty thousand dollars. All I knew that it was getting harder and harder for me to take care, I mean to keep the bills up. I was calling different finance companies to see if I could get you know, another loan. I had no idea of how bad things were really. It just built up from fifteen thousand to thirty eight thousand plus a balloon. Beware of balloon loans, which require a large final or balloon payment. In Veronica's case, she owed a balloon payment of twenty nine thousand dollars at the end of her loan when she would be eighty three years old. Plus if she couldn't pay it, she'd lose her home. And refinancing or flipping her loan, taking out another loan to replace the first one, just put her deeper in debt. Then they put me in a homeowner's insurance that I really didn't need because I didn't know they were doing this. What Veronica's really talking about is credit insurance. It's a policy often sold to subprime borrowers and financed in the loan. It's used to pay the debt if the borrower dies, becomes disabled or unemployed. Brokers often push these policies because they get big commissions. Also be aware that credit insurance primarily protects the lender, not you, the borrower. Ethel Mintz had just two years left to pay on her mortgage when she decided to change her oil heat to gas. Unfortunately what she got was a lot of hot air and an enormous debt. I was looking just for a heater, $3,800. But no, I couldn't do it that way. You have to do this, you have to do that. I had to pay off this, I had to pay off that to solidate everything. And I, and I never questioned it at that time. I really didn't. Ethel was convinced the people she was dealing with really wanted to help her, but in fact they were really helping themselves. She finally called attorney Irv Acklesburg who specializes in predatory lending cases where lenders take advantage of uninformed borrowers. This mortgage refinanced her existing mortgage to a higher rate, to a higher rate than she was already paying. It forced her to pay a prepayment penalty for that existing, for paying off that existing mortgage. It charged her over $2,000 in points. It charged her $1,600 for a life insurance product that she wasn't even eligible for. I mean thousands and thousands of dollars loaded into this loan and remember all she wanted was $3,800. So she said, well this is this. I didn't, honestly I didn't read it and I signed it. And this is this. I signed it this and that. I don't know how many pages, but I did. I signed them off. Number one, if you don't understand what you're signing, don't sign it. Mortgage transactions are very complicated. There are a lot of lawyers who can't understand some of these transactions. Ethel's contract with the lender also included an arbitration agreement.  And they don't know this all the time, but see they didn't tell you this. What it is, very simply, is a waiver by the consumer of any right to go to any court to rectify any wrong that has been committed. These businesses are getting the consumers to waive their right to the American legal system. Newlywed's Christopher and Elizabeth love everything about their new home, but as they get ready for dinner on a typical night, they recall their mortgage experience and the bitter taste that's left in their mouths. Initially they thought they were approved for a rate that sounded too good to be true. As it turned out, it was. Literally it was like a day beforehand that we were told that it wasn't okay and that they would have to restructure the whole financing thing and like add like 300 bucks on top of our monthly payments. They knew that we had no other place to live. They knew that we've relinquished our apartment. They knew that we had no kind of council. So when they said to us verbally and in an email, your only option is to close. You know, we went to refinance and there was no no refinancing. It was. Didn't work out. Both Chris and Elizabeth say they should have done more shopping around for a mortgage. They especially wish they had an attorney or a credit counselor meet with them to review their loan documents before closing. Finally, they realize they should have had a backup plan. You don't want to put yourself in a situation where you're sitting at the closing table and they come to you with a new deal and you don't have the opportunity to say, you know what? I'm not comfortable with this. I want to take a second. I need to think about this. Levi Moore inherited his house from his parents and lives there with his wife and son. It was paid for. But when the house was damaged by a fire, he had trouble finding a bank loan for repairs and renovations. That's when he finally listened to a man who kept knocking on his door. And we just gave in to him because he was sticking with us. So after we went through the channel with him, you know, we thought we was on easy street, but we was in a jam. In Levi's case, he only saw a portion of the $35,000 he borrowed to repair his house. He says most of it went directly to the contractor even before the work on his home was complete. And after a few weeks, the workers disappeared. They left it in a worse shape that it was them before they got here. And to make matters worse, Levi had to refinance and now has a debt of $90,000 to be paid over the next 30 years. If you're happy and you know what cut your hand. Leslie Thomas was also contacted by a contractor who told her that he could do needed repairs to her home, which she had inherited. But the few thousand dollars she needed turned into a $31,000 loan with a high interest rate. Soon she fell behind. I think I missed one payment. That's when they had sent out, you know, that they're going to take my house. Like when I tried to, um, like make arrangements, they wouldn't let me. Levi and Leslie are typical victims of contractor loans. Attorney Irv Acklesburg says separating the actual home repair contract from the loan will help. Never sign up for a loan that home improvement contractor has brought to you. If you need home improvements, shop separately for the home improvements and for the money. If you think that you need to borrow money, you should go shopping for the money like you would shop for anything else. Don't take the loan that that is brought to you. Find the loan that's right for you. Never borrow more money than you need. If you need $5,000, then find a loan for $5,000. Try to find a loan for what you need. Don't let some loan broker convince you that what you really need is a loan for three or four or five times that. On behalf of the Philadelphia Fed, we hope you found this video helpful. And so do the victims who have allowed us to tell their stories. They all want you to have the knowledge that they gained the hard way. So here are a few suggestions our participants wanted to share with you. Followed by advice from Dee Dee Myers, Vice President and Community Affairs Officer at the Federal Reserve Bank of Philadelphia. I was calling different finance companies to see if I could get another loan. When you need more money, don't mistake more debt for more income. Don't be like us and don't go into it with one. Pay attention to what people say to you. Pay attention to where your money's gone. Pay attention to the statements that these people are sending you. If you borrow, here's what you need to do. Get a commitment letter in writing before the closing date. The lender is required by law to give you a truth and lending statement that details the amount of your loan, the annual percentage rate, the monthly payment, and the term of your loan. Get help from somebody else before you get a second or third opinion before you fall into the same trap that I did. And that's a hurting situation. Have your written loan commitment reviewed by an attorney or a housing counselor. Also have your closing statement reviewed. Understand every single line or just don't sign. I blame myself for not reading, but if anybody else is getting this, make sure you have somebody with you that can read each and every line of the contract because that's how I got stuck. Be especially aware of excessive fees for the broker, prepayment penalties, or credit insurance. Just because your lender or broker treats you politely doesn't mean he has your best interest at heart. Be wary and protect yourself.  Get somebody to look over it. If it's shady, leave it alone. You know, the majority of lenders are honorable, but a few prey on the uninformed. There are thousands of mortgage lenders, so don't settle for a bad situation that you're going to have to deal with for many years to come. If the money comes finding you, go the other way. People knocking on your door, sending you letters in the mail or calling you up at night telling you about a mortgage product. I would say, hang up the phone, close the door, throw out the letter. Those generally are not going to be paths to happiness. If you think something is wrong, it probably is. Just get up and walk away. If you think you may be the victim of an unscrupulous lender, or you know someone who is, here are a few places that can help you. Consumer Credit Counseling Services of Delaware Valley, Home Ownership Counseling Association of the Delaware Valley, Community Legal Services and the Pennsylvania, New Jersey and Delaware Departments of Banking. We hope hearing these stories has helped you understand how to be a more cautious borrower. Thanks for watching.


Vicks' matinee theater, starring Victor Jory. Vicks, the makers of Vicks' vapor rub, Vicks' Vatronol, Vicks' cough drops, and Vicks' inhaler presents the matinee theater, starring Victor Jory and Charlotte Brontë's immortal classic Jane Eyre. You know, more and more millions of people are using Vicks' Vatronol nose drops to relieve distress of head calls, benefit by their experience. Ladies and gentlemen, today from the stage of the matinee theater, Vicks brings you Charlotte Brontë's unforgettable masterpiece, a love story as wild and unpredictable as a storm over the English Moors, the story of Jane Eyre. On Field Hall, gray and forbidding in the early dawn, the biting wind drives across the lonely stretches of heather and hurls itself against the great house. It is an eerie, somehow evil house, a house with only the faint glimmer of candlelight through a single, grated window in the west wing, and in the window, the shadow of a woman, stern and direct, silhouetted in the half-darkness. Mustn't be best, Mr. Thurther. I wonder what you'll be like, Thurther. Sadelle's new governor should find Thornfield Hall a cheerful place with laughter such as yours. Fire, fire in the sky. Fire in the sky. We'd like to see Thornfield go up in flames and all of his perish in the ruins were too. Well, perhaps some day that may be the fitting end to all this. But not now, while revenge is so sweet. I, Grace, whose pool shall see that nothing saves your life. Well, Mr. Rochester's housekeeper, I expect you should be here any moment. What a wonderful fire. And only you stay in Thornfield the more you'll appreciate warmth, Miss Eyre. Pardon? Oh, yes, Mr. Rochester. Yes, sir. Yes, sir? I saw the coach drive up while I was riding on the moors. Welcome to Thornfield Hall. Thank you, sir. Well, sit down. You're quite young, and you're not unkind to the eye. Though, obviously, too fair and pale in spirit to endure in this house of gloom. I believe I shall find it very comfortable. That remains to be seen. I don't understand. You don't understand this year? What are you doing out of bed, Adele? I, I only thought... Never mind what you thought. Adele, this is your new governor. Your daughter's lovely, Mr. Rochester. This is not my daughter. She's my ward. Mamazelle Eyre. See, I cannot say her name. That is because they are mostly friends. Then you must call me Miss Jay. Now see, that is much better. Now Adele, take yourself upstairs. You'll have plenty of time to know Mamazelle Eyre. Hey, Mr. I'm sorry, but there's something wrong.  Do as you're told. Well, you thought me brusque with a child, didn't you? You appraise me as though I were the one who required references. I understand very well that I'm the servant and you are the master. Where did you come from, Miss Eyre? Lowered School. Oh, a charitable institution, isn't it? How long were you there? Eight years. Eight years? You must be a hardier soul than you appear. Your parents? I have none. I see. Well, for heaven's sake, say something. What shall I say? Whatever you like. Don't stand there looking so self-righteous. What do you think of me? Am I my handsome? No, sir. Hmm, tactful young lady. Go on, what fault do you find with me? Yes. Look well. Do you think me a fool? Do you find me hard and ruthless? Your manner is strange and unpredictable. Mr. Rochester. There's no need for a long time. Didn't you hear? It was ghastly. Nonsense, nonsense, it's only the servants. Probably Grace Pool, my housekeeper. Sometimes she lets her spirits get out of bounds.  That's her.  What must Miss Eyre think? Fire in the sky. Fire. I'll tell you what she thinks. I see it in her eyes whenever she looks at me.  I wonder what diversions I find here in the West Wing to make me so wildly happy. Look at them riding on the moors. Don't they make a handsome couple of their undefeated head? Come here often. As often as I need to. What do you mean? I mean when my soul is oppressed in there. Seems no end to the darkness in which I live. The moor is beautiful. No, it's barren and savage. Only the meanest flowers can survive here. Heather that claws into the earth and resists wind and storm. If there's beauty in it, it's the majesty of its unconquerable spirit. And to know what you must stand here when the wind and rain are like a whip flashing the breath out of your throat. In a moment like that, you can almost believe that a man's spirit can find the same strength and defiance to crush down pettiness and deceit. And even madness. Well, we might sit down, Miss Eyre. Oh yes, thank you. No, I've observed your almost saintly patience with my ward. Adele loves being spoiled. She's her mother's daughter. Now that when she was a high-spirited woman, Lily, a French beauty who charmed English gold out of my English britches. Are you sure you want me to hear this? Adele is her child. Another sin for me to account for. Aren't you shocked? No. You... You see that beach tree just below the west wing? Yes. With its gnarled limb. I've often fancied it one of the hags who appeared to make bet on the heat of forest. And I fancied her saying, you like Thornfield? And then with a bony finger, she'd write in the air and lured hieroglyphics that run the entire length of the west wing. Like it if you can. Like it if you dare. You know what I've got myself saying? No. I shall attack. I will like it. I dare like it. And I'll keep my word. I'll overcome every evil that stands in the way. Mr. Rochester, it's raining. All right, we'll go back. You'll know what it means to ride in the teeth storm. Before you know it, we shall be back to the quiet refuge and cheerful heart of Thornfield Hall. Mr. Rochester, wake up. Wake up. Wake up. What's that? The curtains, they're on fire. Jane, what is it? Help me, sir. Stay away from those curtains, Jane. Hand me the water jug. Yes, sir. I'll tell them down. Yes. Well, be careful. Never mind about me. Open the window. This wounded smoke is terrible. Close the door. There's no use of alarming the household. I must have fallen asleep in my chair. How did this happen? I don't know. A day woke me up. I heard someone laughing. The same awful laughter. Lord. I rushed out into the corridor. The door was open and I saw the flames. Yes. What else did you see? Something brushed against me in the darkness. Something brushed. It must have been Grace Poole. Listen to me, Jane.  Just who is Grace Poole? She is... How many times do I have to tell you she's my housekeeper? Won't you tell me what's wrong? Let me help you if I can. No one can help me. No, Jane. Don't go. I must. It's cold in here. Then come closer. I don't feel I should stay in this house any longer. But you must. You can't go away. I don't want to. I've come to love it here and I've been happy, but can't you tell me... I can't tell you anything. Someday, perhaps, I'll be free to make you understand. But promise now you'll stay. Will you, Jane? Will you? Yes. Yes, I will. Ah, bless you, Jane. Bless you. This is a lovely picnic. We never used to have picnics until Miss Jane came. We're going to have many more, dear. Miss your artiste, if you send me off to school, will Miss Jane stay at Thornfield and wait for me to return? I don't know. Perhaps I may decide to take her with me to the moon where we'll live in one of the white valleys among the volcano tops. Sounds wonderful. But you will have nothing to eat. You will starve. We'll gather manna to eat. Morning and night. I, of course, in the hillsides of the moon are white with manna.  Miss Jane and I will watch you from the crag and when you're through, I'll be down to fetch you. I know what I will do. I will make a reed of bluebells. Oh, just smell the heather. Let me see you do that again, Jane. What, sir? Breathe in deeply like that as though you were drinking in all the beauty of the world. The world? I'll just lie and know about the world. What would you like to know of it? Everything? Well, I'll tell you everything there is to know. It'll take a surprisingly short time to acquaint you with it. Everything there is to see of the world you can see right here. All the beauty, the savagery, the mystery of the world, right here. The sun like gold on the purple heather there's nothing anywhere as glorious as that. Jane, you see that hawk circling the sky waiting to plummet down on some unsuspecting prey? Where else would you find such calculating savagery? And drabness? That's all about us too. The desolation of the moor bare rock and thistle biting at your legs as you walk and over there, housing as much mystery and darkness as ever crowded the human soul. Thornfield Hall. Yes, Jane? All the world is right here. I can't believe that's all there is to it. Back at lowered school I used to lie awake at night and dream about all the wonders I read about in books. The islands of the Pacific, the golden domes of Constantinople. But nothing as wonderful as you lying there smiling up to the sky. Oh, Jane. Jane, you're lovely. You shouldn't say that, Edward. Edward? I'm sorry. Don't be. You couldn't go on calling me sir and Mr. Rochester. No, Jane. Jane, I have no right to say this. I have no right to, but I can't stop myself. I... What is it, Edward? I love you. I know. You know. Yes. You see, I love you too, Edward. My darling. Edward, you're so unhappy. Because my soul is my own. I have no right to love anyone, yet I must have you. There's nothing else in life for me. We can face anything together if you love me. Oh, Edward, what is it? What can there be that you can't tell me? There's nothing, nothing. You can't love me very much if you can't trust me. Oh, Jane. I love you so much more than a kiss can tell. Oh, but Jane, suppose once, once say you committed a blunder, and suppose as a result of that blunder, that stupidity you were plunged into a lifetime of darkness and hate. That would be horrible, wouldn't it? Edward? Yes, but if a time came and you saw the hope of your salvation right, within your reach, love, sanity, and gentle warmth, tell me, Jane, would you not claim it, despite every obstacle, every customer convention? Would you not take it? I cannot say without knowing more. Oh, of course you can. That's why it's up to me to take it. And by heaven, I'm going to. Jane, I want you to marry me. Soon. Right away. In just a moment, act two of Jane Eyre, starring Victor Jory. Friends, have you ever noticed how some people seem to resign themselves to the misery of a cold in the head? 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Vic's Vatronol Nose Drops The curtain now rises on the second act of Vic's matinee theater starring Vic Jorri's Rochester and featuring Gertrude Warner's Jane Eyre. Evening. The sky glowers angrily over the moors, and the great gloomy hall of Thornfield, Edward Rochester is carrying out his vow to marry Jane Eyre. I require and charge you both, Edward Rochester and Jane Eyre, that if either of you knows of any reason why ye may not loyfully be joined together in matrimony, ye do confess it. Wilt thou, Edward Rochester, have this woman for thy wedded wife? No. This cannot be. He cannot take this woman for his wife. Mr. Rochester, I... That man, whoever he is, he's mad. Edward. Go on with the ceremony. Please, sir, what's the meaning of this interruption? My name is Briggs. I'm a solicitor from London. By the merest coincidence, my client Richard Mason learned of this travesty. This man, Mr. Rochester, already has a wife. His wife is Bertha Mason's sister of my client. She is living right here in this house. Edward, what is he saying? Commit me. I shall answer that. I affirm and I can prove that Edward Rochester was married to Bertha Mason in Jamaica, West Indies. No, he can't mean that. Well, it seems that marriage, my dear, like murder, will out. Mr. Rochester, if this is true, how could I... How could I what? Please recta no platitudes. Come all of you. As long as you know about my wife, you should meet her. This way, please. Now, my friends, you shall see the Mistress of Thornfield Hall. Mrs. Poole, we have company. Friends to see my wife. What do you mean? You know she's asleep? Come in, recta. Mr. Briggs. There you see your client's sister. And Jane, this sight should be more eloquent than anything I could have said in words. Wake her up, Mrs. Poole. Wake her up! Wake her up, I said! You tried me? Yes, better, better. Oh, this is too horrible. Steadily Jane. Well, gentlemen, speak. This is my wife. Ten years I've worn with that. She wasn't mad at first, but she came of a mad family, and it wasn't long before I knew it. And now the law and the form of Mr. Briggs is here to keep me tied to this, this maniac. I only did what I thought was right. Hear him, Jane, what the Solista thought was right. Everybody seems to be the judge of what's right and what's wrong but me. Tell me, gentlemen, is hers the only woman the embrace I'm ever to know? You're fighting us. Or her endearment's the only one I'm to have through all my empty days. You're intelligent men. Judge now if I haven't the right to love this girl, compare these clear eyes with those of that mad woman and then judge me. I defy you, man of the gospel and man of the law. And remember, as you judge, so shall you be judged. I can't stand this. I can't look at her, I must leave it here. Jane, Jane. Jane, Jane, I must talk to you. Well, don't, don't turn away from me. Don't shrink from me those though I was some kind of a monster. Have you ceased loving me? No, I do love you. Now more than ever. And I must leave you, must leave Thornfield. No, no, in Heaven's name, no, no, you're the only woman I shall ever want as long as I live here. Edward, we're only torturing ourselves. Oh Jane, Jane, my darling, be merciful. I beg of you. Edward, hurting me. I see I've lost you. You're stronger than I am. Poor Edward. I don't know who's strong. But I must leave. I'll have old John drive me to Millcote in the morning. Goodbye, my dearest. Hope the coach isn't rocking you too much, Miss Ehr. What? Oh, I'm all right, thank you. Begging you pardon, what's all this talk about the master's crazy wife? Please, John, I don't want to talk about that. Oh, well as you wish, Miss Ehr. I was only inquiring. Look, stop, John, stop. Whoa, whoa. What, what is it, Miss? Look back there. Can't you see it? A fire, a house on fire. What? Lord, help us, you're right. It's fawned to you. Yes, and it's blazing like f**k it is. Turn around, John, turn around. And hurry, hurry. Hey, see up there, see up there. You must be cold standing out here in the wind. Mrs. Poole, what happened? Well, don't let her down.  She stole the keys out of me pocket again, took a lamp and set fire to your room. Jane, Jane, what are you doing here? Why would I? Well, now you see fawn field and it's crowning glory. As long as you're safe, I don't care. Mrs. Poole, good Lord. But, Lord, she's still in there. Mrs. Poole, I thought you'd pull. I tried to drag the bitch out, but she ran back in a room and locked herself in. Oh, dear, God, dear. God, I can't leave her in there. Edward! Edward, come back, come back! No, you're scarring after him unless you want to die, too. Oh, I should never have lived. You should never have come here in the first place. You tried to play the role of misguidance. Look, they're in the window. She's coming out of the room. The Rochester Hill never gets back. Look, Miss Eyre, the whole West Wing is beginning to crumble. Is he today? Much better. Had he lived through that night, I'll never know. Can I go in and see him now? Yes, but just one moment. Yes? I didn't want to tell you this. But he's all right. You said he was. He'll live, but... But what? Miss Eyre, I'm afraid Mr. Rochester will never see again. Blind? Yes. Thank you for telling me, Doctor. It's Jane. I didn't mean to awaken you. Awake me. I shall never be awake again. I'll always be at your side. Strange. Strange to hear your voice without seeing that strong little face. Let me...  You'll never be alone as long as I live. I'll not have you chained to me as a nurse. I want to be your wife. You? Do you know what you're saying? Do you know what it means? I only know that I love you. No, I'm still the master in my own house. You must leave at once. I'm staying, Edward. And there's nothing you can say to stop me. Nothing I can say. Gentle Jane. Thin as a reed, but rooted so strong. What shall we do? Shall we go to the moon, the white valleys, the volcanoes, away from all the meanness of the world? Just you and I?  The planes and the hillsides are white with it. Yes, dear. Wherever you go, I shall go. But right now I want to pull back these curtains. Pull them back and let the sunlight in. There. I shall be your eyes now. My darling. Tell me then. What do you see? I see the sunlight gold on the heather. I see a sky with not a shred of cloud in it. I see more blue bells than the dell can make into reeds for the three hours. As long as we live. Yes, yes, yes. Don't stop talking, Jane. Let me hear your voice. Cornfield is lovely today. Is it? Yes. Lovely. As lovely as you are. My darling. As lovely as the world before us. If you say so, I'll believe Jane. Just as an eye. I believe in God once more. In just a moment, a word from Mr. Jory.  Miserable with stuffiness and constant sniffling and sneezing. If you're one of them, my friend, will you do a simple thing to help relieve the misery? Just put a few drops of Vic's Vatronol in each nostril. That's all. And instantly, Vatronol will start to work right where trouble is. It soothes the sneeze irritation. It helps relieve congestion. It reduces swollen membranes and opens up the nasal passages so that breathing becomes easier. So friends, let me repeat. If you're suffering from a cold in the head and want quick relief from distress, by all means, try Vatronol. I think you'll appreciate this friendly tip. Just follow the simple directions in the package. Vic's Vatronol Nose Drops. This is Victor Jory. Your choice for next Sunday's play is the tender and romantic paramount picture which starred Charles Boyer and Olivia de Havilland in Hold Back the Dawn. I want to thank you very much for your kind letters and ask you once again to please help us select the plays to follow. It is our desire to present your favorites at all times. Write Me Care of Vic's Matinee Theater Columbia Broadcasting, 22, New York. Today's play, Jane Eyre, was adapted by David Victor and Herbert Little Jr. and was directed by Richard Sanville. The role of Jane Eyre was played by Gertrude Warner. Music for the series is under the direction of Mark Warner. Victor Jory is currently co-starring with Miriam Hopkins in The Perfect Marriage. Be sure to listen next week when Vic, the makers of Vic's Vapor Rub, Vic's Vatronol, Vic's Cough Drops, and Vic's Inhaler present the Matinee Theater's production of Hold Back the Dawn, starring Victor Jory. This is CBS, the Columbia Broadcasting System.


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