xisxisxis

A colleague died a few years ago from lung cancer. I heard his spouse was upset at the medical advice they received near the end from a colorectal oncologist. I was astounded that they would listen to a colorectal oncologist instead of the lung oncologist. Why, they're both oncologists? Because it makes a difference (lung biology is different than colon and the cancers are different). All of these "experts" really need to be ranked based on their "expertise". Obviously, an infectious disease expert is better than a pediatrist, but a microbiologist is not as good as a communicable disease specialist (both infectious disease). Using WAR as an example we would see comm disease (6 WAR), microb (2 WAR), pediatrist (0.1 WAR). "Medical Scientists" actually aren't that common. A Medical Doctor is not a scientist. They have likely never been trained in any way on performing research/studies. Most medical training is learning pattern recognition and probability - symptom X, Y, Z = disease I (42%), Disease II (25%), Disease III (19%), etc. Some MDs do "research" which often is similar to the study at the Henry Ford where they look at hospital records and look for any "findings". If the MD has a PhD then, yes they went through training to understand the principles of research. Having worked for 30 years with MD, MD/PhD and PhDs, there is a clear ranking of the average person within each field and yes, MD is by far the lowest in aptitude for research. That doesn't mean that the top %centiles don't have some good researchers, but that the vast majority are not good (like asking a pediatrist about coronavirus). "Infectious Disease Experts" are hard to find because for too many years there has been no emphasis in medicine on this specialty. Most IDEs work on HIV. In my department we only have 2 and both are senior citizens (not the AARP kind, but collecting Social Security kind). There is almost a generation of faculty without a single expert in Infectious Disease. Mostly because it isn't sexy and specialization in medicine/research is to go for the sexy and where the money is and the money has not been in Infectious disease research. It's a disappearing specialty and we are seeing the effects of that with the current state of "experts". "respected medical journals and peer reviewed studies" is an important consideration. The number of journals that publish scientific papers is astounding. In infectious Disease there are over 300! They aren't the same and where a study is published should be part of how it is ranked for importance/significance. The study from Henry Ford was published in the 62nd ranked journal in that field. Sure, there are other journals that are HIV specialized that are ranked higher, or publish only review articles and the rankings from 40-60 are likely pretty subjective, but this paper was not published in a highly respected journal. Why? Likely a multitude of factors, but none of which lead to a positive spin on the paper. As a scientist we learn how to "present" our data/papers in such a way that we are challenging the reviewers to question the findings. It's not uncommon to state "we found no side effects from treatment" when you haven't measured for anything (worst case) or when your measurements don't really capture side effects accurately (common). It's true that you didn't find anything. The challenge for the reviewer is to make sure the authors stated clearly what and how they measure for side effects. You can also be vague in your criteria hoping the reviewers don't catch something. Is this dishonest? Some would say yes, but ultimately you include very clear language about the impact, etc. and if someone gets an impression that isn't stated that's not the authors responsibility. In many ways it's a game. The game is best played when the reviewers are smart enough to catch the unclear, unstated issues. I teach a class on review of scientific literature. Year after year the students biggest surprise is that papers they thought were good and had no problems were actually riddled with issues and that almost every peer-reviewed published paper has inherent issues that can invalidate some or all of the findings. Peer-reviewing has it's own issues. Scientists are busy and have their own careers to develop. I'm not going to review a paper from a 62nd ranked journal. I'll review for the top journals in the field because it's a valuable use of my time and I can put that onto my CV and it is a positive. So the reviewers for the 62nd ranked journal are the ones that can't get the 40th ranked journal to give them the time of day and won't stoop to review the 100th ranked journal. So you can drive tanks through the holes in a review if the reviewers aren't good (that's true also of higher ranked journals, but much less likely to happen - i.e. the reviewers will catch the issues). The former cancer center director at my institution would spend half of their lab meetings going over how you present the data for maximum impact. I stopped attending because a few months in I didn't need another reminder on the best font, title for a graph/table, etc. But for some it's all about presentation - putting lipstick on a pig. What friends and I call form over substance. While it's important to present the data in the best possible way, you should still have a clear finding that you are just improving. I reviewed a paper from a colleague prior to submission and asked why did you subset the subjects at point X. That was the only place they could subset the data for their to be a significant finding! So if you move point X by 5%? no finding. Is X relevant biologically? Nope. The author should not be publishing in that case and when they try the reviewer needs to find the problems. Unfortunately, the quality of the reviewer mirrors the quality of the journal. The other reason so many of these studies never amount to anything is that there are severe biases that have been introduced. I worked with a FUNDED MD who insisted on knowing the status of a sample prior to running tests. DING DING DING. Alarms should be going off because as Igor stated blinded (double blinded) samples are critical. So we gave them a bunch of samples with random assignment of status and guess what? Every sample we labeled as a case, came back looking like a case and every sample labeled as a control came back looking like a control based on the "scientific testing". When we reassigned based on known case/control there was nothing. When presented with the data, the MD fought that this was an incorrect approach and their approach was better. Why? because the testing is subjective and they needed a "hint" for them to believe certain events within the test are "real". Many assays/tests are still subjective and don't rely on a clear value or metric. Unfortunately bias happens all the time in clinical trials as the inclusion of individuals in a study, or the arm they are put into can be influenced by bias. Removing subjects can also have bias and can skew the findings (all studies should have clear criteria for removing someone that isn't a function of the outcome you are measuring). That's why it's so important to increase sizes as much as possible, but more importantly have it repeated by others because they hopefully don't have the same criteria/bias. So the Henry Ford study could very well be effected by a clear bias in selection of how to put patients on each arm of the study, how to remove patients, when the endpoint is measured (yes, people will move the goalposts) that is driving the results. One study means nothing. And one principal investigator who believes a certain treatment is better than another can subconsciously (or even consciously - i.e. fraud) effect the outcome. There's a lot that goes into how you should rank what is an expert. Most scientists are experts in a very narrow area and while they may have some knowledge of the general field, their knowledge of another very narrow area is not as good as those working in that area. Nobel Laureate? Nope, I've met some that are truly very bright people and others that are bumbling idiots (except in one very tiny specific area where they are THE expert). Titles are no guarantee. WAR might be a good example of the need for a metric that combines lots of different components into a measure of what is an "expert".

And even with a yearly flu vaccine, TENS of millions in the US contract it and 0.1% die from it. That's not completely protective. Yes, even people who get the flu vaccine will get the flu. And it's a strawman argument that something is "possible" that it weighs merit if the likelihood is so low to be functionally zero. No, I can't disprove that space aliens landed and infected us with a novel virus to see how we would respond because I can't prove a negative (like aliens don't exist or they didn't land in Wuhan). The chance a completely protective vaccine is possible is so low that no credible person should use that as a basis to change policy. Policy should be based on highly likely possibilities. Otherwise you just end up killing more people. Giving people stuff and expecting either a positive finding or no harm is the reason we need the FDA. Often you harm people while trying to help them. I worked in a biotech company years ago and our first product made it through phase 1 clinical trials, but went down in phase 2 when it actually killed more people than if they received the control treatment. More died with the drug than without! That happens often. Too often to just shrug off the dangers. There's some data from China how to proceed with severe cases, not sure anyone in the US is paying attention because the WHO said it. I have no problem with doctors trying novel approaches when dealing with severely ill people, within certain guidelines. This isn't ebola or SARS, the mortality rate is much lower so the waiving of "experimenting" on patients isn't as justified.

They took Chloroquine Phosphate which appears to be used to clean fish tanks. This is an example of natural selection. Darwin thanks you...

There are none. Initially several anti-viral drugs already approved for other viruses were hoped to help. I believe 2 have been tried and the results are they FAILED to work as hoped. Both didn't do anything compared to controls to stop COVAD-19. Another hope is the anti-malarial drug hydroxychloroquine. It has been used to treat the parasitic infection that causes malaria. One uncontrolled tiny "study" indicated hydroxychloroquine might help. How an anti-parasitic drug will be better than an anti-viral drug in treating coronavirus is not mechanistically clear. At this point hydroxychloroquine is a YUGE long-shot given that tens of thousands of drugs that show promise in small uncontrolled experiments end up with no positive result when properly tested in large studies. The greatest hope, to date ,was a japanese anti-viral that has been showing very good results with other viral infections and it failed. And for the vaccine rumors. There will be no completely protective vaccine. PERIOD. We have been searching for a vaccine for the common cold forever. The common cold is caused by Rhinovirus, coronavirus (human versions - COVID-19 jumped from animals) and several other viruses. Flu (influenza) has so many variants that when you do get a "yearly" flu vaccine you get many strains that they hope will be the common flu for the year - some years it works well, other years different/new strains are common that they didn't predict. So every year we get new shots for new/existing strains. COVID-19 is a coronavirus that is related to the human coronavirus that causes the "common" cold. There's a reason Fauci always says a vaccine is a long way away.

There's lots of problems with the Icelandic population. I don't remember the exact numbers, but roughly 50% are related to a small group of settlers that discovered the rock. Years ago there was great promise tracking down genetic disease genes because in addition to a small founder population, they have extensive birth records so you can track the families almost back to the discovery. Turns out a lot of the genetics didn't translate to non-icelandic populations. I can't remember the biotech company that was founded their and promised to identify all the genes involved with disease because you don't hear much about them anymore. While it's interesting information, it could have zero application outside Iceland. Maybe they just have a genetic background that is favorable for preventing viral infections. The cell receptor that the virus uses for entry has quite a bit of genetic variation which may be unique or common in Iceland. For example, there is a subset of individuals who never get infected by HIV because they have 2 copies of the receptor that contain a variant that the virus can't infect. That's just a single genetic change and they are completely protected.

Yes, which just reinforces the point I was making. Basing any conclusions strictly on numbers without accounting for how those numbers are calculated/determined is very risky. If you want to use those numbers literally you need to take the death and recovery numbers literally too. The point is you can't take any of those numbers literally. Unfortunately we live in a time when attention spans are so short that when you say "yes that is the current number, but there is a problem with how it is measured..." and the person you are trying to discuss the point with has already stopped listening and is searching their phone/google for other data... They've moved on and just remember the number they saw/heard and that's it. The CDC will be the main gatherer of that information because knowing who survives and recovers is just as important as who doesn't. While looking at mortality associated data can give you an idea of what the at risk group looks like, you can't accurately predict risks without also knowing the numbers for recovered and their associated data.

It may be best to not rely on "confirmed" cases to base any conclusions. There has been an avalanche of information that testing has not kept up with demand due to a shortage of testing kits. The testing shortage is also likely skewed and rural areas may have a 5% chance of getting a test done while urban areas will get preference because the demand is so much higher (if you have 5 tests available are you going to run a test from 1 doctor in Rhinelander or 50 doctors in Milwaukee?). There is one interesting bit of data on that figure: 4 deaths, 1 recovered... Now if you want to believe the data as presented, that's a pretty scary set of numbers.

Ventilators are useless. Once your lungs get that bad, no matter what you do they won't oxygenate the blood sufficiently. What worked in China was to put the patients with reduced lung function on a form of dialysis where the red blood cells are oxygenated outside the body then returned to the patient. That helped significantly in keeping people from suffocating to death. With sufficient oxygen they had a chance for their bodies to fight off the virus. Did it save everyone? no, but it significantly improved outcomes for many.

Is that 3-4 million in the US, or globally? The other thing is that almost all of these people are elderly and comorbid to begin with - they don't have a lot of time left anyway. I'll bet the younger ones (under 70) are or were heavy smokers. I'm not diminishing the loss of life either, but my 92-year-old grandmother passed away three weeks ago and she was in very poor health and had been for the last couple of years. In and out of the hospital for the last six months, and about a month or so before she passed was diagnosed with a rare form of skin cancer. My father agreed to give her infusions of I believe Keytruda... at 92 years old??? I'm sorry, but if you're over 80 and have serious comorbidities (like the average person in Italy who has died) you're not going to have some miraculous reversal of health. If you're in a nursing home, you aren't going to recover. You're allocating resources to people who simply are not going to benefit from it; you're keeping people alive for the sake of keeping them alive, just like my grandmother. You have to let go and allocate those resources to people who can benefit from it. But we live is such a litigious society, and the medical profession has learned that if you don't do everything possible or if something goes wrong you get sued. Yes, decisions are going to have to be made on who to treat and who not to treat, and that sucks. But that means family members making decisions for the greater good, not selfish decisions, and not punishing doctors for making decisions for the greater good. Numbers are US. I agree with much of what you said. There is plenty of evidence in Italy that with the health system near collapse, they are making decisions to let nursing homes and other collections of very high risk individuals fend for themselves. At some point we will have to make decisions on allocating health care, but hopefully we don't get to a point where low risk people are being compromised/die because we don't have the medical capacity. I think that's one of the main reasons to slow things down now. Nobody is going to get in front of a camera and say we are going to let the old/sick people die to protect the rest of us... But that's what's likely to be the end result. And there will be benefits coming out of this. The demographics will ease some of the drain on the SS system. Many of the deaths will also remove chronically ill people from the healthcare system and reduce those costs. This is the THIRD novel virus to arise in China over the last 20 years. How the "west" works with and interacts with China needs to change. Free trade should not equate to free to export deadly disease. This is also the country that had multiple companies making baby formula and other food that was substantially plastic components. If they don't have any regulatory and testing services in place then any item from China should be taxed an amount that the US can test. If it makes dog food from China too expensive, tough. We don't need to continue to be poisoned and infected by a country that can afford to implement the necessary regulatory changes. The issue is that China doesn't give a **** about the rule of law, because then Party members could be accountable, and safety shouldn't impact profits. It's time we get rid of the false idealogy of "free" trade.

On Monday, I received an email with the results of one of the first studies to look at the effectiveness of approaches to stopping the coronavirus spread in Wuhan. I don't know if the paper has been released publicly and I haven't seen any mention in the press so I will just summarize the details: "I would like to share with you our analysis results of 25,000+ lab-confirmed COVID-19 cases in Wuhan until February 18, 2020. The strategy of lockdown+mitigation (social distancing)+home quarantine helped but was not good enough to stop the outbreak based on the Wuhan data. It reduced R from 3.88 to 1.25. This is because family transmission is common. Family members and close contacts are likely to be infected, and then infect others. Centralized quarantine of ill patients in mobile cabin hospitals and exposed subjects in hotels/dorms effectively stopped the outbreak (R=0.3). " To be clear, based on the Wuhan data, the only way to stop the outbreak is quarantining ALL INFECTED ("hospitals") AND ALL EXPOSED ("hotels") individuals. Social distancing HELPS, but is insufficient. I've spoken with Chinese colleagues and they guess that some of the quarantine efforts were to lock families into their homes and wait for them to 1) recover or 2) die. A strategy a Democracy is not likely to attempt. At this point our efforts are likely only to slow the progression, not stop it. Edit: R is rate of transmission. Other notable findings: 1) Health Care workers are 3-4X more likely to be infected then the general population; 2) the outbreak started from the urban districts and gradually spread to the suburban and rural areas, leading to strong geographic differences with the highest rates in the urban districts; 3) at it's peak there were ~150 cases identified per 1,000,000 people. Extrapolating to the US would be roughly 45,000 cases per day if the entire country was equal. Likely the pandemic will show significant differences in progression across regions. Extrapolating to LA or NY would be 1,000 to 1,500 cases per day. (none of these are unexpected findings).

I understand that people may be freaking out about this, but we are way too early to be drawing any conclusions about the scope of this pandemic. But a few points: 1) Even if half our population is infected we are still likely losing 3-4million people. On a human being scale that is a huge hit, but overall it is only a small fraction of the population. I don't want to diminish the loss of those individuals and how it will effect families and friends, but on a societal level these are not world ending numbers. Will our society change? Yes, but it changes for many reasons all the time and if anything human beings are resilient. I have 100% faith that once we have to rebuild that even those that are beyond freaked out right now will be able to function during the recovery. We survived disco, bell-bottoms and ass-crack pants, and we will survive social distancing. 2) Is our economy ruined? Well what production capabilities have been destroyed? None. Supply side will recover relatively quickly. On the demand side, we will likely have some changes, but eventually there will be demand in more than just toilet paper and hand sanitizer. With the fed and government committed to making money flow we should have enough priming to get the economy moving again faster than in 2008. 3) While much of the uncertainty relates to the Coronavirus spread, the major issue with the stock market were triggered by Russia and Saudi Arabia starting a price war with gasoline that they show no signs of stopping. When we've recovered from Coronavirus and bailed out US oil production, we should be making some plans as to how to best "F" them both up. So much dishonesty (and unknown being put out as “facts”) being printed by journalists it’s not funny. I don't really know what you mean without specifics. The issues are complex. Each country tests and manages their patients differently. Everyone is trying to extrapolate the numbers without all the details. That will lead to mistakes. My only beef is that with all the people now out of work, why can't most of these outlets hire a friggin copy editor. Earlier today an article said that "France" had surpassed China in deaths - No, It's ITALY. Some people need to lose their profession when this is all said and done I can think of 539 that need to start working for a living instead of collecting a paycheck, the best health care, and a cushy retirement while being absolute crap at their job. Personally I would rather live next to a pedophile than a politician because the pedophile at least stands for something no matter which way the wind is blowing. Never let a good crisis go to waste. I really can't wrap my head around the idea that this is some form of manufactured self-destruction. The issue is pretty simple to me. We are attempting to keep the pandemic from spreading out of control across the country so that we don't lose 100's of thousands of people to a disease because the health care system has collapsed under the volume of ill people. All of this is trying to make sure we don't lose 20million people because we weren't vigilent enough in the beginning to make the right decisions. Is it worth a recession of we save 100,000 people? 1 million? 10,000,000? I don't think we can answer that as we will never know how bad it would be if we didn't risk a recession to take the steps to save lives. I think it's better to have a discussion on how we can make sure this doesn't happen again.

And a clue from that article why Italy's mortality rate is so high - they are only testing people with SEVERE Symptoms. So there are likely 3-4 times as many infected that just haven't been identified as they are either asymptomatic or have mild symptoms. Sounds like the Germans are testing anyone they can.

One thing to keep in mind is that there is no SINGLE COVID-19 virus. Each time it replicates there is a chance that a mutation occurs that either 1) makes no difference; 2) makes the new virus more "severe"; or 3) makes the new virus less "severe". While infected you will have multiple different subtypes in your body that will go through selection during it's course and through any treatment. Each infection (new individual) is another round of "natural" selection. There will be subtypes and subtypes "evolving" over time. Part of the reason for not letting it infect everyone is that it just increases the chance that a really bad killer version occurs. It's just math. The killer evolution isn't likely a single mutation and is likely very rare, but nonetheless it is possible. Keeping the numbers down until we begin to acquire immunity is very important. The reason HIV was so hard to treat, initially, is that due to the mutation rate, almost every individual had a variant subtype that was resistant to the first line of treatment. So while they got better initially as the susceptible virus went down, the variant multiplied then the patient relapsed. Combination therapy finally worked because the chance that a mutant virus was resistant to all drugs was much lower than the viral load in an individual.

True, but the impact is hard to predict due to the long time it takes to get here by ship: Tokyo to Seattle is 20–24 days. To San Fransisco is 18–25. Shanghai to Long Beach, CA is 22–26 days. Shanghai to San Francisco is 23–30 days. So 3-4 weeks just to get a container ship to the west coast and another 3-5 days from the port to destination in the US. So shortages can take a month to recover once they've shipped from China. Longer if there are delays producing more. I imagine with prices surging that there are manufacturers ramping up production. I just heard from a friend that the delay in testing kits in the US is due to a shortage of the kit used to prepare the sample to be tested (purified nucleic acids are required for the actual test) and that the manufacturer is ramping up production (in the US - it's a German company so European stock will likely go to testing in Europe). Unfortunately, standard protocol is to approve 1 kit and they didn't approve other kits so there's a bottleneck...

There's a lot of reasons for shortages, a few: 1) Most companies have moved to just-in-time purchasing of supplies instead of having a large amount of stock on hand - when demand spikes then a shortage happens even on some basic supplies. 2) Unfortunately making 2-10X selling to panicked people on Amazon beats selling at low-price to a hospital chain. The surgeon general already warned about a possible shortage of surgical masks due to the large demand from the general public. Go on Amazon to see what items are selling for and what are out of stock. Two weeks ago, it was hard to find Purell and other hand sanitizers (I bought the component reagents at normal prices). This week the components are almost all out of stock or 4-10X the price they were when I purchased. Alcohol wipes are being bought because Lysol wipes are out of stock. People are buying the high priced items to the point of buying out the stock. Hospitals are scrambling to get stock. Crazy.

The Chinese repurposed numerous hospitals as treatment centers to handle the influx of individuals and modified existing instruments to help reduce mortality. For serious cases they received oxygenation of RBC outside the body as their lungs were shutting down. That means lots of people on dialysis with the proper machinery to highly oxygenate the blood. It's not clear the US health industry can 1) act in a coordinated manner as in a dictatorship, and 2) even have the necessary hardware to deal with a large number of infected/severe cases.

One issue to keep in mind is the transmission rate. The flu has been around forever, there are probably thousands of strains and many people are vaccinated each year. Yet, we still have significant numbers of deaths (20-60K per year). Everyone has antibodies to a subset of influenza which provides partial protection and slows transmission. Nobody has immunity to COVID-19 so there will be an extremely high transmission rate as there isn't any part of the population that is currently protected. With the slow progress to symptoms there will be significant time for an infected individual to infect others. So in theory this is a very serious health outbreak. It appears shutting down areas of infection for ~4-6 weeks is successful with reducing the transmission and containing the issue. Efforts should be made to test anyone who has had an interaction with an infected individual and for many people to self isolate as possible in affected areas and for people outside effected ares who have had contact with individuals in those areas.

He wasn't the same player after he was suspended for steroid use...

OASDI is Social security. Based on this paystub he hit the yearly max on his first paycheck.

The entire section on Hader, for those who don't subscribe with the part from IIAY in bold:

If nothing else it should serve as a sobering reminder to all of us. Whether it be flying in bad weather, rushing to get to work in time, trying to reply to that text while driving, taking an unnecessary risk at work, driving drunk... It's never worth your life. Ever. Just wait. I think it's more basic than that. His choice to fly was due to his desire to not miss out on his children's lives because he missed a school play while sitting in LA traffic one time. He decided to take helicopters as a way to reduce his travel time. Sounds great, except you now are 30-90 TIMES more likely to have an accident/fatality (even higher as the "accidents" that occur during a clogged freeway are much less likely to lead to death because of reduced MPH). He added a significant amount of risk and thought nothing of continuing that lifestyle (he no longer has to attend practice ~100 times a year and probably the easiest drive in LA is on a Sunday morning). Unfortunately so many people ignore the downside of their decisions because the "event" that leads to fatality or a severe accident are so rare that it doesn't seem a real risk. He just had a new baby and bad decision on top of a risky decision leads to 2 kids who will basically never know their father. Sad story.

Is the team capable of going 19-2 for 3 weeks in September without their best player? Sure, did it last year. So can every team in baseball, but the chances are different for each team. And if you believe that 19-2 streak was anything but a fluke, then you likely also believe the Brewers will be a world series contender if Yelich is out for the year. The Brewers were 3 games above 500 for 83% of the year before their unprecedented run. Have they added enough talent after their losses to make them a contender for the Wild Card Playin? Meh... Note: the most condescending posts over the last 3 months are the ones pointing out the date. By a long-shot. That's a classic definition of condescending... 'if only you were smart enough to read a calendar you would know how stupid your comment is'...

It takes a really special kind of stupid to complain about a rookie coach whose team went 13-3 in the regular season, including 6-0 in the division with 2 wins against a Vikings team that beat the 2nd best team in the NFC at their home in the playoffs, won a tough game at home in the playoffs and lost to the best team in the NFC at their home in the NFC championship. Any intelligent football analyst knew their was a talent gap between the Packers and Niners and for the Packers to win they had no margin for error and had to execute their game plans flawlessly. Didn't happen.

Oh, Yes, Please!... That's exactly what the Astro's deserve...

I'd say o-line play, the running game, and pass rush all improved significantly, as did FG kicking. The return game was much better after Ervin was acquired as well. Still deficiencies in run defense (and d-line, LB play), underneath pass coverage, and the passing game. This may shock you, but I actually agree with most of what you posted. I liked the post from LouisEly (in another thread somewhere) that the Niners built through the draft by emphasizing their lines (offensive and defensive). I have always and will always be an advocate that you build them and over-draft for the lines because with dominant OL and DL play you can tolerate average performances in so many areas. I'd like to see the Pack emphasize the following this offseason: 2 x DL 1 x OL 2 x ILB 1 x WR 1 x TE (although I still think Sternberger will end up as an above average TE, so maybe 2 x WR) 1 x QB (need to start drafting for Rodgers replacement)