 So, my name is Crystal Van Hoof and I'm the Assistant Director of the C I H R Institute of Gender and Health. I'd just like to get us all on the same page about what is sex, what is gender, why does it matter to health research generally, why might it matter to the research that you're doing. I'll highlight some of the latest evidence, might not be the latest, but maybe for me at least the most interesting, and give some examples of how SGA, which is sex and gender-based analysis, could actually open doors for you in your research and in your career. So, first I just want to do a quick check-in. We did send out the modules, I believe, the Institute of Gender and Health training modules, online modules to everyone before, and I see a show of hands who had a chance to complete module one, anybody have a chance to do module two, and module three, cool. I actually thought there'd be more for module three, I think that you guys might actually find module three really interesting, so if you have time and people did module one, you might actually want to go and check out module three, because it's a, it's an analysis of data for human circumstances, so it's kind of cool. So this is the modules, you want to go back, discoversexandgender.ca, where you can find them, so now I'm going to test your knowledge, so hopefully you remembered what you, what you did, hopefully everyone completed it successfully and got their certificates. So true or false, the term sex and gender, me and the same thing, can be used interchangeably in health research, two things that that is true. Excellent. False. False. Sex refers to biological differences between males and females, genes, sex, hormones, physiology, immune response, et cetera, et cetera. Gender refers to psychosocial differences between men, women, boys, girls, gender, guys, people, things like behaviors, roles, your personal health identity, and there's cultural and societal influences and what is expected of you based on your physiology and your culture. So the bottom line is that every cell has a sex and every person is gender, which is a really good way of remembering it and another really important thing, is mice do not have genders, rats don't either, no animals have genders, please stop, just stop, stop, stop, okay, so just very quickly to show you how complex gender is and why likely mice don't have them is its roles, its identities, its relational, and its institutionalized, so this is all about things that are within society, within your culture, they change across cultures, they change across society, across time, geography, anything that you can think of, these things are interchangeable and they move their intergenerational, right, so you need to have some sort of intergenerational history and memory for these things to exist, for gender to exist, so again, why no mice, no gender, okay, so I want you, if you do any kind of research or will ever in your life do any kind of research involving animals raise your right hand, okay, now repeat after me, I solemnly swear, keep your right hand up, I solemnly swear, on the scientific method, that I will never again refer to the gender of animals until mice can speak, and they tell me otherwise, thank you, I will be watching, stop it. Okay, true or false, if the data set includes the sex, male, female, of human participants, but no direct gender measure, you can probably still analyze gender, who thinks that's true? Who thinks it's false? A lot of undecided in the room. True. So if you had done the third module, you would know that using the correct techniques, researchers will often be able to identify gender story, or construct a gender variable using secondary data, what does that mean? It could mean a lot of different things, these are just a few examples, primary finger status, personal income, hours of housework, you're giving responsibilities. That might sound really stereotyped, because it is, because gender is stereotyped. So if you were to look at these things, and then you were to apply them to your participants, using sex as a dependent variable, what might you find you might find that these things end up more likely with biological males or biological females, and there, boom, you have gender, right? Yeah. You're validating it with the biological sex again. Yeah. Yeah, because that's what gender is, right? Is is the expectations of you, because of your biological sex? That's usually what gender if we're talking about gender norms and roles? Yes. And what about the gender diverse? I think that's the main issue here. Yes. So when I'm talking about relational gender or gender norms or gender roles, that's what I'm sort of talking about here, personal gender identity is different, and that you can basically get from a survey question. So that's a lot easier to get at. You ask people what is your felt gender, and then you provide a list of responses and usually an open question box, right? So that's probably the easiest aspect of gender to measure. The other things are a lot more difficult because they change based on the culture and the system and the time, right? Does that make sense? Maybe, maybe not. Okay, we can talk later. Okay. So second check in. Who thinks that sex is relevant to their research? Who thinks gender is relevant to the research? Who thinks both? Who thinks neither? We'll talk later. I'm working with gender. Sex still might be relevant. Depending on the photo. Okay, I have a friend who does cancer research and endogenous worms, so it's not always relevant. For sure. Okay, true or false. It's safe to assume that conducting single sex pre clinical studies will have no effect down the line on humans. True. False. So false. Cell based studies may or not reported, which we generally know. Animal based studies, 75% are done in male animals. Human trials, 67% men. More women actually use healthcare for them because post market females have two times the risk to develop adverse drug reactions. Correlation on causation, I don't know. But can you genuinely say that there's no effect 100%? I would say not. I would argue you can't actually say for sure. So probably better to check and probably better to have some sort of, you know, sex based analysis and what you're doing. So true or false. Female animals are intrinsically more variable than males do their ester cycle, making them generally less suitable for baseline study models. Who thinks this is true? Who thinks it's false? Okay. False. Two recent meta analysis found for most applications. Female mice and rats are no more variable than males. This is key. No more variable than males. Males also have hormones. Let's not forget. Okay. What made us think that males are the standard and females are the deviation? Where did that come from? males have hormones. Are you controlling for the testosterone variability in the males? Because I'll tell you what, metabolism hormone morphology purple is males. You know, maybe we need to think about that. Yes, most applications, most applications. Okay, I'm not saying all. Always. Okay. Intrinsically more variable than males due to their ester cycle. So this is this is what I'm saying is like generally use a lot of those general type words because obviously it's never going to be always true or always false. But I don't think that an argument can be made that in the majority, and let's say like animal studies 75% are all male. Do we believe that that is the percentage that it should be? Probably not. I can tell you, there's been a lot of research done on this, a lot of analysis done on this and definitely not. Definitely not. We know that there's huge differences in pain research, for instance, in preclinical pain research, and yet at least 70% of pain research in animal models is done in males only. There's no good reason for it other than that's the way that it's always been done. What? First, the first part is just to see the safety first, to do a lot of clinical trial and just for safety, nothing going to be affected. So I should be happy because they're only killing the males. I get it. Be nice to the girls. I'm actually vegetarian. I'd like to leave all the mice alone, but whatever. So if you were to consider even if females were more variable, would you justify their exclusion from preclinical research? Hints? No, because the bottom line is that people are not just males plus messy variables. And that seems to be the reason that we're giving for not including them. So you can tell me that females are more variable all you want, but more variable than what? Then males, they're different. It's not just males plus weird variables plus weird hormones. No, males have hormones too. When you cage them together, you can actually get more variability in the testosterone in a day in the males than you get in the females over their whole ester cycle, right? So it's just different variability. It's not more or less than one another. You know, it's a bit of a paradigm shift, I think. True false. While diet can differ by gender, dietary effects on the gut microbiome are not mediated by sex. Who thinks this is true? Who thinks this is false? False. Men and women exhibit sex specific responses to the exact same diet and have distinct microbiome patterns populating the gut semi-obstress, ovarian hormone, sexism with brain processes, but all potentially play a role here. So those are just a few examples. And now I want to tell you what could you maybe get out of this? So this is sort of like the carrots, let's say. So there's some breakthroughs, there's potential breakthroughs. You know, if you look, you've got the data anyway, maybe look, see if there's a difference. Maybe you'll find something, maybe you'll have a breakthrough. A lot of the best sex differences researchers that I know found things accidentally that really shot their careers forward. There's funding available and quite a bit of it, and more and more as the as the goal long into the future. And it can help you to get ahead of the curve because there are rules coming that you may have to adhere to at some point. Breakthrough. So a microbiome example, this isn't super recent, I think is 2013. This is from Jane Danz's lab at sick kids found male to female only microbiome transfer protects against type one diabetes and autoimmunity and found that testosterone is a key mediator of the microbiome transfer effects. And there's an so there's an indication that microbiome alterations can cause and not really a consequence of autoimmune disease. And so what could this actually mean down the line in humans? Well, you know that there's evidence already of intestinal dysbiosis in human autoimmune patients. So there's a microbiome autoimmune interaction. And then sex hormones may also modulate sexual demorphism in human autoimmune diseases is something else we know from the research. So that's a sex hormone autoimmune interactions, you've got sort of both of these things happening that we know about already, which are supported by the the most model that she was using. So email to male bias of rheumatoid arthritis and multiple sclerosis declines of age, along with testosterone decline. Is this a coincidence? I don't know. Maybe someone should look into it. So a gender example, and I think this this is an interesting one. It's not to do with the microbiome necessarily, but I think it's interesting to think about how we sometimes see differences between males and females and assume that it's sex. When in fact it could be gender, it could be psychosocial. Right. So this is the example of acute coronary syndrome. This is from Louise Peeleclaw at McGill. And she was asking a question is sex or gender more predictive of acute coronary syndrome. And the question that I ask is, are you sure? Because someone's like I said, you might see a sex difference and assume that it's biological. So she developed a composite gender score. And so this is taking a lot of different things that are generally associated with gender roles, gender behaviors, applied it, created a variable, applied it to her participants specifically. So these were individuals who had had a heart attack, had been hospitalized and were under 55, 18 to 55. So this is applied directly to her cohort. And this is what she got. Men tended to be more towards what was determined to be the masculine characteristics and women were more spread out. Masculine again here, like I was saying before, was defined as the characteristics that were more often found with the biological males and feminine were the characteristics that were more often found with the biological females. So it's only within this cohort. So in that way, it's a little bit more objective than a lot of other gender scores that were sort of created in the 1970s and are still being applied today, right? So once she applied this and looked at the differences where previously she had thought that women were more likely, biological females, were more likely to have a second heart attack within a year of the first. She actually found that higher feminine gender score independent of biological sex was associated with higher rates of recurrent acute coronary syndrome. So if you scored higher on the gender score towards feminine, whether you were biologically male or biologically female, you were more likely to have a second heart attack within a year of your first heart attack. So that's interesting. Something to think about. So here's the carrots. So some of you might be thinking I've heard sex and gender research or sex differences research. It's a bit weird. It's fringe, not serious. My supervisor told me to ignore that data. My supervisor told me not to put it on my poster. I hear that a lot actually. Oh, I found something really interesting, but it didn't match the male, so I just left it out. So you might also think even if I were interested, there can't be much funding for sex and gender science or to look into these differences. Is it really worth my time and effort? So I started to think about this and I, a couple weeks ago, when a research net looked at all of the funding opportunities that were at the time two weeks ago currently open for applications that have some sort of component where you need to integrate sex and or gender or have a sex and gender champion on the team or some of them you actually have to complete one of our modules. So there you go. For those of you who have done it, you've already done it. If you want to apply to one of those. And these are all of the ones that were just at that time up on the website. And then this is the amount of money that was associated with each of them. Which in the end, if you ask, is it really worth your time and effort? Well, it's eighty seven point five million dollars worth your time. I would say probably maybe. I don't think that any one of those is like particular. Some of them were a bit smaller, but they're a good size grant. So, you know, and they can add up, of course. So if you didn't see anything there in the list, here's a little carrot for you. Coming soon, sex is a biological variable catalyst grant to. So this is the second round of the grant that we already did two years ago now. And so in the round one, we were able to fund 18 grants and around to we're funding up to 23. And we have a number of different institutes who are partners on this spring. So that's coming soon. I can't tell you one. I can't not really like to tell you much about this, but there you go. Keep an eye out for it. Sign up for newsletters from the institutes and you'll hear all about these things. So how might you say ahead of the curve and the curve in some ways is what I would refer to rather than the carrots as the sticks. So there's funding policies that are coming or already here and they're publishing rules that are happening that are changing. So these are just a few different funding organizations that currently have funding policies related to sex and gender. The National Institutes of Health in 2016 instituted the sex as a biological variable policy, which means that in studies with vertebrate animals, you either need to include sex as a biological variable or provide a very good reason why they're not. And like I said, there are good reasons, but there are fewer and further between than we often tend to think. Our Institute obviously has ongoing requirements and whenever we partner with other institutes, those requirements are applied in different ways. There's the CIHR application questions, which you have ever applied for CIHR funding that you know about. You've seen sort of the box. Did you consider sex? Did you consider gender? Why or why not? There's training for reviewers at CIHR that's being rolled out, was developed in 2016, being rolled out right now. And there's a CIHR SGDA action plan, which was asked for by the Standing Committee on Ethics, and that's in its develop and it's currently being implemented. So what does that actually mean? This is the box. How many of you have seen the box, the sex and gender box on CIHR applications? So this is with every single CIHR application you need to check yes or no, and you need to fill out this box. Now for those of you who've filled it out, have you ever received comments about it from a reviewer? Raise your hand if you have. Nobody. So part of the SGDA action plan is actually to move the contents of this box into the methods section of the paper to train reviewers on how to review the content and to make a requirement that reviewers must comment. So you may want to start thinking a little bit harder about what you put in this box in the future. Publishing guidelines, these are the sex and gender equity in research guidelines that came out of the European Association of Science Editors. They are trying to have journals internationally take up these guidelines. They're pretty basic. It's basically tell us the sex of your mouse, tell us the sex of your rat, don't just say in mice, say in male mice, and then disaggregate your data. It's the basics of it. There's more use gender, apply gender when it's relevant, but a lot of it has to do with sex. This pillar one or biomedical scientists tend to do what we call the bad kids. Most other pillars they tend to think of these things a little bit more, but it takes some convincing. So this is one way that publishing editors are looking to do some convincing with a, as I would call it, a stick. So the Canadian Journal of Public Health applied these guidelines last year. The Journal of Neuroscience Research applied something similar to the Sager guidelines, essentially the Sager guidelines about saying so, and so they established a policy applying all authors to ensure proper consideration of sex as a biological variable, and they have guidelines for their reviewers to determine whether or not it's relevant and to what extent it's been applied in an appropriate manner. So in some, SGBA can support your discoveries, your funding, your publishing, and the bottom line is that neglecting sex and gender in research, when it's appropriate, tend to scientific rigor and reproducibility. And so true or false, you can make a difference in ensuring microbiome research is rigorous and generalizable and that emerging therapies have the potential to benefit all people. True! Yes. So where could you start, compare males and females in your research, whatever it is that you're saying, just come to it, have a look, see if you find something. Just see. You know, second step is to document, analyze, and report the results and the outcomes by sex. If you don't know where to report these, if you're not sure if your usual journals will accept the data, biology of sex differences is a great journal that you can check out. They have some really interesting stuff. They've got great stuff on the microbiome, data from humans, record and pay attention to sex differences, and then if you find them, consider if they might be gender-related. And that is more or less relevant depending on the type of research that you're doing obviously. So third check in. So tell me again, who believes neither sex nor gender is relevant to your research? Anybody? Okay, tell us why. Ah, soil microbiome. You're good. Anybody else that's not working with soil or endogenous worms? Food. Food. Food, so the actual bacteria on the food. Yeah. Okay. Anybody with less good reasons? Soil microbiome. Okay, no more soil. Anything having to do that could eventually potentially translate into humans and you think that sex or gender is not relevant? Okay, thank you. Okay, so I was going to say one on that. I was going to make other people tell you why that's wrong. Okay, so if you would like to learn more, you can take another one of our courses. You can learn more about us on our website. You can subscribe to our newsletter and if you're all about finding opportunities from across the IHR because we tend to invest across the institutes. You can subscribe and you can join the conversation. There's some really interesting stuff if you check out Twitter. If you look up the hashtag sexandscience or SABV for sex as a biological variable. And you can of course feel free to contact me if you have any follow-up questions or anything like that. And that's from me. Thanks.