Cancer Drug Proves to Be Effective Against Multiple Tumors

The 86 cancer patients were a disparate group, with tumors of the pancreas, prostate, uterus or bone. One woman had a cancer so rare there were no tested treatments. She was told to get her affairs in order.

Still, these patients had a few things in common. All had advanced disease that had resisted every standard treatment.

All carried genetic mutations that disrupted the ability of cells to fix damaged DNA. And all were enrolled in a trial of a drug that helps the immune system attack tumors.

The results, published on Thursday in the journal Science, are so striking that the Food and Drug Administration already has approved the drug, pembrolizumab, brand name Keytruda, for patients whose cancers arise from the same genetic abnormality.

It is the first time a drug has been approved for use against tumors that share a certain genetic profile, whatever their location in the body. Tens of thousands of cancer patients each year could benefit.

“This is absolutely brilliant,” said Dr. José Baselga, physician in chief at Memorial Sloan Kettering Cancer Center in New York, which has just hired the study’s lead investigator, Dr. Luis A. Diaz Jr.

After taking pembrolizumab, 66 patients had their tumors shrink substantially and stabilize, instead of continuing to grow. Among them were 18 patients whose tumors vanished and have not returned.

There was no control group, which meant the results had to be absolutely compelling to be convincing. The study started in 2013 and is funded by philanthropies; the drugmaker’s only role was to supply the drug. The study is continuing.

The drug, made by Merck, is already on the market for select patients with a few types of advanced lung, melanoma and bladder tumors. It is expensive, costing $156,000 a year.

A test for the mutations targeted by the drug is already available, too, for $300 to $600.

Just 4 percent of cancer patients have the type of genetic aberration susceptible to pembrolizumab. But that adds up to a lot of patients: as many as 60,000 each year in the United States alone, the study’s investigators estimated.

Clinicians have long been accustomed to classifying cancers by their location in the body — patients are diagnosed with lung cancer, for example, or brain cancer.

Yet researchers have been saying for years that what matters was the genetic mutation causing the tumors. At first, they were certain they would be able to cure cancers with drugs that zeroed in on the mutations, wherever the tumors were lodged.

But cancers were more complicated than that, said Dr. Drew M. Pardoll, director of the Johns Hopkins Bloomberg-Kimmel Institute and an author of the new paper.

A mutation that appeared in half of all melanomas, for example, turned out to be rare in other cancers. And even when scientists pinpointed that mutation in 10 percent of colon cancers, the drug that worked for melanoma patients did not work for other cancer patients.

“It was a great dream,” Dr. Pardoll sighed.

The new study was based on a different idea. The immune system can recognize cancer cells as foreign and destroy them. But tumors deflect the attack by shielding proteins on their surface, making them invisible to the immune system.

Pembroluzimab is a new type of immunotherapy drug known as a PD-1 blocker, which unmasks the cancer cells so that the immune system can find and destroy them.

The drug is the happy result of a failed trial. A nearly identical drug, nivolumab, was given to 33 colon cancer patients, and just one showed any response — but his cancer vanished altogether.

What was special about that one patient? Dr. Diaz, a geneticist at Johns Hopkins until now, and lead author of the new study, found the answer: a genetic mutation that prevented the tumor from repairing DNA damage.

As a result, the man’s cancer cells contained a plethora of mutated genes, which produced thousands of strange-looking proteins on the surfaces of the cells. Once the tumor’s cloaking mechanism was short-circuited by the drug, the man’s immune system had no trouble targeting the foreign proteins on the cancer cells.

That led to the idea for the Dr. Diaz’s new study. He and his colleagues sought patients whose tumors had the same genetic defect, which can arise in any of four genes in a pathway that repairs damaged DNA. They gave these patients a PD-1 blocker and were surprised by the results.

The drug’s effects have been so durable that the investigators do not know how long the results should be expected to persist or how long these patients might expect to survive. That kind of result, Dr. Baselga said, “is insane.”

by Gina Kolata, NY Times |  Read more:

Image: Medscape

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Henri-Cartier Bresson. Vitaliano Bassetti, Italy 1954
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Slow Crash

Two years before the 2008 Wall Street crash that toppled the global economy into deep recession, Harper’s Magazine published a dark prophecy of what was to come. In “The New Road to Serfdom,” economist Michael Hudson laid out how millions of Americans had taken on huge debts to buy houses on the presumption that they could later sell them at a profit. “Most everyone involved in the real estate bubble so far has made at least a few dollars,” he wrote. “But that is about to change. The bubble will burst, and when it does the people who thought they would be living the easy life of a landlord will soon find out that what they really signed up for is the hard servitude of debt serfdom.” As the twenty million people who lost their homes discovered, Hudson got it entirely right.

Today, unemployment is at record lows, and the stock market is at record highs. Allegedly, we have recovered from the disaster. I talked to Hudson, Distinguished Professor of Economics at the University of Missouri-Kansas City and the author, most recently, of J is For Junk Economics, A Guide to Reality in an Age of Deception, about his pre-crash prediction, and what he now sees in our future. (...)

So are we heading for another explosion comparable to 2008?

I’m not sure it’ll be an explosion. It’s more like a slow crash. It’s more like people are getting desperate. They’re having to live off their credit cards, not to buy luxuries but just simply to break even. They’re falling further and further behind, and as they fall behind the interest rate rises, the penalties rise, so people are getting more and more squeezed.

That’s why where I live in New York City, on all the big shopping streets there are more and more storefronts for rent. The stores are going out of business, especially the stores that are either mom and pops, or small well-known stores like art supply stores that have been there for a generation. Only the big chains are surviving, and even the chains are closing down, Sears and others. Entire shopping malls are going into default.

But we keep being told that this is because people are shifting to online shopping. Is that not the case?

Certainly many people are shopping online, but that’s not the real cause. The real cause is that overall retail sales are going down, because the average wage earner is only able to spend between a quarter and a third of their income on goods and services, after what’s left over from housing and taxes. The Federal Housing Authority now guarantees government mortgages up to 42 percent of your income. In New York City it’s normal to pay 40 percent of your income for rent.

Assume that 40 percent of your income goes for housing. Maybe 15 percent of your income is taken right off the paycheck by the FICA [Federal Insurance Contributions Act] for Social Security and essentially pre-saving for Social Security medical care (which provides the government with enough money to cut taxes on the higher brackets.) There’s another 10 percent to 15 percent in income taxes, local income taxes, and sales taxes. In addition to paying the mortgage debt, people have to pay bank debt, auto debt, and credit card debt. That’s about 10 percent. When you add all of these up, there’s only about maybe 30 percent of the income that they can spend on goods and services.

Economic textbooks talk about a circular flow, where the workers will get paid wages and they buy what they produce. That’s why Henry Ford paid his workers $5.00 a day, so that they could afford to buy cars. Now they only have a little bit to buy what they produce, and the rest of their money goes to the banks and to the government to give tax cuts for the top 10 percent. You’re having a slow squeeze on the middle class and the working class in this country, and it’s stifling the domestic market.

How do you explain what are billed as record low unemployment figures?

People are desperate to go to work. But if you look at where the jobs are, these are minimum wage jobs. Most of the jobs are in retail, trade, or in other low-paying jobs. Yes, employment is going up, but at very low wages that don’t enable families to save. You can see this particularly every two years when the Federal Reserve publishes a survey of consumer finances. You can see for instance that blacks and Hispanics have almost no savings at all, and 50 percent of the American population as a whole doesn’t have any savings because if you’re earning a low salary, then almost all of what you do earn has to go to pay for rent and for bank credit and for taxes.

You say the most likely prospect for the future is a “slow crash” but when your Road to Serfdom piece ran in Harper’s, the Case-Schiller national home price index stood at 184.38. As of February this year it stood at 185.56. Why shouldn’t there be a similar blow-up?

Nowadays nearly all residential mortgages are guaranteed by the government’s Federal Housing Agency (and have been since 2008), so banks are not threatened. The government is on the hook to guarantee American mortgage loans as well as student loans.

A large portion of the millions of homes that were foreclosed have been bought by hedge funds, often for all cash – because they can make more money renting them out than they can make in the financial markets. So this real estate is not debt leveraged.

Wall Street’s investment banks and bondholders were rescued, not the economy. The debts were left in place, and continue to grow not only by compound interest but by arrears and penalties compounding. The proportion of national income paid as interest, insurance fees and economic rent is rising faster than the economy is growing.

Banks lend mainly to other financial institutions. They don’t lend to factories that are creating jobs. They don’t lend out for goods and services. They lend to other financial institutions. The whole economy has turned into trying to make money on speculation and arbitrage, not on producing goods and services, not on hiring people to actually do work. The economy therefore is very fragile.

The whole economy at the end of the road is going to look like Greece or Spain or Portugal or Italy. All of these economies are shrinking by what’s called debt deflation. In other words, people have to pay either so much debt or they have to have forced saving, like pension fund saving, that the economy is shrunk for financial reasons, for putting more and more of its money out of the real economy of goods and services into the financial sector.

Is that your prediction for our future here in the United States? Greece?

Yes, a slow crash as more and more money is drained from the economy to pay the FIRE sector—finance, insurance, and real estate—not the goods and service producing sector.

by Andrew Cockburn, Harper's | Read more:

Packing and Cracking

Gerrymandering has a long and unpopular history in the United States. It is the main reason that the country ranked 55th of 158 nations — last among Western democracies — in a 2017 index of voting fairness run by the Electoral Integrity Project, an academic collaboration between the University of Sydney, Australia, and Harvard University’s John F. Kennedy School of Government in Cambridge, Massachusetts. Although gerrymandering played no part in the tumultuous 2016 presidential election, it seems to have influenced who won seats in the US House of Representatives that year.

“Even if gerrymandering affected just 5 seats out of 435, that’s often enough to sway crucial votes,” Mattingly says.

The courts intervene when gerrymandering is driven by race. Last month, for example, the Supreme Court upheld a verdict that two North Carolina districts were drawn with racial composition in mind (see ‘Battleground state’). But the courts have been much less keen to weigh in on partisan gerrymandering — when one political party is favoured over another. One reason is that there has never been a clear and reliable metric to determine when this type of gerrymandering crosses the line from acceptable politicking to a violation of the US Constitution.

[ed. See:  The Mathematicians Who Want to Save Democracy]

Are the Warriors' Brogrammer Army the Most Hated Fans in Sports?

It was hard to find anyone who begrudged Cleveland fans their championship 12 months ago. The fanbase had suffered through decades of losing and crushing defeats; there had been tears and screams and, yes, even flames. The collective futility of the Cavaliers, Indians and Browns had endured year-round, one failed season rolling into the next. And all the sports misery occurred at a time when the city and the entire region of northeast Ohio was struggling just to survive. So only the cruelest of souls were upset by the sight of a million people in the streets of Cleveland celebrating the city’s good fortune.

Good luck finding a person alive who feels the same way about Warriors fans. Golden State are two wins away from winning their second NBA title in three years and entering the conversation about the greatest basketball teams of all time. They’re also two wins away from making Warriors fans perhaps the most despised in all of American sports.

All due respect to the widely loathed supporters of the Patriots, Yankees, Cowboys and Lakers, but the Warriors are building a fanbase that could dwarf them all for unlikability. Golden State fans’ negatives are on a hockey stick growth curve as Oracle Arena increasingly fills with – apologies for the poor attempt at using Silicon Valley lingo – brogrammers who truly believe they offer a value add to the organization. (And for the sake of clarity, it is this new breed of fan that attracts ire, rather than the Warriors supporters who pulled for the team even during the bad old days.)

Part of the problem is simple demographics. Bandwagon jumpers are considered to be the lowest form of fan – even below drunk, belligerent and face-painted – whereas the diehard, thick and thin, fan-since-birth group is the most respected. Because of the massive influx of people into northern California with the tech boom, many of those filling the choice seats at Oracle Arena have ties to the region that are tenuous even compared to those of Kevin Durant. Yet they’re cheering their hearts out for their beloved Warriors every night, while across the street the last place A’s – with the second-worst attendance in all of baseball and portions of the upper deck covered in tarp – don’t seem to have captured the imagination of Silicon Valley big wigs. The new Warriors fan has not suffered anything near the sports heartache of a Cleveland lifer. Their toughest season to endure was one in which the Warriors won an NBA-record 73 games. Sad!

The biggest example of the new strain of Golden State fan is none other than Joe Lacob himself, the team owner. Born in Massachusetts, he grew up a Celtics fan before his family relocated when he was a teenager to Los Angeles ... upon which he became a Lakers fan. Who knew that kind of swap in loyalty was even legal? But avoiding charges, Lacob started a venture capital firm in the late 80s, became part owner of the Celtics in 2006 (another flip!) and then majority owner of the Warriors after the 2010 season. Like the worst Silicon Valley stereotype, he credits tech culture for his team’s success, telling the New York Times Magazine last spring: “We’ve crushed them on the basketball court, and we’re going to for years because of the way we’ve built this team. We’re light years ahead of probably every other team in structure, in planning, in how we’re going to go about things. We’re going to be a handful for the rest of the NBA to deal with for a long time.”

Lacob is undoubtedly correct that his team is positioned to win for a long time, but that has more to do with hitting on Stephen Curry in the 2009 draft – a selection that came before Lacob arrived – and the ensuing benefits Curry’s abilities have afforded (on an under-market contract, mind) than it does with any sort of ingenious tech management style we in the small-brained community can’t comprehend. The Portland Trail Blazers and Sacramento Kings also have owners with tech backgrounds, don’t they? But their tech culture hasn’t created much success without the likes of Curry and Durant (who is deeply involved in Silicon Valley himself) on the rosters. Having an owner that irks is a near-necessity for despised teams, however – see Jerry Jones and Robert Kraft – and Lacob goes the extra mile there with his comments on how he and his fiancee had sex alongside the Larry O’Brien Trophy following Golden State’s 2015 title win. Thinking of that is like Uber but for vomiting.

by DJ Gallo, The Guardian | Read more:

Image:Ezra Shaw/Getty Images

Carriage of Musical Instruments

SUMMARY: The Department of Transportation is issuing a final rule to implement section 403 of the FAA Modernization and Reform Act of 2012 regarding the carriage of musical instruments as carry-on baggage or checked baggage on commercial passenger flights operated by air carriers. This rule responds to difficulties musicians have encountered when transporting their instruments during air travel.

DATES: Effective Date: This rule is effective March 6, 2015.  (...)

Background

On February 14, 2012, the FAA Modernization and Reform Act of 2012 (the Act) was signed into law. Section 403 of the Act requires U.S. air carriers to accept musical instruments on their passenger flights either as carry-on baggage or checked baggage, provided that certain conditions are met. The passage of Section 403 is Congress’ response to difficulties musicians have encountered when transporting their instruments during air travel. The statute directs the Department of Transportation (Department or DOT) to issue a final rule to implement the requirements set forth in section 403.

During the past year, the Department has been engaged in dialogue with musicians as well as representatives of airlines and industry associations to address the difficulties musicians face when traveling by air with musical instruments. In July 2014, DOT Secretary Anthony Foxx hosted a ‘‘Flying with Musical Instruments’’ meeting to provide airline representatives, musicians, and government officials an opportunity to exchange ideas on ways to prevent or resolve difficulties encountered by musicians when flying with their instruments while still ensuring the safety of passengers and crew. At the meeting, several members of various musician organizations described problems that musicians encounter when traveling by air with their musical instruments, particularly when bringing instruments as carry-on baggage. Airline representatives in attendance described their policies for transport of musical instruments as carry-on or checked baggage. Many airlines have already adopted policies concerning the air transportation of musical instruments that mirror the requirements in Section 403 of the Act. The stakeholders recognized that, while most airlines’ current policies regarding musical instruments are consistent with the statute, frontline customer service agents and flight crew may not always be well-versed in those policies and may not communicate those policies accurately and effectively to musicians. By the same token, the meeting attendees also agreed that many musicians were not very well informed about airline policies regarding transporting musical instruments or about the measures they can take to better prepare themselves to ensure that the transport goes smoothly.

Since then, the stakeholders have voluntarily taken certain steps to better understand the extent of the problem and prevent or minimize confusion over musical instruments as carry-on baggage. (...)

Section 403 of the Act and this final rule provide that carriers are required to allow passengers to stow their musical instruments in an approved stowage area in the cabin only if at the time the passenger boards the aircraft such stowage space is available. With the exception of certain disability assistance devices, overhead bins or under seat stowage space is available to all passengers and crew members for their carry-on baggage on a ‘‘first come, first served’’ basis. Accordingly, carriers are not required to remove other passengers’ or crew members’ carry-on baggage that is already stowed in order to make space for a musical instrument. However, this also means carriers are not allowed to require a passenger to remove his or her musical instrument that is already safely stowed (e.g., in the overhead bin) to make room for carry-on baggage of other passengers who boarded the aircraft later than the passenger with the musical instrument. This is true even if the space taken by the musical instrument could accommodate one or more other carry-on items. Because the rule does not require that musical instruments be given priority over other carry-on baggage, we encourage passengers traveling with musical instruments to take steps to board before as many other passengers as possible to ensure that space will be available for them to safely stow their instruments in the cabin. This includes utilizing preboarding opportunities that some carriers offer (usually for a fee). This rule also states that carriers are prohibited from charging passengers with a musical instrument as carry-on baggage an additional fee other than any standard fee carriers impose for carry-on baggage. By including such a requirement in the statute, Congress clearly meant to require carriers to treat musical instruments in the cabin as no different from other carry-on baggage. For example, many carriers’ FAA approved carry-on baggage programs permit one piece of carry-on baggage plus one personal item such as a purse or a briefcase. If the passenger with the musical instrument already has these two standard items and the musical instrument is the third carry-on item, that carrier may not permit the passenger to board the aircraft with a third carry-on item. (...)

§ 251.3 Small musical instruments as carry-on baggage. Each covered carrier shall permit a passenger to carry a violin, guitar, or other small musical instrument in the aircraft cabin, without charging the passenger a fee in addition to any standard fee that carrier may require for comparable carry-on baggage, if: (a) The instrument can be stowed safely in a suitable baggage compartment in the aircraft cabin or under a passenger seat, in accordance with the requirements for carriage of carry-on baggage or cargo established by the FAA; and (b) There is space for such stowage at the time the passenger boards the aircraft. § 251.4 Large musical instruments as carry-on baggage. Each covered carrier shall permit a passenger to carry a musical instrument that is too large to meet the requirements of § 251.3 in the aircraft cabin, without charging the passenger a fee in addition to the cost of an additional ticket described in paragraph (e) of this section, if: (a) The instrument is contained in a case or covered so as to avoid injury to other passengers; (b) The weight of the instrument, including the case or covering, does not exceed 165 pounds or the applicable weight restrictions for the aircraft; (c) The instrument can be stowed in accordance with the requirements for carriage of carry-on baggage or cargo established by the FAA; (d) Neither the instrument nor the case contains any object not otherwise permitted to be carried in an aircraft cabin because of a law or regulation of the United States; and (e) The passenger wishing to carry the instrument in the aircraft cabin has purchased an additional seat to accommodate the instrument.

by Federal Register, Vol. 80, No. 2 / Monday, January 5, 2015 / Rules and Regulations | Read more (pdf):

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Real vs. Fake: The Eames Lounge

I know this post is kind of a departure from my regular programming ’round these parts, but what can I say? It’s Monday, it’s almost the end of March, it’s snowing, possibly this is the rapture, my apartment building has no heat, and I woke up feeling like it was high time to nerd out over chairs.

So. Remember how I used to have a fake Eames lounge chair? Back when my living room looked like this:

Yeah. Well. When we received the very special things from my grandparents’ house, there was a brief hot second when I had two Eames lounge chairs—the real deal, straight out of Zeeland, Michigan circa 1972, and the fakey guy who I think was manufactured by Plycraft, probably a few years later.

“Reproductions” and “replicas” and “inspired-by” designs have been around for forever, but it seems like only in more recent years have these unauthorized replicas inched closer and closer to looking like the real thing. Now. There is a whooooollllleeee long debate to be had about “real” vs. “fake” and the legal standing of intellectual property surrounding furniture designs and who is getting ripped off and how and what this means for society and design and quality and whether the sky is blue. Frankly, I’d rather not get into that because everybody has their own opinions and I find that type of squabbling annoying. Personally, I can’t picture myself buying a newly-produced knock-off piece of furniture for a number of reasons, but I think the rules change a little when you’re talking vintage and secondhand. Nobody’s getting hurt, it isn’t perpetuating the lousy knock-off furniture industry—it’s just good clean old-fashioned thrifty fun times. I support that.

Point is, people often wonder what the differences are between authentic and knock-off furniture—Eames lounge chairs, specifically—and it’s hard to find a good guide explaining it. So being in the unique position of owning both concurrently, I thought it would be a good time to put together a little show and tell.

by Daniel Kanter, Manhattan Nest |  Read more:

Images: Daniel Kanter

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Max Ernst Visits Frida in a Dream
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Is Pharma Research Worse Than Chance?

The two most exciting developments in psychopharmacology in the 21st century so far have been ketamine for depression and MDMA for PTSD.

Unlike other antidepressants, which work intermittently over a space of weeks, ketamine can cause near-instant remission of depression with a single infusion – which lasts a week or two and can be repeated if needed. Ketamine use may be successful in 50-70% of patients who have failed treatment with conventional antidepressants. Ketamine treatment has some issues right now, but the race is on to create an oral non-hallucinogenic version which could be the next big blockbuster drug and revolutionize depression treatment.

MDMA (“Ecstasy”) is undergoing FDA Phase 3 clinical trials as a treatment for PTSD. Preliminary research has been small and underpowered, but suggests response rates up to 80% and effect sizes greater than 1 in this otherwise-hard-to-treat condition. None of this is on really firm footing – that’ll have to wait for the Phase 3. But signs are looking very good.

I say these are the two most exciting developments mostly because no other developments have been exciting. In terms of normal psychiatric drugs, the best that the 21st century has given us has probably been pimavanserin and aripiprazole, modest updates to the standard atypical antipsychotic model. These drugs are probably a bit better than existing ones for the people who need them (especially pimavenserin for psychosis in Parkinson’s) but they don’t revolutionize the treatment of any condition and nobody ever claimed that they did. And most drugs aren’t even at this level – they’re new members of well-worn classes with slightly different side effect profiles. The landscape was so quiet that ketamine came in like a bolt from the blue, and MDMA is set to do the same in a couple of years when the trial results come out.

(if I’m wrong, and history decides these two drugs weren’t the biggest developments, the most likely failure mode is that psilocybin turned out to be more important than MDMA)

There’s a morality tale to be told here about how the War on Drugs choked off vital research on some of the most powerful psychiatric compounds and cost us fifty years in exploring these effects and treating patients. I agree with this morality tale as far as it goes, but I also think there’s another, broader morality tale beneath it.

Suppose that neither ketamine nor MDMA were illegal drugs. Ketamine was just used as an anaesthetic. MDMA was just used as a chemical intermediate in producing haemostatic drugs, its original purpose. Now the story is that, fifty years later, we learn that this anaesthetic and this haemostatic turn out to have incredibly powerful psychiatric effects. What’s our narrative now?

For me it’s about the weird inability of intentional psychopharmaceutical research to discover anything as good as things random druggies use to get high.

For decades, pharmaceutical companies have been coming out with relatively lackluster mental health offerings – aripiprazole, pimavanserin, and all the rest. And when asked why, they answer that mental health is hard, the brain is the most complicated organ in the known universe, we shouldn’t expect there to be great cures with few side effects for psychiatric diseases, and if there were we certainly shouldn’t expect them to be easy to find.

And this would make sense except in the context of ketamine and MDMA. Here are some random chemicals that affect the brain in some random way, which people were using mostly because they felt good at raves, and huh, they seem to treat psychiatric diseases much better than anything produced by some of the smartest people in the world working for decades on ways to treat psychiatric diseases. Why should that be?

One could argue it’s all about numbers vs. base rates. There are way more chemicals synthesized each year by people who aren’t looking for psychiatric drugs than by people who are. Even if the people who are looking for drugs are a thousand times more likely to find them, the people-who-aren’t-looking can still overwhelm them with sheer numerical advantage. And maybe when a psychiatric drug is discovered by people who weren’t looking for it, what this looks like is a few random people trying it, noticing it feels good, and turning it into a drug of abuse.

And I’m sure this is part of the story. But that just passes the buck to the next question. Abusers take the vast flood of possible chemicals and select the ones they think will feel good at raves. Psychopharmacologists take the vast flood of possible chemicals and select the ones they think will treat mental illnesses. How come the abusers’ selection process is better at picking out promising mental health treatments?

Here’s one hypothesis: at the highest level, the brain doesn’t have that many variables to affect, or all the variables are connected. If you smack the brain really really hard in some direction or other, you will probably treat some psychiatric disease. Drugs of abuse are ones that smack the brain really hard in some direction or other. They do something. So find the psychiatric illness that’s treated by smacking the brain in that direction, and you’re good.

Actual carefully-researched psychiatric drugs are exquisitely selected for having few side effects. The goal is something like an SSRI – mild stomach discomfort, some problems having sex, but overall you can be on them forever and barely notice their existence. In the grand scheme of things their side effects are tiny – in most placebo-controlled studies, people have a really hard time telling whether they’re in the experimental or the placebo group.

Nobody has a hard time telling whether they’re in the experimental or placebo group of a trial of high-dose MDMA. I think this might be the difference. If you go for large effects – even if you don’t really care what direction the effect is in – you’ll get them. And if you go for small, barely perceptible effects, then you’ll get those too. The dream of the magic bullet – the drug that treats exactly what it’s supposed to treat but otherwise has no effect at all on you – is just a dream. The closest you can come is something with miniscule side effects but a barely-less-miniscule treatment effect.

by Scott Alexander, Slate Star Codex |  Read more:

Image: stockphoto via

The Wine Shop Alternative: Gas Stations

It's the most incredible miracle in the Bible: Jesus turns water into wine during a wedding in Cana, a dusty and sunny place in Galilee where he performed his first "signs." And his very first sign would prove to be his best.

Its distinction has nothing to do with the miracle itself. Save for one thing, turning water into wine could not compete with, say, the resurrection of the dead, such as the daughter of Jairus (Jesus tells her father that she's not dead, but sleeping), or the curse of death, like the unfortunate fig tree mentioned in the gospels of Mark and Matthew (Jesus was hungry, he saw a fig tree, he walked to it, found it had no fruit, and cursed it, causing it to wither immediately).

What happens is this: Jesus is chilling at the wedding with his mother when it is announced that the party has run out of wine. The party wants to go on, but it can't do so without wine. It's a real crisis, because in these olden times, you can't just make a quick run to the supermarket or even a mini-mart and grab some bottles or cases of wine. There is nothing like that in Cana, or Galilee, or the whole Roman Empire. If you run out of wine, you have to hope a prophet is around, because these are the days of miracles and wonders.

Jesus's mother knows her son is also the son of God and asks him to do his thing. He reluctantly tells the servants to fill jars with water, which they do. Then he says: "Give it to the governor of the feast." When the governor tastes it, he discovers it's not water, it's wine. But that's not what makes this miracle more impressive than raising the dead or damning the living. The thing is, the wine is good.

Jesus could have turned the water into okay wine, or at least wine that was as good as the wine served at the start of the party. But that wasn't his style. His wine was unquestionably good. How do we know? It's in the Bible. King James version: "'Every man at the beginning [of a party] doth set forth good wine, and when men have well drunk, then that which is worse [is served,' said the governor]. 'But thou hast kept the good wine until now [when everyone is well drunk].'" Can you feel that? There's no bad resurrection or good damnation, but the miracle of transforming water into wine can be thus judged.

Let's keep all of this in mind as we turn to the Porter's at the gas station on Rainier Avenue. Though it has a view of Beacon Hill's verdant section, which is capped by the monument of modern architecture, the Pacific Tower (formerly the Pacific Medical Center), the location of the mini-mart is unrelentingly unlovely. Its little car wash looks like a car trap, its huge parking lot bakes when the sun is out, and it sits next to a stoplight that always fries the brains of impatient drivers. There are dying and dead signs here and there. You enter the mini-market with the goal of getting out as soon as you can. Gas stations are such miserable places.

But once inside this Porter's, a miracle occurs (gas stations are, after all, as American as Jesus). Just beyond the checkout is a stack of open wine boxes that are crowned by a sign: "Wine Specials." Avoid these. All the wine there is bad: Oak Leaf, Sancho, the Naked Grape—cheap crap. Behind this display on the left is where you find the good stuff. One shelf is lined with Château Roc De Segur (a surprisingly rich merlot blended with cabernet sauvignon and cabernet franc for $5.99), Château La Freynelle (a stiff Bordeaux for $10.99—and one that does not taste like the nimble feet of a pretty peasant is stiff), Château Haut-Roudier (a Bordeaux that does have a dash of the peasant's feet for $9.99), and Vieux Papes Blanc (a simple sauvignon blanc blended with crusty chardonnay and a bold ugni blanc for $6.99). All of these wines are more than drinkable. They are respectable.

The reason I often buy wine here is because I like to buy roasted chicken from San Fernando, the Peruvian restaurant that's across the street. I kill two birds with one stone and then jump on the 7 bus, which takes me home.

by Charles Mudede, The Stranger |  Read more:

Image: Getty

Be Careful Celebrating Google's New Ad Blocker

Google, a data mining and extraction company that sells personal information to advertisers, has hit upon a neat idea to consolidate its already-dominant business: block competitors from appearing on its platforms.

The company announced that it would establish an ad blocker for the Chrome web browser, which has become the most popular in America, employed by nearly half of the nation’s web users. The ad blocker — which Google is calling a “filter” — would roll out next year, and would be the default setting for Chrome when fully functional. In other words, the normal user sparking up their Chrome browser simply wouldn’t see the ads blocked by the system.

What ads would get blocked? The ones not sold by Google, for the most part.

The Chrome ad blocker would stop ads that provide a “frustrating experience,” according to Google’s blog post announcing the change. The ads blocked would match the standards produced by the Coalition for Better Ads, an ostensibly third-party group. For sure, the ads that would get blocked are intrusive: auto-players with sound, countdown ads that make you wait 10 seconds to get to the site, large “sticky” ads that remain constant even when you scroll down the page.

But who’s part of the Coalition for Better Ads? Google, for one, as well as Facebook. Those two companies accounted for 99 percent of all digital ad revenue growth in the United States last year, and 77 percent of gross ad spending. As Mark Patterson of Fordham University explained, the Coalition for Better Ads is “a cartel orchestrated by Google.”

So this is a way for Google to crush its few remaining competitors by pre-installing an ad zapper that it controls to the most common web browser. That’s a great way for a monopoly to remain a monopoly.

There’s more to the story, however. The real goal for Google appears to be not just blocking ads sold by other digital suppliers besides Google, but to undermine third-party ad blockers, which stop Google ads along with everyone else’s.

According to the Financial Times, Google will allow publishers what it’s calling “Funding Choices.” The publisher could charge the consumer a set price per page view to use third-party sites that block all advertising. Google would do the tracking of how many pages users view, and then charge them. Users could then “white list” particular sites, allowing ads to be shown on them and removing the charge. If users decided to pay to block ads, Google would receive a portion of that payment, sharing it with the publisher.

Web users will quickly recognize their only options: pay to use the internet, or uninstall the ad blockers and surf the web for free. At least 11 percent of all web users, and perhaps as many as 26 percent of all desktop users, have third-party ad blockers on their devices, a number that will likely grow in the next few years. But it’s easy to see how Google’s policy would depress ad blocker usage — except for the case of Google’s ad blocker, which creates preferences for Google’s own ads.

David Dayen, The Intercept |  Read more:

Image: Lluis Gene/AFP/Getty Images
[ed. Not related, but another Intercept essay worth reading: Jared Kushner Still Has a Job Because Washington Only Fears Republicans.] 

Baby Boomers Are Downsizing — and the Kids Won’t Take the Family Heirlooms

For 30 years, Pat Fryzel stored her children’s memorabilia, and her grandmother’s, too. But when she and her husband downsized, from a large Winchester home to a two-bedroom Boston townhouse, there was no room for the American Girl dolls or Nana’s cake plates. So Fryzel asked her grown kids to collect what they wanted.

She was not met with much enthusiasm. “They said, ‘Take a picture and text it to us,’” recalled Fryzel, 64, a retired nurse practitioner.

For generations, adult children have agreed to take their aging parents’ possessions — whether they wanted them or not. But now, the anti-clutter movement has met the anti-brown furniture movement, and the combination is sending dining room sets, sterling silver flatware, and knick-knacks straight to thrift stores or the curb.

And feelings are getting hurt, as adult children who are eager to minimize their own belongings — and who may live in small spaces, and entertain less formally than their parents did — are increasingly saying “no thanks” to the family heirlooms. (...)

The cold math of downsizing can be seen in a 2016 profile of buyers and sellers from the Massachusetts Association of Realtors. From the ages of 18 to 54, when a person sells a house, the next home he or she buys is larger. When sellers hit 55, the homes they buy next are smaller.

But the square-footage numbers don’t capture what space means in emotional terms, in memories: the mahogany hutch Grandma inherited as a young bride, too big for the dining nook in her retirement community apartment; the books that have been like friends, too voluminous to take along; the kids’ art projects and book reports from long ago. (...)

“I have a lot of mementos from my grandmother that my mother foisted on me,” said Fine, 59. She dutifully stored them for three decades, in boxes she never opened, and while she doesn’t expect her daughter to take them, she’s now facing a quandary.

“How can you take these things to a consignment shop?” she asked. “It’s almost like a burden that we carry with us through life. Sometimes I wish we had less connection to our possessions.”

The burden is only likely to grow. The number of Americans ages 65 and older is projected to more than double, from 46 million to over 98 million by 2060, according to a 2016 report by the nonprofit, Washington, D.C.-based Population Reference Bureau.

by Beth Teitell, Boston Review |  Read more:

Image: Shutterstock
[ed. No surprise here. I'm in the process of moving and the storage units in my town and the one I'm moving to are all booked (1200+ units).  Talk about a growth industry.]

How Online Shopping Makes Suckers of Us All

As Christmas approached in 2015, the price of pumpkin-pie spice went wild. It didn’t soar, as an economics textbook might suggest. Nor did it crash. It just started vibrating between two quantum states. Amazon’s price for a one-ounce jar was either $4.49 or $8.99, depending on when you looked. Nearly a year later, as Thanksgiving 2016 approached, the price again began whipsawing between two different points, this time $3.36 and $4.69.

We live in the age of the variable airfare, the surge-priced ride, the pay-what-you-want Radiohead album, and other novel price developments. But what was this? Some weird computer glitch? More like a deliberate glitch, it seems. “It’s most likely a strategy to get more data and test the right price,” Guru Hariharan explained, after I had sketched the pattern on a whiteboard.

The right price—the one that will extract the most profit from consumers’ wallets—has become the fixation of a large and growing number of quantitative types, many of them economists who have left academia for Silicon Valley. It’s also the preoccupation of Boomerang Commerce, a five-year-old start-up founded by Hariharan, an Amazon alum. He says these sorts of price experiments have become a routine part of finding that right price—and refinding it, because the right price can change by the day or even by the hour. (Amazon says its price changes are not attempts to gather data on customers’ spending habits, but rather to give shoppers the lowest price out there.)The price of a can of soda in a vending machine can now vary with the temperature outside.

It may come as a surprise that, in buying a seasonal pie ingredient, you might be participating in a carefully designed social-science experiment. But this is what online comparison shopping hath wrought. Simply put: Our ability to know the price of anything, anytime, anywhere, has given us, the consumers, so much power that retailers—in a desperate effort to regain the upper hand, or at least avoid extinction—are now staring back through the screen. They are comparison shopping us.

They have ample means to do so: the immense data trail you leave behind whenever you place something in your online shopping cart or swipe your rewards card at a store register, top economists and data scientists capable of turning this information into useful price strategies, and what one tech economist calls “the ability to experiment on a scale that’s unparalleled in the history of economics.” In mid-March, Amazon alone had 59 listings for economists on its job site, and a website dedicated to recruiting them.

Not coincidentally, quaint pricing practices—an advertised discount off the “list price,” two for the price of one, or simply “everyday low prices”—are yielding to far more exotic strategies.

“I don’t think anyone could have predicted how sophisticated these algorithms have become,” says Robert Dolan, a marketing professor at Harvard. “I certainly didn’t.” The price of a can of soda in a vending machine can now vary with the temperature outside. The price of the headphones Google recommends may depend on how budget-conscious your web history shows you to be, one study found. For shoppers, that means price—not the one offered to you right now, but the one offered to you 20 minutes from now, or the one offered to me, or to your neighbor—may become an increasingly unknowable thing. “Many moons ago, there used to be one price for something,” Dolan notes. Now the simplest of questions—what’s the true price of pumpkin-pie spice?—is subject to a Heisenberg level of uncertainty.

Which raises a bigger question: Could the internet, whose transparency was supposed to empower consumers, be doing the opposite?

by Jerry Useem, The Atlantic |  Read more:

Image: Justin Fantl

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The Doctor Is In. Co-Pay? $40,000.

When John Battelle’s teenage son broke his leg at a suburban soccer game, naturally the first call his parents made was to 911. The second was to Dr. Jordan Shlain, the concierge doctor here who treats Mr. Battelle and his family.

“They’re taking him to a local hospital,” Mr. Battelle’s wife, Michelle, told Dr. Shlain as the boy rode in an ambulance to a nearby emergency room in Marin County. “No, they’re not,” Dr. Shlain instructed them. “You don’t want that leg set by an E.R. doc at a local medical center. You want it set by the head of orthopedics at a hospital in the city.”

Within minutes, the ambulance was on the Golden Gate Bridge, bound for California Pacific Medical Center, one of San Francisco’s top hospitals. Dr. Shlain was there to meet them when they arrived, and the boy was seen almost immediately by an orthopedist with decades of experience.

For Mr. Battelle, a veteran media entrepreneur, the experience convinced him that the annual fee he pays to have Dr. Shlain on call is worth it, despite his guilt over what he admits is very special treatment.

“I feel badly that I have the means to jump the line,” he said. “But when you have kids, you jump the line. You just do. If you have the money, would you not spend it for that?”

Increasingly, it is a question being asked in hospitals and doctor’s offices, especially in wealthier enclaves in places like Los Angeles, Seattle, San Francisco and New York. And just as a virtual velvet rope has risen between the wealthiest Americans and everyone else on airplanes, cruise ships and amusement parks, widening inequality is also transforming how health care is delivered.

Money has always made a big difference in the medical world: fancier rooms at hospitals, better food and access to the latest treatments and technology. Concierge practices, where patients pay several thousand dollars a year so they can quickly reach their primary care doctor, with guaranteed same-day appointments, have been around for decades.

But these aren’t the concierge doctors you’ve heard about — and that’s intentional.

Dr. Shlain’s Private Medical group does not advertise and has virtually no presence on the web, and new patients come strictly by word of mouth. But with annual fees that range from $40,000 to $80,000 (more than 10 times what conventional concierge practices charge), the suite of services goes far beyond 24-hour access or a Nespresso machine in the waiting room.

Indeed, as many Americans struggle to pay for health care — or even, with the future of the Affordable Care Act in question on Capitol Hill, face a loss of coverage — this corner of what some doctors call the medical-industrial complex is booming: boutique doctors and high-end hospital wards. (...)

For patients, a limit of no more than 50 families per doctor eliminates the rushed questions and assembly-line pace of even the best primary care practices. House calls are an option for busy patients, and doctors will meet clients at their workplace or the airport if they are pressed for time.

In the event of an uncommon diagnosis, Private Medical will locate the top specialists nationally, secure appointments with them immediately and accompany the patient on the visit, even if it is on the opposite coast.

Meanwhile, for virtually everyone else, the typical wait to see a doctor is getting longer.

by Nelson D. Schwartz, NY Times | Read more:
Image: Chris B. Murray

Retirees Flock to Latin America to Live an Upper-Class Lifestyle on $1,500 a Month

To casual visitors, this colonial town in southern Ecuador looks like it was torn from the pages of history. With its cobbled streets, soaring cathedrals and bustling markets, it exudes a lazy, old world charm.

But Cuenca is also on the cutting edge of a very modern trend: providing a safe haven for U.S. retirees who have found themselves unwilling — or unable — to live out their golden years at home.

The growing wave of ex-pat seniors is not only upending notions about retirement in the hemisphere but reshaping the face of communities throughout the Americas. And the trend is expected to grow as waves of baby boomers exit the workforce ill-prepared for retirement.

There’s no accurate way to measure the phenomenon, but the Social Security Administration was sending payments to 380,000 retired U.S. workers living abroad in 2014 — up 50 percent from a decade ago.

In the Americas, records show that seniors are flocking to Canada, Mexico, Colombia, the Dominican Republic and Ecuador.

Best known for the Galapagos and providing asylum in its London embassy to WikiLeaks founder Julian Assange, Ecuador is home to 2,850 retirees receiving benefits, according to the U.S. government. But that number doesn’t tell the full picture. The city of Cuenca recently conducted a census that found its municipality alone was home to almost 10,000 foreign retirees, most of them Americans from Texas and Florida. (...)

In Cuenca, a city of about 350,000 people, they’ve found robust public transportation, an extensive museum network, solid healthcare and markets bursting with fresh fruits and produce. It’s a place where their two-bedroom, two-and-a-half bath apartment costs less than $400 a month. They’ve found that for about $1,500 a month, they can live a solidly upper-class lifestyle, dining out frequently and traveling. (...)

If there is a real driving force for retirees, it’s healthcare. Although the Trump administration has said it will leave Medicare untouched, its desire to scrap the Affordable Care Act amid rising premiums has created anxiety among seniors, said Prescher with International Living.

“Look at what retirees [in the U.S.] are facing,” he said. “They have a fixed income, maybe their investments haven’t been doing that well and now nobody knows what public healthcare will look like in the United States.”

“In the face of that … if you can live in a place where you can cut your cost of living in half while getting access to high quality healthcare, you have to think seriously about it,” he added. (...)

Cuenca’s survey of retirees found that most were either paying for healthcare out-of-pocket or had private healthcare. But some are reliant on Ecuador’s public healthcare system. Foreigners only need to pay into the system for three months before they have access to full benefits.

Because Medicare doesn’t cover most costs abroad, the Herrons, for example, were paying $84 a month to belong to the public healthcare system. When Michael, a 76-year-old retired IT worker-turned-novelist, recently ended up in the emergency room for a cardiac issue, the total bill was $133. In the past, the same procedure in the United States had been billed to his insurance company at $186,000.

Crespo, the city official, said the retirees are pumping money into the economy, but there are growing concerns over how they might be affecting the healthcare system.

“We’ve heard about cases where someone night need brain or heart surgery that might cost $300,000 in the United States and they have the operation here for $300 because they had paid into the system for three months,” she said. “The price differences are abysmal.”

Congresswoman Soliz said the legislature is planning on doing a comprehensive study of how foreign retirees might be straining public resources.

by Jim Wyss, Charlotte Observer | Read more:
Image: Jim Wyss

Océanic Surcouf 1956 
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