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Dean Pomerleau

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About Dean Pomerleau

  • Birthday 11/12/1964

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  1. This is clearly off-topic, but I've long had a similar perspective and so will chime in. I said above that the accepted fundamental theory of stock valuation involves summing up the company's future discounted earnings. But why should future discounted earnings be valuable to a would-be investor, particularly when it comes to growth stocks which almost never pay out their earnings, i.e. in the form of dividends. Case in point, Amazon which has been losing money for most of its history and has never paid a dividend but instead plows its profits back into growing the company. Stock buy-backs have been popular lately, and explain (to a point) why stock prices have risen over the last few years - fewer shares available in the face of a fixed demand means the stock price will go up. But that doesn't explain why there is a demand in the first place. As a stock investor, you own a tiny share of the company, and therefore might get something back if the company was ever liquidated. But even that is unlikely since in the very rare event of a liquidation, stockholders are very far down in the hierarchy of creditors. Once a company issues stock (and gets the proceeds), its relationship and obligation to shareholders also seems very tenuous. What does Amazon care about its own stock price? Jeff Bezos certainly does care given his large holding in his own company's stock. So there is that connection and stock options for company employees is a similar way that the interests of shareholders and employees/managers can be aligned. But this doesn't explain why the pieces of paper have value in the first place. Heck, you don't even seem to get any paper these days (as far as I can tell)! Like Moderna recently with their hopeful vaccine results, when things go well and the stock price goes up, the company can issue more stock and raise more capital. But new stock issuance is a very rare event. Given how tenuous these links seem to be, the stock market has always seemed to me to be more like a ponzi scheme than a lottery. You buy stock because you believe you'll be able to sell it down the road to someone who will pay more for it, based loosely on how well the company seems to be doing. If so, it's a ponzi scheme that has been going for over 400 years since the Dutch East India Company issued the first shares. I figure it will probably continue for a least a few more decades until we are all dead. Given the shaky underpinning for stock valuation, maybe Bitcoin doesn't seem so bad Tom? 😉 --Dean
  2. Dean Pomerleau

    My random notes/stream of consciousness thread

    OK Guys, You got me. Inquilinekea is one of my bots. 🙂 But seriously. We've been discussing who is Alex K Chen (aka InquilineKea) and why he asks so many questions for years. Here is one example. There is even a thread about him that I started in 2016 on the admin/moderator board for these fora called "Mr. Questions - Alex K Chen (aka InquilineKea)". We concluded he is harmless, and very occasionally makes thoughtful contributions rather than just asking questions (e.g. here). He was even active on the CR mailing list back to at least 2012 before these fora were created (search "simfish" Tom). We've had it easy for the last few years since Alex went quiet here around 2017. But he's continued to ask lots of questions (and answer quite a few) on Quora. His Quora profile shows he has asked 62K questions since 2013. Here is a good one. He's also very active on Reddit. I've even communicated with Alex via email. He asked if we might meet up during a visit he made to Pittsburgh a couple years ago. It didn't work out so I couldn't verify his humanity first hand. 🙂 If he's a bot, he is a very good one. I for one welcome our new AI overlords. 🙂 --Dean
  3. Dean Pomerleau

    Acarbose better than Metformin?

    Evidence? This appeared to be true in one of Luigi Fontana's early study of some of us [1], but that appeared to be mediated by the relatively high protein diets many of us were eating at the time and subsequently discontinued. I'm not aware of more recent evidence that most CR folks have elevated IGF-1. I for one do not. --Dean ----- [1] Aging Cell. 2008 Oct;7(5):681-7. Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans. Fontana L, Weiss EP, Villareal DT, Klein S, Holloszy JO. Abstract Reduced function mutations in the insulin/IGF‐I signaling pathway increase maximal lifespan and health span in many species. Calorie restriction (CR) decreases serum IGF‐1 concentration by ~40%, protects against cancer and slows aging in rodents. However, the long‐term effects of CR with adequate nutrition on circulating IGF‐1 levels in humans are unknown. Here we report data from two long‐term CR studies (1 and 6 years) showing that severe CR without malnutrition did not change IGF‐1 and IGF‐1 : IGFBP‐3 ratio levels in humans. In contrast, total and free IGF‐1 concentrations were significantly lower in moderately protein‐restricted individuals. Reducing protein intake from an average of 1.67 g kg−1 of body weight per day to 0.95 g kg−1 of body weight per day for 3 weeks in six volunteers practicing CR resulted in a reduction in serum IGF‐1 from 194 ng mL−1 to 152 ng mL−1. These findings demonstrate that, unlike in rodents, long‐term severe CR does not reduce serum IGF‐1 concentration and IGF‐1 : IGFBP‐3 ratio in humans. In addition, our data provide evidence that protein intake is a key determinant of circulating IGF‐1 levels in humans, and suggest that reduced protein intake may become an important component of anticancer and anti‐aging dietary interventions. PubMed PMID: 18843793; PubMed Central PMCID: PMC2673798.
  4. We touched on this topic earlier in this thread. I'll observe again that the state of the stock market often does not reflect the current state of the broader economy. I'm not saying we won't see a serious correction, especially if there is a big second wave in the fall. But there is a pretty good argument to be made that with the fiscal and monetary policies in place, this may simply be another case by which the system is rigged so the rich (capital owners) getting richer and the poor (labor class & small business owners) getting poorer. Part of it is that the stock market and the major indices are dominated by large companies (esp tech) and they are forward looking, with 90% of the value of stocks coming from the discounted future corporate earnings beyond the one year time frame. Equity investors believe that we will get past this and strong companies will weather this downturn, with many of them (e.g. Amazon or Costco) gaining market share when mom and pop stores go belly up. Here is Jim Cramer making this argument better than I can. It doesn't seem fair or healthy for our society, but contrary to your assessment Annik, it does make some sense. --Dean
  5. Thanks Gordo. Here is another interesting look at the timeline of deaths from covid-19 among different countries from ourworldindata.org: --Dean
  6. Thanks Tom. This result appears to confirm the earlier finding that A-type blood increases risk of a bad outcome while O-type blood decreases risk. From the article: A lead SNP was also identified on chromosome 9 at the ABO blood group locus, and further analysis showed that A-positive participants were at a 45% increased for respiratory failure, while individuals with blood group O were at a 35% decreased risk for respiratory failure. The authors say that early clinical reports have suggested the ABO blood group system is involved in determining susceptibility to COVID-19 and has also been implicated in susceptibility to SARS-CoV-1. Meanwhile the big hydroxychloroquine for covid-19 treatment study in the Lancet was retracted today over questions about the data. The medical research community has made some unfortunate missteps during this crisis, undermining its credibility. Hopefully it won't spill over into the vaccine development effort. --Dean
  7. Thanks Gordo! Those results are somewhat encouraging. But I say only somewhat because of some of the limitations of the study. For example: These were tests of surgical masks, which aren't the cloth masks the CDC is recommending, although some of us are lucky enough to have access to surgical masks making the study more relevant. As you point out, the "coronavirus" patients in the study didn't have SARS-cov2, but one of the seasonal coronaviruses that we refer to as part of the "common cold" family. All the participants in the study were symptomatic and what we're mostly worried about is preventing asymptomatic / pre-symptomatic spread via mask wearing. Building on #2, most of the people tested were coughing quite a bit during the data collection sessions. For example, the coronavirus patients coughed a median of 17 times during the 30 minute collection session. Again frequently coughing people aren't what we're really worried most about. In the few sessions where the patients didn't cough, there was no virus detected in either the droplets or aerosols collected in the coronavirus patients: A subset of participants (72 of 246, 29%) did not cough at all during at least one exhaled breath collection, including 37 of 147 (25%) during the without-mask and 42 of 148 (28%) during the with-mask breath collection. In the subset for coronavirus [who did not cough] (n = 4), we did not detect any virus in respiratory droplets or aerosols from any participants. In the subset for influenza virus (n = 9), we detected virus in aerosols but not respiratory droplets from one participant. In the subset for rhinovirus (n = 17), we detected virus in respiratory droplets from three participants, and we detected virus in aerosols in five participants. This last point makes me question somewhat the relevance of these results for prevention of the spread of the SARS-cov2 virus, since it is thought that this virus is unusual in its ability to proliferate in large quantity in the throats of asymptomatic and pre-symptomatic individuals and then spread through respiratory droplets and aerosols generated while talking or simply breathing. If other viruses, including other coronaviruses don't seem to spread in the same way, it may be that surgical masks or especially cloth masks, won't be effective at preventing SARS-cov2 spread. Having said this, it seems intuitive to me that both cloth masks and more so surgical masks should provide some level of protection against the spread of SARS-cov2 and this study provides some evidence to support this intutition. So it seems to me wearing a mask should reduce the risk of transmission at least by a bit, so long as one doesn't engage in more risky behavior as a result of believing masks will dramatically lower your risk on contracting and/or spreading the virus, i.e. the well known phenomenon of "risk compensation". --Dean
  8. I learned quite a bit from this video from the head of UMinn CIDRAP group (Osterholm) on the almost total lack of evidence that cloth face coverings can effectively reduce virus transmission. He says that the gaps around the edges and the poor filtration mean that cloth masks (and to a somewhat lesser extent, surgical masks) will only (partially) stop respiratory droplets and will have little effect on aerosolized particles. Since asymptomatic transmission is likely driven more by the latter than the former (since droplets are generated mostly by coughing and sneezing when you are sick, at which time you should stay home), cloth masks won't help (much) and may hurt by giving the wearer or those they interact with a false sense of security, encouraging them to take more risks like ignoring physical distancing guidelines. He also discusses the unfortunate politicalizing of the mask issue and how politics and peer pressure has clouded decisions making on this topics, including at the CDC. --Dean
  9. Here is a neat interactive visualization of cases, deaths and tests by country. Here are two views - total deaths per million and total new daily deaths per million. The first shows how much Europe has dominated the total deaths per million and how North and South America (with UK, Kuwait and Sweden) are dominating the new cases per million. --Dean
  10. Here is the full text of the UMinn hydrochloroquine prophylactic study [1]. The accompanying review letter discusses some of the paper's limitations, but weirdly doesn't mention the lack of a zinc chaser: This trial has many limitations, acknowledged by the investigators. The trial methods did not allow consistent proof of exposure to SARS-CoV-2 or consistent laboratory confirmation that the symptom complex that was reported represented a SARS-CoV-2 infection. Indeed, the specificity of participant-reported Covid-19 symptoms is low,6 so it is hard to be certain how many participants in the trial actually had Covid-19. Adherence to the interventions could not be monitored, and participants reported less-than-perfect adherence, more notably in the group receiving hydroxychloroquine. In addition, those enrolled in the trial were younger (median age, 40 years) and had fewer coexisting conditions than persons in whom severe Covid-19 is most likely to develop,7 so enrollment of higher-risk participants might have yielded a different result. The trial design raises questions about the expected prevention benefits of hydroxychloroquine. Studies of postexposure prophylaxis are intended to provide an intervention in the shortest possible time to prevent infection. In a small-animal model of SARS-CoV-2 infection,8 prevention of infection or more severe disease was observed only when the experimental antiviral agent was given before or shortly after exposure. In the current trial, the long delay between perceived exposure to SARS-CoV-2 and the initiation of hydroxychloroquine (≥3 days in most participants) suggests that what was being assessed was prevention of symptoms or progression of Covid-19, rather than prevention of SARS-CoV-2 infection. So this study is far less than perfect and leaves open the possibility that hydroxychloroquine (plus zinc?) may still turn out to be an effective prophylactic against the virus. --Dean ------------ [1] The New England Journal of Medicine A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19 David R. Boulware, M.D., M.P.H., Matthew F. Pullen, M.D., Ananta S. Bangdiwala, M.S., Katelyn A. Pastick, B.Sc., Sarah M. Lofgren, M.D., Elizabeth C. Okafor, B.Sc., Caleb P. Skipper, M.D., Alanna A. Nascene, B.A., Melanie R. Nicol, Pharm.D., Ph.D., Mahsa Abassi, D.O., M.P.H., Nicole W. Engen, M.S., Matthew P. Cheng, M.D., et al. June 3, 2020 Abstract BACKGROUND Coronavirus disease 2019 (Covid-19) occurs after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For persons who are exposed, the standard of care is observation and quarantine. Whether hydroxychloroquine can prevent symptomatic infection after SARS-CoV-2 exposure is unknown. METHODS We conducted a randomized, double-blind, placebo-controlled trial across the United States and parts of Canada testing hydroxychloroquine as postexposure prophylaxis. We enrolled adults who had household or occupational exposure to someone with confirmed Covid-19 at a distance of less than 6 ft for more than 10 minutes while wearing neither a face mask nor an eye shield (high-risk exposure) or while wearing a face mask but no eye shield (moderate-risk exposure). Within 4 days after exposure, we randomly assigned participants to receive either placebo or hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 additional days). The primary outcome was the incidence of either laboratory-confirmed Covid-19 or illness compatible with Covid-19 within 14 days. RESULTS We enrolled 821 asymptomatic participants. Overall, 87.6% of the participants (719 of 821) reported a high-risk exposure to a confirmed Covid-19 contact. The incidence of new illness compatible with Covid-19 did not differ significantly between participants receiving hydroxychloroquine (49 of 414 [11.8%]) and those receiving placebo (58 of 407 [14.3%]); the absolute difference was −2.4 percentage points (95% confidence interval, −7.0 to 2.2; P=0.35). Side effects were more common with hydroxychloroquine than with placebo (40.1% vs. 16.8%), but no serious adverse reactions were reported. CONCLUSIONS After high-risk or moderate-risk exposure to Covid-19, hydroxychloroquine did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure. (Funded by David Baszucki and Jan Ellison Baszucki and others; ClinicalTrials.gov number, NCT04308668. opens in new tab.) DOI: 10.1056/NEJMoa2016638
  11. Looks like I may have been wrong in my recent prediction that hydroxychloroquine would turn out to be an effective prophylactic based on Trump starting to take it after talking with a researcher from UMinn who was running a trial to test the idea. Here are highlights of the now published UMinn study from an NPR article out just minutes ago. It doesn't look like the paper is yet available on the NEJM website. No Evidence Hydroxychloroquine Is Helpful In Preventing COVID-19, Study Finds Taking hydroxychloroquine after being exposed to someone with COVID-19 does not protect someone from getting the disease. That's the conclusion of a study published Wednesday involving 821 participants. All had direct exposure to a COVID-19 patient, either because they lived with one, or were a health care provider or first responder. To qualify, people had to be within a few days of their encounter with a COVID-19 patient and not have any symptoms of the disease themselves. Encounters meant being within 6 feet of a sick person for more than 10 minutes while wearing neither a face mask nor an eye shield or while wearing a face mask but no face shield. The volunteers received either a five-day supply of hydroxychloroquine, or a placebo. As Rajasingham and her colleagues report in the New England Journal of Medicine, 107 of the 821 participants developed disease; 49 in the group receiving hydroxychloroquine and 58 in the placebo group. That turned out to be a reduction in risk of 2.4 percent. That difference was not statistically significant, and "it's also not clinically meaningful," Rajasingham says. She would like to have seen a reduction of 30% or more before recommending hydroxychloroquine to asymptomatic patients. She says hydroxychloroquine can have serious side effects, although the side effects reported in this study were relatively mild. I'm not sure why the difference in the rate of infection between the two groups (49 vs. 58) is only a risk reduction of 2.4 percent - perhaps it was a result of adjusting for confounders. The article doesn't mention if participants were given zinc along with the hydroxychloroquine, so I think it safe to assume that they weren't. So perhaps there still is some hope for its effectiveness as a prophylactic. It will be useful to see the full published study to know the answer to these open questions. --Dean Update: This Business Insider article explains the 2.4%. It also provides more info on side effects, which were statistically higher (although mild) in the hydroxychloroquine group: The researchers tracked both groups, who routinely filled out online surveys about their health. Approximately 12% of people taking hydroxychloroquine got COVID-19 compared to 14% of the placebo group, according to a University of Minnesota press release. The difference was not statistically significant. However, one finding was meaningful between the two groups: those taking hydroxychloroquine had much higher rates of side effects. About 40% on hydroxychloroquine registered side effects compared to 17% on placebo. These were mild reactions — most commonly nausea, diarrhea, or vomiting — with no reported serious side effects.
  12. Dean Pomerleau

    Dean's Diet & Exercise Regime, Tips, and Motivation

    Sci-hub is your friend :-). Here are the tables from the paper in question [1]: The p-values are impressive in Table 2 due to the large number of people in the study (n=3355). But the magnitude of the difference in cognitive test scores between quartiles of IGF-1 appear quite small relative to the within-quartile variance. For example, look at the TMT-B test I've highlighted. The difference in average test score between the top and bottom quartile is ~5.5, but the within-quartile range is around +-15, indicating there is much more variation within quartiles than between the various quartiles of IGF-1. This suggests to me there are likely several factors that potentially contribute to having a low IGF-1. The speculation is that like with another growth-promoting hormone testosterone, there may be benign and potential even health-promoting reasons for having low IGF-1 and there may be other reasons that are associated with (or casually responsible for) poor physical and/or cognitive health - hence the wide within-quartile variance. But it is a speculation which we've discussed many times before in threads focusing on the potential pros and cons of high vs. low testosterone and/or IGF-1 including the ones I linked to in the post above. --Dean ----------- [1] Neurobiol Aging. 2015;36(2):942‐947. doi:10.1016/j.neurobiolaging.2014.10.035 Association of insulin-like growth factor-1 with mild cognitive impairment and slow gait speed. Doi T, Shimada H, Makizako H, et al. Abstract The decrease in serum insulin-like growth factor-1 (IGF-I) with aging is related to the neurobiological processes in Alzheimer's disease. IGF-1 mediates effects of physical exercise on the brain, and cognition has a common pathophysiology with physical function, particularly with gait. The aim of this study was to examine whether mild cognitive impairment (MCI) and slow gait are associated with the serum IGF-1 level. A population survey was conducted in 3355 participants (mean age, 71.4 years). Cognitive functions (attention, executive function, processing speed, visuospatial skill, and memory), gait speed, and demographic variables were measured. All cognitive functions and gait speed were associated with the IGF-1 level (p < 0.001). The association of IGF-1 with slow gait was weakened by adjustment for covariates, but MCI and the combination of MCI and slow gait were independently related to the IGF-1 level in multivariate analysis (p < 0.05). Our findings support the association of a low IGF-1 level with reduced cognitive function and gait speed, particularly with a combination of MCI and slow gait. PMID: 25467636
  13. A while back I expressed concerned about the developing world getting hit hard by the virus. It appears to be happening, especially in South America with Brazil, Peru and Chile. New daily cases in Brazil are rapidly approaching the peak we saw in the US, which was just under 40K cases: Perhaps not surprisingly given their limited medical infrastructure, the number of deaths relatively to number of diagnosed cases is already nearly identical to that of the US (5.8%). This may be due to more diagnosed patients dying as a result of less-effective medical care or fewer cases being diagnosed due to limited testing. India and Bangladesh are also seeing a consistent rise in new cases: Fortunately the reported covid-19 deaths in both countries are relatively low. --Dean
  14. The Washington Post has an interesting article with a graphic showing changes in foot traffic to various types of businesses since early March both by state and as a national average. Here is the data from Georgia, which was one of the earliest states to reopen (late April) compared with the US average (dashed line): It looks like several types of Georgia businesses are seeing a slightly greater rebound in foot traffic than the national average. But everything except grocery stores, fast-food restaurants and barbers/salons are still way down both in Georgia and across the US. The recovery looks to be progressing rather slowly so far. --Dean
  15. Dean Pomerleau

    Brian May - "Very healthy" but "near death"

    I didn't notice it until you pointed it out. Maybe my eyes are going :-). I'll leave it that way to avoid ruining your clever quip. Except for the white hair I didn't think he looked too bad especially for someone who recently had a heart attack. But I'll grant you he doesn't look significant younger than his chronological age. From his seemingly upbeat attitude (although I know he does have a history of depression) and lack of physical disabilities, I suspect that like you, he doesn't consider himself to be "over the hill." That's why he was so surprised when he learned of his heart problem. I think it is gift of human psychology that allows us to "spin" all kinds of things to make life bearable - including our own self-image in the face of inevitable aging. Like your advice to Clinton on how to be resilient by not dwelling on the setbacks but instead finding positives ("well I've still got my health...") when things go pear-shaped in life. --Dean