Early Cancer Detection Did Not Save Lives

Screening for ovarian cancer did not reduce early deaths

From: University College, London

May 13, 2021 -- The latest analysis looked at data from more than 200,000 women aged 50-74 at recruitment who were followed up for an average of 16 years. The women were randomly allocated to one of three groups: no screening, annual screening using an ultrasound scan, and annual multimodal screening involving a blood test followed by an ultrasound scan as a second line test.

A large-scale randomised trial of annual screening for ovarian cancer, led by UCL researchers, did not succeed in reducing deaths from the disease, despite one of the screening methods tested detecting cancers earlier.

Results from the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) have been published in a report in the medical journal The Lancet.

In the UK, 4,000 women die from ovarian cancer each year. It is not usually diagnosed until it is at a late stage and hard to treat. UKCTOCS was designed to test the hypothesis that a reliable screening method that picks up ovarian cancer earlier, when treatments are more likely to be effective, could save lives.

The latest analysis looked at data from more than 200,000 women aged 50-74 at recruitment who were followed up for an average of 16 years. The women were randomly allocated to one of three groups: no screening, annual screening using an ultrasound scan, and annual multimodal screening involving a blood test followed by an ultrasound scan as a second line test.

The researchers found that, while the approach using multimodal testing succeeded in picking up cancers at an early stage, neither screening method led to a reduction in deaths.

Earlier detection in UKCTOCS did not translate into saving lives. Researchers said this highlighted the importance of requiring evidence that any potential screening test for ovarian cancer actually reduced deaths, as well as detecting cancers earlier.

Professor Usha Menon (MRC Clinical Trials Unit at UCL), lead investigator of UKTOCS, said: "UKCTOCS is the first trial to show that screening can definitely detect ovarian cancer earlier. However, this very large, rigorous trial shows clearly that screening using either of the approaches we tested did not save lives. We therefore cannot recommend ovarian cancer screening for the general population using these methods.

"We are disappointed as this is not the outcome we and everyone involved in the trial had hoped and worked for over so many years. To save lives, we will require a better screening test that detects ovarian cancer earlier and in more women than the multimodal screening strategy we used."

Women aged between 50 and 74 were enrolled in the trial between 2001 and 2005. Screening lasted until 2011 and was either an annual blood test, monitoring changes in the level of the protein CA125, or a yearly vaginal ultrasound scan. About 100,000 women were assigned to the no screening group, and more than 50,000 women to each of the screening groups.

Blood test screening picked up 39% more cancers at an early stage (Stage I/II), while detecting 10% fewer late-stage cancers (Stage III/IV) compared to the no screening group. There was no difference in the stage of cancers detected in the ultrasound group compared to the no screening group.

The initial analysis of deaths in the trial occurred in 2015, but there was not enough data at that time to conclude whether or not screening reduced deaths. By looking at five more years of follow up data from the women involved, researchers are now able to conclude that the screening did not save lives.

Professor Mahesh Parmar, Director of the MRC Clinical Trials Unit at UCL and a senior author on the paper, said: "There have been significant improvements in the treatment of advanced disease in the last 10 years, since screening in our trial ended. Our trial showed that screening was not effective in women who do not have any symptoms of ovarian cancer; in women who do have symptoms early diagnosis, combined with this better treatment, can still make a difference to quality of life and, potentially, improve outcomes. On top of this, getting a diagnosis quickly, whatever the stage of the cancer, is profoundly important to women and their families."

Professor Ian Jacobs, from the University of New South Wales (UNSW Sydney), a co-investigator who has led the ovarian cancer screening research programme since 1985 and who was lead investigator of UKCTOCS from 2001-2014, said: "My thanks to the thousands of women, healthcare professionals and researchers who made this trial possible. The multimodal screening strategy did succeed in detection of ovarian cancer at an earlier stage, but sadly that did not save lives. This is deeply disappointing and frustrating given the hope of all involved that we would save the lives of thousands of women who are affected by ovarian cancer each year."

Professor Jacobs noted: "Population screening for ovarian cancer can only be supported if a test is shown to reduce deaths in a future randomised controlled trial. I remain hopeful that a new effective screening test will be found eventually, but it will take many years to conduct a large trial of the test. Realistically, this means we have to reluctantly accept that population screening for ovarian cancer is more than a decade away."

A huge wealth of samples and data from the trial has been donated by the participants for future research. This resource, referred to as the UKCTOCS Longitudinal Women's Cohort (UKLWC), is now being used by researchers worldwide, helping to improve understanding of ovarian cancer as well as other cancers and other diseases such as cardiovascular disease.

Researchers say that the study has also generated insights into how best to design, conduct and analyse a large-scale randomised clinical trial particularly in individuals who have no signs of disease. These insights will be helpful to future trials in all areas of health. It has also contributed to advances in risk assessment, prevention and diagnosis of ovarian cancer.

The UKCTOCS trial was funded by the NIHR Health Technology Assessment (HTA) Programme and the charities Cancer Research UK and The Eve Appeal.

Michelle Mitchell, Cancer Research UK's Chief Executive, said: "Trials don't always find the result we had hoped for, but we need long-term studies like this to know whether new tests save lives. Cancer Research UK will continue to fund vital research into aggressive forms of ovarian cancer so we can reduce the impact of this disease.

"Screening is for people without symptoms, so it's still important that if you notice unusual or persistent changes to talk to your doctor. Symptoms of ovarian cancer can be quite vague and similar to symptoms caused by less serious conditions, which can make spotting the disease tricky. Whether it's needing to go to the toilet more often, pain, bloating, or something else, raise it with your GP -- in most cases it won't be cancer but it's best to get it checked out."

Professor Nick Lemoine, Medical Director, NIHR Clinical Research Network, said: "These important findings from a large-scale trial, involving 200,000 participants, show that annual screening did not succeed in reducing deaths from ovarian cancer.

"However, it's important to note that negative results can be as important as positive. The study has provided important new evidence and insights into how to conduct and analyse future large-scale randomised clinical trials into ovarian cancer, in the hope that this will prevent and diagnose this disease more effectively in the future.

"We thank every single person who took part."

Athena Lamnisos, CEO, The Eve Appeal, said: "The threshold for introducing a national cancer screening programme is a mortality benefit. Of course this is key -- saving lives. It's disappointing that this research programme did not show a reduction in mortality from ovarian cancer and so can't be recommended as a national screening programme. However, the impact it had on earlier diagnosis is impressive and important.

"Ovarian cancer is so often diagnosed at stage 3 or 4 and shifting diagnosis one stage earlier makes a huge difference to both treatment options and quality of life. Earlier diagnosis will often reduce the amount and intensity of treatment, and this makes all the difference to women and their families who are living with cancer. It may have also given them more precious time with their loved ones."

          https://www.sciencedaily.com/releases/2021/05/210513173552.htm

Inflation Will Kill This Stock Market

By David Haggith for The Great Recession Blog

May 12, 2021 -- I’m not saying nothing else can do the job before inflation fully gets here, just that the kind of inflation I’ve been writing about certainly will do it if nothing else does. That’s what terrifies the market and for a very good reason that may not be the first one that comes to some investors’ minds.

Many talk about the “risk premium” of investing in stocks. As inflation rises, bond yields rise to offset what will be lost to inflation. As bond yields rise, stocks become less competitive.

That’s a problem, but it’s not the big problem. Not this time.

The big problem is that we all know where the money for stocks is coming from — the Federal reserve and the US government by borrowing and distributing the money the Fed prints. So, the big problem is the Fed.

The Fed is getting tangled in a mess of its own making

Having made the case in a number of previous articles that high inflation is now already a given, it won’t be long before the Fed is caught in a trap where it needs to continue creating money in order to keep the market rising and to keep stimulating the economy, but it won’t be able to because it will be blocked by the inflation monsters it is creating. That’s why we hear the Fed talking incessantly about how inflation is “transitory” right now. The Fed NEEDS to have all investors believe that the rapidly dawning period of inflation will be short so it can be ignored. The Fed needs the market to believe it CAN and WILL keep printing money.

However, the Fed is just fooling itself. The longer it claims inflation is temporary so that it can ignore the rapidly rising numbers, the more inflation will move out of control because the Fed and the federal government keep the money printing and the armored cars for transporting it to the masses running around the clock. (Figuratively speaking, of course.)

The Fed may fool itself to its (and our) long-term harm, but it is not likely to fool the market much longer because the inflationary numbers will be coming in too high for the market to ignore. We saw that on Wednesday in how the market responded to news of the highest inflation in years — a number annualized at 4.2% in April, which is well below the level of inflation we’re about to see this summer. That’s just the wind-up for the strike-out pitch.

How inflation will fight the Fed and win

The danger inflation imposes is that, if it rises as high as I am certain it is going to rise (double digits), then the Fed will be forced to raise its interest targets because the market will shove interest up regardless, making the Fed look dumb for claiming an interest target it cannot hold. The Fed won’t be able to what it takes to hold interest down without creating massively greater inflation through its creation of new money.

However, it is not just that the bond vigilantes will wrest control of interest out of the Fed’s hands, it’s that the stock market will force the Fed to deal with inflation by fearing it whether the Fed says it should or not. Consumers will also press congress to press the Fed to deal with inflation. The longer it delays, the more massively the Fed will have to raise interest rates, just as Paul Volker did in the 80’s to get inflation under control.

This conundrum is starting to materialize now at a time when the stock market is at absurdly perilous heights. Faint realizations of inflation are no longer so faint, which is why the market is running out of momentum. Investors are starting to believe the Fed will lose control of interest rates. Investors are starting to doubt the Fed’s words of confidence.

Of course, to crash, momentum has to turn downward, and that won’t likely happen until the market is certain the Fed is going to lose control; but that can happen slowly at first and then quickly as it did in 2018.

Inflation is a time bomb on the Fed’s back. My thesis is that every month now the Fed is going to find it harder and harder to maintain the illusion that it can keep creating money, pumping it into mom-and-pop investor hands (retail investors, the Robinhood crowd, etc.) through government stimulus programs (at the government’s demand) and keep trying to maintain low interest to pump money into the stock market via corporate stock buybacks funded on loans. Inflation will crush easy money. It rules. The Fed can rule over it, but only by taking away money and crashing markets that are utterly dependent on that money.

The plate spinner is starting to lose control of all the plates it has to keep twirling on the ends of little sticks. Today’s action in the market shows the market is starting to pay attention to the clatter of falling plates as inflation shows up worse than investors feared. The real fear — the deep paralyzing fear that is only now being foreshadowed — is not competition from rising bond yields (certain as that is to come) but that inflation will become hot enough that the Fed will be forced to turn off all of its go juice.

Inflation has the power to suddenly turn market sentiment on its head because, well, follow the money back to where it is coming from.

Stocks headed sharply lower as inflation jitters percolated again, following a report showing U.S. inflation in the year to April rose at its fastest pace in about 13 years, amid the recovery from the COVID pandemic.

MarketWatch

Inflation jitters will become inflation panic when it becomes clear that the rise to 4.2 is not just a blip but the first step on the consumer side of many steps to come. Hopefully none of my readers were paying much attention to economists who were forecasting a meager 3.6%.

“Inflation destroys wealth. Period,” said Patrick Leary, head of trading at Incapital, in an interview with MarketWatch. “We see inflation showing up in markets. If it’s indeed transitory, markets can live with it. But if it’s not transitory, that’s when it is going to become troubling for stocks.”

The destruction of wealth is one concern, but the bigger concern, I believe, is the loss of the Amazon-scale, easy-money stream into the market. This is why the market went up when the jobs report was truly horrible. The report of slackening employment eased feelings of concern about inflation causing the Fed to turn off the flow. Its why the market plunged today on solid news to the contrary of higher inflation than many were expecting.

The Fed’s hand may soon be forced by reality; and if you’ve been reading here — particularly the Patron Posts that focused intensively on inflation, you’ve had a good idea of what is coming. One won’t have to wait until the Fed tightens to stop inflation, however; one only has to wait until stock investors become convinced the Fed will have to tighten, regardless of what the Fed claims to assure investors it won’t.

As MarketWatch noted yesterday,

Tuesday is looking dicey for stocks, notably the technology space, as inflation jitters continue to ripple across markets. The sector has been bearing the brunt of concerns that higher inflation may prompt an early end to the Federal Reserve’s COVID-19 pandemic-driven accommodative stance. After last week’s downside jobs surprise, some fear Wednesday’s consumer price data could also deliver a nasty shock.

The market is top-heavy and jittery under its own load to such an extent that it will crash if it merely believes the Fed will be forced to tighten. That’s why it jolted as a foreshock today, but it wasn’t a shock at all if you’ve been reading here. It was expected.

Inflation is the “worst-case scenario” for this ticking-time-bomb market full of complacent investors, warns our call of the day from Thomas H. Kee Jr., president and chief executive of Stock Traders Daily and portfolio manager at Equity Logic.

And here’s the key:

“Arguably, the ONLY reason stimulus has even been possible is because there has been no inflation. If inflation comes back, all of the safeguards investors have been given (free money from stimulus) will be dissolved and won’t be able to come back to save the day,” Kee told MarketWatch…. He said recent jobs data indeed suggest price rises will be “more serious than previously thought….”

“The declines can be much worse than 25% and if the FOMC [Federal Open Market Committee] is handcuffed because of inflation, the swift bounce back that investors have been used to will not happen either,” said Kee. “The fair value multiple on the SPX SPX (^GSPC) is not 30 – [to] 35x. It’s more like 15x….”

What would bring that down to earth is the return of natural-risk perceptions among investors — severely lacking right now. “They have been given free money by the government, stimulus programs are in full effect, and investors don’t perceive any risk at all. That is the most dangerous thing!” Kee said….

“When the big buyer is not there … that is when natural perceptions of risk come back, and if that happens … watch out below!!”

You see, rising inflation has the power to cut the Fed off at the knees. The kind of inflation I’ve been writing about can suck the mojo right out of the Fed, and that is why Powell is already doing his best to convince financial markets that the Fed wants higher inflation and convince them that the higher inflation it wants is temporary before it even begins.

Market susceptibility

Notes Lance Roberts,

There is no way this bull market doesn’t end very badly. We all know that is the reality of this liquidity-fueled market, but we keep investing for “Fear Of Missing Out.”

Seeking Alpha

How much does all that stimulus money from Fed and Feds pouring into the market create the cashflow that made the past year’s insanity possible?

Over the past 5-MONTHS, more money has poured into the equity markets than in the last 12-YEARS combined.

Do the math and ask yourself what happens if the money HAS to be turned off because inflation forces the Fed to stop creating to much new money in an environment of to few goods due to previous COVID-shutdown shortages and the continuing problems they’ve set up.

And, if you don’t think the market is precariously riding high on easy money, look at how much it is rising on rising margin debt (money owed to brokers):

Seeking Alpha

When the Fed is pressed hard to raise interest rates and stop printing money, brokers aren’t going to be so free in lending money. Right now, it’s easy money at almost free rates. More to the point, though, when the market does start coming down because of concerns about the Fed cutting off easy money, all that margin debt starts unwinding in a hurry as people are forced to sell assets and reduce their margin debt.

As you can also see, huge, rapid spikes like this in market debt tend to happen right before severe crashes:

Seeking Alpha

In the short term, fundamentals do not matter. However, in the long term, they matter a lot.

Sentiment can cause investors to overlook economic fundamentals for a long time, but a sudden change in perception of fundamentals long overlooked in an environment of high margin debt and bring a rapid correction of one’s frame of reference.

Currently, investors are overlooking fundamentals on the expectation the economy and earnings will improve to justify the market overvaluation.

That is not likely to happen. Even if it does, perception of the financial landscape (the core value of of money) has been far too optimistic in most circles, as seen by the shock today; but you could see this coming from a year away.

The Fed talks as though it still doesn’t see what is coming, but that’s the same Fed that talked about how easy tightening was going to be. It appears it had no idea that it didn’t have an exit plan that wouldn’t send sentiment sharply south and crash the market. Yet, that, too, could be seen from years away by those who were not worshipping at the feet of Father Fed.

When, or if, expectations of recovery are disappointed, the market will begin to reprice itself for its intrinsic value. Given that the market is currently trading more than twice the level of underlying economic growth, which is where corporate profits come from, such suggests a significant risk.

That’s why the Dow fell 682 points (2%) today, and the S&P fell 2.14% and the NASDAQ, 368 points (2.67%). There wasn’t much of a safe space to be found in stocks.

Don’t tell me inflation doesn’t matter to this market. Worst day in six months. More on this in another Patron Post.

Now let me, once again, do the kind of corrective reporting I said was going to be essential at this time. First, the fake news:

One big reason for the acceleration was base effects – at this time a year ago, the economy was hit with the worst of the Covid pandemic and inflation was unusually low.

CNBC

That isn’t accurate. As I said in my last Patron Post, wherein I also laid out the statistical facts and source to back up my statement,

Food prices and many other prices rose like they normally do last March, in spite of the pandemic. In fact, after March, they rose worse than normal with every month in the remainder of 2020 coming in between 3.5% and 4% on an annualized basis.

“Inflation Tsunami Sirens Are Screaming!“

I noted in particular one economist who said groceries and fuel were now just making up for last time:

So, like groceries, gas is catching up to get back to where we would actually expect it to be….

What predominantly happened last year was that fuel prices plummeted due to nothing being transported and lack of vacationing and lack of commuting, but groceries? Come on!

“Catching up” may be true for gas if you look back to where prices were in 2018, but it’s total horse manure when you embrace groceries in the comment. Groceries have no catching up to do whatsoever. The average rate of inflation for food for all of 2020 was 3.4%, which compares to rates that 0.3%-2.5% for every year going back until 2011 where the average for the year was. 3.6%.

And while overall inflation was less than normal for April through June last year, what does that have to do with this year? [Overall] prices still rose last year; so, it is NOT as if you are comparing to an anomalous year where overall prices fell in those months, meaning some of this year’s gain was just making up for last year’s unusual loss. Then you could truthfully say there was a base effect.

So, inflation is coming in much hotter than the Fed led people to believe; and, as my recent Patron Posts have laid out, there is plenty more inflation already baked in on the producer side that will certainly be passed through. I noted you could expect to see that starting to show up on the consumer side now, and you just did. It’s going to be an inflation-hot summer, which can sour sentiment, so stocks won’t take well to that. To be sure, there is a lot of testosterone still determined to press stocks up no matter what, but a hot and humid summer will zap that sentiment, as it did today; and it will keep zapping it no matter what the charts readers are prognosticating based on current sentimental trends. Trends can change quickly in the face of facts if the facts crash in with enough vigor. I think high inflation is the much-feared fact that can break through by stopping the Fed’s plans from moving forward.

If the Fed does keep moving forward with the same kind of blind ignorance and stubborn resolve to prove itself right that led it to keep pursuing its economic tightening regime (as I claimed it would do for too long in 2018, contrary to good judgment), it will really be making things worse for itself and harder to tame. I think that is not unlikely.

“There are people who think the Fed is not just behind the curve, they’re maybe missing the point and by the time they start to play catch up, it’s too late,” Wall Street veteran Art Cashin said Wednesday

CNBC

As one economist noted,

“We doubt this report will change the view of officials that inflationary pressures are ‘largely transitory,‘” wrote Michael Pearce, senior U.S. economist at Capital Economics. “It’s just that there’s a lot more ‘transitory’ than they were expecting.”

CNBC

Indeed. A lot more. What will they do when they run out of a fake base effect to blame it on?

                   https://thegreatrecession.info/blog/inflation-will-kill-this-stock-market/

World’s First Programmable Digital Computer

The Z3 German computer was a German electromechanical computer designed by Konrad Zuse in 1935, and completed in 1941. It was the world's first working programmable, fully automatic digital computer.  The Z3 was built with 2,600 relays, implementing a 22-bit word length that operated at a clock frequency of about 5–10 Hz.  Program code was stored on punched film. Initial values were entered manually.

 

The Z3 was completed in Berlin in 1941. It was not considered vital, so it was never put into everyday operation.  Based on the work of the German aerodynamics engineer Hans Georg Küssner (known for the Küssner effect), a "Program to Compute a Complex Matrix" was written and used to solve wing flutter problems.  Zuse asked the German government for funding to replace the relays with fully electronic switches, but funding was denied during World War II since such development was deemed "not war-important".

The original Z3 was destroyed on 21 December 1943 during an Allied bombardment of Berlin. That Z3 was originally called V3 (Versuchsmodell 3 or Experimental Model 3) but was renamed so that it would not be confused with Germany's V-weapons.  A fully functioning replica was built in 1961 by Zuse's company, Zuse KG, which is now on permanent display at Deutsches Museum in Munich.

The Z3 was demonstrated in 1998 to be, in principle, Turing-complete.  However, because it lacked conditional branching, the Z3 only meets this definition by speculatively computing all possible outcomes of a calculation.

Thanks to this machine and its predecessors, Konrad Zuse has often been suggested as the inventor of the computer.

Design and Development

Zuse designed the Z1 in 1935 to 1936 and built it from 1936 to 1938. The Z1 was wholly mechanical and only worked for a few minutes at a time at most.  Helmut Schreyer advised Zuse to use a different technology. As a doctoral student at the Berlin Institute of Technology in 1937, he worked on the implementation of Boolean operations and (in today's terminology) flip-flops on the basis of vacuum tubes.  In 1938 Schreyer demonstrated a circuit on this basis to a small audience, and explained his vision of an electronic computing machine – but since the largest operational electronic devices contained far fewer tubes this was considered practically infeasible.  In that year when presenting the plan for a computer with 2,000 electron tubes, Zuse and Schreyer, who was an assistant at Wilhelm Stäblein's de Telecommunication Institute at the Technical University of Berlin, were discouraged by members of the institute who knew about the problems with electron tube technology.  Zuse later recalled: “They smiled at us in 1939, when we wanted to build electronic machines … We said: The electronic machine is great, but first the components have to be developed."  In 1940 Zuse and Schreyer managed to arrange a meeting at the Oberkommando der Wehrmacht (OKW) to discuss a potential project for developing an electronic computer, but when they estimated a duration of two or three years, the proposal was rejected.

Zuse decided to implement the next design based on relays. The realization of the Z2 was helped financially by Kurt Pannke, who manufactured small calculating machines. The Z2 was completed and presented to an audience of the Deutsche Versuchsanstalt für Luftfahrt ("German Laboratory for Aviation") in 1940 in Berlin-Adlershof. Zuse was lucky – this presentation was one of the few instances where the Z2 actually worked and could convince the DVL to partly finance the next design.

Improving on the basic Z2 machine, he built the Z3 in 1941, which was a highly secret project of the German government.  Joseph Jennissen (1905–1977), member of the "Research-Leadership" (Forschungsführung) in the Reich Air Ministry acted as a government supervisor for orders of the ministry to Zuse's company ZUSE Apparatebau.  A further intermediary between Zuse and the Reich Air Ministry was the aerodynamicist Herbert A. Wagner.

The Z3 was completed in 1941 and was faster and far more reliable than the Z1 and Z2. The Z3 floating-point arithmetic was improved over that of the Z1 in that it implemented exception handling "using just a few relays", the exceptional values (plus infinity, minus infinity and undefined) could be generated and passed through operations. The Z3 stored its program on an external tape, thus no rewiring was necessary to change programs.

On 12 May 1941 the Z3 was presented to an audience of scientists including the professors Alfred Teichmann and Curt Schmieden of the Deutsche Versuchsanstalt für Luftfahrt ("German Laboratory for Aviation") in Berlin, today known as the German Aerospace Center in Cologne.

Zuse moved on to the Z4 design, which he completed in a bunker in the Harz mountains, alongside Wernher von Braun's ballistic missile development. When World War II ended, Zuse retreated to Hinterstein in the Alps with the Z4, where he remained for several years.

Z3 as a Universal Turing Machine

It was possible to construct loops on the Z3, but there was no conditional branch instruction. Nevertheless, the Z3 was Turing-complete – how to implement a universal Turing machine on the Z3 was shown in 1998 by Raúl Rojas.  He proposed that the tape program would have to be long enough to execute every possible path through both sides of every branch. It would compute all possible answers, but the unneeded results would be canceled out (a kind of speculative execution).  Rojas concludes, "We can therefore say that, from an abstract theoretical perspective, the computing model of the Z3 is equivalent to the computing model of today's computers. From a practical perspective, and in the way the Z3 was really programmed, it was not equivalent to modern computers."

This seeming limitation belies the fact that the Z3 provided a practical instruction set for the typical engineering applications of the 1940s. Mindful of the existing hardware restrictions, Zuse's main goal at the time was to have a workable device to facilitate his work as a civil engineer.

                      https://en.wikipedia.org/wiki/Z3_(computer)

 

= = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = =

 

Afterword by the Blog Author

Thank God German politicians didn’t recognize the importance of these early computers.  The devices could have extended the time of the European theater for World War II or perhaps altered the outcome of the conflict.

Hypersonic Flight Is Closer to Reality

“New technology could bring hypersonic flight into a reality by enabling jets to reach up to Mach 17 [that is 13,000 miles per hour!] without releasing an out of control detonation.”

“Scientists at the University of Central Florida developed a new propulsion system to stabilize the detonation, which is a type of explosion that sends waves faster than the speed of sound.”

Much more at: https://www.msn.com/en-us/news/technology/new-propulsion-system-could-enable-jets-to-reach-speeds-up-to-mach-17/ar-BB1gAiyA?ocid=msedgdhp

A Little Child Shall Lead Them…Downhill

Cocky kids: The four-year-olds with the same overconfidence as risk-taking bankers

From: University of Sussex

April 2, 2021 -- Overconfidence in one's own abilities despite clear evidence to the contrary is present and persistent in children as young as four, a new study by the University of Sussex Business School has revealed.

The cognitive bias has been consistently observed among a number of professions including business executives, bankers and physicians across different countries and cultures but a new study led by Dr Dominik Piehlmaier indicates that overconfidence is persistent and widespread during early childhood.

The research also found that girls were more successful than boys at a card game in the study thanks to a more low-risk strategy but also experienced greater swings between overconfidence and lack of confidence in their abilities.

Dr Dominik Piehlmaier, Lecturer in Marketing at the University of Sussex Business School and the study's author, said: "Much of our knowledge on judgment and decision-making is based on adult participants but there is no reason to believe that humans only develop such an omnipresent cognitive illusion once we reach adulthood.

"My findings indicate that effective interventions that increase an individual's knowledge about their own knowledge and its boundaries might be needed to target much younger individuals if one wants to efficiently calibrate a person's irrational confidence."

In the study, children were asked to play a card game known as the Children's Gambling Task where they choose cards from one of two packs.

The card is then turned over to reveal how many stickers the participant has won and lost. One pack had cards with significantly higher wins and losses than the other.

At intervals, children had to decide whether they thought they would win more, about the same, or fewer stickers than previously in the game.

Each participant started off with four stickers after the initial six practice trials. On average, every participant gained 0.3 stickers per turn and left the game with an average of 6.67 stickers, ranging from zero to 33.

The study showed that more than 70% of four-year-olds and half of all five and six-year-olds were overconfident in their expectations after playing ten turns and six practice trials.

Dr Piehlmaier said: "A vast number of repetitions, learning, and feedback in the study did not diminish the misplaced confidence in the success of the majority of participants.

"The children played more than 60 turns and saw their payoff balance rose and fell, yet every third child still thought that they could do better than they had done in the previous 50 turns.

"The Children's Gambling Task closely resembles a very simplified version of the financial markets with relatively safe options providing low but steady average return rates and highly risky assets that promise much higher short-term gains with a catastrophic long-term yield.

"The finding that overconfidence is persistent even in the face of own shortcomings mirrors results from previous studies that looked at the performance of investors."

Overconfidence is widely seen as a male trait but the study also had interesting findings when it came to the general performance of boys and girls.

In general, girls outperformed boys by an average of 2.87 stickers thanks to a less high-risk strategy of choosing relatively more safe cards which offered smaller but more sustainable gains.

Dr Piehlmaier added: "Boys seem to follow a negative trend line that indicates slow but steady learning on what might be considered 'reasonable expectations'.

"Girls' behaviour is much more unpredictable. When the girls' overconfidence plot is compared to their payoffs, it can be noticed that they closely align.

"This indicates that girls overestimate their abilities if they have a winning streak and underestimate themselves whenever they lose a few times in a row.

"By the end of the experiment, there were relatively more overconfident girls than boys; a finding that contradicts previous reports regarding more calibrated girls in metamemory tasks."

https://www.sciencedaily.com/releases/2020/04/200402110135.htm

Artificial Intelligence Improves Microscopes

Machine learning helps some of the best microscopes to see better, work faster, and process more data

From:  European Molecular Biology Laboratory

May 9, 2021 -- Collaboration between deep learning experts and microscopy experts leads to an significantly improved data-intensive light-field microscopy method by using AI and ground-truthing it with light-sheet microscopy. The result is the power of light-field microscopy available to biologists in near real time vs. days or weeks, AND the expansion of biologists' ability to use this microscopy for many things more things requiring the most detailed observation.

To observe the swift neuronal signals in a fish brain, scientists have started to use a technique called light-field microscopy, which makes it possible to image such fast biological processes in 3D. But the images are often lacking in quality, and it takes hours or days for massive amounts of data to be converted into 3D volumes and movies.

Now, EMBL scientists have combined artificial intelligence (AI) algorithms with two cutting-edge microscopy techniques -- an advance that shortens the time for image processing from days to mere seconds, while ensuring that the resulting images are crisp and accurate. The findings are published in Nature Methods.

"Ultimately, we were able to take 'the best of both worlds' in this approach," says Nils Wagner, one of the paper's two lead authors and now a PhD student at the Technical University of Munich. "AI enabled us to combine different microscopy techniques, so that we could image as fast as light-field microscopy allows and get close to the image resolution of light-sheet microscopy."

Although light-sheet microscopy and light-field microscopy sound similar, these techniques have different advantages and challenges. Light-field microscopy captures large 3D images that allow researchers to track and measure remarkably fine movements, such as a fish larva's beating heart, at very high speeds. But this technique produces massive amounts of data, which can take days to process, and the final images usually lack resolution.

Light-sheet microscopy homes in on a single 2D plane of a given sample at one time, so researchers can image samples at higher resolution. Compared with light-field microscopy, light-sheet microscopy produces images that are quicker to process, but the data are not as comprehensive, since they only capture information from a single 2D plane at a time.

To take advantage of the benefits of each technique, EMBL researchers developed an approach that uses light-field microscopy to image large 3D samples and light-sheet microscopy to train the AI algorithms, which then create an accurate 3D picture of the sample.

"If you build algorithms that produce an image, you need to check that these algorithms are constructing the right image," explains Anna Kreshuk, the EMBL group leader whose team brought machine learning expertise to the project. In the new study, the researchers used light-sheet microscopy to make sure the AI algorithms were working, Anna says. "This makes our research stand out from what has been done in the past."

Robert Prevedel, the EMBL group leader whose group contributed the novel hybrid microscopy platform, notes that the real bottleneck in building better microscopes often isn't optics technology, but computation. That's why, back in 2018, he and Anna decided to join forces. "Our method will be really key for people who want to study how brains compute. Our method can image an entire brain of a fish larva, in real time," Robert says.

He and Anna say this approach could potentially be modified to work with different types of microscopes too, eventually allowing biologists to look at dozens of different specimens and see much more, much faster. For example, it could help to find genes that are involved in heart development, or could measure the activity of thousands of neurons at the same time.

Next, the researchers plan to explore whether the method can be applied to larger species, including mammals.

Artificial intelligence makes great microscopes better than ever: Machine learning helps some of the best microscopes to see better, work faster, and process more data -- ScienceDaily

Why Birds Engage in Preening

Preening is a maintenance behavior found in birds that involves the use of the beak to position feathers, interlock feather barbules that have become separated, clean plumage, and keep ectoparasites in check. Feathers contribute significantly to a bird's insulation, waterproofing and aerodynamic flight, and so are vital to its survival. Because of this, birds spend considerable time each day maintaining their feathers, primarily through preening. Several actions make up preening behaviour. Birds fluff up and shake their feathers, which helps to "rezip" feather barbules that have become unhooked. Using their beaks, they gather preen oil from a gland at the base of their tail and distribute this oil through their feathers. They draw each contour feather through their bill, nibbling it from base to tip.

Over time, some elements of preening have evolved to have secondary functions.  Ritualised preening has become a part of some courtship displays , for example. It is also a displacement activity that can occur when birds are subjected to two conflicting drives. Though primarily an individual function, preening can be a social activity involving two or more birds – a behaviour known as allopreening. In general, allopreening occurs either between two members of a mated pair or between flock members in a social species. Such behaviour may assist in effective grooming, in the recognition of individuals (mates or potential sexual partners), or in reducing or redirecting potential aggressive tendencies in social species. Most allopreening is confined to the head and neck, smaller efforts being directed towards other parts of the body.

Ingestion of pollutants or disease-causing organisms during preening can lead to problems ranging from liver and kidney damage to pneumonia and disease transmission. Injury and infection can cause overpreening in caged birds, as can confining a bird with a dominant or aggressive cage mate.

Importance of Preening

Preening is a maintenance behaviour used by all birds to care for their feathers. It is an innate behaviour; birds are born knowing the basics, but there is a learned component. Birds that are hand-reared without access to a role model have abnormalities in their preening behaviours.  Despite spending considerable time in their efforts, they do not use proper techniques to groom effectively and may do a poor job overall as a result.  Displaced feathers can cause birds considerable trouble; such feathers might become damaged, could interrupt the smooth flow of air over a flying bird, or might allow the bird's body heat to escape. Preening allows a bird to reposition such displaced feathers. There is evidence that filoplumes specialised feathers buried under a bird's outer covering of contour feathers, help to signal when contour feathers have been displaced.  Mechanoreceptorsat the base of the filoplumes only fire when contour feathers are displaced or the filoplume moves.  Preening enables birds to remove dirt and parasites from their plumage, and assists in the waterproofing of feathers.  During moult, birds remove the sheaths from around their emerging pin feathers while preening.

Because feathers are critical to a bird's survival – contributing to insulation, waterproofing and aerodynamic flight – birds spend a great deal of time maintaining them.  When resting, birds may preen at least once an hour.  Studies on multiple species have shown that they spend an average of more than 9% of each day on maintenance behaviours, preening occupying over 92% of that time, though this figure can be significantly higher.  Studies found that some gull species spent 15% of daylight hours during the breeding season preening, while another showed that common loons spent upwards of 25% of their day preening.  In most of the studied species where the bird's sex could be determined in the field, males spent more time preening than females, though this was reversed in ducks.  Some ratites, which are not dependent on their feathers for flight, spend far less time on maintenance behaviours. One study of ostriches found that they spent less than 1% of their time engaged in such behaviours

Preen Oil

Fully grown feathers are essentially dead structures, so it is vital that birds have some way to protect and lubricate them. Otherwise, age and exposure cause them to become brittle.  To facilitate that care, many bird species have a preen or uropygial gland, which opens above the base of the tail feathers and secretes a substance containing fatty acids, water, and waxes. The bird gathers this substance on its bill and applies it to its feathers.  The gland is generally larger (in relation to body size) in waterbirds, including terns, grebes and petrels, but studies have found no clear correlation between the size of a bird's gland and the exposure to water that its lifestyle dictates.

Preen oil plays a role in reducing the presence of parasitic organisms, such as feather-degrading bacteria, lice and fungi, on a bird's feathers.  One study of Eurasian hoopoes showed that the presence of symbiotic bacteria (Enterococcus faecalis) in their preen oil inhibited the growth of the feather-degrading bacteria Bacillus licheniformis.  Enterococcus faecalis did this by releasing a bacteriocin.  Female hoopoes transfer preen oil onto their brood patches and eggs, which results in the transfer of bacteria as well. Preen oil and bacteria are rubbed into microscopic pits on the surface of the eggs during incubation.  This alters the colour of the eggs (darkening them) but there is also evidence that the bacteria may help to protect the developing chicks.  Other studies have shown that removing or restricting access to the uropygial gland typically results in a higher bacterial parasite load on the plumage, though not necessarily of feather-degrading bacterial species.  Preen oil may play a part in protecting at least some species from some internal parasites; a study of the incidence of avian malaria in house sparrows found that uninfected birds had larger uropygial glands and higher antimicrobial activity in those glands than infected birds did.  There is even evidence that the foul-smelling preen oil of hoopoes and wood hoopoes may help to repel mammalian predators.

Preen oil helps to maintain the waterproofing of a bird's plumage. Though the oil does not provide any direct waterproofing agent, it helps to extend the life of the feather – including the microscopic structures (the barbs and barbules) which interlock to create the waterproof barrier.

While most species have a preen gland, the organ is missing in the ratites (emu, ostriches, cassowaries, rheas and kiwis) and some neognath birds, including bustards, woodpeckers, a few parrots and pigeons.  Some species that lack a preen gland instead have powder down feathers which continually break down into a fine dust that the birds apply to their contour feathers while preening.  These powder down feathers may be scattered throughout the bird's plumage or concentrated into dense patches. As well as helping to waterproof and preserve the bird's feathers, powder down can give a metallic sheen to the plumage.

                      https://en.wikipedia.org/wiki/Preening