Full transcription of the interview
Jordan: A very warm welcome to the Research Beat hypertrophy. If you’re a gym goer, you’ll know exactly what that is. But today we’re not talking about muscular hypertrophy. We’re talking about cardiac hypertrophy with Yasmin Dickinson, Ph.D. in cardiovascular medicine at the William Harvey Research Institute. Yasmin, welcome to the show!
Yasmin: Hello. Thank you for having me!
Can you tell us a little about your research?
Yasmin: Yes, of course. So my research focuses on cardiac hypertrophy and the development of heart failure. More specifically, heart failure with a preserved ejection fraction or also known as hef.
So this form of heart failure counts for approximately 40 to 50% of patients, where the individual display symptoms of heart failure, however, still maintain a normal or near normal eject fraction. My lab is demonstrating the importance of C type in a triatic peptide, and it’s CMP for shorts, and it’s a [00:01:00] peptide that has many roles in maintaining cardiovascular homeostasis.
My research will try to identify the role of CMP in Hef P and whether or not targeting specific pathways could be a novel therapeutic approach.
Jordan: It’s a complicated process. We’re looking at the deep mechanisms inside the body. So we’re gonna break it down. And first of all, you are studying the molecular mechanism responsible for cardiac hypertrophy.
Yeah. So let’s start with looking at that hypertrophy:
What is cardiac hypertrophy and where do we find it in everyday?
Yasmin: So cardiac hypertrophy is a normal reversible physiological adaptation to cardiovascular volume or pressure stress. So hypertrophy itself is the thickening of the left ventricle wall, and the purpose of this is to compensate for an increased workload.
So this form of hypertrophy is also referred to as acentric hypertrophy, and it occurs, for instance, during gas station and in athletes due to an intense cardiovascular workout.
Jordan: And I mentioned hypertrophy at the very start of the [00:02:00] episode. Jim Goers know exactly what hypertrophies is for the muscles, so it’s that same thickening process, but this is not in the external muscles. This is in the muscles of the heart, right? Yeah. Yes, correct. So:
When is this kind of hypertrophy beneficial and when is it harmful?
Yasmin: So I just spoke about her per, in the context of it being in healthy conditions. So in contrast, hypertrophy in response to pressure overload.
For instance, during hypertension or ischemia or myocardial infarction, it results in pathological or concentric hypertrophy. , whilst this change can acutely maintain cardiac output, over time it becomes maladaptive and it results in heart failure and.
Jordan: What might set off something like this, what might set off heart failure in everyday?
Yasmin: So part of my research is going to try to investigate this a bit further, but what is, is what is known so far? So initially her [00:03:00] sets off following a pressure overload. For instance, this could be due to a high blood pressure. So this mechanical stress is sent by mechanical receptors, which converses extracellular signal into a intracellular biochemical signal.
And so this leads to an increased expression of vasoactive factors such as angiotensin two and endothelin one. And these factors are known to use hypertrophy, but over time, , and with increased stress and with, for example, with increased hypertension, in the context of pathological hypertrophy, the left ventricular wall stiffens and so it’s not able to contract correctly anymore, and this a bit affects its ability to pump and this is what can lead to heart failure.
Jordan: So putting it into context, when we’ve got that kind of beneficial hypertrophy in athletes, everything’s going well. , it’s a response to pressure, but a good, healthy response to pressure. And there’s still flexibility instead of this stiffness that you just described, Yeah. So it’s something that can be [00:04:00] good and it helps us when we’re exercising, when we’re working hard, but it’s also something that have a very terrible effect. so, Yasmin, you mentioned initially the CMP peptide.
Can you just give us an idea of what that peptide is exactly and how it’s working?
Yasmin: So the primary function, or a primary function of CMP is to stimulate vasodilation. , it is also known to inhibit hypertrophy and fibrosis of cardiac tissues. So treatments targeting specific CMP pathways may come useful, for example, in decreasing pressure, stress on the heart and subsequent hypertrophy, and this will be a good means of treating heart failure
Jordan: Roughly how long might it take to develop these kinds of treatments from your research into the cmp pep?
Yasmin: Okay, so my work involves both in vitro and in vivo aspects. So that’s both working in cells, , and in animal models. So that’s, this is will always be the starting [00:05:00] point of research, and we have to really make sure that , The concepts that we are trying to investigate are very clear at this stage,, and that we are seeing it, for instance, in animal models and human models, and we’re seeing , similar patterns in cells.
And when we’re confident with our results, we can then move on to patients. But this does take quite a while. Um, every, , investigation is slightly different, but we have to be very confident with the beginning parts that we see in the animal models and in ourselves before even thinking about, , moving onto patients and clinical trials.
It’s a long process, isn’t it? Yeah, it is quite a long process, but it has to be just to make sure.
Jordan: . With a lot of detail and a lot of checking each stage, I imagine. Yeah. Yeah. So Yasmin:
Is there still some mystery surrounding what causes some people to undergo cardiac arrest at certain points during their life?
Yasmin: both yes and no. The main cause of someone having a cardiac arrest is having an abnormal heart rhythm, so having ventricular fibrillation, and we know that certain heart related conditions [00:06:00] can lead to cardiac arrest, such as heart valve disease, cardiomyopathy, and having a heart attack. Also, lifestyle risk factors such as a physical activity.
Smoking comorbidities such as diabetes, all contribute to the risk of having a cardiac arrest. I think where the mystery lies at the moment is how to accurately predict cardiac arrest because of its nature of occurring suddenly, the only clinical practice currently used to predict such an event is the measurement of the left ventricular ejection fraction.
But this tends to only be useful for those, , at a higher risk. So all those, , for instance that may be younger in age or have no other underlying cardiovascular condition, these will be the individuals that may get missed.
Jordan: So are we just talking about environmental factors here, or do you think that some people may be genetically vulnerable , to the harmful kind of cardiac hypertrophy?
Yasmin: Um, with all cardiovascular conditions it can be quite, quite complex because it may be, , the influence of both, , environmental [00:07:00] and genetics.
But there are instances where people do have, , a genetic, for example, with the case of cardiomyopathy, that’s a genetically, , inherited condition of the, , cardiovascular disease. So they will be, At a higher risk of then later on developing other types of cardiovascular conditions and which could lead to heart failure , or a heart attack or a cardiac arrest.
Jordan: And what do studies tend to say are the environmental factors, that really do have a significant measurable effect on this kind of process?
Yasmin: , so , a major one would be the physical activity of the individual, how active they are, how much they exercise, if they’re quite, if um, they’re not quite lazy.
What’s the word? Is it sedentary? ? I don’t want to say lazy on the podcast. Um, is it quite, is it sedentary? Where you, you’re quite, you sat down. Exactly, but it depends on their physical activity, how active they are. Another main cause is smoking. , and um, example, , an unhealthy diet. This is mainly the case, for [00:08:00] instance, with, , atherosclerosis is where you get deposits of, , lipids within the vessels, , and for instance, other comorbidities or other conditions, diabetes mellitus.
These are all considered environmental factors that can contribute to the development of heart failure.
Jordan: And normally would living a sedentary lifestyle be considered, , a risk factor or something that makes this kind of negative hypertrophy more likely? I believe so,
Yasmin: yes. But , you had to take it in consideration with other aspects of their lifestyle.
Um, for instance, if they already had, , a genetic predisposition to heart failure, , having that sort of lifestyle would only make their situation worse. Maybe another individual that doesn’t have that genetic, , influence, having that more laid back lifestyle wouldn’t affect them as much as the individual who has that genetic predisposition.
Jordan: There’s a very interesting relationship between a sedentary lifestyle, a healthy lifestyle with lots of exercise and the possibility of cardiac arrest [00:09:00] because we actually have an example in recent years, a number of footballers, most notably for Fabrice Muamba in 2012, and Christian Ericksen in 2020.
Have actually suffered heart attacks in the middle of broadcast matches. Now, that’s not necessarily what anybody would expect because we are talking about young and physically fit athletes. Absolutely not. They’re absolutely not living a sedentary lifestyle. So:
Fabrice Muamba in 2012 and Christian Ericksen in 2020. Could you explain why this might happen to such, a fit and capable person?
Yasmin: I know it does seem quite paradoxical for athletes who are fitter than ever to be the ones in some cases that suffer from cardiac arrest or a heart attack. Um, like I mentioned before, athletes go through, intensive long-term exercise and this can develop healthy cardiac hypertrophy in their hearts.
But in some cases this can become maladaptive and irreversible because you have to remember, these athletes will be pushing their bodies and their hearts to the limit on a regular basis. , the left ventricle from hypertrophy may become so stiff , it can no longer contract correctly and pump blood around [00:10:00] the body. , in the younger athletes, the vast majority of incidences or deaths is due to an underlying hereditary disease, such as cardiomyopathy. However, increased stress, tension and pressure all increase the risk of erythemia and studying cardiac arrest.
Jordan: So that’s really interesting that there’s. A combination of factors, like you mentioned before, somebody could have a genetic predisposition. Yeah. But also this sense of kind of overwork that they mm-hmm. , they really are, in some respects, just working too hard and then it leads to the stiffening of the heart.
Yasmin: Yeah, exactly. Cause they’ll be doing things more than the, the, the normal individual, they’ll be really pushing their bodies. , and the heart for a, for a certain amount of time can cope. But then after a while, it becomes too stressed and that’s when the hypertrophy becomes IRRs.
Jordan: So Yasmin do events like this, which a lot of people really paid attention to.
Do they have any bearing on your work?
Yasmin: Not particularly. That’s more the study of cardiac [00:11:00] electrophysiology, which is also really interesting. But my work is more on the pharmacological side of things in the development of HEPA and heart failure in general.
Jordan: So would your pharmacological work, have any kind of influence , on those footballers who underwent problems in matches?
Would your kind of treatments be able to help somebody in that situ?
Yasmin: That’s the hope with the research. So we are just trying to elucidate further the role of cmp. And its influence in both the physiological and the pathological, , types of hypertrophy. We want to know its role in both situations so we can better understand what leads to pathological hypertrophy and when we find out which pathways are more closely related to pathological hyper, we can focus on those pathways and see whether or not they will be , good therapeutic targets.
Jordan: And would these kinds of treatments be preventative or would they take place after the fact or even , during the incident, if you’re able to answer that question.
Yasmin: , I believe they would be more on the preventative side because [00:12:00] the hope is with, , for instance, in my research we’re looking at, he. P, which is a heart failure with a preserved ejection fraction. So this is the stage where the individual still has an ejection fraction within the healthy range. So 50% and above.
So if we can, , treat Tef or heart failure at this stage, it doesn’t have to lead onto the worst stage, which is Hef ref . Heart failure with a reduced ejection fraction. So it could be possible that if we find out , the role of CMP in Hef and we can know about it more in that stage, that hopefully we can come up with a preventative sort of, , therapeutic approach.
But it’s still very early days, so we still need to know about the pathways further before we can think about, , therapeutic.
Jordan: And so hopefully it would be a case of identifying individuals who you can see are going towards a case of eventual heart failure and applying these treatments , to try to stop it from happening in the first place.
Yasmin: Yes, exactly. Yep. The, the other thing about Hef P is that it happens alongside other comorbidities. , like I’ve mentioned, diabetes mellitus, [00:13:00] hypertension, , pulmonary, , hypertension. So sometimes the symptoms can get masks. That’s why Hef p um, usually can go , misdiagnosed or , mistreated or misdiagnosed.
So it’s really important to be able to understand it very well at that stage to then help, , treat patients who are at that stage of, , healthcare.
How is AstraZeneca connected to the work that you’re currently doing?
Yasmin: My PhD is partially funded by AstraZeneca, so through this collaboration I have or will have access to training and specialist equipment and techniques used in industry, which I wouldn’t have access to otherwise in academia, , which is a great advantage.
This includes, for instance, doing transcriptomics and proteomics and with all industry funded PhDs. Some of my work may be used by AstraZeneca or maybe it won’t, so I can’t specify exactly the details of this, just.
Jordan: I think it’s very helpful to, , an aspiring researcher to have a connection, a close connection between industry and the actual PhD itself.
Yeah. [00:14:00] is this something that’s becoming more commonplace?
Yasmin: Um, I think so. A lot of the time when we think of we’re going to, when we think of doing a PhD, we assume that we’re gonna go straight into academia. But I feel nowadays with PhD students, they’re becoming more used to the idea of knowing what their options and knowing that they can go into academia, but also there’s industry for them too.
Knowing both the pros and cons of both.
Jordan: Absolutely. We’ve spoken recently to guests who, , have moved into industry from academia, , or who have started developing ties with industry during their master’s degree or their PhD, and they’ve generally said that the experience has been invaluable to them.
Yasmin: Yeah, I think even for me, I feel like I’ll be doing techniques that I wouldn’t have the chance to otherwise. , working in, , universities or , in academia for instance, I’ll hopefully have the chance to be doing some 3D cell culture, which is a really exciting and new technique. , so we get to see how other cells interact with our cell of interest.
So it mimics what is happening in the human body , a lot better. [00:15:00] So I, I’ll be really excited to try that technique, , at AstraZeneca.
Jordan: Yamin, in this section of the show, we want to give you the opportunity to talk about the issues in academia that really matter to you. So:
What for you are the big issues in academia?
Yasmin: I think a major concern scientists find working in academia is the short contracts and probably the lack of security. Of course, it depends on the lab that you work in as well.
Some labs are well funded, so if that’s the case, your contract may be renewed no problem. But generally, contracts for post-op positions can be only for two to three years. There’s no job security in that. So it becomes more difficult, say when you want to put down a deposit for a house or you want to settle down.
Um, there’s also the unpredictable working hours, working sometimes late into the evening or coming in on weekends. Um, that’s the case for me. , anyways, again, this depends on the types of experiments that you’re running. I’ve been working now in academia for some time, and I [00:16:00] actually do like the flexibility that I have with my working hours.
I prefer it to the normal nine to five. I feel I’m more in control of my working hours this way, so, um, I, I enjoy it. I think, , that’s probably one of the benefits I’d say of academia, , in comparison to industry. So
Jordan: you may end up working, , very late hours one night. Yeah. But that would be more or less under your control and you might compensate for it on another day by doing slightly less work.
Yasmin: Yeah, exactly. So every week is not the same. Every day is not the same. So if, for instance, I’ll know that on Thursday and Friday, I have certain experiments that I’ll have to work into the night. , but then I can take off other days during the week. , so you have a lot of control in your work schedule, , which is, I think, different to maybe other types of jobs.
Um, so I really love that aspect of it.
Jordan: Looking in more detail at the issue of contracts. Do you think that this problem generates a kind of fear in aspiring academics, even those who are quite well established, [00:17:00] a fear of not knowing exactly what’s coming, and a kind of panic and a need to do something in order to maintain paid work?
Yasmin: Oh, definitely. I feel that a lot of, , PhD students or scientists, the reason why they go into research is because of their love for science and how they want to make an impact, , on a wider scale. But if you have in the back of your mind that you, if you go into industry and you won’t have that job security, it makes you have to think long term as well.
So it, it, it can dampen , your idea of whether or not you want to do, go into academia or research, which is a shame. Because as scientists we do, we do want to answer these unknown questions. We do want to explore the unknown. And in academia it’s a beautiful place to be able to do just that. But we also have to take it, take into consideration your life outside of work.
How would working at an academia affect that? There’s pros and cons to everything, but um, working at the group that I work in, I can see for myself how they are all able to manage their work life balance and they all do so really well. So [00:18:00] it is possible, I don’t want anyone to think that it’s not possible.
and if working in academia is something they really wanted , to do, they can,
Jordan: I think that’s a really important message, , to say that it is absolutely possible Is there a way, through this issue of short contracts, do you think there there are choices available to academics?
Do they simply have to take the shorter contracts and kind of do their best to balance their life with the work? Or is there anything that they can do to to try to confront this problem?
Yasmin: , well, if there is, I would like to know because person, personally, myself, I don’t think there is at the moment, and it really does depend on the lab you work in.
, for instance, some labs would be so well funded and they have so much research they have yet to do that the contracts can roll almost, , and they can continue working in the same lab for a long time. But for other individuals, this may not be the case. They’ll have to switch from a different lab to a different lab.
Some people might prefer because they get to travel, they get to relocate, they get to try working in different fields or applying their skills in different ways. So, , they might enjoy it in that [00:19:00] sense.
Jordan: So Yasmin, the life of a PhD student is an extremely busy one, and we would love to ask a few questions to get to know you better as an individual.
What drives you on your research journey?
Yasmin: well, the reason I went into research in the first place was to do something beneficial to the general public and to be able to help people on a wider scale.
So I hope to aid the expansion of global scientific knowledge in my field. The thought of, , my research helping to answer, for example, remaining questions in cardiovascular health and disease. And, , hopefully getting closer to better diagnostic and therapeutic approaches to heart failure. That means the world to me.
, and it’s thoughts like this that drive me to do good research and , I’m really thankful that I have a career that I love so much. , no day is the same and I actually wake up really excited to come into work.
Jordan: That’s a wonderful feeling.[00:20:00] It’s clearly very, very important to you to try to solve these problems.
What is the reason for that? What led you into cardiovascular research in the first place? Everyone
Yasmin: asked me this question, and sometimes it is just fate. Um, I remember when I did my undergraduate degree, I had lots of different, I had loves for all different fields. I loved neuroscience, I liked microbiology.
But when it came to choosing, , my undergraduate thesis, I chose one in cardiovascular medicine because the project sounded great. I liked the techniques in bold. And then through doing that a thesis, Found a love for cardiovascular medicine and I wanted to stick to it. I then went and did my master’s in molecular biology.
And again, when I did my thesis, I chose to focus it on cardiovascular medicine. Um, but then to know whether or not I can see myself working in research, I thought it would be wise to, , work as a research assistant for a bit before applying for a PhD. So this is when I worked at the University of Oxford and we focused on preeclampsia and hypertension.
And I got to, , use my skills that I had learned through my studies [00:21:00] in proper scientific research in the cardiovascular field. And this is where my love for cardiovascular medicine grew more and more. And I was happy and I said to myself, yes, I’m ready to do a PhD and to contribute my own work into the cardiovascular field.
Jordan: I think that’s a great step to take because, , a lot of people jump straight from undergraduate to masters and then to PhD level, but to actually take the time to see how it would really feel to exactly to do the kind of work that you would end up doing. . ,
Yasmin: there’s no right or wrong. Some people may decide from their undergraduate, they’re ready, they wanna go straight into their PhD, but for me, I just really wanted to make sure because. , it’s a beautiful feeling to know that you really love the work that you do and you wake up and , you’re excited to go to work.
And I always wanted that for myself. So I had to make sure if I saw myself working in research, if this was for me, if not whether I want to apply for , another degree or so. I think it was really wise for me personally to do my masters, get the laboratory [00:22:00] skills that I needed, work in research, and then see whether or not, yes, this is the field for me and continue my career that.
Jordan: Yasin, you do quite love science, communication. So how did you get started in that?
Yasmin: Well, I first started my account like a lot of, many other side comments that I know during lockdown. I had just started my dream job of working in cardiovascular research at the University of Oxford, and then two months in lockdown had happened and I couldn’t work from home like most people, as my work needs to take place at a lab bench.
Um, so, I started my Instagram account. Where I shared posts of science in the news, I taught laboratory techniques and I also gave an insight into the life of a scientist for anyone who was curious. Um, I always loved talking about science and teaching science.
That was something I always had in me. But it wasn’t until I started doing science communication that I really, that I realized that this was the best way for me to do just that. I have felt really fulfilled, , since starting my cycle journey, and it’s something I [00:23:00] see myself doing always.
Jordan: I think the restrictions in a lot of cases prompted this feeling of wanting to share, , work, research and science with others.
And it led lots of academics to, to set up social media accounts so that they could do exactly that during a difficult
Yasmin: time. . And I think as scientists, it’s also really important that not only are we doing research, but we have to be able to explain our research to the wider public, because that’s who we’re doing it for.
So I thinky should be a practice that all scientists take into consider.
Jordan: Absolutely. And do you find that your followers are generally, , people already inside the academic world, or, or are there lots of people from outside it who are taking an interest in what you’re doing? I, I think
Yasmin: it’s a range and I like that because I don’t want everyone to already be in science.
, I want to also inspire those who are thinking about it or who are thinking, what career should I go into? What should I study next? And I get a lot of messages from, , young individuals who say, oh, I love the work that you do. You’ve really inspired me. Can you tell me the steps you took?[00:24:00] , what do you think about doing this degree?
Will I be able to do, , this sort of career afterwards? So I’m really happy that I’ll be able to get to help those sort of individuals through my psych. I also do have followers who are scientists just like me, probably from different fields, but we all get to see what we do , in all of our specialist fields.
And it’s really beautiful to see, , different sides. For instance, I follow neuroscientist accounts, I follow pathology accounts, and I get to see what they do as.
Jordan: It must be a really nice feeling to be able to hand on that advice to those who are almost following in your footsteps.
Yasmin: Yeah. , I think that’s one of the, the main things that makes me want to keep going.
Jordan: Do you think that it’s particularly important for scientists like yourself , to share your work with the public and why?
Yasmin: , I think definitely as a scientist, it’s important to share it with the public because our work, our research, everything we do is for the public interest. We’re trying to develop medicines or understand certain diseases better for their sake.
So , it’s important for us to be able to explain [00:25:00] what we are doing and the research that we’re doing to them. . Science shouldn’t feel like a mystery to the public. And sometimes it can do because it’s quite technical.
And even when we are talking a scientist among ourselves, if we’re from different fields, when we hear , how they explain their as such, it just sounds like nonsense to us because it’s so complex. So imagine how it would sound to someone from the wider public who doesn’t have a science background. So it’s really important for us to know how to be able to explain science in a way that is understandable, , to the general.
Jordan: I think that’s very important point that you’ve picked up on, and , it’s an important relationship between , the wider public and academics and scientists, because like you said, , most academics and scientists are working for, the public good and, and trying to, , make society, , and the world better.
So this ability to share , and have a clear understanding is critical, I think.
Yasmin: Yeah, exactly. I agree with that.
Jordan: So Yasmin, how would you describe your [00:26:00] style?
Yasmin: Um, well, , I always wanted my psych to be educational and accessible. , I want to encourage members of the general public to engage in scientific discussion and hopefully inspire those thinking of studying or working in STEM to achieve both their goals and their dreams.
Jordan: That’s, a beautiful attitude and a beautiful foundation for your science communication.
What do you do in your free time to keep yourself balanced?
Yasmin: I know many people assume that a PhD consumes your life, but it’s actually quite manageable to balance with your everyday life. Then again, I’m only just moving into the second year of my PhD, so who knows what’s to come. Um, but I’m actively trying to do things outside of the lab. , I’m trying to be that well-rounded person, for instance, , I do dance glasses.
, I go to yoga. I do, I go to the gym. I also want to learn how to do pottery, but I keep telling myself, Yasmin, please one thing at a time. , but in all [00:27:00] seriousness, it’s important to do other things that you love alongside your PhD. It’s really healthy.
Jordan: It’s, it’s really important. But , I feel like , I feel like people are gonna be asking you after this.
Yamin. How, how on earth , do you keep a balanced lifestyle? Because,
Yasmin: and I will say to them, I don’t know, you just have to try .
Jordan: Yeah. So, so, so many PhDs say, , I literally have no time to do anything except work. So I think maybe, um, people are gonna be, People are gonna be curious. I think at
Yasmin: the start of your PhD you’ll definitely feel like you dunno how to manage everything because it’s such a large workload that you’re getting all of a sudden.
It’s very different to being a student, but I feel like with time you will learn how to manage it, , how to manage your workload and then say, look, I’m gonna make time for this on this day. I’m gonna make time for that because it is achievable.
Jordan: So yeah. Guys, , if you’re listening and , you are having some problems at the start of your PhD.
Listen to Yamin. So take it easy, .
Yasmin: [00:28:00] Keep going. Have hope. It’s possible.
Who are your inspirations, either in research or the wider world?
Yasmin: Um. For me, I love seeing women in positions of power or excelling in a career that they love, but also being great mothers and balancing a family life too, because those are the things that are important to me personally. So to think of women off the top of my head, , a male Clooney who I also share a birthday with on fact, um, princess Diana, Michelle Obama.
Basically, I love any woman who breaks the mold. Really. I find them really inspiring and I, I can, I hope I can be. Well with
Jordan: Inspirations like that, we hope that you can achieve, a really high and prestigious position in your field. Thank you, Yasmin.
How can our listeners reach you if they’re interested in contacting you or learning more about what you do?
Yasmin: I’m most active on my Instagram account, the cardiac scientist, but I also have a [00:29:00] TikTok account by the same name. I also have Twitter and LinkedIn that I can be reached by. I’m always happy to connect with others and give other study advice or career advice.
So if you’re out there listening, always feel free to contact me. I’m more than happy.
Jordan: Yasmin, thank you so much for joining us today. It’s been an absolute pleasure to have you. ,
Yasmin: thank you for having me. I really appreciate it. I’ve had.