So Lyme disease incidence depends on factors that affect which organisms? This is what makes, I think, Lyme disease more complicated even than malaria, in terms of trying to understand the effects of climate change versus non-climate drivers. Because we have to be thinking about the effects of climate and non-climate drivers, and first the tick. Here, you see a questing adult female. So for example, climate and other factors could affect questing behavior. Questing means that they're looking for a blood meal, essentially. That female is ready to jump on someone. So here again, I showed this slide before, the life cycle, just to point out that there are factors that could affect each stage of a life cycle. The eggs, the larva, the nymphs, and the adults. That all needs to be studied. There could be climatic factors, as well as non-climatic factors affecting those stages, both the speed of development as well as the survival at each of those stages. Okay. We also have to think about factors that affect the spirochaete, the pathogen. So climate certainly could affect the pathogen. We have to think of factors that affect the white-footed mouse and other reservoir hosts. If there are no reservoir hosts, then we have no Lyme disease. We have to think about factors that affect the white-tailed deer, even though it's an incompetent host. It's very critical because the adults depend on the white-tailed deer and other large mammals for their blood meal and survival. Then finally, we have to think about factors that affect human beings. So let's dispose of the human beings in terms of human behaviors first. So human behaviors could affect Lyme disease incidence in terms of the location of homes in relation to tick-infested areas. There are more homes being built adjacent to woods, and so which would be the tick infested areas. Outdoor activities and tick-infested areas. Of course, that's not a bad thing. In fact, it's good to get out into the woods for variety of reasons, but it does expose people to Lyme disease. We have to think about the protective behaviors that humans are taking in tick-infected areas. Tucking your pants into your socks, tick repellent, taking a shower afterwards. It turns out that it takes a number of hours for the tick to firmly attach, so that if you take a shower shortly after you finish your hike, for example, it's likely that you'll actually just wash the tick off down the drain. Then finally, deer hunting practices are another human behavior that will influence, in this case, the deer population, and therefore, Lyme disease incidence. So what are determinants of tick and host abundance? First, we have habitat. Have to have a suitable habitat. Secondly, and these are kind of interrelated, presence of tick and host predators and pathogens. If there are a lot of predators, then that would keep down the host under tick population. Conditions at the ground. So ticks, remember, they only take three blood meals: once by the larva, once by the nymph, once by the adult. So ticks took spend 95 percent of their lives at the ground level, often buried underneath leaf litter. So conditions at the ground are important, such as the level of moisture in the leaf litter and the soil type. Land-system change will also determine tick and host abundance. If there is deforestation, for example, that will reduce tick and host abundance. Then we have climate, temperature, precipitation, and humidity. I think you could probably see by now, that it's very difficult to disentangle the effects of climate and these non-climate factors. So let's look though at results of some laboratory and field studies of the tick in particular, that could shed some light on this. Most of the studies listed here are actually laboratory studies, but there were some fieldwork. So first, high temperature, 30-40 degrees centigrade, and low humidity limit tick movement, questing, and survival. In particular, ticks have a very high susceptibility to desiccation. Second, the duration of developmental stages and overall life cycle is roughly inversely proportional to cumulative temperature, up to about 30 degrees centigrade or so. So that means the higher the temperature, the faster the development and the faster the life cycle goes. Third, extreme cold is lethal, less than minus 15 degrees centigrade. Fourth, egg hatching success decreases markedly at less than 10 degrees centigrade. Finally, the onset of activity in the spring by overwintering nymphs, remember, the key for transmission ranges from 4-15 degrees centigrade. That's a pretty wide range, and this actually needs more research to determine that range more precisely. So cold could kill the tick, as could extreme heat. However, if you don't reach extreme heat, warmer temperatures actually promote tick development. So as I've mentioned previously, laboratory studies have limitations. It's difficult to recreate field conditions, so even though ticks are very susceptible to desiccation at high temperature and low humidity, they could just simply seek refuge in human leaf litter, soil, or shade. Also, with regard to the very low temperatures in the winter, snow cover could actually insulate ticks. If they're underneath leaf litter and then there's a nice snow cover, it could actually insulate them from that extreme cold. So climate can potentially influence the geographic distribution of the tick and Lyme disease, tick abundance and Lyme disease incidence in endemic areas, onset of Lyme disease season. So there's actually an empirical study that shows or strongly suggests that the Lyme disease season has been starting a bit earlier in the Eastern US due to warming, and the earlier onset of spring. Climate can potentially influenced timing of peak tick activity and peak Lyme disease incidence. Finally, the duration of a Lyme disease season. That's all because of the climate. The effects of temperature and humidity on tick abundance, that I mentioned previously. So to make a long story short, the potential geographic distribution of the tick appears to be determined by climate. Again, this concept of climate envelope. So currently, the Eastern North American envelope, we have a Northern limit that's determined by low temperature, and we have a Western limit that's determined by low rainfall and humidity, as well as by prairie habitat. So where there are no forests is not really conducive to tick abundance. Within the envelope, tick abundance is determined by habitat suitability, host abundance, and conditions at the ground. So it turns out because of this, that tick abundance can actually vary markedly over small geographic areas that have similar temperature and humidity conditions. I think some of that is quite obvious, where we could see high tick abundance, let's say in a local park, a wooded area. Whereas in residential areas that are not adjacent to the park or to other woods, we see very low tick abundance. So what about models predicting the effect of future climate change and Lyme disease incidence? So those model suggest that dramatic expansion of the climate envelope. However, the models are not entirely consistent with each other, although broadly they are consistent. Because the maps actually differ in terms of exactly where the climate envelope is, although it does expand according to all the projections pretty much. But the fact that the maps differ weaken their relevance to public health planning. Secondly, the onset of Lyme disease in the Eastern US. This was a study that looked at all four RCP scenarios. In 2025-2040 was projected to be 0.4-0.5 weeks earlier and, 2065-2080 between 0.7 and 1.9 weeks earlier, depending on the scenario. So for the RCP 8.5, the business-as-usual scenario, it was 1.9 weeks earlier than currently. So finally, I should mention that ixodes is also the vector for other tick-borne diseases, anaplasmosis bacterium, babesiosis, which is a parasite and powassan encephalitis, which is caused by a virus. Those diseases which we don't have time to talk about are also taking on increased importance.