And now we're going to move on to the first, basic epidemiologic design. This is the first one, in a way, that was used. And I'm calling it time, space, and disease, but it also might be called the ecological approach. The most important, or maybe the most famous, example of this is the cholera epidemic in London in 1855. And this is, you know, classic. A guy named John Snow. If you're in London you could actually go to the John Snow Pub, which is at the pump which John Snow identified. So here's what John Snow wrote. The most terrible outbreak of cholera which ever occurred in this kingdom, is probably that which took place in Broad Street, Golden Square and adjoining streets. That's where the John Snow Pub is. A few weeks ago. Within 250 yards of the spot where the Cambridge Street joins Broad Street, there were upwards of 500 fatal attacks of cholera in ten days. This is a feroceous epidemic. Mortality in this limited area probably equals any that was ever caused in this country, even by the plague, and it was much more sudden. As the greater number of cases terminated in a few hours. Cholera is very sudden and dramatic because it kills people in hours or a few days. And this is a picture of Snow for those of you who like personal, pictures from Leann Gordis's book. This is an example of a sign that appeared at that time. And basically, there were so many people dying that they filled up the graveyards. They had to say, you can't bury people anymore, because they're dying too fast and they're piling up. And this is from Punch magazine in the 1850, and the theory about cholera was basically, you can imagine, trying to sort out a cause from this diagram, there are all kinds of different causes for a supposed, for cholera. And one of the major ideas about cholera was that it was the air. There was something in the air, and there was something in the air near the Thames River. So, for example, you see the cholera deaths per one, 10,000 on the, Y-axis there. And the height above the Thames River. And so the rich people [LAUGH] all lived away from the Thames River, way up in North London. And the poor folks lived down near the river, down near the Broad Street pump. And so at the elevation of, say, 25 or 30 feet above the Thames River, cholera was 100 per 10,000. But as soon as you got to 100 feet above the Thames river, it dropped to 20 per 1,000. So the idea is there's something in the air that is causing cholera. But Snow thought it was someting in the water, and this is a map that Snow actually used. I've elaborated it a little bit, but what it shows is. The streets around the Broad Street pump, and the little black boxes are deaths which occurred, according to residents. And the, pumps have little red arrows by them, and people are getting water from the pumps. And the big red arrow is the Broad Street Pump. So, even just by looking at this for a few seconds, you can see there are lots of deaths around the Broad Street Pump. And that's what lead Snow to think that the water from the pump was actually connected to the cholera. So, for example, he did a lot of different studies. This is just one example. He said, look, we're going to look at different supplies of water, Southwark and Vauxhall, which is one supplier of water. And Lambeth, which is another company which supplied water. And Southwark and Vauxhall supplied water to 167,000 people in 1851. And there were 114 deaths per 100,000 in the population, the areas supplied by that company. But Lambeth, there were a smaller number of districts, 14,000 people. But there were no deaths in people who were taking water from the Lambeth company. Now, I think you can kind of guess, Lambeth was upstream of Southwark and Vauxhall. They were taking their water from upstream. But this again, this suggests, and this is not a proof, this is a suggestion. A clue to etiology that it's in the water. So, this is what shows the temporal occurrence of the epidemic. And so that's days in August, August 19th and 21st and so forth, going up to September, and you can see that this epidemic is very dramatic. It's occurring over a week or so. The peak day is September 2nd, with more than 120. You can imagine 120 deaths in one neighborhood, on one day, would be very dramatic. So Snow thought, look, I think it's the water. And he walked in there on September 8th, and he basically did, the conclusion of his research was that water was the cause, and the pump was where the water was coming from. And he took the handle off the pump. And the epidemic then subsided, and this is the classic example of epidemiology and prevention. Turns out, Snow was probably lucky, the epidemic was probably coming to a conclusion by itself. But it makes a good story. So now, one of the interesting things about Snow's work is that there were exceptions. So for example, in the area around the Broad Street pump, there was a brewery and also a workhouse. And there were very few deaths in the brewery, so people said well why, you know, if it's water, why were there no deaths in the brewery? Well, it turns out, if you're British in the 19th century, working in a brewery, it's much better to drink beer than water. So they weren't drinking the water. And it turns out the workhouse had its own pump, had a separate pump. And then there was a cabinet maker who lived way outside the area, but it turns out he worked in the area. So he took water from the Broad Street pump during the day. There were two schoolgirls who lived way outside the area, however they went to school at Dufour's place in Broad Street. They died. And then, there was a 59-year-old widow way out on the west end. But there was a cart that passed by daily, and she actually liked the taste of the Broad Street water which was in that cart. So she drank that water and died. And her niece visited her on August 31st, and drank the water, and died too. So he had a explanation for basically all the exceptions. And that is, again this isn't proof, but it's very suggestive and led people to conclude that something in the water. They didn't know what yet, for another 20 or 30 years, because they didn't know what bacteria was, but something in the water was causing the disease. So that's the time space ecological approach. And it's actually kind of hard to find an approch like this for drepressive disorder. And I'm showing you one. This is no where near as dramatic and fun to look at as John Snow, but it's Eric Messias study of inequality and depression. So you can see there's something called the Gini coefficient, which is large when there is lots of inequality in a state. That means that rich people in a state and poor people in a state, but the income is not divided equally. And, the so, New York, for example, has lots of wealthy people and lots of poor people. Down there in the lower right and then depression is on the the rate of depression from the behavioral risk factor survey is the left axis. So this is only a small correlation but it is statistically significant effect that higher rates of inequality are associated with higher rates of depressive disorder. And we can wonder how that would occur. Depressive disorder, again, it occurs partly through mental understanding of one's conditions of life. And, I think, we can surmise that people understand inequality. For one reason or another they compare themselves to others, and see that they're disadvantaged, and perhaps that makes them have a higher risk for depressive disorder. So this is an ecological study of depression and Gini coefficient. And just to conclude, this is an example of the ecological approach applied to depressive disorder.