There we go. Sorry. I promised we'd get started on time, so we will get started. Hello and welcome. I'm Lisa Ord and I'm the director of the patient support program here at the John A. Moran Eye Center. A few little things. Handouts. There is a link in the chat if you are online. Otherwise, they're out front. Restrooms out to your right. A few snacks in the back. And please stick around afterwards. We will talk about how we're doing things that have worked for us or things that haven't worked for us. So without further ado. So I am very happy to introduce Dr. Kathleen Degree. Dr. Degree specializes in neuro ophthalmology and headache and practices here at the John A. Moran Eye Center. She evaluates and treats complex visual complaints which can be due to optic nerve or brain disease, such as papillodema, photophobia, vision loss and diplopia. She also treats migraine headaches and other unusual headaches. She is also listed in the best doctors in America. Thanks. Thank you so much. And I'm just pleased to do this. We do this every year. I have an update on idiopathic intracranial hypertension because this is much more common than people realize. And the way I structured this lecture is I want to start with things that are just an understanding of the review of what is IIH or idiopathic intracranial hypertension. And then I'm going to be going into kind of what's new. And those of you online, you can put your questions in the chat, and we will answer all your questions this evening. We don't want anybody having questions at the end, and then stick around because we can have a discussion about what works for people and what doesn't work. And I'm sure there's things that people would like to talk about and maybe meet online other people who have this disorder. So I'm going to review how we call idiopathic intracranial hypertension, talk about the symptoms, the signs that go to make up the diagnosis. And then we're going to talk about why obesity and being overweight is a big part of it and what we can do about that. And then we're going to talk about treatment of the disease to prevent visual loss. And we'll cover medical treatments and also treatments about headache. And I'm just going to start with a case. This is a person we saw many, many years ago, who Sharon, who is 34 years old, and she was sent to our clinic for disc swelling and headaches, and she had recent weight gain, otherwise she's been healthy. Her symptoms were dimouts of vision, a wishing noise in her head, and headaches that were more severe than her normal headaches. She also had migraine. Her visual fields when we did them showed that she had big blind spots and we'll talk about visual fields and why these are important. And when we looked in the back of her eye, she had papillodema. That means swelling of the optic nerve. And I'm going to explain what that is and how you get it. She had imaging done of her brain because everybody with this disorder has to have imaging, usually an MRI scan. And we look for very characteristic findings like flattening of the, of the, the globe in the back of the eye, where all the fluid comes up and pushes on the eyeball. And we look for a big empty cell and other things that we can see. She had a lumbar puncture and had an opening pressure that was 350 where normal is less than 250. And we'll talk about that. And then her fluid was normal. So this, I just want you to see how this is a case, a typical case that comes into our clinic with this disease. Now the first problem is what do you call it because you're going to see idiopathic intracranial hypertension listed in some places and pseudo tumor cerebri listed. Well, this, this condition has been around for a long time. It started out as benign intracranial hypertension, but it's not a benign disease. So why call it benign. So we got rid of that one. Then the idiopathic intracranial hypertension came into vogue. And that just is one part of it because that you can have primary increased intracranial pressure and you can have secondary increased intracranial pressure, and they can look the same. So pseudo tumor cerebri is the name that got put in next and meant a false tumor pseudo means false, a tumor in the brain but you do the imaging and there's no tumor in the brain. The primary form of this disease is what we call idiopathic intracranial hypertension. And that's what I'm going to be talking about. But providers doctors have to take patients history and exam and that's why we do all these tests is to look for the also look for these secondary causes, like thrombosis of the veins and I'll talk about why the veins are so important. And then underlying medical problems like Addison's disease, parathyroid problems, chronic obstructive pulmonary disease or what we call COPD, heart failure, sleep apnea, anemia even can cause a picture that looks identical to the idiopathic form and if you don't look for it, you might miss it and this is really important. Also medications can cause high pressure and if you stop the medicine, usually people get better. And the biggest offender is usually tetracycline minocycline, but things like vitamin a lithium, anabolic steroids, nor plant and Marina have been associated with this condition, and some antibiotics. So that's why the provider has to go through a very detailed history to understand what's going on. Now one of the causes is sleep apnea. And so we always ask our patients about sleep apnea. And this is a little handout that I have for you on on the questions that if you are positive. In this questionnaire, you should talk to your doctor about sleep apnea. It comes from, it's called stop bang. And it's a mnemonic for snoring, tiredness, observed apnea and high blood pressure, that's the stop part. And then the bang part is BMI, and we're going to talk about BMI, age, neck circumference, if you have a big thick neck and gender, males are more at risk for sleep apnea. So I gave you this handout because people who have idiopathic intracranial hypertension are at higher risk of sleep apnea, about 64% of people who have IIH have sleep apnea as well. And a sleep test might be necessary. Now, now we're going to just turn our attention to idiopathic intracranial hypertension. And I want you to understand that while this disease is sort of rare one per 100,000 in people who are overweight or overweight, it's 10 to 20 per 100,000. And that means it's as common as multiple sclerosis. And everybody has heard about multiple sclerosis. But how many people have heard about IIH? Not that many people have heard about this disease. So it's really important that we pay attention to the IIH just as much as we pay attention to things like multiple sclerosis. The age of onset is a little bit between 14 and 60. So it hits women more than men, almost 90% of the people who have this are women. In childhood, it's equal between boys and girls. And we're going to talk about the genetic aspect. There's no gene that's been identified, but there are people who have this disorder that are genetically. Now, the symptoms of increased intracranial pressure are headache is the most common symptom, followed by transient visual obscurations. Those are dimouts of vision. Back pain and neck pain are very, very common, especially pain between the shoulder blades. Dizziness, light sensitivity and almost half people. Pulsatile tinnitus. We'll talk about that. It's a whooshing noise, whoosh, whoosh, noise. Visual loss is in a third. Cognitive slowing or having difficulty with thinking in about 20% double vision also in about 20% of people and ridiculous pain just means pain going down the arms or to the leg, the legs. Headache is the most common symptom. It's also the one that disables the most people. It also is associated with pain with eye movements. And how bad the headaches is does not correlate with how high the pressure is. In other words, you can have a very high pressure and have almost no headache. What's really interesting is 40 to 60% of patients with idiopathic intracranial hypertension have a previous migraine disorder. That means that there's this overlap between migraine and this disease. Normally, in the normal population, 20% of women, 10% of men have IIH, but in this disease, almost half of the people have underlying headache or migraine, and the headache piece correlates with worse visual quality of life. So the other symptom is hearing symptoms. And they're very common. This whooshing noise, sometimes hearing loss, sometimes dizziness. Cognitive impairment also can occur. And there's many studies out there that show that the thinking can be slowed. It's important because when you do a visual field, which is how we follow this disease, sometimes that thinking being slowed can give us erroneous visual fields. And the slowing of the thinking can be related to a number of different things like how high the pressure is, how bad the headache is, whether somebody has sleep apnea, whether their executive functioning is also reduced. Now, so those are the symptoms. Next, I'm going to go to the signs. That is, what do we look for when we see patients? The first thing we do is visual acuity. And that really is important, but it's not enough. It's the last to go. If you've got problems with this disorder, that's why we have to do visual fields. And anybody who's done a visual fields know if you've put your little chin in this Humphrey machine or in this Goldman machine, this can be a tedious task because you have to push the button when you see the light go on. And this is an example of a visual field that we get on people with IIH. And visual fields predict the visual outcome. So that's why we have to follow the visual field because if the visual field is abnormal, then the visual outcome could be poor. And we don't want bad visual outcomes where we don't want anybody to lose vision in this disorder. Next, we look in the back of the eye. The reason we do that is we're looking at the optic nerve. So here's a cartoon of the eyeball, and it's connected to this optic nerve, which is connected to the brain. And the pressure in the brain gets distributed along the optic nerve, and that's what causes the papillodema to occur. So when we look in the back of the eye, we're looking at this optic nerve. Here's a picture of the optic nerve. Now, what does papillodema look like? Well, this is somebody who doesn't have very much papillodema or no papillodema at all. It looks like a normal nerve. That's what it should look like. But here, look at this. This one, you can see that there is that C-shaped swelling along the nerve. There's even some wrinkles in the retina. This person has swelling all the way around the nerve. This one has really severe swelling to the point where there's hemorrhages in the back of the eye. And that's what we're looking for is papillodema, which is disc swelling, which is a sign of increased intracranial pressure. And I already showed you a picture of the imaging that we look at. We look at the optic nerve sheets. You can see how that fluid has come along the optic nerve and is pushing on the back of the globe, giving us that picture of the way that looks. The lumbar puncture is necessary because we need to know what the pressure is. 250 is considered normal. In children, it's a little bit higher. It's up to 275. And the fluid has to be normal. If the fluid isn't normal, then it could be one of those secondary causes that I talked about at the beginning. So we have to know what the fluid is. Now, we are looking for the genetics of this disorder, and that is one of the, it's kind of the holy grail. But I'm going to share with you other hypotheses of what causes this. Because everybody goes, well, why do I have this? What's going on? Genetics is one part. The venous system may be one part. Lymphatic drainage may be one part called the lymphatics. And then obesity, and I'm going to talk a lot about that because about 90% of the people who have this are either overweight or obese. In the genetics, we have many examples in the literature of mothers, sons, daughters, sisters, brothers that have the disorder. I had twins that are symptomatic. I had one case of twins where one came in with symptoms and I looked at the sister sitting in the room and she had it too, which was really interesting that they would genetically have it at the same time. The data is needed. We have studies going on here at Moran Eye Center looking for families. So if you have family members with this disorder, we'd love to hear from you and we'd like to include you in our study. Now, in order to go further, we have to know about how spinal fluid is made, and then how the pressure goes up. This is a cartoon of the brain, and the brain is covered with a dura, and then of course we have our skulls on the outside. But CSF is made in a structure called the choriplexus and it lives in our ventricles, and it secretes spinal fluid. It secretes a lot of spinal fluid. In fact, the spinal fluid is renewed every six to eight hours in our brain. Can you imagine? Every six to eight hours that fluid has to be washed through our brain. And it's absorbed by these arachnoid granulations that live up by the venous sinuses and it goes into the venous sinuses. It's all over our cerebellum.  Okay, it's what protects our brain from injuries. So the veins are all over too. There we've got these big, big veins and many, many, many veins. We have the sagittal sinus, we have straight sinus, we have transverse sinus. But you can see these little arachnoid granulations that stick out into the, to the big veins. And that's where the fluid gets absorbed into our system and also through the lymphatics, which are by the veins. So the venous hypothesis is, as the pressure goes up, the veins collapse, and as the veins collapse, the pressure goes up. So people who, let's say, are bodybuilders, trumpet players who exert a lot of pressure in their abdomens can increase their venous pressure and can, for a while, increase their spinal fluid pressure, but we don't run around, tuning a trumpet or lifting weights all the time. So the venous sinuses can be compressed in this disorder and, and, or they can be absent or a trophic or have little arachnoid granulations in them. So that's why we have to look carefully at those venous sinuses, because they can be affected in this disease. Now lymphatics have been known for years, but these have been just shown to be present in brains where the drainage occurs. And these lymphatics take all the sewage from our brains from the day to get rid of the waste and cleanse our brain and get rid of all this, this way. So they are an important part of our, our brain chemistry, and they may be involved in this disease as well. They could play a role by stopping the spinal fluid exit through those arachnoid granulations, and also they could cause, if they don't drain properly, they could cause more stenosis of the veins, and thereby increase the pressure. So this is a disease that's kind of complex. And, and, you know, the fluid gets made in that chloride plexus, and, and it gets picked up by these arachnoid granulations, and then the venous sinuses can also get compressed, and that leads to the pressure getting higher as well. So it's kind of a sort of a whole system problem. And if there is obesity, and we're going to talk a lot about this because this occurs in this disease alone. This disease is, is not everybody who's obese has this disease, but people who have this disease are overweight, have over be are a little bit overweight and or obese. And that alone may release other factors that play a role in, in this whole disease so you can see that it's a complex disorder of the brain, the spinal fluid, and the egress of the spinal fluid. So now I'm going to talk about obesity, and, and this has been recognized since early on that 80 to 90% of everybody who has this has a little bit of problem with weight. And weight loss does improve this. And weight, the obesity can be associated with lots of different other syndromes like orthostatic edema syndrome. This is a syndrome where people are upright during the day and they collect fluid and then at night, they have to pee all night, because they've, they've got this edema thing going on. People have increased venous pressure, and I already told you that that can really increase the intercranial pressure. They're more at risk for sleep apnea I told you 60% of people with this disease can have sleep apnea. They're more at risk for polycystic ovarian syndrome and we don't know how those hormonal changes play into this. And they're more at risk for metabolic syndrome and metabolic syndrome is associated with diabetes and then having metabolism metabolism go haywire as well. So this graph is just of the United States. This was 10 years ago. And I want you to see that the dark red here is 35% of the people of, let's say Mississippi and West Virginia are obese. And then, as you can see as time goes on, our country is becoming more and more obese this is 2020. And you'll notice now it's 35 to 40% in that dark red. And you're going to notice that the dark red is 40 to 45%. They had to change the color coding in Utah where fortunately we're on the lower end but we're still 30 to 35% of our population is obese. And we're not alone. Look at many, many other states are with us as well. So what is obesity and how do we characterize it we go by what's called the BMI body mass index, and it's your height, and by feeding inches and your weight, and then you compute of this. Overweight is a BMI of 25 to 30, and obesity is a BMI of over 30 and there are calculators on the internet, and also handouts that we've given you so you can check what your BMI is because I'm going to tell you some of the studies that have been done about a certain level of BMI about what, what we should be offering more of.  That's how this graph works.  All right. Now, what is the rationale about relating obesity to increase pressure. Well first, abdominal adiposity or the fat we have in our abdomen can exert pressure on the venous system so that's one piece. I was really curious about the obesity and overweightness of IIH is there are metabolic factors that keep people from losing weight. So, like, insulin resistance so there's problems where insulin is released but it doesn't work the same in people who have IIH compared to women who are of the same BMI and the same age. And it's like it's not fair.  Then there's inflammatory markers that are present in people with IIH that aren't in present present in other people with out IIH. And as the weight goes up in some individuals so does the pressure. But what we do know is if we can lose the weight, five to 10%, we can bring this disease into remission it can go away. So this is just a cartoon about all the things that go wrong and IIH compared to women of the same BMI that don't have the disease. So this insulin resistance, hyperleptinemia, different changes in the fat cells and different changes in the fat and the body as well. So it's a metabolic disorder really that is really present in this IIH. Now the evidence for weight loss has been for a long time. Dr. Newberg did a study where she put people on a rice diet. Can you imagine eating rice all the time? Anyway, these people lost a lot of weight and look at and she published that their papillodema went completely away within about three months of being on that rice diet. Harvey Sugarman did bariatric surgery and normalized the weight in individuals with IIH and their papillodema went away. Mark Coopersmith in New York found that a 10 pound weight loss improves papillodema and Alex and Claire put, and her colleagues put people on a 425 calorie diet for three months and watched their weight go down and also their papillodema went away and their endocrinial pressure reduced. But 425 calories. Can you imagine living on 425 calories? That sounds almost impossible. Now the reason we have to consider this weight also is because in IIH, if you have this disease, you've got to get it under control because there is a higher risk of other cardiovascular disease. Heart failure is almost twice as common in women who have this disease. Stroke is also twice as common. Type II diabetes is more common as is hypertension. So it's important that we get this under control so that our future vascular risk factors are not there either. So what can be done for weight loss? Well, there's lots of weight loss programs. They need to be multidisciplinary. They need to take in consideration diet, exercise, but they also have to consider emotional factors, medication factors, body factors. So you want to work with people who know what they're doing. Weight loss drugs, which I'm going to talk to you about, should be done by specialists, and then weight loss surgery has also been shown to be helpful in people who have BMIs over 35. Now, in the news, I'm sure many of you have heard about these new drugs for weight loss. Oprah Winfrey was on one of these and lost a ton of weight. They're called GLP-1 agonist, glucagon-like peptide-1 agonist. It's in the news. It's a hot topic. It's secreted by the gut neuropeptide. It's secreted in the small intestines after a meal. And this drug has been used to treat diabetes and also for weight loss. What it does is it signals satiety to the brain, so it tells the brain, hey, you're not hungry anymore. It stimulates insulin to secrete more insulin and inhibit glucagon, and that lowers the glucose. There are receptors in the coroid plexus, so that means these drugs can affect the CSF secretion. Remember, I told you that the spinal fluid comes from the coroid plexus. And then they've done studies on rodents that have lowered intracranial pressure by putting them on these drugs and does lower the intracranial pressure. And I'll tell you about studies that have been done on IIH. There are many different types of these drugs. I'm just bringing out the two most common ones. Semaglutide and exenotide. Exenotide also goes by biata, which is an injection for diabetes. Semaglutide with Jovi or with Govi is for weight loss, but the same drug semaglutide is ozympic for diabetes. Don't ask me why they have different names of the same drug, but anyway, it can lower the weight by 15%. So there have been trials in idiopathic intracranial hypertension, and one trial was done in Great Britain by Alex Sinclair and Susan Mullen, their group, where they enrolled women to exenotide or placebo. These women had agreed to have a pressure monitor put into their brain and monitor their pressure for 12 weeks or three months, and they were able to show that in two and a half hours, the pressure was lowered by four millimeters of mercury. And this lasted for 24 hours and also for three months, whereas the placebo group did not have any adjustment in their pressure. What was kind of sad was their headache days per month did decrease, but the severity did not. Then there have been other studies. This group had an open label study where they put 39 patients with IIH on semi-glutide or lyraglutide, and they got 12% weight loss versus 2.8% in placebo. So the people who are on this drug definitely lost weight. They had a reduction of headache days per month of four. They had a lower dose of acetazolamide, and they had very mild side effects. However, I want to caution everybody that these drugs have other side effects and many are just being discovered. For example, there is a nine times risk of pancreatitis, a gastroparesis of three-fold, and bowel obstruction because the stomach doesn't empty as quickly, and so then there can be other side effects. So it's not a drug that you want to just put everybody on because you got to think about what the consequences could be. But if it's done appropriately by providers that know what they're doing and giving this drug, it may be helpful. Next, I want to cover surgical weight loss procedures. Now, I've got cartoons of what happens. This is called a laparoscopic adjustable gastric band, where they put a band around the top part of the stomach, and it just makes it so that there's just this little pouch for food to come in and makes you full, and you can't eat anymore, and it still uses the same stomach all the way down. Then there is a vertical banded gastroplasty, which just bands part of it from the esophagus into the stomach. Then there is a major surgery where you hook up, the intestine gets hooked up to the stomach and it bypasses. That's why it's called a bypass surgery. It's called a ruin my bypass. And I'm going to tell you about the studies that were done on weight loss procedures. It's been used in people who are obese and have diabetes, metabolic syndrome, sleep apnea and hypertension. So these are gaining popularity. The ruin Y gets the most weight loss, but it also has higher complication rate. This study also came out of Birmingham, England, the Susan Mullins and Alex and Claire group, where they studied women over five years, who had BMI over 35. So you have to check your BMI to see if you'd be a candidate. They were all enrolled in a current weight watcher program, but they had a group that went for bariatric surgery. So the control group was just the weight watcher program. So that's the control group and the bariatric surgery is the actual surgery. And they had different types of surgery, although different types I mentioned, but they were able to get a lot of weight loss 21 kilograms, which is 46 pounds of weight. Their quality of life improved by seven points. Their headaches improved in the weight loss program and the weight loss continued for over two years. 24% of the people had had normal pressure with the weight loss, and they had only one bariatric complication. And this graph just shows you how the weight went down with a surgery group. And then they, and this graph shows you this is the intercranial pressure, the intercranial pressure went way down with the surgery group compared to the just the current weight watcher program. Those people lost some weight, but not a lot of weight. So, so that's the story on weight. Now, we don't, when we see people in our clinic, the first thing we want to do is get the pressure off the optic nerves so that the people don't lose vision. So, we give people acetazolamide, and that has been shown in several trials to be very important to preserve vision, reduce papillodema, and it may help a little bit with weight loss as well. And in the most important trial that came out on this, the idiopathic intercranial hypertension treatment trial, and the University of Utah, Moran Ice Center was a part of this study. We found that if you got, if you went on acetazolamide and a diet together, you had a better result in improving your visual field outcome. And you can see that the placebo and diet, they got a little bit better too, but not as well as the people who were doing the acetazolamide and the diet. And you can see here the weight loss was much more with the acetazolamide and diet compared to the people who just were in the weight loss program. What they found was the papillodema grade also reduced. So, these people, their papillodema got better also within six months. It went down to much lower grade of papillodema. The acetazolamide group had fewer failures. So that and all the people that failed were those people that I showed you that had the high grade papillodema and had visual field defects kind of right off the bat. Their quality of life got better with the acetazolamide and diet and all the different measurements that we did for quality of life. The unfortunate thing was that acetazolamide did not treat the headache so the headache didn't get that much better in either group so the headache stayed the same and that's kind of the bugaboo of this disorder. The pressure did get lower so we did in a number of people agreed to get their spinal fluid pressure checked and we found that their pressure definitely reduced by almost 60 millimeters. So if you were at let's say 300, you would go down to 240 within the normal range. Now, acetazolamide can have effects. There weren't that many serious effects. The normal stones occurred in two people but out of, you know, 300 change in liver function and one pancreatitis and one, and then very various other things the most common side effects are pierce these are tingling around your mouth and, and your hands taste changes. So a little pop and any kind of carbonated beverage is going to taste terrible. It can cause fatigue some people have nausea some people have vomiting diarrhea tinnitus, and some people their electrolytes go a little bit off so we recommend people drinking Gatorade light to combat some of these peristhesias and changes in taste. What we found was the acetazolamide plus weight loss diet and weight loss program did work, and, and we recommend the maximally tolerated dosages of acetazolamide it's really important to get up there as much as possible. So there are if you can't tolerate acetazolamide what other choices do you have methozolamide is a cousin to acetazolamide doesn't work quite as well hasn't been studied but does work pretty well. So it's like a rosamide also has been used a milleride also can reduce spinal fluid production, our triatide can also work for some people, and a drug that we use for headache to pyramid also does reduce the entercranial pressure so this is a drug that people can can take, and I will combine to pyramid anacetazolamide together to get the best reduction in the intracranial pressure and the best headache result. So my ending part is to deal with the bugaboo of headaches. It's the most difficult part of treatment. I'm going to talk about visual loss and what we do with that. But the headache piece of this is so hard for people. And part of it is that half the people who have this disorder have constant daily headaches. They're hit six. How bad the headache is is 60. That means it's bad. And over 40% to 50% have pre-morbid migraine, meaning they already had migraine. And then on top of this, they have the pressure headache. And then you can get the papillodema gone. You can lower the pressure. And then the headaches continue in about 43%. And so the best outcome is usually is in people who are younger who've had high pressure and we bring down the pressure and get it under control right away and control the intracranial pressure. That's usually the best outcome. What we learned from that idiopathic intracranial hypertension treatment trial is that most people, the phenotype of the headache that people have with IIH is migraine or probable migraine. And that a third of people have what's called tension type headache. That means that they have no nausea, no light sensitivity, or sound sensitivity. But about half the people in that group had medication overuse, which makes headaches worse. And the worse the headache was, the worse the quality of life was. And here's another thing that just boggled my brain. The headache disability did not correlate with the opening pressure. So you could have a high pressure and have no headache. It didn't correlate with the BMI. So the higher the weight didn't correlate with the headache. How much weight they lost didn't correlate with the headache. How bad the disc swelling was, the papillodema or the visual field didn't correlate with the headache. So this headache is like its own behemoth problem. And there's no difference between the pressure with or without headache. In other words, they looked at the people who didn't get any headache and they looked at the people with headache and the pressures were identical. So how do we treat it? Well, we work on the weight loss because we know the papillodema will go away and remember even 5% to 10% can be helpful. And there are studies that show in chronic migraine if you can lose some weight, the headache can get better. So weight loss can help chronic migraine too. We use medications that lower the pressure like acetazolamide and those other diuretics I mentioned. And the best treatment is the diuretic plus a migraine preventative.   And then you have to watch what medications you're given because some of those medications can cause weight gain. So here's kind of a list of the diuretics, acetazolamide, methozolamide, ferrosamide, chlorothaladone. These are diuretics that can be used to lower the pressure and these are the migraine medications to pyramid remember may lower intercranial pressure all by itself. So this one is one we use a lot plus it does help with weight loss. Tricyclics are great, but they can have weight gain. Velproate definitely causes weight gain. The new kids on the block, CGRP monoclonal antibodies once a month shot for migraine does work and has been reported in IIH and on a botulinum toxin. If the phenotype of the migraine is chronic migraine has been reported to be very successful as well. So these are ones that we go to if the headaches are really severe. So now I'm just gonna mention the surgical treatments for visual loss. If people lose vision with this disorder what's in and they've been on their medical therapy and they're still losing vision, what can we do? Well, we can do lumbar punctures and sometimes in this high risk group of people who've got bad papillodema, bad visual fields and already have visual loss. We will put a lumbar drain in and stabilize the pressure to get the pressure off the optic nerves, but that's not a long-term solution.  Can you imagine getting part of your skull removed? I wouldn't recommend that one at all. So we don't do that anymore. Gastric bypass I mentioned but that's not a treatment for visual loss. It's only a treatment for weight loss. So the three procedures that we can have for this disorder with vision is optic nerve sheath decompression, I'll show you what that looks like. Shunting, lumbar peritoneal versus ventricular peritoneal shunts but ventricular peritoneal shunts are way more popular now and programmable valves are more popular and then what we call venous stenting and I'll show you that. So first ventricular peritoneal shunts. So here's a cartoon, they put this little shunt in the ventricle and then they run the tube all the way down underneath the skin into the abdomen and put the fluid the spinal fluid into the abdomen. Now, these shunts fail, okay? They have to be revised, they get removed, they get replaced and the failure rate is about the same for the lumbar peritoneal versus the ventricular peritoneal and here's the bottom line, if you are using a shunt for headache, 50% will have chronic headaches eventually after the shunt is placed. So the shunt is not a panacea for the headache. It does get the pressure off the brain no question about that. People who have idiopathic endocrineal hypertension without papillodema do worse with these shunts so we do not recommend it. Optic Nershie Fenestration, this is a, if you don't like blood, close your eyes. This is a person's eyeball and this is what we call a lateral approach. We don't do this approach anymore. Now we do a medial approach or a supraproach where we go above the eye crease so you can't even tell it but our goal is to get this fluid off the optic nerve. This is the optic nerve going into the eye. It's usually straightforward done by an oculoplastic surgeon. It protects the optic nerve. There are very few reoperations. It helps the headache a little bit but not as much. There are complications of course and problems. It's not available everywhere. Not everybody has an oculoplastic surgeon. It may not help the headache and you can get some double vision afterwards. Sometimes there's a pupillary change and so on but most of the time it's pretty safe. The other one is venous stenting. I told you that the veins get compressed in this disorder by the pressure and if you do a lumbar puncture frequently the lumbar puncture will allow the vein to open up and then the pressure can drop. But sometimes people have those little arachnoid granulation sitting in the veins and it like here is an arachnoid granulation that's plugging up this vein and then the stent is like a tube that's put in the vein to open it up and it really is good maybe for people who have failed all medical therapy, other surgical therapies. And here's what it looks like. This is a vein and this is a big arachnoid granulation that's plugging up this vein or sometimes there are septi that plug up the vein but here's the caveat is you have to show a gradation over the eight millimeters of mercury or more across this stenosis otherwise there's no point in doing it. And you have to have a pressure in the head of over 300 millimeters and you have to have no contraindication to dual platelet therapy.  And people do it sometimes for disabling headache, focal neurologic deficits, papillodema and visual changes. Now there was a big study that took all the studies in the literature together and said what happened? So they found 49 studies and 250 patients and they found that the pressures got to normal so pre-stent the average pressure was 330 after the stent was normal at 197 the visual obscurations got better in 81% the whooshing noises got better in 85% the headaches got resolved in 36% improved in 70% but were the least likely to resolve in every study. The papillodema resolved in 41% improved in 38% and these are just pie charts showing that most people got better their symptoms got better, their tinnitus got better but headaches didn't get much better but there were serious complications thrombosis where the vein can clot off or you can get a hemorrhage or you can get swelling in the brain or the stent can migrate where it shouldn't go and there's even been a report of death.  And I've just shown you here comparison of the procedures the papillodema and all the procedures gets better the visual fields improve and all of them and the headaches improve as well. So our future here is we need to understand this disease better. We've gotta get the genetics down here I think if we can understand the genetics why would somebody who has the same BMI and then have completely different metabolic features going on? We've gotta understand these arachnoid granulations better the glymphatics better. We definitely have to understand the weight loss here. It's complicated, it's not simple. And we have to have better treatments to improve the quality of life. We've gotta have better treatments for visual loss and we really need to treat these headaches better because it's what disables most people. Now I've got, we're gonna, if you want a copy of these slides Dr. Ord will send these to you and set it up for you to look at the slides but there are resources for you. There's this book, idiopathic and cranial hypertension explained. You can do it on Amazon or order it from the bookstore. I also want you to know that the novel library which was founded with the North America Neuroophthalmology Society, I'm a neuroophthalmologist and the Eccles Health Sciences Library here at the University of Utah set up a whole library and we've got a patient portal and that patient portal has all kinds of resources for all kinds of neuroophthalmic conditions including Pseudotomorcerabri and we have information brochures. You can look at other people who have this disorder. You can connect to other groups and in your handouts, I've given you one of the handouts that they have on idiopathic and cranial hypertension or Pseudotomorcerabri which goes through kind of what we've taught I've gone through in a little greater detail. I also looked up two days ago when I finished this talk and I just want you to know people are studying this disorder. You can see that over the years it's becoming more interesting to researchers and publishing more. There's almost 3,000 articles on IIH in the literature. Medline Plus is also a really good resource for you and then I want to tell you that here at the Moran Eye Center, we have been studying IIH since I came to this place over 35 years ago and we're still studying it and we're not giving up and we've got lots of resources in our Moran Core which is the clinical ophthalmology resources for education and this lecture will be placed on the Moran Core by Dr. Ord and our colleagues here. And with that, I wanted to make sure I left time for questions so that we can answer questions from our Zoom audience as well as our questions from our audience here. So I'm gonna stop sharing right now and please, and you can unmute yourself and ask or you can put questions in the chat. We're happy to answer questions either way. Any questions from our audience here? Did I explain it well enough that you feel like you've got a better handle on what this is about? So how does medication reduce pressure I use to pyramid and what happens if you stop it? That's a really good question. And to answer that question, it's been shown in laboratory animals and in people but there's never been kind of a controlled trial on this but to pyramid has been shown to lower the intercranial pressure in laboratory animals and in people. And so the way it does it is it's the same mechanism as acetazolamide where it has a carbonic and hydrates inhibition so it reduces the amount of spinal fluid being made. So that is how that drug works but it also has a lot of other actions for migraines. So for example, it's been shown in many, many, many studies for episodic migraine and chronic migraine it reduces migraine headache. So that's why we often will use to pyramid if there's a lot of headache going on we'll use it along with acetazolamide we have to be a little bit careful with electrolytes because they both do a little bit of the same thing. Now, if you stop the to pyramid could you have an increase in your pressure? Yes, you could. If you stop the to pyramid, could your weight go up? Yes, it could. If you stop the to pyramid, could your headaches go up? Yes, it could. In to pyramid, the secret to tolerating that drug is to start low and go slow. So I start like with 12.5 milligrams and every week increase it by 12.5 milligrams to 25 and then 25, 37.5 and then 50 and then you can see how I do it very, very slowly. Okay, a question is do I have to have a referral to Miranda Eye Center to discuss or receive drugs like acetazolamide or to pyramid? You have to have those prescribed by a provider. Now, if you have a provider that takes care of you and you could have a discussion with them about acetazolamide and to pyramid and ask them if you could be put on those drugs but we won't give out drugs unless we've seen the patient because we have to follow people and we wanna make sure we're doing the right thing for people and we don't want people to have bad side effects or have complications and all of that. And yeah, IH is a journey. It's a journey for everybody. It's a journey for us. I have to say I am studying this disease as often as I can. Every single thing that comes out new, I'm studying it. I'm talking about it at the American Headache Society meeting later this month because people with chronic headaches have this disease and nobody knows what to do about it. So, okay, do you consider stenting or other surgery in cases without papillodema but where the other symptoms aren't getting treated by medication? When you know the patient still has high pressure via an angiogram or LP. That's another good question. Yes, we consider it but we are very careful because remember I told you that if you don't have papillodema, the people that get shunted don't do very well. They still have chronic headaches. Stenting, same problem. The headache can still be severe. Although, I would definitely talk to your provider about a vinaigram to see if you have a fixed stenotic area that could be taken care of with a stent. But I'm very careful about it because I really, I mean, I told you about the complications, thrombosis, hemorrhage, edema, death.  You have to really think about whether you wanna do this or not. Okay, how long can you take medication? I've been on my tapirumate for five to six years. Well, I've got people who've been on acetazolamide for about 15 years, 15, 20 years. Now, I try to reduce it whenever I can but then if the papillodema comes back or if there's weight gain and the papillodema comes back, they're back on the acetazolamide. So that unfortunately is something that you know, is a problem. Yeah, people can be on these medicines for a long time. We, you know, I work in the headache clinic too. So I have lots of people who've been on tapirumate for many, many years and it's controlled their migraine and if they go off, the migraines come back, they go back on, the migraines get better. So they wanna stay on it. I don't have any data about long-term complications of tapirumate or acetazolamide. Another question is, I've noticed cognitive impairment since my diagnosis, what tools can you suggest to help combat this symptom? Good question again, very good question. So cognitive impairment I think comes from multiple angles. One is the pressure itself. So getting the pressure down can help with that. The second thing is the headache, getting the headache control because if you've got a chronic migraine headache going on all the time, I can tell you, your brain does not work very well at all. You've got cognitive impairment right there. So the key is to get those symptoms down. And then the third thing, I just wanna mention depression and anxiety. Depression does run with this disorder. A lot of people have depression and if you're depressed, your cognition is not good either. So it's another one of those things that takes your brain out of gear. So it's like, you gotta control the pressure, you gotta control the migraine or the headache part, you gotta control the depression, anxiety. And I mean, it's like a whole package of unfortunate things that you have to be on top of and it's like not fair. Pyramid is topomax. Yes, topyramid is the generic name, topomax is the trade name as well. Topyramid is not usually used in mood disorders. In fact, topyramid occasionally can cause depression when you first start it. So you have to be careful if depression increases when you get topyramid, if it doesn't go away, you should immediately talk to your provider about it because we don't want people having depression on top of everything else they've got going on. That's right. Pain can really wear you down. It's, that's exactly, that's exactly right. Anybody have any more questions? And I'm gonna get Dr. Ord up here. Oh, here. I think my family member could have the disease as well but they do not have insurance. They have similar symptoms as me and have a partially empty cella. Is there a good recommendation for screening?  If there's papillodema, they can get referred up here and we take care of people. Okay, what's the long-term prognosis if you're diagnosed as a teenager? Okay, good question. Well, I can tell you this. That study was done by one of my mentor, James Corbett where he brought in people 25 years after the diagnosis did spinal taps on several of these and many of them had continued to increase intercranial pressure. So it is a chronic disease. It is not like a one and done. And if the weight comes back, that is the number one trigger for the condition to come back. So that's why it's so important to get the weight down the pressure down, the headaches under control trying to get everything under control so that you don't have the long-term consequences of this disease. Is it safe to get pregnant with IIH? Another really, really good question. So yeah, it is. Now, acetylzolamide, we tend to try to stop it in the first trimester, but the studies have been done on taking acetylzolamide throughout pregnancy. There've been no major birth defects and no major complications and you can have a pregnancy. We recommend not getting excessive weight gain and then work with your provider to make sure your optic nerve and your visual fields are followed. Oh, here's another question. In terms of birth control, I've been advised standard birth control should be avoided previous marina patient. Are there recommendation discoveries in this area? Are hysterectomies feasible possibility? Well, we don't recommend hysterectomies unless there is a gynecologic reason to get a hysterectomy. Tubal ligations work great for birth control and the other problem for oral contraceptives, well, marina IUDs have been associated with this disorder, although the data are not completely clear. Oral contraceptives that have a lot of estrogen are not good for people with migraine because of increased risk of stroke and heart disease and blah, blah, blah. So it's like rock in a hard place here. There are some progestin only birth control options that could be tried and IUDs are great. The non-alluding IUDs, ones that don't have the hormone in it are great for birth control as well. I just got a Kylina and unfortunately, I don't know what a Kylina is. So, okay, it's an IUD, all right. And does it allude a hormone, do you know? Because I don't know that one. Oh, progestin, okay. Yeah, well, that's marina is a progestin alluding IUD. So I would just keep an eye on it. Keep an eye on the pressure of the papillodema, the visual field, headache, et cetera, and make sure that there's nothing that's getting worse. Any other questions?


The University of Pittsburgh and the University of California, Irvine worked collaboratively on the Association of Research Libraries, Research Library Issues Framework Initiative, exploring the question, how do the library's special collections specifically support and promote teaching, learning, and research? I am Jean-Anne Haas, and I am going to focus on Pitt's initiative. Our objective was to create a rubric and assessment tools that align with the ACRL-RBMS SAA guidelines for primary source literacy. We experimented with the rubric and assessment tools in a variety of student learning engagement opportunities. Our goal was to create a robust toolkit that was adaptable across different disciplines and institutional settings. We applied the rubric with the Archival Scholar Research Awards, ASRA, through two successive cohorts. Later, we received a SUB award and adapted the rubric for classroom learning. This semester-long ASRA program matches each student in a cohort of 10 to 12 with a librarian or archivist and a Pitt faculty mentor to engage in an in-depth research project drawn upon primary sources found in the University of Pittsburgh Libraries. Studying the Archival Scholar Research Awards, we assessed the initial and intermediate learning outcomes of primary source literacy and used entrance and exit surveys and research outputs as assessment tools. We created a rubric based on the ACRL-RBMS SAA guidelines and applied it to the outputs produced by the ASRA 2020 cohort and found that it did not always align and therefore was often inconclusive to determine if students gained any primary source literacy skills. The ASRA 2020 cohort was interrupted by COVID-19 and the remainder of the program was transitioned to an online environment. We noted that the assignment prompts for ASRA 2020 did not map specifically to the guidelines. The outputs were more reflective of the student research experience and did not necessarily provide insight into the skills that they may or may not have attained through this experience. We extended our research project to include the ASRA 2021 cohort and revised the entrance and exit surveys to transition from a confidence-based to a knowledge-based assessment. The team reworked instructions and assignment prompts that mapped specifically to the guidelines. The instructions for the Tumblr blog and OMECA exhibits focused on the primary source such as creator, materiality, historical context. The end-of-term presentations focused on motivation for research, how primary sources contributed, supported, or disputed research questions, and whether the research question changed, pivoted, or was amplified because of what a student discovered in the primary sources. The analysis of the outputs revealed that students demonstrated an initial or intermediate attainment of primary source literacy skills in the blog posts and OMECA exhibits. They positioned their primary sources in context of place and time, discussed the creator, audiences, and materiality, and physical features. The presentations revealed that the questions about their research approach were too involved for students to have ample time to discuss in three minutes and revealed little about skills attainment. The ASRA students were adept with research and topics and were confident in answering questions about the research process. The team acknowledged that for future cohorts prompts should focus on a select one or two aspects because of the time limitations. The responses to the entrance and exit surveys revealed that the program had a proven effect on student learning. A few areas of weaknesses were identified, using databases and questions related to compliance with copyright and privacy laws. The program's strengths included utilizing finding aids and primary sources in various capacities. I'm Cathy Haines and I'm going to discuss our sub award for instructors in classroom learning. We applied for and were granted a sub award in July of 2021. We developed a lesson plan that incorporated the rubric and captured instructor goals. We asked instructors to collaborate on in-class exercises and or activities that match course objectives, share anonymized student outputs with the research team, and participate in a follow-up discussion to provide feedback on the value of the rubric in designing and assessing classroom engagements. We worked with five instructors from consultation through curation and design of student engagements, including in-class exercises such as guiding questions, close reading, group work and discussions. After the class visit, the team used this toolkit to measure student acquisition of primary source literacy skills and thereby assess the degree of success of the librarian archivist in meeting instructor goals. For example, this slide shows one instructor's goal for students to view multiple versions of a specific text and learn about its materiality that allows inferences about historical audiences and how books might frame readers' expectations. The instructor's goals map to the guidelines for iterations, physicality, creator and context. During the visit, students examined curated text and completed independent work with guiding questions co-created by the librarian and instructor. Students were then asked to share a highlighted aspect that they found interesting. Librarians observed that students were able to comment on iterations, physicality, creator and context. Had the discussion not shown compelling evidence of skill acquisition, then we would infer that the guiding questions needed to be strengthened. After coding and analysis, we met with each instructor individually, shared the primary source guidelines, presented the rubric and lesson plan, and reviewed whether students were able to demonstrate skill acquisition. We asked for feedback about the use of the rubric for assessment and whether it was an appropriate tool for understanding student acquisition of primary source literacy skills. We also discussed the value of incorporating the rubric more overtly into the consultation process. After the conclusion of the individual instructor meetings, we reviewed, coded and analyzed the meeting transcripts and summarized our findings. We held three focus groups with a total of 12 instructors participating. All instructors had previously brought classes to archives and special collections. We showed the instructors how we used the rubric and analyzed classroom activities and asked for their thoughts on the value of using the rubric for future consultations. The conversations revealed unsurprisingly a split of opinions about rubrics in general. Some did not advocate their use and others welcomed them. The former, though, had great interest in the content of our rubric and deemed it a valuable tool to think through their goals for the class visit. After the conclusion of the focus groups, we reviewed, coded and analyzed the meeting transcripts and summarized our findings. Our big takeaways were the following. Instructors valued the identification of goals for the class visit and sharing an abbreviated arrangement of primary source guidelines. The majority of instructors' main starting point for class visits was having students encounter materials and experience awe and delight. Instructors value engagements such as prompt, guiding questions and are interested in seeing examples we created for other classes. And finally, archivists and librarians are valued for their expertise and their support of primary source learning and are increasingly accepted as collaborators with assignments that are not limited to a single class visit. Thank you to our team, Jean-Anne, Claire, Diana, Veronica and myself for all of our work on this project, especially through some less than optimal times with COVID and to University of California, Irvine, Derek, Crystal and Jimmy for their help in the planning phase of this project. Finally a big thank you to Gordon Danes, Sue Bauman and ARL for their support and guidance throughout the whole process.


I'll go back to another one. If you are new to the channel, I'm Gold Pony, Andy, new car track, SCV reviews on YouTube and today we are in the brand new 2023 Mazda CX50 courtesy of Jack Tumbaldo Mazda in York PA for more information on their inventory. Please feel free to check out the link in the description box below. And so we are in this one today because this is an all new model from Mazda for 2023, not only that every single trim level gets all-wheel drive as well. There is no front-wheel drive configuration that you typically find on the competition, so I do like that. And if you were curious, the CX50 is slightly larger than the CX5 with a more rugged or more aggressive styling. So ultimately in this video we will be testing out and going over everything about this one from acceleration to braking, steering feel, ride quality, sound system, exhaust clip, all that fun stuff. So having said all of that, what do you guys say? Let's just go ahead and jump right into it. And as always, let's start with pricing. And so as you can imagine, there are several different trim levels for the 2023 CX50. There are way too many to name quite honestly, so I am simply just going to list them on the screen right now. So essentially it starts at $28,825, top trim level then starts at $43,575. But so you can imagine with all of those trim levels there are a couple different engine configurations for the 2023 CX50. First one is going to belong to all the trim levels that don't say turbo in it. That power plan is a 2.5 liter naturally aspirated inline four cylinder, 187 horsepower at 6,000 rpm, 186 pound feet of torque coming in at 4,000 rpm, power sent to all four wheels. There were six speed automatic. Red line comes in at 6,500 rpm with MPG numbers coming in at 24 in the city, 30 on the highway, taking regular unleaded fuel. But then there is that other engine configuration belonging to all the trim levels with the turbo in the name. That one is the one we have today and that one is powered by 2.5 liter turbocharged four cylinder, 256 horsepower at 5,000 rpm, 320 pound feet of torque coming in at 2,500 rpm, again sent to all four wheels through a six speed automatic. Red line coming in at 6,300 rpm, 0 to 60 times 6.6 seconds with MPG numbers coming in at 23 in the city, 29 on the highway, taking either regular or premium unleaded fuel. So there's numbers that I just gave you the horsepower and torque numbers. That was for the premium fuel configuration. However, you can put regular unleaded fuel in this particular engine setup, but it will give you a pretty substantial loss of power, approximately 25 horsepower. So just wanted to mention that. So before we do any kind of fun acceleration or paddle shifter test here in the CS50, I wanted to mention to you guys the drive modes. There's a little drive mode toggle switch located just to the left of the shifter. These drive modes will include sport, off-road, and normal, essentially adjusting things like the throttle response, the shift points, and actually there's an off-road mode that essentially helps prevent drive mode spinning in off-road driving situations. So I did want to mention that as well. So now having got all of that out of the way, I'm going to go ahead and change it to sport driving mode, which actually changed the center speedometer to a red hue, which is pretty cool as well. And let's go ahead to find a straightaway. Let's put the paddle shifters and acceleration here to test at the same time. Let's see how quickly the paddle shifters are going to react, and let's see how quickly we can get our turbocharged CX50 here up to speed. All right, and so before we do this acceleration test, I did want to mention to you guys there is a full manual shift mode. To put it in full manual shift mode, just slide the shifter all the way to the left, and it's actually going to tell you what gear you're in up on the digital portion of the gauges. But here we go. Three, two, one, go. Quick paddle shifters. All right. Yeah, that's definitely going to get the job done. I actually really like the paddle shifters. Typically, with six-speed automatics and CVTs and things like that, you're not going to get that quick pack. You're not going to get that quick of reacting paddle shifters. But in the CX50, you actually do, which really surprised me. So I am a big fan of the paddle shifters. Acceleration was plenty fine, as I expected. This is a turbocharged engine, of course. So yeah, you're not going to have any issues emerging onto the highway either, obviously. But anyways, to go along with that acceleration as always, braking is equally important. So up front, you will find 12.8-inch ventilated front discs. In the back, 12.8-inch solid rear discs. 60-0 stopping distance goes. That is going to come in at 118 feet, which is absolutely amazing. Braking feel is 100% on the firmer side of things as well, which I personally prefer. And that is kind of what you're looking for in the CX50 anyways, because this is kind of like a more of a driver's SUV. And I can tell you that right off the bat, because that's what Mazda is known for. And the steering feel is brilliant. We'll get to that in a second. But anyways, braking feel is on the firmer side of things. Instantly brings you to a stop. There's new softer dead spots in the braking. So that's typically what you get in SUVs actually. But you don't get it here in the CX50. So I'm a big fan of that. The touching on suspension and handling up front, you're going to get a McPherson strut front suspension. In the back, torsion beam, rear suspension, front and rear stabilizer bars. As far as ride quality goes, it's fine. It's been perfectly fine. It's pretty much as you would expect the CX50 to ride like. It's definitely absorbing Pennsylvania's road imperfections quite nicely. So I haven't had any issues there. As far as steering feel goes, like I said, that is the first thing I noticed when I got in the CX50. It's 100% on the heavier side of things. So that is wonderful, because it simply points you in the direction that you want to go. Better driver feedback. And really that is what Mazda is known for. And I absolutely love it. Because like I said, it's more driver emotion. Typically with SUVs, you're going to find loosey-goosey steering feels. But that is not the case here in the CX50. And that's why people buy Mazda. Because the driver dynamics are just 100% on point. You got the turbo-charge engine. You got the incredible braking, 60-0 and 118 feet. And the incredible steering feel as well. This is a driver's SUV. I can tell you guys that without a doubt. So I am loving it. As far as cabin noise goes, we got this roof rack up here. So there's a little bit of wind noise because of that. But if you didn't have this roof rack, that is 100% going to be completely eliminated. And it should be a perfectly fine serene cabin. So didn't want to mention that. Touching on visibility. It's not going to be as good as the CX5 because of its shape. But having said that, it's still worth it. The looks on this thing are a lot better than the CX5 in my opinion. And honestly, I can see perfectly fine out the back. Second row headrests aren't that big either. So that's not going to impede your visibility either. Another thing though, rain-sensing windshield wipers touching on four visibility actually come standard across the board. So essentially what that is, is whenever this thing detects any kind of mist or rainfall, it's going to automatically turn on those windshield wipers for you. So it's just one less thing you got to worry about. So you better help keep your eyes on the road. Not only that, I am looking at a head-up display right now, giving me my speed, speed limit and safety features up on my windshield. So again, assisting with four visibility yet again. But that pretty much rounds out the performance segment of this review guys. Let's now go ahead and take a look at the exterior of our brand new 2023 Mazda CX50. Alright, so here she is you guys, the new 2023 Mazda CX50. Let me first start with one of the things that you probably never guess about the CX50, which is where it is made. So when you look at the VIN, the first character of that VIN is going to be a 7, which I personally never seen before on any recent new vehicles. So what that 7 indicates essentially is that the new Mazda CX50 is built in New Zealand, as opposed to Japan, which is where you would think, or at least the USA, because I'm in the USA so you would think that as well. But never would I have thought that the CX50 would be built in New Zealand. So a little fun fact for you there, that's kind of cool. But anyways, more rugged design again than the CX5, but it's just slightly larger as well. Let's go ahead and start up front on the CX50 here. LED headlights with auto-leveling coming standard for every single trim level across the board. That auto-leveling feature typically will not come standard on just about every other manufacturer out there. So that is pretty cool. Automatic headlights, of course, coming standard. Automatic high beams as well, meaning when you have your high beams on at night and it senses a vehicle coming in the opposite direction, it's going to automatically turn them back to low beams. Then when the vehicle is gone, it's going to automatically bounce it back up to high beams. So that is a convenient feature there. LED daytime running lights, of course, coming standard. But here's another big one. Adaptive front lighting system coming standard on every single trim level across the board. Again, another feature that you will not find coming standard on most other manufacturers out there, even luxury manufacturers. Essentially what that is is when you're going around a bend at night, those headlights are going to swivel based on the direction of your steering angle, better help illuminating what is around that bend. So you're less likely to hit a deer or a possum or really anything. So that is a pretty cool safety feature and a pretty cool illumination feature at night. So I'm a huge fan of that as well. You do have front air curtains to the bottom corners there, helping direct air around the wheel and tire combination. So overall, a very more aggressive look to the front end, including those more angular headlights. And another kind of interesting feature when I got up close here, the bottom portion kind of surrounding this front grille, these are kind of like rugged kind of grooves in the upper portion of it. So I don't know. I thought that's an interesting design element. I just wanted to point that out. I'm not for against it, but overall the front end definitely looks good in my opinion. I guess is what I'm getting at. So pretty much rounds out the front. Listen, I'll go ahead and make our way to the side. All right, so we're now making our way to the side of this one. You guys can see those silver roof rails coming standard on the top there. But again, the roof rack is optional. So again, I wanted to mention that you're going to get a little bit of wind noise, but it is there and it is available. So let's just say that blue privacy glass is going to come on the select trim level and up gloss black power adjustable side mirrors will come standard with LED integrated TIRS signals also coming standard. That's another thing you typically won't find standard on all trim levels of the competition. Heated side mirrors for the preferred trim level end up. And if you were to go with the premium or premium plus trims, you will get power folding side mirrors then as well. And I like the aluminum trim accents found on the side skirts. All the side skirts and the fender surrounds are in matte black. It kind of works for the CX50 because it is a more rugged look overall. So then touching on the wheel configurations, they will differ pretty substantially amongst the trim levels. So 17 by seven inch aluminum alloys coming with the base select preferred preferred plus and premium trims 20 by eight inch aluminum alloys for the premium plus and the turbo trim levels. Then for the turbo meridian, you're going to get 18 by eight inch alloys. So again, they are going to be a wider wheel setup if you go with the premium plus or the turbo trim level. So do want to emphasize that. Let's not go ahead and make our way to the back. All right, so now since we are around to the back of the CX50, there is a very small little shark fin antenna all the way to the top. Just underneath of that rear spoiler with an integrated brake light just below that rear window wiper LED taillights coming stated across the board in that cool CX50 design. So big fan of that. You got some silver trim accenting found on the very bottom portion of that rear bumper as well. But my very favorite Mazda does exhaust outlets very well. Dual exhaust outlets with chrome tips for every single trim level across the board. That is pretty cool. You're actually going to get larger outlets than for the turbo trim levels as well, which of course is what you guys are looking at right now, but very well done. A lot of SUVs are kind of tucking them away and making them hit it, which isn't as cool of a look in my personal opinion. But nonetheless, I do believe you guys know what we have to do next. It's always here is that exhaust clip. All right, so now since we are around to the back of the CX50, when it comes to opening that rear tailgate, it is going to be a power tailgate for the preferred trim level and up manual tailgate though for the base and the select trim levels. There should say the S not the base, but you get what I'm saying. So manual tailgate for those two, but there's a button on the key fob itself on the side of the key. There's a button by the driver's side left knee and the button on the tailgate itself of course, as well. But once opened up, cargo capacity comes in at 31.4 cubic feet. If that was not enough space, there is a 6040 split meaning the rear seats do fall down, bumping that up to 56.3 cubic feet then. There is some cargo lighting back there, but it's not just halogen ball that is an LED cargo light. So big fan of that. There are four grocery bag hooks that's typically more that you see and even SUV. So I was a fan of that. Of course, there's tie down acres back there. There is a 12 volt power outlet back there. There's a little bit of storage on the right side in the back as well. Then if you were to lift up underneath of that cargo floor, you're actually going to find a spare tire in case you were curious. But that make your way up to the rear legroom that I just going to come in at 39.8 inches for reference. I mean even six feet tall. This is how much space I had sitting back there. Dual rear USB charging ports though coming for the select trim level end up. I love that rear ventilation coming standard as well. And there is a rear center armrest with cup holders also coming standard for every single trim level across the board. So well, the Mazda, you don't always get that for all trim. So then make your way up to the front seats. Cloth seating is going to come with the S half leatherette trim seats coming with the select preferred and preferred plus trims. Leather seating for the premium trim level and up heated, heated front seats for the preferred trim level and up and then ventilated front seats for the turbo premium and turbo premium plus trim levels. You're going to get an eight way power driver seat with power lumbar for the preferred trim level and up and then memory settings for the premium trim level and up. So like I said, so many different trim levels. So there are a lot of options that can be had. Having said that, I love everything about the seats, especially the power lumbar with the exception of one thing and there is a giant horizontal seam kind of going through the upper portion of my back that makes it not as comfortable for that one particular reason, which is why I typically like to emphasize to manufacturers that watch my videos at least, vertical seams are always best. If you could pull it off like Lexus does, like so many manufacturers do because then you don't get those awkward pressure points that we have here unfortunately in the CX 50. But like I said, other than that, the power lumbar was absolutely amazing. Shouldn't have any issues, but I'm just saying this for the passionate pursuit of perfection as Lexus puts it. Anyways, then take a look at the steering wheel. It is telescoping and is going to be leather wrapped for the select trim level and up and then heated for the turbo premium and turbo premium plus. So was a big fan of the steering wheel wouldn't have minded if the 10 to two grips are a little bit thicker though, but still pretty fine. Then make your way to the startup. Let me start by showing you guys the key here. You got your Mazda logo on the one side, absolutely nothing on the other side because all of your buttons are located on this side of the key, which is pretty cool lock on lock. And of course, that button to pop the power tailgate within our particular case as well. But it is all keyless entry with the push button start. So all I'm going to do here simply put my fun of the break and press that black engine start button located just by the driver's right knee there. And so once started up, when it comes to the gauges, there is a seven inch digital gauge cluster kind of coming standard here. Because like I said, it has to be digital because when I changed the drive modes, it did adjust the colors a little bit. So that's pretty cool. Like I said, when you put it in sport driving mode, it's going to kind of show up in some red hues.  So that's pretty cool too. I like the Mazda did that. Good job Mazda. But anyways, got your tachometer all the way to your left engine temp and fuel information all the way to your right against speedometer and front and center. And again, there are buttons on the left side of the steering wheel to control what kind of gauge readout you wanted to put up there. So there's your traditional speedometer, but there is also a digital speedometer you could choose to select up there along with safety features. So a couple different loadouts you could put on the center portion of the gauges, which I think is pretty cool. But then make your way to overall interior quality of panoramic moonroof coming with the preferred plus trim level and up dual zone climate control for the select trim level and up LED interior landing for the turbo premium and turbo premium plus auto demigrafing mirror with whom light controls throughout the three different garage doors I'm seeing here on the premium trim level end up wireless phone chargers going to come on the turbo premium plus trim level. So overall when it comes to interior quality, honestly, Mazda crushed it. Absolutely amazing. I like the brown contrast stitching found on the doors as well as just about the passenger side glove box and all that. That looks absolutely amazing. Even the accents on the door grips, how they're kind of texturized rather than just leaving a boring matte black. So that is good as well. I like all the gloss black accents surrounding the shifter. Do you have a little bit of rubberized storage in front of the cup holders? Of course, cup holders as well. Then within the center armrest, let's see how much storage we got decent amount. Actually, there's a couple USB charging ports actually in there as well. And the bottom portion super soft. Yeah, I like that. Now let's go ahead and make our way to the infotainment screen here. And so for the standard S trim level, you're going to get an 8.8 inch infotainment screen. But for all other trims, meaning the select trim level and up, you're going to get a 10 and a quarter inch infotainment screen. Now, one thing I have to say with Mazda is they typically won't do a touchscreen and that is the case as well with this particular setup. So the way you control that infotainment screen is through the circular dial and buttons located directly behind the shifter. And so when you press that, it actually is pretty easy to kind of scroll through here. And I would imagine it would be something that you would get used to pretty easily. And quite honestly, it's a heck of a reach anyway. So I wouldn't want it to be touchscreen. So I don't mind the circular dial and buttons actually. So Bluetooth and audio streaming does come standard Android Auto as well. Wireless Apple CarPlay for all trim levels across the board, not the wireless Android Auto, just the wireless Apple CarPlay. But you can still, of course, have Android Auto. You just got to hook it up via USB cable. But factory navigation system coming with the Turbo Premium Plus trim level, of course, you can check out your radio information up there. And so when it comes to the sound systems, you're going to get eight speakers for all trim levels, but the Turbo Premium trim levels because those trims are going to give you a 12 speaker Bose sound system, which actually is the sound system that we have with us here today. So hallelujah. Let's go ahead and turn on the radio, see what we got playing today, and let's test out the clarity of our Bose sound system that we have with us here today. This is insane, man. Like the bass is 100% on point. That was ridiculous. Clarity is perfectly fine. I've had Bose sound systems in my cars before that never failed me, never broken on me. But the bass was insane. Really, that sound system is incredible. The Bose sound system is incredible for the CX-50 without a doubt. But anyways, let's think I wanted to mention to you guys on the infotainment screen is when you do put the CX-50 in reverse, you will find a rear view camera coming standard across the board. But the Turbo Premium Plus is actually going to give you a 360 degree monitor, which is going to give you that bird's eye view, which is always going to lead us into safety. And so to start, the very most important part, IIHS Top Safety Pick Plus, which is the very highest designation given by IIHS that pretty much does it all right there. Front side side current airbags do come standard driver and passenger knee airbags as well. In the back, you're going to have latch, aka lower anchors to tether your children for the rear car seats, rear child door locks, tire pressure monitoring system, but also coming standard for all trim levels, blind spot monitoring system with rear cross traffic alert, adaptive cruise control with stop and go, smart brake support, lane departure warning, lane keep assist, and driver attention monitoring system as well. So overall, when it comes to my final thoughts here of the CX-50, the steering feel is 100% incredible, best in class without a doubt. Nothing comes close. Great braking as well. The 60-zero stopping distance is 100% on point. I absolutely love that. But the steering feel is the main star of the show. Great interior quality as well. The contrast stitching is wonderful. The leather wrapped steering feel also 100%. As far as room for improvement goes, I'm just going to be nitpicky, honestly, quite honestly, I'm a big fan of this thing. So wireless phone charger being only on the very top trim level, that's kind of weird. Most other manufacturers won't do it that way. They'll at least give it on the middle trim levels at minimum. But anyways, also just because this is a driver's car, typically with driver's cars, you find the 10 and 2 grips on the steering wheel bolstered a little bit thicker. I'll just put it that way. So Mazda, if you're watching this, take a look at BMW's grips and their M Sport vehicles or the M vehicles. I'm not sure how much it would cost to add some thicker bolsters in this thing. But because this is a driver's SUV and the very best driver's SUV in its class, in my personal opinion, I think that would make it even better. The thicker grips just give the driver a better feeling of being in control of my personal opinion. But anyways, let me know what you guys think of the CX-50 in the comment section below. That is about it for this one. You guys, thank you so much for watching. Feel free to follow me on social media, bottom of the screen if you want to see what's coming next on the channel before it gets to YouTube. Be sure to hit the subscribe bell notification button. If you're into new car reviews, that is what we do here on this channel after all. Do appreciate you guys watching more than you know, and I will see you guys all in the next video. Stay Gold!


So far, we've been assuming that the number of outputs is the same as the number of inputs. So that means that we take our kernel, we flip it, it's odd numbered, and we put that central value of the kernel, line it up with the first value of our inputs, and then do our sliding dot product across and stop do our last evaluation when the center value of the kernel lines up with the last element in our signal. What that does then is it gives us an output result that's exactly the same length as the input. There's actually no reason why this has to be the case. So we can do something called padding, which is adding reasonable values to the end of our signal so that we can convolve that kernel across the whole length so that even when the far right tail of that kernel first touches the first non-zero value of the signal, it can still give us an output result. When we pad with zeros, we can get a reasonable set of outputs to go along with that. When we, the process that we were talking about before is essentially padding with zeros, assuming that everything that is outside of that is zero and treating it as such. But there are other things that we can do. There are lots of ways to pad. We could actually pad with a constant value. This then might be more representative of the data that we're using. The goal of padding is to extend the data set in a neutral way so it doesn't introduce new information or new artifacts any more than necessary. So it could be that for your particular data set, let's say you're estimating temperatures, and you'd like to pad that out a little bit, an average temperature wouldn't be zero. An average temperature on neutral temperature might be 50 degrees Fahrenheit, 20 degrees Celsius. And you can use that as a fairly neutral way to extend your data set. Notice, though, that it does give you a different result. Those padded values matter. They get folded into the convolution result. So you want to think about what you use there. Another thing you can do that might be more representative of your data is to do a mirror padding. So if you want to pad with, say, five values, you actually go and take the last five values of your data set, flip them around, and tack them on to the end. Similarly, you can take the first five, flip them around, and tack them on to the beginning. This mirror padding gets you a nice neutral extension of your data set for the most part. But you have to be careful of weird cases. For instance, if you're tracking weekly phenomena and, say, your weekends are very different from your weekdays, if you do this, you might end up with 10 weekdays in a row or four weekend days in a row. So it's not entirely neutral all the time. You have to be aware of what your data means. Notice, again, when you look at the results, the results are different depending on how you pad it. Another thing that you can do that occasionally makes sense is to do circular padding. So now, instead of taking the elements off the end and flipping it and tacking it on the end, as we do in mirror padding, we take our five elements off the end, reach back around, and tack them on to the beginning of the data set. Similarly, we take our five elements, or in this case, our four elements, off the beginning and reach around and tack them on to the end of the data set. This can be particularly useful if you're working with data that you know to be cyclical, you know to change on a regular basis, and if you sampled it over a round number of those cycles, it can be a nice neutral way to extend the data set. Again, though, notice that it gives you a very different answer depending on how you pad. So the takeaway here is to pad mindfully because when you're padding, you're actually adding data to your signal. If you don't do it well, you can end up corrupting your signal.


The M.T. Albert model is a novel approach to address the challenges associated with predicting pharmacological properties of small molecules. It uses a large-scale pre-training process to extract contextual information from smile strings, leverages multitask learning to share information across multiple downstream tasks, and utilizes smiles enumeration to increase data diversity. This enables the model to achieve superior performance compared to other state of the art methods on most of the 60 data sets. Furthermore, the model employs attention mechanisms to focus on smiles character features essential to target properties, providing valuable insights into the model's decision-making process. This article was authored by Xiaochan Zhang, Chengkuan Wu, Jiaqai Yi, and others.


Hello, I'm Chanatastic and today is day number 25 of React Holiday, our 25 day crash course through React. Now, right now we have a little bit of a problem. And as soon as I hit the last Pokemon on this collection, if I hit next again, everything breaks. And it didn't just not show a Pokemon, it actually broke. So the button disappeared and everything. It'd be nice if we could conditionally render certain components based on whether or not we have data to actually show. So here's our Pokemon component. And I'd like to wrap that inside of a condition. Now, inside of JSX, we cannot use if else statements. Fortunately, JavaScript gives us another syntax like a one liner syntax for for conditionals. And it's called a ternary operator. Now anytime we want to use an expression inside of JSX, we need to use curly braces to interpolate it. Now a ternary operator looks like this condition, question mark, what happens if it's truthy, and colon and what happens if it's falsely. So our condition is just going to be Pokemon. If we have a Pokemon, we want to render a Pokemon. So the truthy case is going to be this Pokemon, we can paste JSX right in here, delete that. And the falsely case can also be JSX. So we'll use a div that says no Pokemon for index. Okay, format and save. Now, as we hit the end, we see this message no Pokemon for index, cool thing, we can actually do more interpolation. So even though we're interpolating this whole expression, we can also interpolate a value here. So index, index, and we'll use the index value that we're getting from state. So next, next, next, no Pokemon for index three, boom, four, five, six. Now you know how to conditionally render something inside of JSX.


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Alright, I'm going to explain this in multiple passes. The first pass will be a high-level overview of the what's, where's, and how's of activation functions. And the second pass I'll fill in the gaps with more details, and we'll walk through a few examples. Exciting stuff coming up. So let's jump into it. Case 1. We have this neural network here with a single hidden layer. Nothing fancy. Take the inputs, multiply it with the weights, add the bias term, and just pass it to the next layer. This neural network can learn how to classify data that is separable by a line. Nice. But what if data is slightly more complicated? I got this. I got this. Yeah. Wait, wait. No, no. No. Why? Won't it fit? Not so easy anymore, is it? Our network is too simple to capture patterns in the data. So instead of just passing the data through the next layer, let's pass it through a non-linear function. Oh, yeah. The network was able to classify this data with a quadratic curve. This function that we passed the data through is called an activation function. This function could be a sigmoid, an arc 10, a relu, a leaky relu, a parametric relu, swift, elu, max out, and the list goes on. Any one of these functions would have worked here. But what if the data was even more complicated? When data gets complicated, well, we add more layers and let's say that we use a sigmoid function for this and see how that turns out. Okay, nicer, a bit better, wait, wait, why? Even though the network is looking at more examples, it's not learning anything. This is the vanishing gradient problem. It happens because of the sigmoid function. It squeezes information. From the back propagation step, the gradients become smaller and smaller until eventually they vanish. No gradients means no learning. A remedy to this is to use an activation function that doesn't squeeze information, like relu. Let's use relu in every neuron and see what happens. Okay. Nice, sir. Oh, yeah, going to town, aha. Relu works well in practice, and this is also why we use it almost everywhere today. But in a random case, or in a few random cases, we may get this. Yes, yes, okay, why do I still have this problem? Looks like we're running into a similar problem of no learning like we did before. This is the dying relu problem. It's similar to the vanishing gradient problem in that the problem was caused then because of sigmoids squeezing the input. Now the problem is caused by relu completely blocking inputs less than zero. So a solution is to introduce some activation even in the negative case. Elu and Reiki relu have handled this pretty well. And so the day is saved. But what about the activation of the output neurons? Well, that depends on the problem we're solving. In classification, we use the softmax output. The number of neurons in this layer is the number of classes in the classification, and the values represent the probability of belonging to a particular class. Now in the case of regression problems, we need a real number output. So we don't tend to use activation functions at all. If the network spits out a single real number, then we only use one output neuron. If it spits out two real numbers, we use two output neurons with no activation. And I think you know where this is going again. Now this is the first pass over the activation functions. We went over four cases and we took a look at the softmax activation for the output layer. Now let's go through these cases again and add some more details. Back to case one, the simple neural network with one hidden layer and no activation. The output is softmax activated. This leads to a line separator. How is this the case? Well, the output neuron can be written as w2h plus b2, where w and b are the weights and biases, and h is the output of the hidden layer. But we know that h is w1x plus v1. And so we can substitute that in the output equation. And then we just expand the brackets and looky looky what we have here. The output is a linear equation of the input. This output is passed through the softmax activation. Since there's two neurons, if we call the two neurons o1 and o2, then the output activation of the first could be written as e to the o1 divided by the sum of e to the o1 plus e to the o2. We can divide both the numerator and denominator by e to the power of o1. We can then substitute the value of the output equations. Then we expand the terms and we can see that u1 minus u2 can be written as some u0, just another constant. And v1 minus v2 could be written as just some v0, which is a constant again. And in the end, it essentially boils down to a sigmoid function. If we use these values to plot a boundary, it's a straight line. Basically, it boils down to logistic regression. This animation captures it pretty well. And for a more psychedelic visual on logistic regression, I have an entire video on it, so you can check that out. Now case two. We have data that can't be separated by a line. And what we did before was we added a sigmoid activation. The output is now more complicated and we get better fitting decision boundaries. Cool. Case three, even more complicated data. And for this, we increase the number of layers. But with functions like sigmoid that squeeze data, this leads to the vanishing gradient problem. Why does this happen? Let's look at the sigmoid function. At points with large positive or negative value, the gradient comes really close to zero. This isn't good. And since in neural networks, these gradients are back propagated. If you look at this neuron, it's in a later layer and say that this neuron has a gradient that is near zero. The neuron in a layer before it will have an even lower gradient. This low value propagates backwards until finally it becomes zero. Once the gradient becomes zero, the neuron is useless and there is no learning. This is the vanishing gradient problem and I think you can see why this is a problem. To solve this, we need to understand the root cause. It is the squeezing nature of the sigmoid function. What I mean by this is that the sigmoid takes a real number and it squishes it between some small fixed range zero and one. This squeezing nature of functions creates small gradients. And we see the same in arctan function which squeezes real numbers between negative one and positive one. The solution to this is to use a function that doesn't squeeze values, like relu. And that's why we used it. But in case four, we saw a situation where we might run into the dying relu problem. Why is this the case? Well, let's take a look at the relu function now. For positive inputs, it lets information pass through it unfiltered. For negative inputs, it's completely blocked and that is the problem. During training, there may be a time where the bias may become very negative. So WX plus B is negative for most neurons. Most neurons are off during the forward step and hence most neurons are also off during the backward step. And what's worse is that if newer inputs are not positive enough to overcome the bias, these neurons remain dead. And neurons don't learn. To solve this, we make sure that learning happens with negative inputs using leaky relu or elu activations. Whew. So once again, the day is saved. I hope this video helped you understand more about activation functions, check out my other content and I will see you very soon. Bye bye.