Dr Louise Newson: [00:00:01] So today on my podcast I've got Saira Hameed who I've known for quite a few years, respected her with all her clinical academic work and now I'm holding her book in my hand which is called Signals, the inside story of our hormones. Now this is fantastic for so many reasons. It came out really quite close with my book The Power of Hormones and so of course I read it cover to cover very quickly and it's just brilliant because you are an endocrinologist. I'm a general physician. I've done endocrinology training, but endocrinology is the study of hormones, basically, isn't it? [00:00:39][37.9]
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Dr Saira Hameed: [00:00:41]  Exactly that. So endocrinology is the specialism concerned with diseases of the body's hormones or glands. And the analogy I like to use is our glands, might be the adrenal glands, the pituitary gland, the thyroid gland. They're like radio transmitters and they are transmitting these hormone signals. The hormone signals travel in the bloodstream and they're destined for target cells. When they get to that cell, they will convey some information and the cell must carry out that instruction. And these hormones are pinging around the body all day, every day. And when things are working well, we don't notice them. Ony when things start to upend, go wrong a little bit, that we begin to think something's not quite right. We intuitively feel something isn't right. And that's when a patient might end up seeing someone like me.  [00:01:40][59.4]
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Dr Louise Newson: [00:01:41] Yeah and we've got hundreds of hormones in our body. I mean I think we've got more than we even realise because there are many that I'm sure haven't been studied as well but we've done a lot haven't we?  [00:01:51][10.3]
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Dr Saira Hameed: [00:01:52] We do, we do. Somewhere in the region of 100 or so, but as you say, those are the ones we know about. And in both our working lives, hormones have been discovered. So the textbooks we used at medical school will now be out of date because new hormones have have been found. Now, these again, have been doing their things since prehistory. It's just that it's taken us a while to find out about them. So you're absolutely right. The exciting thing about the field is that more will come through. And that's really good for patients who haven't had an explanation to date, who know that they don't feel well. And we've said, well, I can see you don't feel well, but to the best of our knowledge and the best of our testing, we can't quite get to the bottom of what's going on. So it's great that so much work is being done so that hopefully in the future, we can answer patients' questions more effectively.  [00:02:43][51.7]
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Dr Louise Newson: [00:02:44] Yeah. So, I mean, one of the common hormones that lots of people have heard of would have been insulin and thyroxine. They sort of always, I don't know, they're always the go-to hormones that I use to explain. When I was doing my endocrinology training, I was a junior doctor but I was running the day unit, so people would come in and have these amazing tests. And what's incredible is that some of the diseases that you've described in your book as well have quite distinctive physical signs as well when we examine people and when I was doing my exam and membership of the Royal College of Physicians, as you know, it's a bit of a theatre show, they always bring in patients and you have to decide in literally 10 minutes what the diagnosis is, which is quite artificial because in a real life situation you would talk to them for a lot longer, you would do tests, but you have to just do it. So it was often endocrinology patients that would come in. People with Cushing's disease or acromegaly. So I found when I was a junior doctor revising for these exams, I knew so much about these quite weird and wonderful, quite unusual conditions. And when I working in the day unit, hardly anyone had them, but we always tested for them. And I think back now about the hormones that I'm dealing with, progesterone, estradiol, testosterone, and how every woman has changing hormone, of those hormone levels in their body. And I think back on the day unit, there were lots of women that were coming in and I was doing all these tests and I knew nothing about those hormones. So it's just weird, isn't it? Because in medicine, we should be learning about the common things. We have to know about the uncommon things because that's when, if I as a GP think someone's got Cushing's, I wouldn't treat it myself. I would say to someone like you, please could you, but I have to know about it. I don't have to know in the detail that I really did all those years ago. [00:04:40][115.4]
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Dr Saira Hameed: [00:04:40] You just have to be alert to it, but not necessarily know the fine print. Yes. But then you're absolutely right. Do we major enough on the common endocrine conditions? So to put it in context for listeners, Cushing's is a condition of cortisol excess. The body is overproducing the hormone cortisol. And it's an unusual condition, but as you say, we need to be alert to it and we need to screen the right people. And you're right, Louise, that in medical education and medical training, it's these really intriguing conditions that get a lot of the spotlight. Because as you say, they can come on quite suddenly sometimes, it can be quite dramatic presentation. In a condition like Cushing's, you might gain 20 kilogrammes in just a few months. Your behaviour might completely change, you know, to the point where maybe you've seen a psychiatrist before you make it to the endocrine clinic. So students tend to learn a lot about it. Whereas when we were just chatting now before we started recording, I was looking through my old medical school notes the other day. These are from the 1990s, but I was living through my old notes. And yes, picking up on conditions like Cushing's lots of notes about those. Another hormone condition called acromegaly. You produce too much growth hormone and so your appearance can change. You have other manifestations of that too. Both of these conditions don't affect that many people. Very important that we find the ones that do. Louise, I couldn't find two really important sections. Couldn't find a section on menopause, but maybe that's not very common, and I couldn't find a section on insulin resistance. So you did mention, you said insulin is one that people tend to know about, and that's definitely a spotlight that's been shone and people tend to know it about it now. So those two things really weren't discussed very much 30 years ago. Certainly when I was training, you're right. Let's focus on what a lot of people have. Let's be alert to that.  [00:06:54][134.1]
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Dr Louise Newson: [00:06:55] It's so interesting, isn't it because if I had a hormonal condition, like I say, such as Cushing's, then I would see an endocrinologist. If I had hormonal change, which I do, I'm 55, I'm menopausal, then if my GP didn't know how to treat me, they would send me to a gynaecologist. Now I've had a hysterectomy, so I don't actually need to see someone who specialises in my reproductive tract. Because firstly, I'm never going to get pregnant at 55 without a womb, and secondly, I don't have pelvic organs for them to worry about. So it feels really weird that it's, they sort of, everyone thinks that gynaecologists own those hormones that are made in the ovaries, but they're made in, the brain, they're in the adrenal glands as well. It's weird isn't it?   [00:07:42][47.2]
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Dr Saira Hameed: [00:07:43] I mean, and that taps into the sort of real kind of magic and wonder of hormones in the endocrine system. We cannot be myopic. We can't just say, well, a hormone is made by this gland and we say that's why we just have to major on the gland. We are a living being of 30 trillion cells and all those cells talk to each other. They do not act in isolation. And the way they talk to each other through hormones. So hormones are the body's language. Even if it seems like one gland is highly implicated in that hormone, like the thyroid gland does produce thyroid hormone, for example, you're right. That gland is really only carrying out instructions and it's under a huge amount of checks and balances, often from the brain, from the pituitary gland and then sitting above the pitutary gland in the whole kind of axis of control, the hypothalamus, the hypothalamus is the brain's master gland, the master strategist. It sort of keeps a check on everything that's going on in the body. Hormones from the body are constantly feeding back to the brain saying this is what's happening, these are the conditions on the ground and then the brain responds accordingly with changes in the hormone levels so that we tick along really nicely. So for example, I'll give you an example related to the thyroid. If this morning, which doesn't, this happens to me a fair bit, you set out for work and you realise, oh, it's chillier than I thought it would be and I haven't got my coat. What will happen is that temperature information is fed back to that master gland, to the hypothalamus. The hypothalamus through thyroid hormone signalling will rev up metabolism. Byproduct of metabolism is heat generation. And so I'm okay, I'm warm enough, you know what, I can cycle to the hospital, I'll be okay. I don't have to go back and get my jacket and risk being late for work. Now, all of that happened, the revving up of metabolism, generation of extra heat, without really any conscious input from me, isn't that, I just find that so even like, you know, all these years later, I still find it pretty magical.  [00:09:52][128.0]
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Dr Louise Newson: [00:09:52] It is amazing, you know, and you would have had a bit more cortisol, the stress hormone, which will have changed your inflammation in your body. Everything is, it's working very, and I, I think like, I feel very privileged, but I'm also in quite a unique situation because I am a general physician who's interested in women's hormones. And when I start talking to a gynaecologist about the role of hormones affecting insulin resistance or metabolism or inflammation. You can see them just look really vacant. Because they haven't been trained in any of that, because gynaecologists, as you know, literally go straight into gynaecology. But then I see a lot of people in my clinic who've had pituitary tumours. They've been under endocrinologists. One of my patients came for a review last Monday, and I've known her for a few years, and it took me a year to persuade her that she needed progesterone and estradiol, testosterone. She'd been under an endocrineologist since she was 16, and she's now 42. So they've given her all the hormones she needs, except progesterone, estradiol and testosterone. After she, after a while she was still getting symptoms. So they gave a contraceptive pill, but that made her feel worse. And they said, well, that's all the hormones you need. And so that's why it took me a long time to get to know her and her to have the confidence to know that what I prescribe is very different structurally, metabolically. It's because what I prescribe is the same as your own hormones, of course. And now she's amazing, so much so she works at the university, local to me, and everyone's coming up to her to say, what's happened to you, like you're amazing, you know, she's been to the gym...  [00:11:26][93.6]
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Dr Saira Hameed: [00:11:26] Well this is the power of hormones!  [00:11:27][0.1]
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Dr Louise Newson: [00:11:27] ...she's lost weight, and all of that, but what's surprising me, and I see it a lot, is that so many endocrinologists haven't, like, you say you haven't been trained in those hormones for men and for women, and so it's a sort of, those hormones just don't belong to anyone properly.  [00:11:43][16.5]
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Dr Saira Hameed: [00:11:45] It's so interesting, isn't it? So it's such an important point. And the things I picked out so much from what you were saying were two things. Firstly, you said, I got to know her. And that's the point that I really make very strongly in my book. That so much of medicine. Yes, there's gee wizardry now. There's scans, there this, there that, you know lovely things going on. But so much of medicine remains rooted in one person telling their story. And the other person trying to make sense of it. And so much of that comes down to the details. It's those details, those nuggets that so far mean that you and I are not yet replaced by an AI chat bot because we speak human and so we can understand our patients and the stories that they tell us. And the second thing, I agree with you. So hormones don't act in isolation and the analogy I sometimes use is like with WhatsApp. You can just WhatsApp one person. So that could be like a back and forth between you, but if you need to get like various messages out to 30 trillion people, shouldn't it be better to be on a group chat and to, you know, because you know we all need, just like how, you know if we all need to communicate something, you know within a group, within a community, within the network, you let's get on that group chat together other than just messaging people individually. The body is basically on a massive group chat, through its hormones.  [00:13:15][89.4]
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Dr Louise Newson: [00:13:18] Yes, totally. And that's why we need to never think of any hormone in isolation. And the other thing that scares me because we, I mean, everyone uses AI in certain ways, but even doing blood tests is such a snapshot when it comes to our hormones, because, you know, so many people are spending, not insignificant amounts of money, on blood tests and then they'd been told, Oh no, they can't have X, Y, Z condition or they can't have a hormonal imbalance because their blood test was normal. And I keep saying it was normal at the time it was taken. [00:13:52][34.6]
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Dr Saira Hameed: [00:13:55] Yes and the other thing is it's so important to point out to listeners that hormone blood tests, even for specialists in the field, take a bit of interpretation.  [00:14:04][8.5]
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Dr Louise Newson: [00:14:04] Yes, absolutely.  [00:14:05][0.6]
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Dr Saira Hameed: [00:14:06] And, you know, when especially now with home testing, when people can send away a blood sample, a saliva sample, and so on, and the result comes to your phone and something's in red and it feels very alarming. It's just that, for example, certain hormone tests have to be done at certain times of day, or they might have to done fasted, like there are various things and certain medications can affect these results and so on. So we have to also be supporting patients to do their testing through us with the trust that we will, you know, feedback, explain, be on the journey with them because I do understand why people do home testing. Either there's a long waiting list or they're not feeling well and they don't have anyone to discuss that with. I fully understand that. But at the same time, I will say that sometimes we get results back, that we as a group of endocrinologists will spend a long time discussing. So, you know, these numbers can be tricky.  [00:15:11][65.2]
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Dr Louise Newson: [00:15:11] Yeah, and I was saying to patients, any test we do, whether it's a blood test or a scan, is always in clinical context as well. And for example, I could see someone who's tired, they could have had a blood test for their testosterone and it's low, but then I could also ask other questions and realise that they're anaemic or they've got low vitamin D or they have got an underactive thyroid gland or they've got type 1 diabetes. And you can have more than one diagnosis in medicine as well! That's so important. [00:15:40][28.6]
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Dr Saira Hameed: [00:15:40] Totally. I fully agree with you. That's the art of medicine. And so you and I, we sit at our computers and we could really tick any test within reason. We could say tick, tick, tick, and we can just tick away because we'd say, let's just cover all bases, even when the patient's story does not suggest that that test needs to be done. And as I point out in my book, the risk with doing that, as you and I know is you come back with a false positive, i.e. a test result that seems to speak of illness when the patient's story did not. And then you've burdened that patient into worrying about an illness they don't have, you as the clinician are then duty bound to do further work up or so on, so we have a duty, not just to tick every box and in fact, it's when we listen to the patient's story, they'll very often tell us the diagnosis. We do the tests then to back up our thoughts about where is this diagnosis going.  [00:16:46][65.9]
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Dr Louise Newson: [00:16:47] Yeah, it's so important. And actually we've even used different laboratories over the years. And we've worked with two that we know really, really well. But after COVID, we were trying with another one because it was more cost-effective for our patients. But the results were, some of them were completely spurious. And then you realise they're using different reagents. They've got different testing and I'm just like, no, I can't do it. And then the finger prick testing is not the same as the venous because it's capillary. Some tests are okay, but others, it changes as well. So, yeah. [00:17:17][30.1]
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Dr Saira Hameed: [00:17:18]  Yeah. I mean exactly as you say Louise, layers and layers and layers of nuance and ultimately you end up with a number on a piece of paper but we need to have a bit more of a deep dive really to be able to understand that.  [00:17:31][13.5]
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Dr Louise Newson: [00:17:32] Yeah, and the other thing I'm very interested in medical practice is to try and prevent disease and a lot of blood tests are set up to diagnose a disease and we want to try and get it almost before the disease. We don't want to wait till someone has got diabetes or they've had, you know, raised blood pressure and found to have Cushing's or whatever, we want to try and pick it up earlier, and not always with hormone treatments, is it a treatment, like if you're thinking about trying to prevent diabetes, you don't wait till someone's diagnosed and then give them a drug like metformin, you actually want to try and look at have they got insulin resistance? Is there something that they can manage with their lifestyle and their nutrition? [00:18:14][42.1]
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Dr Saira Hameed: [00:18:14] Yes.  [00:18:14][0.0]
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Dr Louise Newson: [00:18:15] Do you see what I mean?  [00:18:16][0.7]
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Dr Saira Hameed: [00:18:16] I totally agree with you.  [00:18:16][0.0]
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Dr Louise Newson: [00:18:16] And it's a way that we weren't really taught in medical school, I think.  [00:18:19][3.6]
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Dr Saira Hameed: [00:18:21] Yes, I think that's right. I think the old model is somebody becomes unwell and then they come to see the doctor. But actually, it makes far more sense to, as you say, pick this up earlier with a condition like insulin resistance, which ultimately could lead to diabetes or fatty liver or high blood pressure or various other manifestations. The warnings are often there years in advance. Those warnings are there that, you know, we then have a duty not to say, well, you know, I don't know, you it's kind of okay,  see you in a year. This is our golden opportunity to help a patient to be on that journey with them to flag that insulin resistance years before it becomes type 2 diabetes. Because with insulin resistance, to explain to our listeners, insulin is a hormone that amongst many other things, clears sugar from the blood. So when we eat blood sugar goes up, pancreas releases insulin. Insulin will clear the post-meal sugar from the blood. If the body becomes resistant to insulin it essentially stops listening to that message. And so insulin needs to work harder and harder and harder to clear enough sugar from blood to keep the blood sugar normal and it can do that for a bit of time. Essentially it will ratchet levels up higher and higher and higher. I always say to patients, your insulin is shouting, but your body can't hear it, right. That's how we need to think about it. Well, when we're still at a point that the blood sugar is normal, even though the insulin is working really hard to keep it that way, we need to tackle why has the body tuned out to that signal. And these are things like a low sugar, low carb diet. Doing some mild intermittent fasting, moving every day. Make sure your sleep routine is okay that you're getting enough sleep. And the biggie, and I don't say this sort of thinking that there is a magic wand, but managing stress because stress massively impacts on this. And that means different things to different people. So you and I obviously can't say that we've got the magic plan for managing stress. For some people that will mean taking the dog for a walk. For other people, it will mean, you know attending their art class or going for a swim. There's lots of different things. Spending time with people you love and who love you, these things will all help. But exactly to your point Louise, we should be addressing this years before it becomes a problem. Helping people to let their hormones work perfectly as they should, giving that education piece, flagging it a long time before it causes a problem. [00:21:09][168.3]
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Dr Louise Newson: [00:21:09] Yeah, it's so important and we need to think differently as doctors really to try and keep our patients as healthy as possible. And that's where understanding how hormones work is really important. And it's interesting because I was talking to someone the other day and they're not medical and I said, I do a lot of work with hormones and they look really shocked and said, gosh, that's bad. And I said what do you mean? They as well, hormones are dangerous. And I said, oh gosh, well talk to me a bit more. Anyway, they do quite a lot of farming and they were thinking about the hormones for meat. And that's really interesting actually concept because I'm very particular with language. And I think the problem is with hormones in meat and food is they're not hormones. They've been synthetically, chemically altered hormones the same way that the contraceptive pill contains synthetically altered hormones. So it's not hormones. And as you know, they used to give DES, which is a form of estrogen that they made commercially to poultry in poultry farms. And the irony of this was, is that it was to make the meat plumper so that you could get more meat from your chicken. And then a lot of men working in the poultry farms had gynecomastia, so they developed breasts. And they became infertile and they said, what's going on and they realised it was this synthetic hormone DES. But then they looked at the effects on women and they'd seen that it was associated with cancer in dogs and mice, but they decided to ignore it and kept giving it to women. And then, as you know, DES was associated with clear cell cancer of the vagina and it's been banned.  [00:22:52][102.6]
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Dr Saira Hameed: [00:22:54] I think what you're saying, Louise, is that hormones sometimes have a bad rep, right?  [00:23:00][5.7]
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Dr Louise Newson: [00:23:00] Well they do, but they're not hormones, you see, this is the thing.  [00:23:02][2.2]
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Dr Saira Hameed: [00:23:02] Yes, but I think also, and I mentioned this quite a bit in my book, you see, when somebody says, I'm feeling hormonal, or you're hormonal or she's hormonal he's hormonal, they are saying this, they're not meaning this as a compliment. Generally, the word hormonal in general conversation outside of medical circles would very much mean that person's bit moody or a bit puffy or, you know, a bit off today. But actually, probably one of the key messages I want to make to readers who pick up my book is being hormonal is a great thing. When we look at the word in its purest form, we are all hormonal all of the time and we have to be because it's hormones that animate us. It's hormones make us who we are. It is hormones that mean that our 30 trillion cells speak to each other. It's hormones that mean that I got out of bed this morning and I could cycle here and you and I can have this conversation and, and, so it goes on. So, you know, being hormonal essentially means I'm human.  [00:24:08][65.8]
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Dr Louise Newson: [00:24:09] Yeah. So we need to think about about hormones differently. I think there's two big areas that have come out of this conversation. One is that we naturally produce dozens of hormones that all have very specific chemical structures, roles in the body. But also our language has to be really careful because the hormones that we produce and many of the hormones we prescribe are the same. There are lots of synthetic hormones that don't work the same and some of them are useful in medicine, but we have to be careful, and farming, but they're different chemical structures. So anybody who's prescribed hormones, it's worth asking your doctor, are these body identical, what is the role that they are doing. And making sure that they're on the right dose, the right type for their right condition. And any other hormonal change has been excluded as well. So no one's just looking at one or two hormones in isolation.  [00:25:06][57.5]
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Dr Saira Hameed: [00:25:08] Yeah, I think that's right. So for example, if we take the hormone GLP-1, probably now the most famous hormone in the world, practically. Now, naturally we all produce GLP 1 after we eat. So it's a naturally produced gut hormone. We eat something, the gut produces GLP1, goes up to the brain, we get the message we're full. We stop eating. That's the way it works in normal biology. And of course, it's so powerful that it's now being manufactured into these GLP-1 injections, Wegovy, Ozempic, and so on. But these are drug mimics of a naturally occurring hormone. So for example, the reason that we can inject Ozempic once a week is that it has been tweaked on its molecular structure so it lasts in the system a week, but the natural hormone will only last minutes because otherwise we'd never eat the next meal. So, you know, it's interesting, exactly as you say, there are hormones, there are drug mimics, and then exactly as you said with the farming story, there are chemicals out there called endocrine disrupting chemicals or EDCs, which disrupt the endocrine system because these chemicals are similar enough to our naturally occurring hormones that they can signal within the body, but not signal in the way that the hormone should, and and we end up with manifestations down the line. And these endocrine disrupting chemicals are not only found in industries like you say, you know, you mentioned farming, but for example, some of them are sprayed on upholstery as flame retardants. They can leach out of plastic that we use in cooking and tableware and water bottles and so on. So it is something to be attuned to. And one of my favourite expressions with my patients is don't let the perfect be the enemy of the good. Because if we ever talk about this in clinic and a patient says, well, yeah, what am I supposed to do? I live in London in the modern age. I can't avoid all these things. That's absolutely a fair point and I and you, and you know, we can't avoid these things, but we could do things like maybe having a metal water bottle, like, you know using cookware that doesn't contain like a non-stick coating, you're choosing not to heat up food in plastic containers, for example. These changes may be that sort of doing what we can, you know, rather than thinking, well, you know nothing's possible because this is such a sort of pervasive issue.  [00:27:40][151.7]
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Dr Louise Newson: [00:27:40] Yeah, and sometimes some of those small changes can be transformational and it's thinking about them. And again, it's something we weren't taught at medical school and it has taken me a long way time to think about endocrine disruptors and the negative effects they have on our body.  [00:27:55][15.3]
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Dr Saira Hameed: [00:27:58] They absolutely can. You're right though, the small changes, because I bet you find this too, that sometimes I'll make a whole shopping list of suggestions to patients. I write very long clinic letters and then the patient will come back a few months later and maybe a tiny one of those suggestions that I didn't, maybe I rattled it off very quickly. I didn't think it was such a biggie. They'll say, Well, you suggested that and it's completely changed my life and you think, well, you think well, that's just awesome. That is the best, best news because that worked for you. That kind of spoke to you. So that's really cool.  [00:28:31][32.8]
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Dr Louise Newson: [00:28:31] Yeah, absolutely. So there's a lot more we need to be learning and exploring about hormones but think about them as a very positive part of our body that we all need. So I'm very grateful for your time. Before I end my podcast, I always ask for three take-home tips. So I am actually going to ask people why they should be reading your book, Signals, the inside story of our hormones?  [00:28:57][25.8]
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Dr Saira Hameed: [00:28:58] Number one, it's written from the perspective of a hormone expert and I think that will be reassuring to people because there is lots of information out there, lots and lots of people online, on social media, telling you about your hormones, maybe telling you you have a problem with your hormones telling you various hacks and tricks and so on. It might get very, very confusing. And I know that people are curious and they want to know about their health and you know, on the whole, they want to do the right thing and look after themselves. So I hope this book sort of speaks to, let's look at the actual hormone system, the actual endocrine system. Let's cut through the noise and kind of tune in to the signals, right. So let's sort of address that piece to people who are curious to find out sort of more expert-driven information. I think the second reason is that I think as humans, we love storytelling. We all just love storytelling. When one of my colleagues presents a patient that they've seen. Yes, I enjoy the medical complexity and let's all have a think about what might be wrong with the patient, but it's the storytelling that's also quite fascinating. Those little details that tell you how has this impacted on this patient, the glimpses to somebody else's life. So I write the book from the point of view of the reader, come and sit next to me on my side of the desk and let's hear these stories together. Let's understand another human being's experience of living through too much thyroid in the system or living with extra weight or whatever the condition might be. I hope it gives somebody an insight of what it feels for us to sit on this side of a desk and sometimes the uncertainty or the awkwardness or all of that sort of thing, because it's not, as you know, not always plain sailing. So I really hope readers enjoy that. And lastly, I would love readers to come away from the book with this renewed sense of awe, kind of wonder, that all day, every day, this system is pinging around the body, keeping us well, keeping alive, keeping us animated, making us human. I think right now it's fair to say there isn't a whole lot of good news around, like we open social media or turn on the television news. Not great stuff at the moment going on. I think this book is inherently full of hope. Whether it's the hopefulness of this magical system inside us, that's a good news story. Whether it is the hopefulness of somebody could come and see you with glitching hormone signalling and when you fix it, you recalibrate a life. I hope readers really enjoy that sense of a happy ending.  [00:31:47][169.0]
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Dr Louise Newson: [00:31:48] Great, very good. So thank you so much and keep on with your very important and good work. Thank you.  [00:31:55][6.7]
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Dr Saira Hameed: [00:31:55] Thank you for the invitation Louise, it's been a pleasure.  [00:31:55][0.0]