The future of movement disorders

Transcript

Russ Altman (00:04): This is Stanford Engineering's The Future of Everything, and I'm your host, Russ Altman. If you enjoy The Future of Everything, please follow or subscribe on your favorite listening app. You'll hear about new episodes and it'll help us grow. Today, professor Helen Bronte-Stewart will tell us how her lab is creating devices that can precisely measure motion and movement in Parkinson's disease patients. It allows them to make better diagnoses, but the new generation of devices is also allowing them to create powerful new treatments. It's the future of movement disorders. Before we jump into this episode, a reminder and a plea to rate and review the podcast. It helps us improve, it spreads the word and helps the podcast grow.

(00:48): Parkinson's disease is an example of a movement disorder. Critical cells in the brain die and that leads to abnormal signaling and the resulting problems with motion. Patients with Parkinson's disease have problems walking. They have spontaneous motions that they don't want. There are motions that they do want to do that they can't do. In fact, there's a thing called freezing where their body wants to move and sends the signals to move, but it just does not happen. This can be dangerous and lead to falls and other accidents. Helen Bronte-Stewart is a professor of neurology and neurosurgery at Stanford University.

(01:24): Her lab creates devices to make precise quantitative measurements of movement so that they can more precisely diagnose Parkinson's disease, but also with the new devices they can more precisely intervene and treat the motion disorders that they see. She will tell us that wearable devices are creating a revolution in our ability to empower patients with the disease. And there are some new technologies coming down the pike that will lead to improved treatments and better motion, better walking and less freezing.

(01:58): So Helen, you study movement disorders, particularly in Parkinson's disease. And so I guess to start out with, and I know this is very complex, but can you give us a simple explanation of what goes wrong in Parkinson's disease, which I think will set us up for talking about the ways in which you then measure and intervene?

Helen Bronte-Stewart  (02:19): Yes, absolutely. So in Parkinson's disease, and I'll stick to the motor problems because we know there are also a lot of non-motor problems, people may develop a tremor, meaning that one of their limbs will shake, they all will develop slowness of movement, and this will be manifest in what they think they do with their hands, the way they walk. Everything slows down. They also develop a loss of spontaneous expression. This is often seen in facial expressions. So family members say, "Hey, this person seems to be a bit depressed. Their face isn't moving that much." Their blink frequency goes down. So they develop what we call akinesia, lots of spontaneous movement and bradykinesia, slowness of movement. And then they also develop something called rigidity, which is stiffness. It's interesting that many people have actually shoulder surgery for frozen shoulders, which turns out to be a limb that wasn't moving because of Parkinson's disease. It's something we quite commonly see.

Russ Altman (03:21): Oh my goodness, so this is an unnecessary surgery?

Helen Bronte-Stewart  (03:25): Well, no, in the sense that their limb has become frozen because they're not swinging their arm when they walk. But because if we had diagnosed it as Parkinson's disease first of all, we might have saved them that problem. So it affects all aspects of the body. People actually can get slowness of thinking, slowness of speech. So this is a systems neuroscience, this is a systems problem. And then as time goes on, they can develop a problem with their walking, which is called freezing. And we have also shown that freezing occurs again in a systems fashion, in finger movements, in limb movements in speech. So the freezing of gait though, obviously becomes quite problematic because you require your body weight to be over your feet to walk correctly and not fall over. And if you get up and then can't move forward, but your body moves forward and your feet don't, you might fall over.

Russ Altman (04:17): I see. Freezing is literally the inability to affect a motion that you're intending to affect.

Helen Bronte-Stewart  (04:24): Yes, and it often starts when it often begins when you are starting a movement. The earliest time we see it is when you're actually getting up from a chair and trying to walk. It can affect speech. Actually, when you swallow, there are five phases of swallowing. In Parkinson's disease, it's that first phase, it's initiating that swallow. That's really a problem. So again, this aspect of not being able to seamlessly go from one motor program to the other is quite difficult. So people may start freezing when they start to walk and classically when they try and turn. So if you think about it, we have a motor program and a plan in our brain for walking, and when we turn, the body has to rotate itself and it's basically another motor program.

(05:09): So I have a nice little trick we do in the clinic with people is instead of turning around, spinning around, you actually just walk, you keep walking, but you walk in a half circle and trick the brain and you turn around and it works. So this aspect of either initiating motor programs or changing between them is the first time that you see this freezing. But unfortunately, as time goes on, even during forward walking, you begin to see the freezing. So people sometimes can't even get up and walk forward at all. They end up being frozen. So the movement problems get worse over time, but unfortunately this new one, this freezing of motion begins later on and gets more problematic later on.

Russ Altman (05:51): Great. So thank you. That gives us a really ... And of course people know that Parkinson's disease is a very challenging disease for the patients, and thank you for that description. So I know that you have an engineering approach, and so I think the next question is tell me how you and perhaps others, but definitely you, assess these movement disorders. I know that you're interested in not just a clinical assessment of a doctor writing down, "Oh, they're having some trouble walking and they're moving slowly." Tell us about what's your vision for how this should be assessed?

Helen Bronte-Stewart  (06:26): Absolutely. Well, this came, I was lucky enough to do a postdoc with Stephen Lisberger at UCSF, where we were deconstructing the simplest three neuronal motor arc of the vestibular ocular reflex. And as an engineer in order to-

Russ Altman (06:27): We're going to skip over that because nobody understands what that is.

Helen Bronte-Stewart  (06:38): Okay, As an engineer, in order to understand the behavior you're modulating, you have to measure it. And when I moved back into human motor control, I found that the only way to quote "measure" these complicated movements in Parkinson's disease was by clinical rating scale, which don't get me wrong, is a great clinical rating scale, and we all use it in movement disorders. But if you're going to try and understand the mechanisms of how the brain controls or doesn't control movement, you need a more engineering level type of movement analysis.

Russ Altman (07:20): Right.

Helen Bronte-Stewart  (07:20): And so when I got to Stanford and developed the human motor control lab, that's what I did. I set about developing computerized objective tools that allowed us to measure what we call fine motor control, so moving with your fingers, limb motor control, and then what we call axial motor control, this gait, freezing of gait, postural control. And that has led to a whole new discovery of how the brain controls movement.

Russ Altman (07:43): Yeah, this sounds fantastic and it sounds like what people want. There's one thing just being examined, but I'm sure that patients love to be studied in detail because everybody has a sense that the specifics of their disease are always a little bit different. So can you give us some examples of the types of measurements you make, the types of devices? I guess I'm giving you a license to nerd out a little bit here.

Helen Bronte-Stewart  (08:05): Be careful about that. So one of the really exciting things that we developed and which we're actually now translating through Stanford to make it available to other people is something that we call the quantitative digitography. And so I started this on a MIDI keyboard. So for those people who know about MIDI keyboards, they're the first keyboards that were attached to a computer. And so we could actually measure movement when people did a simple trill, alternating finger tapping. We've now moved on-

Russ Altman (08:38): Just to be clear, these are like piano keyboards.

Helen Bronte-Stewart  (08:40): These were piano keyboards.

Russ Altman (08:42): Okay.

Helen Bronte-Stewart  (08:42): And then we worked with Intel's digital health technology group who, Andy Grove was very interested in these quantitative measures. And we built an engineered device. And now we've gone on and we've re-engineered that device. So we don't call it a piano keyboard anymore because people are getting confused about a computer keyboard. But it's very important that you can measure the amplitude and the timing. And with this little simple 30 second task, we can actually give you all the validated metrics of all those motor signs I just told you about. And they correspond to both the upper extremity and lower extremity assessments. So again, we get back to the brain, and this is systems neuroscience, so that what you measure in your fingers is actually also correlated with what's going on in your feet, i.e. your gait.

Russ Altman (09:30): Does that imply that the disease advances as a whole, so that if there's a deficit in the fingers and if it gets worse, you can also assume that the feet and the other parts of the body will also have gotten worse? It's not a patchy disease.

Helen Bronte-Stewart  (09:44): No. And actually that's a great question because it comes out first in the fingers. That's the canary in the mine.

Russ Altman (09:52): Perfect.

Helen Bronte-Stewart  (09:54): Actually, the Postuma group have shown, they've looked at what we call prodromal Parkinson's disease, so people who act out their dreams actually can go on and develop Parkinson's disease, and they use this same tapping task. They actually just measured number of taps per minute, they could identify people who are going to develop Parkinsonism up to 12.9 years before they did with this finger tapping task. So we've known for quite a long time that the fingers are really, as I say, the canary in the mine. They're showing the deficit before you see it in the limbs and specifically in the gait and the balance. So that's been a great task. And then the other thing is I've been using wearables for a very long time, before wearables were called wearables.

(10:34): So we used a solid state gyroscope that measured angular velocity because I was always trained that the brain codes for angular velocity and it's now standard of care in our operating room. It's standard of care when we do our initial programming. So now we've moved on to using the wearables, what we call the inertial measurement units that everyone's using, and we use those in most of our tasks now. We even put them on the back of the hand when people are doing the finger tapping so that we can measure tremor and the movement of the hand, and we use it for gait and we strapped them onto the legs and that we have 11 of those now strapped on the body where we can measure the truncal movement, the limb movement, the leg movement, et cetera. So everybody's what we call instrumented. And then we also developed a very cool stepping in place task on these force plates that usually measure your balance.

(11:27): So we used that to develop one of the first measures of this funny odd thing called freezing of gait. And then we developed a forward walking task through these barriers which simulate situations in the normal environment that trigger freezing of gait. And so we simulated that in the clinic because when you normally walk in these wide open spaces in the clinic, people don't freeze. And there's a big explanation for that that may be too complicated. But we developed these tasks now, so we now can really measure and elicit all these abnormal movements that we see in Parkinson's disease. So now we have our engineering widget factory as I call it. So now we can actually measure things like what's the brain doing, what changes when we give this therapy or that therapy. And we're now beginning to see industry and pharmaceutical companies beginning to take on mostly wearables, because those are the ones that are FDA approved right now, and they're actually beginning to use these in clinical trials, which is something I've been wanting for years.

Russ Altman (12:29): Fantastic. So let me ask a couple of follow-ups, because you just said a bunch of exciting things. The first thing is for the keyboard, for the trill test, is that available for clinical use or is that mostly a research tool?

Helen Bronte-Stewart  (12:43): So it's currently research tool, but we were lucky enough to get one of the Catalyst Awards, and we are now working to make this what we think is going to be the first comprehensive remote monitoring system system of Parkinson's.

Russ Altman (12:55): Wonderful.

Helen Bronte-Stewart  (12:55): So we're hoping it will be available once FDA approved, and we're working towards that right now.

Russ Altman (13:00): And the other question is, you talked about the wearables, and I'm wondering if the consumer level wearables like the Fitbits and the Apple watches and things like that, are they useful to you or do you still need to have special purpose hardware for whatever reason?

Helen Bronte-Stewart  (13:14): So Apple's done a lot of work in Parkinson's disease, and we actually did a nice study with them. They have now developed the MM for PD set of measurements. So the watch now, a company called Run Labs has got this through the FDA as a valid measure of tremor. It can also measure one of the complications of medication, which is what you call dyskinesia, involuntary movements. But the other thing that this health kit and health app has in Apple, in the watch, is you can put your phone in your pocket, you can actually measure gait as well.

(13:50): And you can measure some of this with the watch. So many of us who are developing and moving some of these other widgets through the FDA, we're currently planning to access some of these other measures so that the person can get a overall comprehensive measure of their movement, both with something like our task, which you do, it's an active task or a passive wearable. And there are pros and cons to both.

(14:16): So I see this as a really exciting complimentary landscape that will help people really be able to, like Fitbit, like Whoop, really understand what's going on with their disease. And we've had feedback from some patients saying, "I really want to see what happens when I change my diet." And this is so exciting because it really engages people to take care of themselves, to really have agency in what's going on instead of these every three to six month visits with the neurologist, which are-

Russ Altman (14:44): I can see so clearly that if they think they're getting better and then they can test it themselves, that really gives them an empowerment as a patient. So I wanted to go to something else. There's so much here, but I know that you're very interested in correlating measurements of the motor behavior that you make with what's going on in the brain. And I know you've invented some ways to do that. So can you tell us about that?

Helen Bronte-Stewart  (15:06): Yeah, so my goal was always trying to understand how the brain controls movement. And one of the ways you can do that is when movement is not going very well, you can ask those questions and then reconstruct what might be normal code. So we wouldn't be able to do this unless we had what's called deep brain stimulation. We implant chronic stimulating leads, which have four or eight electrodes on each lead into the deep structures of the brain. And that is a wonderful therapy for Parkinson's disease, dystonia, tremor. And now we're looking at other neuropsychiatric diseases. But one of the advantages for that for research is we can now access the brain signaling in these motor pathways deep in the brain, which of course we wouldn't normally do in a human subject and in monkeys or rodents, you can only train them on a specific movement.

Russ Altman (15:59): Right.

Helen Bronte-Stewart  (15:59): What happens with humans is you can ask them to do a very complicated movement. Now that we've got our widget factory set up, so we have nice analyzed, validated, reproducible metrics of movement, we can now synchronize the recordings in the brain to those kinematic measures. Now, we would only be able to do this in the operating room until the first, what we call sensing neurostimulators were developed by Medtronic. And so we very early on were lucky enough to be able to use these in a research fashion.

(16:29): And now in our lab, we could have synchronized neural and kinematic signals in people doing complicated movements such as that stepping in place, walking freely, doing the movements with their upper limbs, doing the keyboard test, the quantitative digitography. And so that has been something we've been doing for the last 10 years. And that actually then allows you to determine what are the neural and the kinematic signals relevant to the pathological motor behavior, the abnormal movements. And then what's really interesting is you rather like, we call it a deep brain computer interface, instead of taking normal neural code, which is what the brain gait and the BCIs and the cortex do-

Russ Altman (17:12): BCI is a brain computer interface.

Helen Bronte-Stewart  (17:15): Yes. And we take in these deep BCIs, we're recording abnormal neural code. So we need to decode that and then write algorithms to say, "Okay, if this abnormal code neural signal does this, then increase your stimulation."

Russ Altman (17:31): Oh my goodness. So let me make sure I have this, because I think you're saying that you're seeing abnormal coding as part of the disease. You can intervene though. You can take that abnormal code and say, "Oh, what it should be telling the muscles is to do something else and we're going to intervene and tell those muscles to do something else so that the patient now experiences a more normal gait or a more normal finger." Is that the idea?

Helen Bronte-Stewart  (17:55): That's the idea. And we can get into details if you want, but that's the most exciting thing that's going on. And it all built from developing the ways to measure movement, recording in the operating room, then moving back into the lab when we had these sensing neurostimulators. So it really allows us to ask fairly basic science questions in the human subject. And as you know, in animal models, it's never quite the real thing. So this has just been, for me, probably the most exciting pivotal part of my research career in my overall desire to understand brain signaling in movement disorders, is we can now record these concurrently and therefore answer a lot of questions.

Russ Altman (18:36): This is The Future of Everything with Russ Altman, more with Helen Bronte-Stewart next. Welcome back to The Future of Everything. I'm your host, Russ Altman, and my guest is Professor Helen Bronte-Stewart from Stanford University. In the last segment, Helen describes some of the amazing devices that she's developing to measure not only movement, but the interaction between brain signaling and the movement that we observe in the body. In this segment, she will tell us that new capabilities are allowing what we call closed loop systems for improving the symptoms of Parkinson's disease. The trial is complete, and the FDA is now evaluating the data to see if this can result in some powerful new treatments. So Helen, in the last segment, you told us about this exciting work with deep brain stimulation as a treatment, but now these sensing deep brain setups allow you to also measure the brain in addition to stimulating it. So tell us and tell me where is this moving toward and what kind of treatments might this enable that are currently not possible?

Helen Bronte-Stewart  (19:40): Yeah, absolutely. So this is one of the most exciting things. I'm going to just make a quick analogy. We have cardiac pacemakers and nobody probably remembers, but early on, those cardiac pacemakers could not sense the rhythm of the heart, and so they just stimulate it. Now, for people who had a resting heart rate that was so low they couldn't get up, that might've helped them, but you can imagine if you feed in the wrong rhythm to the heart, you'll probably kill someone.

Russ Altman (20:07): And also if you're running, you need a faster heart rate than if you're just sitting around.

Helen Bronte-Stewart  (20:13): So it's inconceivable to many of us to think that you could have a cardiac pacemaker that would be blind to what or deaf to what the heart's doing. Well, for the last 30 to 40 years, we've been using brain stimulators that are blind and deaf to what's going on in the brain. So now what we have with these sensing neurostimulators is we can read and we can record that neural signal, and then as we were talking about before, we can decode that and figure out what's wrong. And one of the things that has turned out to be very, very important in Parkinson's disease is something called the beta rhythm. Now, you can call this a brain arrhythmia. However, the beta signal is normal in the brain. We all have these little signals going on between 13 and 30 hertz in our brains. That's how our motor network uses these.

(21:05): But we need to understand when they become abnormal, and when they become abnormal is that these beta band oscillations, these neuronal oscillations begin to get clumped together and synchronized. And that results in what we call a beta band burst. A burst of power that lasts too long, is too synchronized. And a good analogy to think of that is normal brain functioning, it's like we're in a crowd, we're in a cocktail party, which hopefully everybody's getting back to these days and we're listening to people talking and there's a hum, but we can hear ourselves talk to our neighbor. A beta band arrhythmia is like being in a crowd that's chanting, a protest that's chanting, and you can't hear yourself think or speak. So it jams the sensory motor coding process. So this is something, this is work that's gone on for the last 20-plus years, and now we understand that this abnormal beta arrhythmia is really related to, not directly, but is related to the lack of motion in Parkinson's disease.

(22:07): So when we record the signal off the brain, we're recording everything in all frequencies. So one of the things we have to do is we have to find the beta frequency and filter the signal in a band that is abnormal. So we have to find that relevant, what I call a relevant neural signal. And then we can watch what's going on over time. We can then see how is that related to all our movements that we're doing in our lab. And then we can say, for instance, we found out that in people who have freezing of gait, these burst durations in the beta band were longer even when they were just normally walking compared to people who weren't freezing. And when they had periods of freezing of gait, they became even longer.

(22:50): So that led to a study that we're doing right now where we have a research device now, which is not one that's available clinically, which can actually get specific enough for us to measure the beta band burst duration and then trim it, basically increase stimulation just when it goes over that normal duration into the prolonged duration. So by trimming these beta band bursts, we're basically removing that excessive synchrony and we're restoring the sensory motor processing. And guess what? It works. So we're just in that early stage of doing this with patients. And so we're finding that yes, that what we call algorithm works, we can also use this beta band power, and that's being used by several groups and is actually what is being used in the first international multicenter pivotal trial, which is run by Medtronic and is actually going to result in closed loop deep brain stimulation being available to everyone. So this is all very-

Russ Altman (23:49): So tell me, what is the technical definition of a closed loop? That sounds interesting, but I guess there's open and closed. What are the differences?

Helen Bronte-Stewart  (23:56): Yeah, so the open loop is like the cardiac pacemaker that doesn't know what the heart is doing.

Russ Altman (24:01): I see, I see.

Helen Bronte-Stewart  (24:02): And the brain stimulator, the brain pacemaker that doesn't know what the brain is signaling. Closed loop is when you use the signal, it reads the signal and you use the signal to feed back and drive the stimulation.

Russ Altman (24:02): I see.

Helen Bronte-Stewart  (24:15): Now the neurologist was sort of the closed loop in traditional programming only working with motor behavior, but the brain signaling was just going on and nobody was recording it.

Russ Altman (24:26): I see. So you need to now do safety trials to make sure that when you let the computer run the show, everything works well and we don't have any kind of disastrous side effects or outcomes that were not expected.

Helen Bronte-Stewart  (24:36): Right, yeah.

Russ Altman (24:36): That's the goal of the trial, I would presume, is to make sure everything is safe.

Helen Bronte-Stewart  (24:40): Exactly. The goal of the trial, the pivotal trial is that it's equivalent to open loop. And actually these people go home for a month or two at a time. And most of our patients who are now in the open loop phase, they're actually on closed loop DBS all the time.

Russ Altman (24:54): If I could ask, you said it that in specifically there was an opportunity to really almost anticipate the freezing and abort the freezing event in ways that you described. Does it also help the baseline performance in walking, or is that a different issue?

Helen Bronte-Stewart  (25:09): No, it helps everything.

Russ Altman (25:11): Okay.

Helen Bronte-Stewart  (25:13): So again, this beta rhythm is not necessarily very specific to one movement or another. It's what we call a state rhythm. So it's related to what we call sensory motor processing in those networks. So that's why I think people who kept looking to see whether it was directly related to the angle of velocity of my hand moving were never going to find a direct relationship. We have just published a paper showing that it is directly related to how much both sides of the brain are synchronized in this abnormal rhythm. And that's really fascinating because we used to think that only one side of the brain controlled limb movement, especially hand movement. Now we're seeing that actually in Parkinson's disease, the both sides of the brain being synchronized in this arrhythmia is actually very, very important. And you can use this closed loop, you can desynchronize one, use just one side of the brain, and you can actually help the other side of the brain as well. So it's really fascinating. By doing this, we're finding out lots of things that we never knew before.

Russ Altman (26:17): So for people who are interested, can you give the likely times? I know that is a trial and you can never predict. The reason we do trials is because we're not sure of anything and we want to make sure. But what is the timing of when the trial will be complete, and then what might happen in terms of the availability of new treatments or new diagnostics based on this trial?

Helen Bronte-Stewart  (26:38): So this trial is complete, and the data, Medtronic are hoping to send the data to the FDA at the end of this year. And then we don't know how long it'll take before it's approved, but it's all complete. All their statisticians are working on the data right now. We're presenting a few methods related publications in meetings, but we can't present the overall results until it's through the FDA. So I wanted to mention that one of the other exciting things is that deep brain stimulation is now being used for other problems such as obsessive compulsive disorder, depression, and we are very interested in actually the cognitive impairment that occurs in Parkinson's disease because there is a motor correlate. So we're primarily a motor lab, but we've now expanded into looking at what we call a cognitive motor syndrome. And what's interesting there is now we're working with one of the other companies, Boston Scientific, to do new forms of deep brain stimulation.

(27:45): Currently, this will be open loop, but they're going to use different patterns of stimulation. So I think we've talked about sensing and using the brain signals to help us provide better treatment. But I think one of the great things to come is understanding signaling so that you don't just use the same signal, the same stimulation parameters for every problem. So this study will actually have the subthalamic nucleus, the stimulators implanted for the motor signs in Parkinson's, and will have a new target also implanted in the brain where we'll use basically an hour of stimulation a day just pulsing it. And I think this is one of the Brain Initiative grants, and it's really exciting working with the FDA, the NIH, an industry partner in academia, because I think this has really moved this field forward faster than we would've done in the past where it would've just been academia.

(28:41): So I'm very excited that we're going to be able to get all these new ideas, stimulation patterns, sensing. There are more rhythms than just the beta rhythm involved in say, cognition and mood. And this is where I see the future going in neuromodulation, is that we'll have a much wider range of diseases we can help people with, and we'll have different targets and different patterns of stimulation.

Russ Altman (29:05): It is incredibly exciting. And so for my last question in the last 30 seconds, a lot of this depends on having an implantable deep brain device. And I'm wondering, first of all, is the bar going to get lowered for who should have these devices? As the power of the devices increases, the risk, benefit trade-off might decrease or change in such a way that we're putting in more deep stimulators because of the great opportunities? So I guess that's the first question is are we going to lower the bar and are we going to see more of these implants? Secondly, is there anything on the horizon for noninvasive use of these ideas?

Helen Bronte-Stewart  (29:41): Right. And the answer to that is yes. So I'm not sure I'd say lower the bar. I'd say that for instance, in epilepsy, we're quite used to putting in multiple depth electrodes to find out where the source of the seizures are coming from. We now can do this also in people, especially in children who may have complicated dystonia. Multiple leads may be in place temporarily, and that then guides where the stimulation leads are being placed. Many of us are using more than two leads now, so I think there will be more leads placed, safely obviously. There will be a better idea of who's a good candidate for this. And there are already noninvasive stimulators such as transcutaneous magnetic stimulation, which is being used for depression and various other disorders.

(30:30): One of the issues is, again, I think issues like depression and cognition, they involve our cortex. It's really important to take the stimulator to where the nodes of the networks are. And so in depression, it's very understandable that you could use a non-invasive device. There may be some non-invasive devices over the cerebellum that we haven't really worked with too much. There may be invasive devices in the cerebellum. So you need to understand where the nodes of these networks are, and that's why we go deep in Parkinson's disease for the best treatment. But yes, there are a bunch of noninvasive ways to stimulate the brain that look very promising.

Russ Altman (31:10): Thanks to Helen Bronte-Stewart, that was the future of movement disorders. If you enjoy the podcast, please consider subscribing or following it on your favorite app. That way you'll never be surprised by the future of anything. Maybe tell your friends about the podcast as well, and definitely rate and review it. It will help us improve and it will help us grow our listenership. We have more than 200 episodes in our archives, so consider checking them out so you can get a full sense of the future of everything. You can connect with me on Twitter, @RBAltman, and you can connect with Stanford Engineering @StanfordEng.