Okay, I think we're mostly back, we're still on time. Good, so I'm delighted to move things forward and talk to you about new and emerging systemic treatment options for minestatic kidney cancer. Trying to hit a few highlights for really more of an overview of the medical oncology field. So going back to the figure I showed you at the outset, kind of an overview of what's available, what we have for kidney cancer in a comprehensive way over time. And as I pointed out previously, changes in the overall concept of approach to treating kidney cancer from a time where there really was no effective therapy and just supportive care for patients to a long interval of immunotherapy, which was a fairly novel for for metastatic cancer. With cytokine therapy, those guys still hang around, both interferon and interleukin too, still have a role for some patients. But the dominant drug in the last 10 years has been agents from what are called targeted therapies. And until just recently, as I made reference to, a brand new and trinted new drug class immune checkpoint blocking antibodies. And so we'll touch on some of the changes, three new drug approvals in the last eight months for kidney cancer. So just to remind you that the diagnosis of renal cell carcinoma is a broad category that includes multiple different subtypes. And the identification is based on your pathologist looking at the tissue under the microscope and reading out the histologic pattern of the tumor growth and declaring what subtype the tumor is. Most of the clinical research and data we'll look at is for better or worse, limited to clear cell patients. So it homogenizes the range of tumors to some degree, but many of you here probably don't have clear cell. And so unfortunately that the talk today really won't touch on some of the nuances for the less common subtypes of kidney cancer. So I put together a table that shows you sort of by drug category, 12 FDA approved therapies that we have available to us. So breaking down the whole family of drugs into either immunotherapy compounds or targeted agents. So the immunotherapy, the old-time cytokines interleukin-2 and interferon-alpha. And then the brand new entrant that is a new drug class, what are called checkpoint blocking antibodies, nevolobab or abdevo. That was FDA approved November 2015. Our targeted therapies, many of the agents attack or block a signal from a hormone, a growth signal called VEGF, vascular endothelial growth factor. That's made by the tumors and acts on the vasculature around the tumor to drive blood flow, oxygen, nutrient supply to the evolving tumor. So blocking that biology either with an antibody, Bevacizumab or Vastin that binds the VEGF hormone itself. Or what are called tyrosine kinase inhibitors, uniformly oral medications that block the signal at the end organ, the vasculature. That's the VEGF binding to its receptor crates. And so two brand new entrants within this field of drugs, two new TKI's approved in this calendar year in 2016. And we'll comment on that a little bit. And then another target within the tumor proper, a signaling hub called the mTOR protein and drugs that block that signal cascade. Temsir limus, Everlimus. So where do we start? Newly diagnosed kidney cancer, you come into the clinic, we're going to talk to you about medical therapy. So a couple of pertinent features. Right now, 2016, we do not have predictive markers we can use that really guide us in a meaningful way to choice of treatment. We'd love to have some molecular profiling that we could look at and we'd give you a personalized roadmap and say these are the best drugs for your cancer. These don't work at all and here's where we're going. And the next patient may be 180 degrees opposite. Lovely idea, personalized medicine. It's a lot of play in the field, but we're really not at that point at this point in time. And the other point is pragmatic. Not all of our drugs have an FDA approval to be used as initial therapy for kidney cancer. So you can't simply prescribe across the board any of the drugs that you choose. If you apply the amount of context, your prescription will be declined as an off-label prescription by most insurance providers. So it boils down to a simplified number of choices. And once again, thinking for the most common presentation, menostatic clear cell. What are we thinking about as standard agents? We're thinking about the option of high-dose interleukin-2, which still has a role in our clinic. For most patients, we're thinking about targeted therapies. And the three agents or combinations that right now are considered the best available therapy as initial treatment are the oral medicines, Sunitinib or Sutent, Pizopinib or Votrient. And then the combination of Bevacizumab with Interferon is considered an equivalent choice. I can tell you I almost never use that combination in patients coming to me from other oncologists in the community. Nobody uses Bevacizumab, Interferon very much. Really, for practical reasons, Bevacizumab's an IV infusion every two weeks. So you have a fixed clinic schedule. Interferon is pretty obnoxious if anybody's had that drug. It's not a friendly drug. So you don't come out ahead with that combination. It's more cumbersome. The oral medicines, Sutent and Votrient, we feel are very patient-friendly. You're taking medicine at home. Patients that want to travel be out of town. It's very flexible. It's a fairly convenient way to go. So a choice between those agents is almost always the first choice for targeted therapy. And not to forget our clinical trials program. All of our treatments are fundamentally imperfect. So we're always looking for what's coming, what's new, what may be better than what we have. And we think participating in a research trial would make sense for where you stand disease-wise is a good choice. So many of you here have been in our clinic and we've had a conversation about three different options for kidney cancer. And that's the different categories we're thinking about. So just a couple comments on IL-2. It is a unique therapy. We're the only center in Seattle to coma that routinely does IL-2 therapy. So we do get some patients coming to us specifically interested in IL-2. It's a toxic therapy. It's cumbersome to deliver. You have to be in the hospital. In fact, you're admitted to the ICU care suite in the hospital. And some of the nuances for IL-2, we only offer it to patients with clear cell histology. It seems to work less well for the other family of kidney tumors. You have to be physiologically young. So you can't have bad medical problems, no organ dysfunctions, good kidney, good heart function. There's a common sensical scale called a performance status in the oncology field.  Is it totally unknown to you? You function at a normal level and it's just a scan that has spots on it? Or is the cancer making you ill in some fashion? So performance status needs to be a person that's functioning at a normal level despite their cancer. We like the idea of treating patients that have very limited disease in their body. And so we're expecting patients that are candidates for IL-2, have seen Dr. Gore or one of his colleagues. They've had so-called cytoreductive diffractomy. We've taken out the primary tumor and ideally the dominant tumor mass in their body. And they're left with small volume tumor findings that are not causing symptoms. They're not poised to cause symptoms or some catastrophe if they grow larger. It does chew up some time to get organized for IL-2. You can't have a cancer that if it grows slightly larger, something awful is going to happen. And there's data that says prior kidney cancer therapies may pose a risk for IL-2 treatment. It may increase the side effect profile. And so we prefer to offer IL-2 as your initial therapy and not leave it for a rainy day after you've had multiple prior treatments. If we're going to do IL-2, we're going to ask you for a couple of screening tests, a brain imaging study, a cardiac stress test to be things that we wouldn't typically do in the clinic for other therapies. Depending on the medical history, maybe a formal lung study as well of pulmonary function studies. Why do we still think about IL-2? It's cumbersome. We put you in the hospital. We've got simple oral medications you can take at home and go about your business. And so these graphs really give you a picture of what we're hoping to accomplish with IL-2 therapy. So starting on the left side here, the response profile, this is data from the NCI campus, the first medical campus that used IL-2 in the country, 20-year experience in their hands. So 86 to 2006, nearly 260 patients that they're reporting on. So what happens to patients?  All findings on their scans went away, 8% of patients in their hands. Another group of patients, the cancer shrunk, but it didn't fully disappear. So partial effects in 12%. So 20% of patients having marked effects in terms of their follow-on scans. Unfortunately, that means 80% of patients went to the trouble of receiving IL-2 and really didn't benefit in a strong way. But it's the complete responders that we're fascinated with in the kidney cancer field. If you have a complete response and you follow these patients over time, and given the very long time IL-2 has been available to us, 20 years of follow-up. The solid majority, 70% of patients with a complete response, maintain that response. The cancer never comes back.  So it's the one scenario in the clinic where we actually talk about maybe truly curing the cancer, where patients can go on and on with a complete effect, but unfortunately only a small fraction of the patients that received that style of therapy. Partial response in a time where there really weren't other therapies to offer patients seemed to have an effect. Patients did live longer. They shrunk the disease, reset the clock. They did better than patients that had no effect by IL-2. So I put together a table that I hope convinces you that we're making some progress in the field of kidney cancer and we look over a very broad interval of time. And so focusing really on the overall survival data with different groups of patients and the doesn't project very well, but the coloring of the different lines corresponds to the timeline I showed you and the different areas of therapy for kidney cancer. So the first line harkens back to studies done with interferon where the comparison with the drugs available in the early 80s or even older drugs, conventional chemotherapy agents, hormonal therapy that was sometimes applied, that was really extremely ineffective, response rates of tumor shrinkage less than 10%, and immediate overall survival of cohorts of patients formally recorded in research studies of six to nine months to the midpoints of the survival, extremely bad for the historical experience of kidney cancer. The cytokine drugs moved the bar. They were good enough to gain FDA approval and become standard treatments, although were highly imperfect. Rates of response of 12 to 20% for interferon and interleukin-2. And in large studies done, phase three studies, median survival in the teens were beyond a year, recognizing that the best response was limited to a very small fraction of patients. So when you look at the midpoint of all patients treated, you're missing the patients deriving the most benefit, but these drugs did seem to be better than what had been available previously. Jump forward to the targeted agents we now commonly use. In the research studies that gained their FDA approval, comparing these drugs to interferon alpha, these drugs came out ahead. So either SUTENT or VOTRIENT response rates now of 30% of patients and median survival of months counted out in the 20s, 22 months, 26 months. The Bevacizumab interferon combination, similar numbers for response and overall survival is not terribly different. So we think we've moved the bar once again with our targeted therapies, but the current state of the art isn't stopping after the first therapy is applied to most patients. We believe the natural history of these drugs has eventual tumor resistance. The tumor grows back and we move on to an alternate therapy. So how can we gain a picture of using multiple sequential agents? That's a really hard perspective and number to come up with to give you something that tells you what's truly happening. But one study that used two drugs in sequence as part of a study, called the record three trial, patients received synitinim or everlimus in sequence and all training sequences were both studied, had to had 50-50 randomization. The synitinim first everlimus second proved to be best, but the point of this is to show you that data was collected over two drugs given in sequence. And so the response rate of first line synitinim, not so different than the phase three study, makes the point that there's some heterogeneity in an absolute number if you look at multiple studies, so you can't be too honed in on the absolute number. But again, looking at overall survival of patients that received two drugs in sequence, so the duration that they're able to use the drugs, progression free survival, that's my mouse, 25 months versus 10 to 12 months for a single agent, and then 32 months median survival, so the midpoint of the population getting two drugs in a row. And we think that effect is manifesting itself as patients move on to third and fourth drugs as currently practiced for many patients, that the average survival is getting better and better. It's kind of hard to capture by individual research studies, but we do think we're making progress that we're moving the bar. This number of 32 months certainly looks a whole lot better than a six to nine month nine month median survival from the late 80s. Time from start of therapy. I wanted to show you a figure that's called the waterfall plot. The way data is commonly reflected in research studies, because I think that response rate number is a little bit misleading, you think. 30%, yeah, that's not such a big number. This drug's not so great. But I think this gives you a better reflection of what we actually experienced in the clinic and what we think about these drugs. So this is a figure from a study with Pizzopinib or Votrient, a drug many of you here probably have actually taken. And there's guidelines about how you interpret radiology studies as you participate in the study, you collect imaging data, and you put a label on what's happening to patients. They're having progression, they're having stable tumor findings, they're having a response, and what that means, a partial or complete response.    So this represents shrinkage of tumor compared to where you started before therapy was applied. So the point of this plot, this is the best response seen at any point in time after starting Pizzopinib therapy on a clinical trial, is that 70 to 80% of patients have their starting tumors shrink down incrementally after they start therapy. Even though, so in this study, the response rate you'd read in the study abstracts is 35% response rate, that's true, and how do they come up with that number? Well, the guidelines for applying a response category say that to label somebody as a responder, you have to have at least 30% shrinkage, the dotted line, of your tumor compared to baseline. So a lot of patients, their tumor gets a little bit smaller, doesn't meet the 30% criteria, and that's labeled as not a response. They're stable disease. If your tumor shrinks down, that's based on the tumors that you had before you started therapy. If you collect a brand new tumor, the guidelines are intolerance to any new tumor findings in your label as disease progression, even if your starting tumors got smaller. So the blue lines here are patients that their baseline tumor's got a lot smaller, but they had a new tumor finding in their label as progressing disease. So you look at that and you realize we're looking at a subset of patients that have pretty significant tumor shrinkage in labeling them as disease response, the 35%, but what we're thinking about when we see them in the clinic, we're saying, well, our drug's imperfect. It's not going to put you into a cure where we're going to stop the therapy.  So everybody that's having a nice effect where the disease really isn't growing in a meaningful way, we're going to roll forward, say the drug's working just fine, that's what we wanted, that's what we expected. And so the percent of patients that we think we're benefiting is the solid majority, 70, 80% of patients with our targeted therapies. And so I think this graphical picture hopefully gives you a better flavor of what happens to individual tumors when you apply these drugs. When you look at research studies and you start seeing 20%, 30%, 35% response rate, that feels like a smaller number than the group of patients that we think are benefiting in how we think about these drugs. So unfortunately, even our best drugs, the natural history for most patients is the tumors become resistant, they start to grow back. And then what do you do next? So right now, state-of-the-art, most patients are going to get offered either Sioux Tent or Votrin. There's nuances to the two drugs. We can talk about that at the end. Our IL-2 patients, if it doesn't work, and unfortunately that's the solid majority of IL-2 patients, we're going to offer them the best available targeted therapy. They're also going to move on to Sioux Tent and Votrin. So just about everybody in the clinic is going to wind up here. At some point in time, we're going to say, oh, it's not doing the job any longer. We need to move on and try second therapy. So what is state-of-the-art for the second therapy you're going to apply to kidney cancer? And that's where things have really changed dramatically in the last eight months. So until November of 2015, there were two drugs that had done large-scale advanced testing in this context, failure of primary therapy. And so we were almost always choosing between Everlimus and Exitinibus, our two best drugs. There was no head-to-head data, so one or the other, there really wasn't a compelling reason to say one was the best. But we now have three brand new options to treat patients in this setting. So the drug Nevolamam or Octevo, an immunotherapy compound, the first entrant for kidney cancer from what are called immune checkpoint blocking drugs, Cabosantinib, an oral tyrosine kinase inhibitor, so related to sutent and votrient, and a third option, Vatinib, another tyrosine kinase inhibitor, another oral agent that was studied in combination with Everlimus, so a two-drug cocktail. And each of these studies compared itself to Everlimus, a perfectly acceptable standard agent that was used in secondary therapy. And each of these three large studies said the new drug was better than Everlimus. So what that means for Everlimus is bad news.  So now we've got three brand new choices, plus we still have Exitinib as being a little bit older drug that's also available to us. Once again, just to point out, again, our therapies are imperfect. Clinical trials are a very sensible choice. That's always in the background when we're talking about what we're going to do next. So kind of a busy table, but I wanted to put out there this truly the discussion that was had at the big clinical oncology meeting ASCO 2016. There wasn't brand new data for kidney cancer. It was rehashing this flurry of activity and three brand new drugs for kidney cancer. And what does it mean? What are we actually going to do with our patients? Which drugs are we going to select? So let's just walk through this and look at a couple of issues. We're looking at four different drugs that are all sensible options. Exitinib and the three new players for previously treated. So the data reflects patients that had a prior tyrosine kind of inhibitor, almost always, Su-10 or Votrint that's failing and they're moving on to a second therapy. The three new guys all compared to Everlimus, the Exitinib data was collected in comparison to Seraphim. And let's look at my highlighting is not really working. The first three lines here are metrics of the anti-tumor properties. So overall response rate and we just spent a minute educating ourselves about, you know, what does that really mean? But we have to have everyone measure in the same fashion so we can compare between trials. And so we know a little bit now about what we're seeing when we're seeing this response, the extent of shrinkage in patients. So overall response rate across the board, the new guys, high teens, 20s, 35% with the combination. Those numbers sound pretty good compared to 9% for the Exitinib drug. But more importantly, I think when you look at survival, at the end of the day, imperfect drugs were really just wanting to stop cancer growth, control it, have you function well, perform at a very good level. So perhaps less important than whether the tumor shrinks or doesn't shrink, are we stopping the cancer growth and you're living the life you want to live. So the survival, I would say, is probably the most important statistic. And so the Exitinib median survival in TKI failures of 15 months with state-of-the-art until last November, and all three of the new guys look to be meaningfully better. So 20 to 25 months of median survival with any of the new agents. So I would have to say, I think right now our practice would be to pick one of the new choices and skip over the older choices that we had. The flip side is, well, we apply a new drug. What are you taking on in terms of nuisance and toxicity? Are we going to make it profoundly ill and it's not going to go well. So the bottom lines here all look at metrics of side effects and problems with the drug. So what fraction of patients had to have the dose of the drug cut back for the two new oral agent options pretty substantial, more than half a patient didn't tolerate the maximum dose and cut the dose back. Nevolumab as it was developed, there was no option for changing dose. It's a fixed dose. And so that's not meaningful for Nevolumab. And then side effects profile. So there's codification research studies for side effects. They all get a list listed out, rostered out. So what fraction of patients have side effects and then there's grading for how extreme they are. One, two, three, four. One and twos are things that are mild that really don't interfere with your daily function. Grade three and grade four make you sick, cause problems. You need a remedy. You have to stop therapy that you're taking. So we're most interested in the grade three and grade four side effect profile. So the Nevolumab numbers for stopping the medication outright or having bad problems, I would say look better than their comparison here. These guys that can really give patients bad side effects. Now the oral agents are fairly flexible. You can stop them for a period of time and let the side effects fade out. You might try again at a lower dose. So there's a lot of work that goes into trying to optimize things. But I would say the field is really quite pleased with Nevolumab. That's being a drug that generally goes pretty smoothly for patients and very often traffics with very few side effects. So we definitely, I think at our institution and as a field, are really taken with immunotherapy. For kidney cancer, for melanoma doctors, it's preaching to the choir. We've been using immunotherapy for 20 plus years and so are kind of outliers in the broader field of oncology. But a point about the immunotherapy drugs, I think this figure really illustrates very well. This is neither kidney cancer or Nevolumab. What this is is a figure of melanoma patients treated with a drug called Urvoi or Ipilimumab. That was the first drug in this class of what are called immune checkpoint blocking antibodies. It's been in clinical development the longest and so we have the longest perspective on what this drug can accomplish. So this is looking at survival of melanoma patients with a timeline that extends to 10 years from the start of therapy. And so what this shows you is that unfortunately for many patients the drug does virtually nothing. Their disease grows, progresses, they die of their disease. But by about three years you hit a plateau where this flattens out. So patients with long-term survival of their disease receiving an immunotherapy compound. And I can tell you that the incidence of a complete response with this drug is really quite uncommon, less than 5%.  So disease control in a subset of patients that seems extremely long-lived, very durable, but imperfect. It's not a complete effect. And so the idea that for some patients with immunotherapy the so-called tail of the survival curve may flatten out and be very long. If you can't achieve a complete cure, maybe the next best thing is more or less permanent control of the disease and you go on and on without the disease changing. So now this is nivolumab and this is kidney cancer and this was data shown this summer at ASCO. The longest survival follow-up observation in patients receiving nivolumab, this is the very first study of nivolumab in a variety of patients including kidney cancer and then a dedicated kidney cancer study at Phase 2 study looking at the same metric overall survival of patients that have enrolled in these studies and got nivolumab and the shape of the survival curve hearkening to the hypolymumab data, although it's less follow-up but lines drawn here at four and five years of follow-up total patient numbers are not terribly large but giving you the feeling that there's a flattening of the survival curve there isn't a steady degradation where eventually you're going to cross the zero line and all patients have died from their disease. So maybe once again we can achieve very long-lived disease control that goes on and on for many years even if it's imperfect and patients still retain findings of their disease on their scans. So let me show you a figure. Is that, that last graph, does that represent people in stage one, two, three and four total or is it... For their cancer? Yeah, what they presented. So these are all patients that have metastatic kidney cancer. To get on to both phase one and phase two clinical trials you already had prior therapy, at least one prior treatment that failed to be eligible to receive what was an investigational compound at the time these studies began. So these are all metastatic kidney cancer patients and once again all clear cell metastatic kidney cancer patients that all received nivolumab as part of these studies. The data is a little bit unclean but that's some patients in this survival data set left the studies, maybe went on to receive other types of therapy and so it's not patients that are ongoing necessarily actively receiving nivolumab but it is the true survival of what happened to these patients that participated in the trials and did get drug as part of the studies. This is not a survival figure but this is a metric of tumor findings in two patients treated here at our campus at the start of the large phase three study of nivolumab that was the data that was criteria for FDA approval. So showing you here in real patients what the biology that we're speaking about so each spot on this graph is reflection of the CT scan findings of these patients time zero is the start of participation in the clinical trial both these patients getting the nivolumab drug and so again comparing their scan findings from overall tumor size to their pre-treatment baseline imaging so both patients every time they get scanned the first couple of scans their tumors get smaller and get smaller but finally sort of hit a plateau here this isn't 100% shrinkage of their tumor they still have abnormalities in their scans that we're calling tumor they've become very stable they haven't changed both patients are well over two years of ongoing nivolumab therapy and so is this now the biology the pattern of existence that we see with the nivolumab drug and melanoma that extends out to 10 years how long is this going to go on is it going to go on 2 years, 5 years, 8 years, 10 years is this you know functionally a complete effect and ongoing durable control of tumor we don't know we need longer follow-up but it's provocative findings that make us think that maybe there's something that's unique about our immunotherapy compounds that may not be common to the targeted agents so it sues us to think about prioritizing the immunotherapy drugs ahead of targeted agents and so last point given what we consider to be a very good patient tolerance with the new immunotherapy drugs they're getting great attention in the field and this is just a little schematic showing you that they're going to become the building block to test combinations of checkpoint blocking drugs with a whole slew of other agents hoping to get a more potent and more durable anti-cancer effect nivolumab is an antibody that blocks a protein called PD1 there are competing antibodies owned by other companies that share that identical biology there are also similar antibodies that block a very similar protein the binding partner for PD1 is called PDL1 so a lock in key phenomenon you can block either side of that interaction and we think you get the same biological effect there are many of these agents in development by different drug companies coming forward and looking to combine with other agents to trump nivolumab and do better with a combination approach and these all reflect research study opportunities that are actively in our clinic now or that we believe are coming to our clinic in the next several months so combining these drugs with interleukin2 combining these drugs with other similar agents antibody molecules that have been generated to be very selective to manipulate other targets in the immune system so each one of these names and numbers here is a protein that's on T lymphocytes the same target for nivolumab and for the urovoid drug so can you find other ways to manipulate the same immune compartment and get a more potent effect so combinations of all these guys with PD1 or PDL1 antibodies a brand new drug class what's called what's a metabolic therapy that blocks glutaminase which degrades glutamine by the tumor the tumor is doing this that's thought to be a bad thing for your T lymphocytes they need glutamine as an energy source so manipulating the so called micro environment around the tumor to augment immune responses that may be occurring in that space combining one drug that works with the second drug that works old school oncology therapy A is good and B is good A plus B might be better so mixing our checkpoint blocking drugs that work in their own right with our target therapy drugs that work in their own right and see if those combinations are a smarter way to go combining these drugs with something called epigenetic modulation for today's purposes won't worry too much about what that means but a way to manipulate tumors that are thought to change gene expression profiles perhaps make the tumor look more inflamed be more exciting to the immune system and give you a better effect so looking what's coming down the road soon what's maybe changing though we practice kidney cancer therapy in the next couple of years so looking to take the immune checkpoint drugs that are approved now for patients that have failed a prior therapy and saying well they look very promising shouldn't we pull them up and use them as the initial therapy for our patients so trying to prove that that's the right way to go in a formal research study that gives you data that makes the case so three different studies with compounds owned by different companies that are similar in concept combining the volumab the drug that's truly FDA approved for kidney cancer with the Uruguay drug or ipilimumab in a two drug combination that's a study that's comparing those two drugs to sutent head-to-head for untreated patients that studies are already completed it's patient enrollment so now we're just going to wait and see if it's presented and what the results are probably a couple years away from a result on that a drug that's a PD-L1 targeting antibody and combining that with bevacizumab that we know is a standard drug for kidney cancer so targeted therapy plus an immunotherapy again comparing to sutent and then a similar approach another PD-L1 antibody owned by a different company combining with the TKI as a combination approach again compared to sutent so as everlimus was beat up with all the new drugs coming available sutent will be the common comparator so we'll have three competing studies that are similar in kind and see if one or more of these approaches gains the upper hand and becomes the standard approach to treating patients a couple years down the road so a couple points I hope came through when you look very broadly over time I would say that the pace of drug development and new drug approval for kidney cancer is accelerating if you look in recent years versus the distant past we think our new drugs are better than what we've had before we're making incremental progress in disease control the most recent flurry of new approvals are all for patients that had failed prior therapy we're very interested in the new immunotherapy that are blocking drugs in their own right and they are going to be the building block for multiple research studies of a variety of combinations looking to improve on their activity there's studies that are looking to change the way we come after patients and apply therapy in the first line setting and so that's all very promising and optimistic but it remains a true statement that true cures of cancer and the ability to stop therapy because the cancer is gone remains a very elusive goal not only for kidney cancer but advanced cancers across the board so that's a very high bar we'd love to see patients start developing complete responses and come off therapy but so far that really isn't part of the equation for advanced kidney cancer so I appreciate the chance to speak today that was kind of a very cursory overview I think we have a little bit of time if anybody has a couple of questions in one of the graphs that you had there you had a papillary type 1 and 2 what's the difference between papillary 1 and 2 and is one more aggressive than the other? so that's a distinction made histologically by the pathologist in terms of the growth pattern of the tumor there's no formal metabolic or molecular profiling that gives you an absolute distinction between those two there are gene differences that are somewhat unique to the two different subtypes generally for therapy there's not a distinction made between those two subtypes so papillary gets bundled together in terms of thinking about what we're going to do therapy-wise and I have one more question you were talking about combination therapies, the OPTIVO plus etillumab? yeah etillumab that's in a research study at present, right? so that was the research study that's completed its enrollment but it's not an active opportunity for patients but now we have to wait to see what the outcome shows okay, thank you so maybe one more and then we should move forward with the next speaker yeah I wondered you were talking particularly about clear cell and I wondered if there was anything that you knew that worked against papillary and then also the secondary thing was it talked about the studies where they compared it to or however you say that but you also had in LIDA or whatever list is there did they compare against that at all? so for papillary kidney cancer overall when you look at the success of targeted therapies if you bundle all the non-clear cell patients together the outcome success is inferior so having a non-clear cell diagnosis is a bad deal the drugs that we have available seem to work less well there are no drugs that were developed specifically for papillary or chromophobe patients in mind so we take what we know about results with clear cell and we apply it to the other subsets but don't really know for sure what's best there is a data set of head-to-head comparison of SU-10 versus the Everlimas drug, a finitor and SU-10 was superior so based on that available data I typically recommend a patient starting with SU-10 for papillary kidney cancer unless we have a research study opportunity and again success is incomplete so if something that looks promising that's brand new we're happy to try and make that available as a choice for non-clear cell patients


Hello and welcome to this CUBE Conversation. My name is Dave Vellante, and we're here with Raj Gosane, who's the Chief Product Officer at Alation. We have some news. Hello Raj, thanks for coming on. Dave, it's great to be with you on theCUBE again. Yeah, good to see you. So, okay, we're going to talk about Alation connected sheets. You know, what is that? Talk to us about what it is, what it does, what it brings to the customers. So we recognize like spreadsheets are really the dark matter of the data universe. And, you know, they're used by over 78 million people use spreadsheets on a regular basis to drive critical business analysis. But there's a lot of challenges with spreadsheet usage. It brings risk to the organization. There's no visibility into where data comes from. And so we wanted to bring the power of the Alation Data Intelligence Platform to business users where they spend most of their time. And that's in a tool that they love and that's spreadsheets. And so we're launching a brand new product next week called Alation Connected Sheets. So to talk more about that. Yes, I get the lineage issue. Like, who did this? Where does this data come from? I got different data. But talk more about the problems that Alation Connected Sheets solves specifically for customers. Yeah, so the big challenges that we see when we talk to data organizations is how do they understand where the data came from? Is it trusted? Is it reusable? Should it be used in this format? And if you look at where most users that use spreadsheets get the data to power their spreadsheets, it's maybe it's a CSV download from a database and then you have no idea where the data came from and where it's going. Or even worse, it's copying and pasting data from other spreadsheets. And so if you take those problems, how can we bring trusted data from governed sources like Snowflake and Redshift and put it in the hands of spreadsheet users and given the power and flexibility of Google Sheets or Microsoft Excel, but use trusted, reliable, well-governed data so that the data office feels great about them using spreadsheets and the end users, the business users can take advantage of the tool that they know and love and do the work that they need to do quickly. So, okay, so I'm furring from your comments there that you've got the ability to take data from, you mentioned a couple, Snowflake and Redshift, other popular data warehouses. So talk about the key capabilities that you have any specific features that we should know about. Sure, so we built the leading data intelligence platform in the leading data catalog and one of the benefits of that catalog is we have visibility into all of the trusted governed data sources that a data organization cares about, whether it's enterprise warehouses like Snowflake or Redshift, databases like SQL Server, Google BigQuery, what have you. So what we've done is we've brought the power of that data catalog directly into both Google Sheets as well as Excel. And the idea there is a user can log into their application, authenticate to Elation, using the Elation Connected Sheets plugin into their spreadsheet tool and browse those trusted data sets that are surfaced in the Elation catalog. They get trust signals, they get visibility into where this data came from. So lineage insights, descriptive information and then with one or two clicks, they can choose a data set from their warehouse, basically apply filtering conditions. So let's say I'm looking for customer data in Snowflake, I can find the right customer table. If I only want it for say 2022, I can apply some filter conditions, I can reorder columns, push one button, authenticate to that data source. So we want to maintain and ensure security is being applied. So only those users that have access to the warehouse can actually download that data set. But once they've authenticated, that data gets downloaded into their spreadsheet and there's a live connection that's maintained to that spreadsheet. So anytime I need to refresh the data, one push of a button and that data set gets updated, I can schedule the updates. So if I have to produce a report every Monday morning, I could have that data set refreshed at 8 a.m. Monday morning or whatever schedule the user wants. So it gives the user the data set they need, but the data organization, they can see where that data came from and they understand the lineage of the data as it is used in analysis in those spreadsheets themselves. So Raj, I know you're at the Superbowl this week, aka re-invent, and I know you've got very close relationships with Snowflake. You've mentioned them a couple of times at the data summit last spring. So, and I know you've done some integration work with those platforms and I'm sure others. So should we think of this as your extending that sort of trust and governance out to spreadsheets? Is that right and stretching that out? That's exactly right. The way we talk about it is, how do we bring data intelligence to business users in the tool that they know and love, which is the spreadsheet? And so the data catalog and data intelligence platforms in general have really primarily been focused on servicing the needs of data users, data analysts, data scientists, data engineers, but our vision, our aspiration and elation is to really bring data intelligence to any business user. And so it's a big part of our strategy to make sure that the insights from the elation catalog and platform can find their way into tools like Excel and Google Sheets. And so that's what you highlighted, Dave is exactly correct. We wanna maximize the likelihood that a business user can have self-service access to trusted, governed data due to the work that they need to do and ensure that the organization has a set of data assets in spreadsheets as frankly as opposed to liabilities, which is the way most data organizations look at spreadsheets is it's almost like a risk factor. We want to convert that risk, that liability into an asset so that people can reuse data sets and they understand where this analysis is actually coming from. It's something that we've talked about for well over a decade on theCUBE. Is data an asset or is it a liability? You obviously want to get value out of it, but if you can't share it, it's not trusted. So what people do is they lock it down and then that constricts value creation. My understanding is this tech came out of an acquisition from a company, Claudio. Tell us about Claudio, why Claudio was the fit there. Yeah, so Claudio is a company, it's about five years old. We closed the acquisition of the company in March of this past year and they had about 20 customers, 10 engineers and we saw an opportunity with the spreadsheet tool that they created to really compliment our data intelligence strategy. And as you said, Dave, extend the value of data intelligence to business users. And so we brought the Claudio team into the fold. I think I'm most excited about as a product guy is within, if seven months of them joining Elation, we're actually shipping a brand new product that's gonna drive revenue and meet the needs of tens of millions of users ultimately. That's really our aspiration. And so the tech they had was extremely modern. It reinforces the platform position that we have with this microservices architecture that we've built Elation around made it easy for that new team to come in and leverage existing APIs and capabilities from our platform and the tech that they brought into Elation to essentially connect the dots and deliver a brand new set of capabilities to an entirely new audience to help our customers achieve their business objectives, which is really creating a data culture across their entire organization, inclusive of business users, not just like I said, the data X users that are already taking advantage of solutions like Elation and Claude warehouses, et cetera. So I have two questions, follow up questions, and I think you might have answered the second one. The first one is like, what's the secret sauce behind Claudio? How's the technique? The second question is, how does it fit into the Elation portfolio? How are you able to integrate it so quickly? Maybe that's the microservices architecture, but start with the secret sauce. What is it? What can you share with me? I think the thing that we saw with Claudio that got us excited and the fact that they, even though it was a small company, they had 20 customers that were generating revenue and they were delivering real value to business users by really enabling business users to tap into the value of trusted governed data and frankly, get IT out of the way. We almost refer to it as like smart self-service, which is they could find a data asset and connect to that source. And just with a couple of clicks, almost like a low code, no code type of an experience, bring that sort of data into their spreadsheets so they could do the work that they needed to do. That opportunity, that tech that the Claudio team had built out, the big gap that they had is, my goodness, what does it take to actually be aware of all the data sources that exist across an organization and connect to them? And that's what Elation does, right? That's why we built the platform that we built so that we can basically understand all of a customer's data assets, whether they're on-prem or in the cloud. And so it was a little bit of, that Reese's Peanut Butter Cup analogy, the chocolate and the peanut butter coming together, the Elation platform, the Elation catalog coupled with the technology that Claudio brought to us, really was sort of a match made in heaven. And it's allowed us to bring this new capability to market that really is value add on top of the platform and catalog investments that our customers have already made. Yeah, so they had this magic pixie dust, but it was sort of isolated. And then you've integrated it into your catalog. And that's the second part of my question. How were you able to do that so quickly? So, we've been on this evolution, enhancing the Elation data intelligence platform. We've moved to a microservices architecture. We're fully multi-tenant in the cloud. And the fact that we'd made those investments over the past few years, gave us the opportunity to make it easy for an acquired business like Claudio or perhaps a future acquisition or third party developers leveraging APIs that we expose to make it easy for them to integrate into the Elation platform. And so, I think it's a bit of foresight. We recognize that in starting with the catalog, the opportunity was much bigger than just providing a data catalog. We've added data governance. We've built out this platform and we recognize that more and more users can and should be benefiting from data intelligence. And so, I think those platform investments have paid significant dividends and accelerated our ability to deliver Elation-connected sheets as quickly as we have. Sounds like a great acquisition, like a diamond in the rough. I mean, I love these big mega acquisitions because the media company can write about them. But I really love the high return, low denominator, high value. So, congratulations. We can people learn more about this. Maybe play around a little bit with it. Yeah. So, we're going to be demoing Elation-connected sheets at AWS re-invent next week. And it's going to be available starting next week, so the 28th of November. And obviously you'll see it online on social media on our website as well. But folks that are going to be in Las Vegas next week, come to the Elation booth and you'll get a chance to see it directly. Awesome. Okay, Raj, thanks for spending some time with us today. I really appreciate it. Great, thanks so much, Dave. Great to see you. Hey, you're very welcome. And thank you for watching. This is Dave Vellante for theCUBE, your leader in enterprise and emerging tech coverage.


What's up everybody, Jason here for JaspysCaseBrace.com 2022 Panini Mosaic Choice Football, just, well, this is a four box break. Pick your teams number four. And again guys, we're giving away $500 in break credit. All you have to do is buy two teams to be entered. So again guys, we'll alphabetize this. We'll see how many customers got entries to see how many got two or more. But first let's do the break. And it is a four box break of Mosaic Choice. So there you go guys. We haven't hit anything massive out of here yet. At least not that I know of. So let's see if we can get something nice. So again, we do have another four boxes left. Pick your team number five will go up soon and that'll be the last one for the time being. Here we go. I've got Joe Green, Buddha Baker, and a nice Breeze Hall there for the Jets. Niko with that one. Matt Judon, nice Bailey Zappi to 80. And a Joe Montaigne to 80. Got a Jameson Williams and a Evelyn. All right, Fletcher Cox. Let me have a Tristan Ebner autograph there for the Bears, Bears that's Raymond. And then of course, Jets was Niko. Bull Melton and then behind Skye Moore. That's too court stuck. Michael Thomas for the Saints to 80. And we've got Carson Strong, Jake Ferguson. And these are all to 80. Had two more to go guys. Oh, we got a heat up guys. I love this choice. I really do, but it's such a big hit or miss though. Always has. All it takes is one card to turn it around. Malcolm Rodriguez, Isaiah Spiller Otto for the Chargers that's going to Patrick. We got Pierre Strong, Jr. Number to 80, Niko Harmon. And a Joe for the Browns. Antonio. Here we go, a little Malcolm Rodriguez. And a Jalani Woods. Lions is Adam Cruz. Glenn with the Browns. Chiefs of Raymond. Karen Steele with the Patriots. All right, come on, let's end it off with a big box. Big box, come on. I know, Brody, but man, there's only one more break, man, so if you don't get anything here, man, there could be something really massive in the last one. Choices, like I said, it's just always been a big hit or miss, but. It's like we're almost at the finish line. We got a Peacock coming up. All right, Drew Brees, let's go baby. Come on, something nice, something nice. Derek Stingley, Jr. Well, he was the number two overall pick. Texans, it's going to Dilo. Zach Wilson to 80. Elijah Moore, and we got a Peacock. And it's a Joe Montana Peacock. 49ers going to Sean Manning. I've done like two of these, right? Jackson and Snoop Conner. What was holding like the ones that Joe did? Was there anything massive? Because if not, the last four boxes might be the lowest boxes ever. There's usually a couple of Peacocks, which we have seen. They on average, they usually put them one nebula per case. And you know, obviously, depending on the autographs, I mean, have we hit a nebula already? That's my thing. I know we hit that Peacock a lot because I remember I hit that one now. Just feel like there's got to be something still nice though. All right, guys, well, let's give away 500 bucks. But I'll put up the next ones in the store, guys. I think there's got to be something massive in there. All right, so again, if you bought two or more teams, you have chances to win. So Cruz, you have a shot. Brody and unfortunate one, so good luck on your Falcons in the next one. D-Low with four, so that's two entries. David Lemons with two, that's one entry. Glenn, two, one entry. Jermaine Harder, one. Karen Steele, just one. Niko with four, that's two. Patrick, two. And Raymond got a bunch of them. Eleven. So technically, it can only give you five. And then Sean Matic, two. All right, out of the possible 16, we got 14. All right, good luck, guys, here we go. Roll, it is a three and a one, four times. Good luck. Top name wins 500, one, two, three, four. And David after four times, congratulations, man, 11th. Boom, $500 in break rate, it coming your way. Let me send it out right now because I don't want to forget. So there you go, man, send you 500 bucks. You can use that on whatever you want. Next one will be in the store, guys, jaspyscasebrakes.com.


Welcome to ToffeeTV, this is the starting 11 show, Everton vs Rusenbjörk in the Europa League, Facelegg at Gudersson Park, obviously the qualifier on Thursday, sold out, get it on the telly if you haven't got your tickets and I've picked the team, this is my team, this is the team I'd like to start, it might not be the team that the manager picks, he might have completely different ideas, I imagine he probably does have completely different ideas to make, but we'll wait and see what Ronald Kuhnman comes up with, but this is my team, in goal, new signing, £30 million, Jordan Pickford obviously go straight into the team, there's no messing about, he goes straight into the side, there'll be no arguments, no complaints, if you pay £30 million for your goalkeeper and you give him the number one shirt, he's the number one, hopefully for a very long time as well. Right back, obviously Sheamus Coleman out injured, still going to be injured for the best part of 2017 if not the whole of 2017, Martina has come in as back up, he ain't starting for me because he just isn't, I'm not saying I don't like the player anything, he's just not starting for me, he's been at the club for just over a week as we stand and no, he's not starting for me, Mason Holgate has played some games at right back and obviously he would be the one that he's probably going to start the game, I imagine, but for me in this, my formation in my team, I don't think Mason Holgate provides enough with, he tends to get the ball, get about three quarters up the pitch and then passes inside, I want to write back who's going to play like a modern day write back like Sheamus Coleman and that man is John Joe Kenny. A start of the under 23 side last year, a start of the England under 20's team that won the World Cup and I think he should go into the right back spot, he is a born and bred, scout set, Evertonian leader and I think he should play, we've got enough experience in this team that any issues he might have with inexperience are covered up, so it's John Joe Kenny. Next to him, Michael Keane, another new signing, £30 million signing from Bayer Lee, he goes straight into the team, for me this season he's our number one centre back, number one centre back, I'm sure he is the number one centre back, I'm sure he's been told he's a number one centre back, I'm sure that's one of the reasons he signed for us because he's the number one centre back, he goes straight into the team, another leader, good in the air, big strong physical lad, decent with the ball at his feet, he's got a little turn of pace as well, everything we've been missing last season, so for me he goes straight into the team. Next to him, Ashley Williams, now there's not a huge amount between Ashley Williams and Phil Jaggelke and if Phil stays at the club I imagine they'll both get on our football this season but obviously he is naturally left-sided, he was brought to the club last year by Ronald Koeman, so I think for me he will play, well for me for the balance in the side, for having that sort of gritty no-nonsense centre back because don't forget I mean whatever you think about Ashley Williams he did help get us a hell of a lot of clean sheets last season, he is a no-nonsense defender and for me at the moment I would have him in the side.  Now we're moving to midfield and on this is where again there's a lot of options, I don't know the state of everyone's fitness and I imagine fitness will have a massive part to start in this game, who is completely fit, who's 100% fit for this game but I'm going for these three at the moment, this doesn't necessarily mean that these are my favourite three because we have to get rid of that notion and in fact I've left the player out to who I absolutely love so but for this game I've left these, this is my three.  So he is our number one defensive centre midfielder, next to him Morgan Schneidel, a player gets the ball, uses it effectively, uses it quickly, opens up space, opens up angles with the way he turns with the ball and uses the ball, a Rolls Royce, we haven't got anyone else like him in the squad to me, apart from Gareth Bally but obviously Schneidel has got youth on his side so he goes in there. Now in front of them, Davy Classen, now it was a toss-up between Classen and Tom Davies or Classen playing in a slightly wider position but the reason I feel Classen needs to play in this game is because it's a home game where we need to score goals and I think that's what he'll help with, he is a naturally attacking centre midfielder. Tom does that brilliantly and we've seen that but I think we just need that little extra little bit of attacking now in this game. Also you know Classen was the captain of the losing finals of last year's Europa League, he knows all about the Europa League and you know this is a great opportunity to give him his home debut at Goddison Park and hopefully for him to get off the mark and score some goals. In front of them I've got a front three, obviously could be different but I'm going again with the tried and tested of what Ronald Koeman seems to like. On the right I've put Sandro, now Sandro can work anywhere across that front three but maybe he'll have a little bit of lack of fitness because he's hasn't had as much training as everyone else and he had great effect on the right in the game against Genk at the weekend. I imagine he'll, if you put him on the right he'll turn up on the left and he'll turn up down the centre but I'm standing on the right because I just feel that he'll work his socks off. He won't be the wit, you know John Joe Kenny will be the wit for me or whatever, the right because he's the wit. Sandro will be the wake-up front, the one who dogs the other players of the opposition, runs around, tries to get in the box as well, does a proper centre-forward job so I've put him on the right. On the left that is Morales. Joe, I don't know why you've picked that picture, it's a side view so you self-outkid, come on let's get better at this, let's get a little bit more professional. That's Kevin Morales now, people might say why have you picked Kevin Morales? Experience, experience of a game like this, you know, we're not, we haven't got, we're not blessed with loads of left-sided players and we could, we could shoehorn someone else in there, a Dominic Alvin Luhmann, a Luchmann or even a, you know, a Kieran Dahl maybe, and Kieran Dahl might start in this game because there is a nice balance in this team, there's experience, there's younger players and there's, you know, that middle section of players so it could be a Kieran Dahl but for just pure experience, I've put Morales in there, just got a good goal against 20, you know, he does drift in and out of games but I think he can be quite clinical when he needs to be so I've put Kevin Morales in, won't be, you know, a lot of people won't agree with me on that but I just think for these games there's a little bit of know-how that's needed, a little bit of an ounce to get you through these games and I think Kevin Morales can provide that. And up front in the central role is Wayne Rooney. Now we talk about class and being the losing captain, this is the winning captain of the Europa League holders. Now Wayne, again, like Sanjo, him and Sanjo could swap quite easily, they could go into a, into a two if needed be and, you know, the midfield could go into a four. I don't think that'll happen for this game but that could certainly happen but you could see a nice interchange between Sanjo and Rooney, you know, bit of silk, bit of steel, you know, Rooney can pick up the pocket space Sanjo creates, Sanjo's going to work with defenders, he's going to push them back, Rooney's going to capitalise on that space, that's where I think Rooney wants to be, he doesn't want to be stuck in midfield, he doesn't want to be stuck out wide, he wants to be sensible where he can do the damage, drop off, even interchange with Klassen, you know, Klassen can be a forward runner from midfield and Rooney can drop into that space, that's what the manager wants, that's the, that's the kind of, you know, naus that the manager wants from Wayne Rooney, it will be, I'm not saying it's going to be a free roll but the manager will trust Wayne Rooney to pick up positions because this man is not stupid, this man is a hard worker, he's an intelligent footballer, he can spread the player and great pass and range, you know, and he's a goal scorer and if we can get all that out of him, you know, we've still got a hell of a player in there, so Wayne Rooney will be up front for me. Now listen, this might not be the team, in fact, I imagine it won't be but maybe, I'm going to say I've got at least nine right, I'm going to say at least nine of this team, but who knows, Sanjo might start on the bench with a lack of fitness, Klassen might start, Tom Davies might play instead of him, you know, Morales might play Kieran Dalmy playing instead of him, you know, these are the options the manager's got and that's fantastic, that is absolutely fantastic that he has those options, you know, Williams might start, Jags might start, they're the options the manager's now got in the squad, you know, so that is healthy, it's fantastic, but this is my team to start the game on Thursday night against Ruzan Biak of Slovakia in the first leg of our first qualifying round for the Europa League, so let me know what you think in the comments, do you agree with this, let me know, yeah, tell me what you think, get this sorted, Joe, nice new snazzy Europa League stuff though, I'm liking it, I'm liking it, yeah, don't forget, make sure if you haven't subscribed already to subscribe, get over to Patreon, if you love our videos, want more, get on Patreon, there's more videos over there, more exclusive videos, get over there, thanks for watching Toffy TV, don't forget, leave your comments, tell me your team, if this isn't your team, tell me your team, tell me why, tell me why whoever you want to bring in deserves it, thank you for watching Toffy TV, we'll see you later.


So I had to schedule this appointment like months in advance so it wasn't really an option to change it and then I ended up having to move on this day as well So like I tried to have everything move this morning Hello. Hi. I'm recording my visit Come on in. I always record my Thank you. Hey Yeah, let's read Okay Yeah, I just I have like I do HIV advocacy so I post all my visits on YouTube and then I've been can see like how like Normal it is Well, cool Oh my god, thank you Figure if I'm getting my blood drawn or you want me to wait till after it looks like actually that we don't we don't check any And then I'm just gonna ask a bunch of background questions just to make sure we haven't missed anything. Okay, any fevers chills sore throat Weight loss night sweats chest pain difficulty breathing imagine vomiting, diarrhea constipation abdominal pain I'm gassed, but I've always been gassy Any rashes or lesions anywhere. No I mean, I do get I mean I've had this ever since I was diagnosed I guess it's like a kind of I don't know if it's psoriasis or what but I'll get like I don't have it now But I'll get flare-ups where it's like bubbly blistery around the edges of my and on my feet, especially around the outside Maybe once every few weeks They might be a little tender, but that's it Yeah, and I noticed sometimes it's after I've had like either a lot of stress or A physical stress like something some sort of pain on my body or something like if I get a wound or get hurt or something I feel like that sometimes causes it to flare up Yeah, he's given me cream to put on it to help And that helped in the past the cream did or nothing. I don't know if I really notice a difference. Okay. Well, but you don't have anything right now But yeah, if you have it again, and it's really bothersome we're not going away And then any burning with your nation blood in your urine Are you sexually active? Yes, I haven't been for a few months, but yes Yeah, I just moved so I'm like I feel disgusting right now. No Moving is really And I got locked out of my unit too with all my stuff in the hallway Okay, um any questions that you have anything that we haven't talked about anything that I Was wondering so my health insurance used to cover going to see chiropractor who was also like a sports therapist Because I had an accident and I might need like was kind of messed up I would go to him to work on that and then other stuff because I bodybuild but Blue shield doesn't cover that anymore chiropractic So I wanted to know if maybe there's a referral to a physical therapist that I can go to or I don't know if you guys specifically have to give a referral or if I can just go How that works And this is for you said you had any injury It's like a year and a half two years ago So typically we do have to give referrals for physical therapy and usually when we give the referral we have Just as a heads up we kind of describe what the problem is So if we we're gonna say like right me since that's where you are yeah issues, but yeah, I would be interested to look into that How often does that pain come? It's been more frequently lately like maybe a couple days a week I just really I just massage it is the only thing I do or stretch I don't know if this is something you know a lot about but my CD4 counts I've talked to a lot of other people and their CD4s go like well about 800 well about a thousand mine peak Have peaked at like eight and then like typically drop back down like 400. It's 500 It's average is that does that usually just indicate a weaker immune system in general? Not necessarily So the CD4 count it depends on what the level was at when you start a treatment for it And so because there's generally A max how high it gets or what it usually gets for most people from the lowest point. Oh, really? Yeah, so so someone who Who CD4 count was? Higher when they first started treatment would therefore reach a higher peak on treatment. Okay, so I guess depending on who you're Exactly, so I think I think around that the average was Is like a 300 rise so it sounds like you're doing pretty good or maybe like kind of float around that level But yeah, so depending on who you talk to they may have had different starting points, you know from So, yeah, so that's why that would be Yeah, but it sounds like you're you've been at a good level for a while. We're gonna repeat all your labs and stuff today So that's good Check your sinuses and your lymph nodes Any sign it's pain You didn't feel anything swollen. Let me check the ones under your arm. Yeah, I remember what that felt like Everywhere Come in I guess you figured out you're teaching young smart doc. Yeah Do you make other videos too? Yeah, like fitness and most of these like blogs Film stuff It's okay, so as I was saying yeah, the appointment and moving coincided on today and I Was like well if I'm going to if I have to be done anyway in the morning for the doctor's appointment And I'm scheduled to work at night. Well, I might as well just go to work because Albeit have been done moving. There's won't be anything more to do and That was dumb. That was not the brightest idea to do all of that in one day But you know say la vie and and my DMV appointments at 8 a.m. Tomorrow morning to handle my car salvage title So Man I've been scrambling all morning. I got I got locked out of my apartment while I was trying to move all my stuff Was in the hallway. It was such a nightmare. I couldn't get ahold of anybody and I finally Based on a neighbor's recommendation was able to break into my own apartment using a credit card So I'll definitely be dead bolting my apartment from that one But I'm so glad that I was able to do that and then I rushed back to my old apartment picked up my Camera and then rushed here. I got here just in time for my appointment And here we are So, yeah, that was enlightening some of the stuff she said I Didn't know and now you know too.  It's great. It's worked wonders for me and Now I'll be able to see in a like blood panel Specific internal type of way how big tarvy has been with my body And now we wait for a glass team my awesome sauce doctor and I will eat these in the meantime So hungry. Oh, and I didn't feel like passing out after I give files and files of blood I got my own little table. Yeah, so cool fancy I probably Soar I'm so sore the mover was making fun of me because I was being such a baby moving stuff Because I did legs yesterday. I know I know not brilliant on my part I'm so sore And my core sore and my back sore and my biceps are sore and I was cramping trying to move things and I was just like Not doing well It's been a rough morning. Yeah That's good Cool Now that you have what is it more space and stuff? You can do that No more space. We can do it and it's important that they fix those Parts of medical care that they don't otherwise see yeah in the hospital. Yeah So, you know, they learn about HIV they learn about HIV prevention They learn about STD. They learn how to talk about sex. They learn about gay men's health Because you know, my favorite topic here is running. I mean, excuse me Pardon me delete that Actually joking aside, if you're gonna take care of patients, you do have to learn how to talk about sex in a way that Is not awkward. Not awkward Doctors awkward talking about sex People are not going to Tell you what's going on. So your knees bugging you I mean Wearing shorts It wasn't planned. I just was moving this morning. Please scoot back a little to you. Yeah, and Point to the part that bugs you Well, it's it depends like a lot of times. It's just general burning It feels like it's here under the kneecap. Okay, sometimes it's on this side. Sometimes it's like so relax your leg. I Went any pain in here? Okay, that's good Okay, good What sort of things aggravated? It's hard to say because a lot of times I feel the pain when I'm like in the driver's seat and my foot's just like Okay, I'm gonna start burning. Okay, or if I'm sitting in a chair, which starts burning Does it limit you from doing I have to like put it straight and if I can't it just builds up more and more, okay? Does that pain limit you or that burning sensation limit you from doing anything like exercise wise usually not exercise Sometimes yeah, and I have to go easy But mostly it's just if I'm sitting in a confined space and I can't fully it'll just get worse and worse Okay, and you stand a lot of work, right? Yeah, does it bother you when you're standing? Do you do any running? No, okay But walking doesn't seem to bother you Can you pop off the table for a second?  Okay, does one side feel tighter than the other you're good when I went when they actually worked on it They said this band out here is really really tight Yeah, I'm a lot of people poke the bunch of holes right here poke the bunch of holes You know acupuncture. No, I went in for a procedure and they I think they injected it with PRP Oh, I see and then the actual band the actual band There there was like a after I woke up There was like maybe like 20 holes there and they put it in the band so that it would okay When did you have PRP a year and a half ago? Did that help?  Yeah So you were seeing a chiropractor was the chiropractor helping? Yeah It was yeah, he's like a sports therapist as well. Okay Sports therapists like physical therapist But your insurance changed and it no longer covers. Yeah, cuz he's technically a chiropractor. Got it So you can't see him at all. No, you were great on TV. Thank you It was weird because she didn't tell me she was starting to film She's like, what's your name and then she started asking you questions. I was like, oh, no, it started probably yeah I can give you a prescription for physical therapy because that's all you need Tight ligaments or telephemeral syndrome can be painful. It can be annoying But it's slowly treatable and I'll recommend a few physical therapy places. Okay, and there you have it So, you know, okay with Victoria. Yeah So it's still I think in my opinion The best HIV medication we have ever seen I think it will continue to be the best we have available for about the next probably three to five years There will be new things coming out there have been new things that have already come out. Yeah There's a new thing. I don't know how much on top of this stuff you you stay But there's a new thing called Devato Which is one pill once a day also very very good. I'm not convinced that it has any advantages over Okay, but I think in three to five years We might have some things that you just inject into your skin as opposed to into your muscle and skin injections are much less Ideally, it would be like one injection every three to six months that to me It's worth paying attention to but I don't think we're gonna have anything earth-shaking until then. Okay. Um, any other questions comments concerns for me Get a flu shot in the fall when they're available Okay, so let me get you a prescription for physical therapy. I'll give you the names of some physical therapy places to go There you have it Yeah Yeah Are you the only one doing this a lot of people? Yeah, I've never seen another video of someone doing that No, that's it


Hi guys! Welcome to my talk on rocket fuel making hydrogen from home. I'm going to be talking today firstly about a bit of rocket science and rocket fuel and that's what I think. I'm going to talk about that for a little while at the start and then I'm going to move into doing a demonstration where you guys can make your hydrogen at home. So to do the experiment you're going to need these things at the bottom here. We're going to come back to those in a moment but because we're going to talk for a little while first you have a second to gather everything together and then we can do it together. So I'm going to start off firstly by talking, oh move to the next one, talking a little bit about myself. So I unlike the other speakers don't actually do astronomy or astrophysics but I really love talking about it. So I'm a science communicator so that's what I actually studied and it's what I do professionally and I really love talking to people about the stars and about rockets and I think rockets are really great fun. So you can see me on the left there talking about how we do spectroscopy. There's been some talks about that in the past so go back through and check them out and then at the top it's our rocket launcher that I made at home. So rockets are this really great thing that everyone can do together I think in terms of science and it's something that I get really excited about when I talk to people about. So what I'm going to do in this talk the first thing I'm going to do is talk to you about what is rocket fuel and then at the end I'm going to take some questions but I really encourage you to ask questions throughout the talk and then they'll come up and I can answer them either as we go through or answer them at the end. Then I'm going to do the experiment live in front of your eyes and at the end and all throughout it ask questions, send in troubleshooting and we'll try and work through it together and join in in that way and I'd really encourage you if you build it along with me to post a picture in the comments and everyone can see what you've done I'll be posting my picture and I'll take questions all throughout that so ask your questions anytime.  The other thing is please make sure you have a supervisor with you for this experiment. You can get a bit fiddly and involves a little bit of an electric current, a little one, so make sure you have a responsible adult with you for this experiment. So what are we going to need? The first thing you're going to need is some aluminium foil this is going to be the going to help us with the batteries to kick start the reaction we're going to do. You want to get a clear container this one's mine it's not too big but deep enough that we can put the aluminium foil in it. Get some plastic cutlery so you can put it along the top of your container it doesn't have to be cutlery necessarily wooden chopsticks or plastic chopsticks will work just as long as something you can prop on the top and that is not metal is the main thing so some plastic knives or something is perfect there. Get yourself some sticky tape some salt and some dishwashing liquid you don't have to have the dishwashing liquid but it can be really cool if you have it and yep so the final product is going to look like this just to give you an idea. I'd really encourage you to get a few batteries double A batteries preferably but not more than four. One is probably not enough but um three or four is a great amount not more than four or you might get a zap and that would be sad for everyone. So let's talk about rockets. So getting off the earth is actually really difficult and there's a few reasons why that is the first reason is gravity pulls us down the closer you are to earth the more gravity you feel and it can be a bigger struggle to launch up and away from gravity and the more weight you have on the ship the harder it's going to be to beat gravity so you think well you know if it's so hard to beat gravity we'll just put more fuel in and we'll get a bigger rocket but the more weight you add through things like rockets and fuel the harder it's going to be to beat gravity. The second thing is that getting through the atmosphere can be really bumpy it's a bit like if you've ever been on a plane and they tell you to put your servo outs on because there's going to be some turbulence and it's the most extreme form of turbulence you can imagine on a rocket and they're strapped really tightly in but what that means for a rocket fuel is it's not something that can be very unstable it has to be something that doesn't get bothered by a lot of heat in the atmosphere and something that's not going to be bothered by a lot of bumpiness so that's that's the reason why getting off earth can be hard and we have to really think when we're designing rockets and rocket fuel. We've got two kinds of rockets that we're going to use to get off earth the first one is solid a solid fuel in like a solid rocket so once this fuel is ignited it's just going to go and go and go you can't turn it down or use it to do things like thrust or steer because it's going to just like keep on going once you've ignited it the second type of rocket then is a liquid rocket so you've got much more control over this type of fuel you have you're able to actually use this liquid rocket to um control the speed of the rocket ship and even turn the rockets on and off completely so the two main ingredients then of liquid fuel are hydrogen and oxygen and that's what we're going to be making today so that's also fun so two kinds of of rocket fuel then so what about hydrogen and oxygen so hydrogen is great because it's really really light it's the lightest molecule on earth and it burns really intensely so over 3000 degrees celsius and it's going to be very very hot for that reason and as it burns and explodes it's going to create a lot of energies it's going to push our rocket along it's actually hydrogen so explosive and so bright in its explosion that an example of it is in the sun and in stars and if you go back and have a look george's talk last week talked about how intensely bright and fiery things like stars and supernova can burn and they're also made of hydrogen so that's why we're going to use hydrogen in our rocket the second thing is oxygen now remember we said that hydrogen is so powerful when it burns but this is called a combustion reaction and you need something else in a combustion reaction so planes also use combustion reactions but they are burning fuel to create energy as well that pushes them along just like a rocket but in order to burn fuel the second thing you need is oxygen and the plane luckily can get that oxygen from the air so our air in our atmosphere provides the fuel with the spark it needs to kind of ignite and burn a lot so it can draw in air from the atmosphere space as you might know is in a vacuum that's why we can't necessarily hear things very well in space and why you know all sorts of friggy things can happen when you go out into space in terms of pressure but what that means is that there's no air and there's no oxygen to burn so when we ignite the rocket we need to get that oxygen from somewhere else to get that burning combustion reaction so we actually need to send that oxygen with them on the rocket and it draws it in from the cylinders so if we go back to those two kinds of fuel actually we need rockets with oxygen for both solid and liquid rockets which is an important thing to know because we cannot get that oxygen once we're in space so how does a rocket work so simply our liquid rockets are going to work by burning hydrogen fuel with the oxygen in a high pressure chamber and we can see it here at the end on the right and we've got the hydrogen fuel in one area the oxygen and other they're going to combine in a reaction and bang it comes out the end in my very explosive diagram here and the direct exhaust out of the nozzle is going to propel the rocket along so we're about halfway now so if you've got any questions ask them now and we can answer them toward the end and there's the rocket being propelled along by the the energy of the exhaust so now you must be looking at a lot of these rockets and the kind of trails that they're creating and thinking like wow this must be pretty terrible for the environment and climate change and stuff like that look at all this explosion and this burning and you know the planet must be pretty sad but actually not so much because when we have a plane and a plane is also burning fuel like we talked about and it's a drawing that air in from the atmosphere to burn that fuel the fuel they're burning is not hydrogen it's something called kerosene which is a bit like diesel you guys might put in your car or your truck or your parents maybe if you don't have a car or a truck yet so you might have heard that like a co2 or carbon dioxide or carbon emissions um this is created when you burn a fuel that is carbon based so diesel is made of carbon so when it burns and it combines with that oxygen that we have in the air what you're going to get is carbon dioxide co2 and too much of this is what's contributing to climate change and the planet being sad like we saw in the last slide but luckily rockets don't actually use a carbon based fuel rockets as we've just talked about use hydrogen combined with oxygen and when you combine carbon no sorry when you combine hydrogen with oxygen what you get is H2O H for hydrogen over oxygen so you get water so actually when it burns it's not actually creating those like terrible carbon emissions it's creating just water which is like much better for the environment rockets aren't totally environmentally friendly you know space junk is a growing problem and making the rockets uses a lot of energy resources can be difficult to collect and it can be really difficult to recycle the materials in rockets once we've used them but hydrogen fuel is certainly a way forward and not necessarily bad for the environment especially compared to something like diesel so if we've decided if we've discovered now that water is the product of rocket fuel combining with oxygen we can make this at home by going the other way so splitting the water back up into hydrogen and oxygen for fuel but they're fixed very tightly as you can see in this diagram here they're really stuck together and we need to do something to break up this very very fond band of triplets and what are we going to do we're going to use electricity to break apart the bonds that are holding water together so my why might we actually do this in space so one of the reasons why we're actually going back to the moon even though we've already been there and we kind of want to go to mars is that before we go to mars we have to be able to make sure we have enough fuel to get to mars so remember the more fuel we have the harder it is to get off earth and the more expensive it is to push our rocket gravity is really hard to beat and it's expensive so we know that there's ice on the moon now and we can see in this diagram here the north and the south pole of the moon the south poles on the left and the north poles on the right there and you can see those blue dots are where ice is and they're in the darkest parts of the moon so the the lighter spots are the parts of the room that's the part of the moon that's the warmest and the dark spot are the cold it's in the really cold dark areas of the moon and we also know that there's water detected under the surface of the moon so if we can separate rocket fuel from this ice on the moon we could potentially use it as a source to kind of fuel up and keep going to mars and beyond and that would be really great for us so this is sort of the last bit we're going to go through before we start the experiment so um if you have any final questions go now but what are we going to do to break up water electricity breaks water up so what we're going to need firstly as we talked about is water and that's what we're going to get our fuel from then we need to put in some metal metal is useful because it's a conductor of electricity so if you've ever been told by your parents start to put a fork in the toaster or if you're like um my mom you've actually put a fork in a toaster and had something horrible happen to you um electricity flows through the metal and it doesn't flow so well through other things like plastic or wood so that's why we're going to use electricity and that's why we're going to be putting our props as not um as not metal because you know we don't want to zap ourselves in our props so the metal's going to bring the electricity into the water then we've got batteries batteries are what's going to kick off our current we're going to have a positive and negative side and connect them together so we have the flow going through um through the metal and into the water and then the last thing we've got to do is sit and watch the water break up and create our gas bubbles so the um on the one side we're going to see hydrogen gas coming off and on the other side we're going to see oxygen gas coming off which one is which you might ask you'll have to try it and see or if you're not going to try it you can just watch me do it and I'll show you so but you said I said that we were going to make a liquid rocket and now we're making gas well you know I hear you but you know it's kind of complicated so to make hydrogen into a liquid you're going to need a lot of compression you need to be very cold and you're going to need somewhere to secure and store it that's not going to leak out once you've created it and made it into a liquid and that's kind of hard to do from home much harder than just you know separating water so if you're interested though in um liquid hydrogen into the future um hydrogen is being looked at as an alternative fuel for things like planes and cars because as we talked about we want to move away from those carbon-based fuels and into one that maybe just makes water instead of carbon emissions so if you're interested in you know liquid fuel um that could be a very lucrative career into the future but unfortunately not today so um if there's no questions uh we might press on so next up we're going to need these things so we're going to need the foil the batteries the container the cutlery sticky tape salt and dishwashing liquid so before we begin there's a few warnings that we should go through so make sure you're working in a very well ventilated space because we're going to be adding salt to the mixture a really small amount of chlorine is maybe going to be produced so you don't want to make your bedroom smell like a pool for the rest of the week so go to somewhere i'm outside you don't have to go outside being in a like an open plant area is fine but maybe don't do it in a cupboard so make sure you disassemble the the assembly as soon as you're done or leave it in a well ventilated space outside if you're not able to leave it outside somewhere where you know your cat's not going to eat it or your little sibling's going to knock it over i have an example of one i've done a few days ago so you can see what it's like you're not missing out anything but if you're going to leave it make sure it's somewhere well ventilated don't do it on a metal bench or a metal sink as we said metal conducts electricity you want to zap yourself try to do your experiment and avoid touching the foil and avoid touching the water and make sure your hands are dry before we touch all those things or you might get a zap you might not but you might so don't do it and make sure your responsible supervisor is with you to do this and if you haven't already get the responsible person and i'm going to remind you of all of this as we go through so let's begin so now i'm going to move the camera down so you can see what i'm seeing and this is my workbench move that out of the way so this is what we're going to need here it all is here on the bench my foil i've also got some towels here to make sure my hands are dry nice and safe my container got my triple-a batteries i'm only using three but remember maximum of four and then we've also got our salt over here so let's begin here's my container the first thing i'm going to do is fill the container with water so it gives the salt a bit of a chance to dissolve i'm going to drive because it's easier but water out of the tap is really fine i'm going to take it off it'll go a bit faster now we add our salt again table salt just fine no brand sponsorship here but iodized table salt will do fine and just eyeball like a few tablespoons and then maybe grab one of your little case of cutlery mix it together and that will dissolve while we do everything else so move it to the side if your hands are wet make sure you dry them because we don't want to combine electricity and water on ourselves just in the experiment okay i've got my three batteries double-a's triple-a's will also work if you have a few of them at a stretch you could use a nine volt battery but double-a's are the best so four maximum of these otherwise you know increases your chance of getting a zap so what we're going to do is combine them together in what's called series so i'm going to use my sticky tape here to stick the batteries together smack tag a second but i'll hopefully take as long as you so you don't need to pause at anything and i'm going to go just like this and really pressing them together as we do that because if there's too many gaps then the electricity won't fall flow through it'll just like get stuck so here's the first one i'm going to do another one and holding them really tight see me i'm struggling with the the effort you know this can be a bit fiddly you haven't got your parent or guardian grab them now they'd be really great to help you with the with the batteries especially this next part which can be a bit fiddly and you can see mine are still a bit wobbly we don't want that so we're going to create a bit of a stirrup down here and what we're going to do is press down and pull down here like that and now that's really secure as you can see we don't want much flex at all if any so the next thing we're going to do just putting our batteries to the side for a second is grab our foil don't need too much foil and what we're going to do is oh excuse me is to connect each end of foil to one end of the battery so scrunch it up a bit like this and stick it on and like the other two if you can make sure you get it as tight as possible so grabbing the sticky tape oh it's stuck to my fingers really pressing it on okay so like the batteries we don't want a lot of movement here either so have a look and see if it's wobbling at all but if it's not you might want to like to put some sort of around the sides or maybe even underneath and then we're just going to put the side a little bit so something we don't want is for this to be touching the other bit of foil so make make sure you don't touch this bit of foil to the other bit of foil as we do this so next bit of foil and make sure you're not like clutching both at the same time just be careful you know try and touch hold the battery see I'm just carefully keeping it away you just bump both of them at the same time so I just don't like grab them both at the same time okay here you go very secure on one side very secure on the other side we've made our little thing now so what you probably want to do now is just gently just like open it up a bit make sure the foil is you know it's all clumped together we want as much surface area as possible to be in our salty water and just double check everything's on really securely yep looks good now we're going to grab our salty water back make sure one last time you could even add a bit more water not water salt if you want it you want it to be really salty make sure you're not using the wet implement give everything a bit of a dry dry dry dry my hands okay two just like this over the top remember if you don't have knives you can use cutlery or something or not cutlery not metal use chopsticks whatever and then we're going to put it in here it might only just fit so lucky me the reaction has begun and if you have a look down here you can see it bubbling away on the left hand side now the question we've got is how much hydrogen does it take to blow up a safe like to get money out I assume I'm not sure I think it would depend how robust the safe was but you can collect this hydrogen if you want and I wouldn't recommend you have a go but yes oh sorry I just realized my left your right camera is flipped so yes on the on the right hand side to you guys here it is bubbling away now something you might ask is I told you that it was going to be hydrogen and oxygen and you're saying what I only see the hydrogen what's happening on this side not much well that's because actually the oxygen that's being created is reacting with the salt in there and instead of creating oxygen gas it's creating chlorine gas which is much yakia and unfortunately not super useful for the audience so you might smell a tiny little bit the smell of chlorine a bit like a swimming pool don't stick your face in it chlorine's not very good for you in case you don't know it's usually used to clean things but that's why you're not seeing anything happening on this other side all the actions going on here and you'll see it's beginning to rise up now this is the time you might want to add the dish soap if you want to and you can see some pretty bubbles forming on the top with the dish soap and yeah so that's it and you can see it sticking to all of the crevices here where there's the most exposed parts and there you've got your hydrogen you can collect it and use it to blow up a safe or power your rocket the choice is yours so the last thing I kind of wanted to show you so it's the last thing so if you've got any final questions about safes or otherwise you can send them in now but if not add them to the comments later and we'll answer them for you is what happens when you leave it overnight so fast forward two days and this is one I prepared earlier I'm just going to swap them out here and you can see it's looking very different so we've got here we've still got our fork and the batteries they've been sitting and running you can see down the bottom here we've got this disgusting looking white foam and on the left it's the foil has become completely tarnished and dark and on the right where it was originally the same size oh sorry on your right and my left um on your right and your left it's completely gone it used to be the same size now it is much much smaller and you can see on top as well we've got some delightful looking metallic foam so this is because we've actually created is an electrolytic cell and what's happened here is an oxidation reaction has taken place and it's demolished this this part where the oxygen and the chlorine is being created and at the bottom you see that reaction between the aluminium and the salt to create a bit of our foamy deposit here so if you want to do that then that's that's what it will look like in a few days um we have a question about why does it stick I'm not sure what it is but if you're talking about the bubbles it's because they haven't quite escaped yet so they're going to cling on until they're able to kind of break that surface tension and rise to the top so yeah if there's no more questions you might just wrap up and let you sit and and think about your next rocket adventure you can actually I'm not sure if it's quite enough you can actually hear the bubbles so the last thing is when you're done with your cell if you don't want to leave it overnight like I did which is totally fair enough you know it looks um a bit disgusting if you don't want to leave it overnight then what you can do is just disassemble it straight away so pull apart the batteries and it's okay to just pour it down the sink it's only salty water at this stage so that's fine if you do want to leave it overnight make sure you put it in a well ventilated area somewhere that someone's not going to knock it over or anything like that but yeah thank you so much for joining me and um oh yes and when you're pulling it apart make sure you don't touch the two metal ends together still although you may not have another end as you saw with mine to come back to at all so be careful with that so yeah thank you so much for joining me um I hope you enjoyed it or you can try it yourself if you didn't watch it if you weren't able to watch it live um and do it with me live but yeah it was great to have you all joining me and yes this was luck bye guys