Indonesian Tsunami Was Powered by a Deadly Combo of Tectonics and Geography


The magnitude 7.5 earthquake that touched off the tsunami occurred amid a complex puzzle of tectonic plates.
Indonesian Tsunami Was Powered by a Deadly Combo of Tectonics and Geography
Rubble and debris lie around the ruins of a mosque following an earthquake, on October 02, 2018 in Palu, Indonesia.

Videos circulating on social media show an 18-foot wall of water advancing on the horizon.

The tremendous wave builds to a crescendo when it barrels ashore, submerging buildings already toppled by the deadly magnitude 7.5 earthquake that pummeled the northern part of Indonesia’s Sulawesi island last weekend (and triggered the inundation). The temblor and tsunami have killed well over a thousand people, with the toll expected to rise. The tsunami surprised the local population and, at first, some geologists, because the fault that ruptured was not the type typically associated with tsunamis.

Most big tsunamis, like the series of waves up to 100 feet high that killed more than 200,000 people around the Indian Ocean Basin in 2004, result from a sudden lurch of a subduction zone —a line where one of Earth’s tectonic plates is slowly diving beneath another. This heaving of the seafloor forces ocean water upward and outward. The tsunami that recently devastated the city of Palu on Sulawesi, however, was associated with a “strike-slip” fault, where two plates are sliding past each other. “It’s not something that you would’ve predicted,” says Jim Gaherty, a seismologist at Columbia University’s Lamont–Doherty Earth Observatory.

But strike-slip faults can also generate tsunamis through a couple different mechanisms that geologists have been evaluating for this event, in real time on Twitter and other social media platforms. The event, they say, speaks to the complex tectonic jumble that lies beneath Indonesia’s 14,000-plus islands.

Underwater Landslides

The earthquake’s shaking may have loosened sediment on a slope below the sea’s surface, triggering a submarine landslide that pushed water out of the way and sent it rocketing toward shore. Such occurrences have long been known to cause massive tsunamis; a rockslide triggered by a magnitude 7.8 earthquake set off the mega-tsunami in Lituya Bay, Alaska, in 1958. It sent water roaring up mountainsides to reach elevations of 1,700 feet, and remains the largest tsunami recorded in modern times.

Another possibility is the movement of the fault itself caused the tsunami. Although the fault moved horizontally and not vertically, the steep slopes and other unique features on the floor of Palu Bay could have pushed water in front of them as they moved during the earthquake. “It’s like pushing your hand through a bathtub,” says Chris Rowan, a geologist at Kent State University. Researchers at the Karlsruhe Institute of Technology in Germany have done a preliminary study with a tsunami model, and found the lateral movement of the fault and the topography of the bay would be enough to generate a tsunami the size of the one that hit Palu.

Neither possibility precludes the other. “I think the most likely [scenario] is there’s a combination of both going on,” says Austin Elliott, a geologist at the University of Oxford. Whatever the cause was, Palu’s location at the end of a narrow, V-shaped bay “is the worst place for a tsunami,” Elliott says, because the steadily narrowing channel funnels the water into an ever-narrower space, making the waves even higher.

Tectonic Jigsaw Puzzle

The Palu–Koro Fault Zone, the system that ruptured during this quake, is in the middle of a geologic tangle where multiple tectonic plates come together. Below western Indonesia the Indo–Australian Plate is shoved below the Eurasian Plate, occasionally creating the classic megathrust earthquakes that can generate huge tsunamis (just as the magnitude 9.1 temblor did in 2004). But in eastern Indonesia, where Sulawesi is located, the Indo–Australian Plate is topped by continental crust that does not subduct —so it is simply ramming headlong into the crust of the Eurasian Plate, fracturing it. “You’ve kind of got this jigsaw of little plates,” Rowan says, creating a complex environment with “lots of active, dangerous faults.”

Credit: Amanda Montañez; Source: USGS

The dangers of the Palu–Koro Fault have been known since the 1970s, Elliott says. Work in the 1990s and 2000s showed the plates on either side of the fault were moving in opposite directions “faster than the San Andreas Fault,” he says, meaning considerable stress was building up along the fault. A 2017 paper identified this fault as the most dangerous in the area, and suggested a future rupture was most likely to occur in the center of the valley where Palu is situated.

Being situated in this spot exacerbated the damage in Palu because the valley is filled with “flat, weak, soft, wet sediment,” says Robert Hall, a geologist at Royal Holloway, University of London who co-authored the 2017 paper. “Building on top of that is like building on jelly,” because this loose ground intensifies the shaking, he says. (The same thing occurred with the Mexico City earthquake of 1985.)

Surveys of the bay floor will need to be done to confirm the cause of the Sulawesi tsunami. They can look for signs of a landslide, and clues as to how much the fault moved. However it was triggered, the event makes it clear that coastal communities in seismically active regions should not only be worried about tsunamis from subduction zones —and this needs to be better communicated to local communities, Elliott and other experts say. The bottom line, he adds, is: “If you’re at the coast and you feel such a large earthquake, you just should assume there was a tsunami.”

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Bill Gates thinks a coming disease could kill 30 million people within 6 months – and says we should prepare for it like we do for war


bill gates
  • The next deadly disease that will cause a global pandemic is coming, Bill Gates said at a discussion of epidemics on Friday.
  • We’re not ready.
  • A flu like the 1918 influenza pandemic could kill 30 million within six months, Gates said, and the next disease might not even be a flu, it might be something we’ve never seen.
  • The world should prepare like it does for war, according to Gates.

If there’s one thing that we know from history, a deadly new disease will arise that will spread around the globe.

That could happen easily within the next decade. And as Bill Gates reminded listeners while speaking at a discussion about epidemics hosted by the Massachusetts Medical Society and the New England Journal of Medicine on Friday, we’re not ready.

As Gates said, he’s usually the optimist in the room, reminding people that we’re lifting children out of poverty around the globe and getting better at eliminating diseases like polio and malaria.

But “there’s one area though where the world isn’t making much progress,” said Gates. “And that’s pandemic preparedness.”

The likelihood that such a disease appears continues to rise. New pathogens emerge all the time as the world gets more populous and humanity encroaches on wild environments. It’s becoming easier and easier for individuals or small groups to create weaponized diseases that could spread like wildfire around the globe. According to Gates, a small non-state actor could rebuild an even deadlier form of smallpox in a lab. And in our interconnected world, people constantly hop on planes, crossing from megacities on one continent to megacities on another in a matter of hours.

According to one simulation by the Institute for Disease Modeling presented by Gates, a new flu like the one that killed 50 million in the 1918 pandemic would most likely kill 30 million within just six months now. And the disease that next takes us by surprise will most likely be one that we see for the first time when the outbreak starts, like happened recently with SARS and MERS viruses.

If you were to tell the world’s governments that weapons were under construction right now that could kill 30 million people, there’d be a sense of urgency about preparing for the threat, said Gates.

“In the case of biological threats, that sense of urgency is lacking,” he said. “The world needs to prepare for pandemics in the same serious way it prepares for war.”

pandemic disease ebola

Stopping the next pandemic

The one time the military tried a sort of simulated wargame against a smallpox pandemic, the final score was “smallpox one, humanity zero,” according to Gates.

But as he said, he’s an optimist, and he thinks we could better prepare for the next viral or bacterial threat.

In some ways, we’re clearly better prepared now than we were for previous pandemics. We have antiviral drugs that can at least do something to improve survival rates in many cases. We have antibiotics that can treat secondary infections, like pneumonia associated with the flu.

We’re getting closer to a universal flu vaccine. During his talk, Gates announced that the Bill and Melinda Gates Foundation would be offering $12 million in grants to encourage the development of such a vaccine.

And we’re getting better at rapid diagnosis, too, something essential since the first step against a new disease is quarantine. Just yesterday, a new research paper in the journal Science announced the development of a way to use the gene-editing technology CRISPR to rapidly detect diseases and to identify them using the same sort of paper strip used in a home pregnancy test.

Yet we’re not good enough yet at rapidly identifying the threat from a disease and coordinating a response, as the recent global reaction to the last Ebola epidemic showed.

There needs to be better coordination and communication between military and government to help coordinate responses. And Gates thinks that government needs ways to quickly enlist the help of the private sector when it comes to developing technology and tools to fight against emerging deadly disease.

As Melinda Gates said recently, the threat from a global pandemic – whether one that emerges naturally or one that’s engineered – is perhaps the biggest risk humanity faces right now.

“Think of the number of people who leave New York City every day and go all over the world – we’re an interconnected world,” she said. Those connections make us all vulnerable.

Donald Trump Warns Flu Shots Are The Greatest ‘Scam’ In Medical History.


The flu shot is the greatest scam in medical history, created by Big Pharma to make money off vulnerable people and make them sick, warns President Donald Trump.
In an interview with Opie and Anthony on Sirius XM, Trump slammed flu shots as “totally ineffective” and declared that he has never had one. Donald Trump Warns Flu Shots Are The Greatest ‘Scam’ In Medical History “I’ve never had one. And thus far I’ve never had the flu. I don’t like the idea of injecting bad stuff into your body. And that’s basically what they do. And this one (latest flu vaccine) has not been very effective to start off with.
Donald Trump Warns Flu Shots Are The Greatest ‘Scam’ In Medical History
I have friends that religiously get the flu shot and then they get the flu. You know, that helps my thinking. I’ve seen a lot of reports that the last flu shot is virtually totally ineffective.” Trump is right on this – flu shots are the greatest medical fraud in history. They are full of “bad stuff” including formaldehyde and mercury – two powerful neurotoxins – and the vaccine industry even admits that laboratory tests prove the popular jab does not work.
Why is a toxic, medical hoax, backed by nothing but voodoo faith-based dogma and clever marketing, pushed on the whole population every year? Vaccines are the one medicine where no scientific evidence of safety or efficacy is required by anyone: not the FDA, not the CDC and not the media. Congress even passed a law protecting the vaccine industry with absolute legal immunity, even when they manufacture and sell defective products that injure and kill people. And vaccine manufacturers have been lying to us for years about toxic levels of mercury in flu shots. Everybody knows mercury is toxic to inject into the human body. That’s not debated except by irrational anti-science denialists. So why won’t manufacturers remove the mercury? And why does Big Pharma continue to push a product that the vaccine industry admits does not even work?
Watch the video,

Is there any real distinction between ‘high’ and ‘low’ pleasures?


<p>Ramen heaven. From Juzo Itami’s 1985 noodle-western <em>Tampopo. Courtesy Criterion Collection</em></p>

Ramen heaven. From Juzo Itami’s 1985 noodle-western Tampopo.

 

Parents often say that they don’t mind what their children do in life just as long as they are happy. Happiness and pleasure are almost universally seen as among the most precious human goods; only the most curmudgeonly would question whether benign enjoyment is anything other than a good thing. Disagreement soon creeps in, however, if you ask whether some forms of pleasure are better than others. Does it matter whether our pleasures are spiritual or carnal, intellectual or stupid? Or are all pleasures pretty much the same?

Utilitarianism, as a moral philosophy, puts pleasure at the centre of its concerns, arguing that actions are right to the extent that they increase happiness and decrease suffering, wrong to the extent that they cause the opposite. Yet even the early Utilitarians couldn’t agree about whether pleasures should be ranked. Jeremy Bentham believed that all sources of pleasure are of equal quality. ‘Prejudice apart,’ he wrote in The Rationale of Reward (1825), ‘the game of push-pin is of equal value with the arts and sciences of music and poetry.’ His protégé John Stuart Mill disagreed, arguing in Utilitarianism (1863) that: ‘It is better to be a human being dissatisfied than a pig satisfied; better to be Socrates dissatisfied than a fool satisfied.’

Mill argued for a distinction between ‘higher’ and lower pleasures. His distinction is difficult to pin down, but it more or less tracks the distinction between capacities thought to be unique to humans and those we share with other animals. Higher pleasures depend on distinctively human capacities, which have a more complex cognitive element, requiring abilities such as rational thought, self-awareness or language use. Lower pleasures, in contrast, require mere sentience. Humans and other animals alike enjoy basking in the sun, eating something tasty or having sex. Only humans engage in art, philosophy and so on.

Mill was certainly not the first to make this distinction. Aristotle among others thought that the senses of touch and taste were ‘servile and brutish’; the pleasures of eating were ‘as brutes also share in’ and so less valuable than those that used the more developed human mind. Yet many would continue to side with Bentham, arguing that we are really not so intellectual and high-minded as all that, and we might as well accept ourselves for the brutes that we are, shaped by biochemistry and animal drives.

The difficulty with resolving this disagreement about the kinds of pleasure is not that we struggle to agree on the right answer. It’s that we’re asking the wrong question. The entire debate assumes a clear divide between the intellectual and bodily, the human and the animal, which is no longer tenable. These days, few of us are card-carrying dualists who believe that we are made of immaterial minds and material bodies. We have plenty of scientific evidence for the importance of biochemistry and hormones in all that we do and think. Nonetheless, dualistic assumptions still inform our thinking. So, what happens if we take seriously the idea that the physical and the mental are inseparable, that we are fully embodied beings? What would it mean for our ideas about pleasure?

The dining table is a good place to start. Along with sex, food is usually considered to be the quintessential lower pleasure. All animals eat, using the senses of smell and taste. It doesn’t require any complex cognition to conclude that something is delicious. Philosophers have generally assumed that to take pleasure in eating is simply to sate a primitive desire. So, for instance, Plato believed that cookery could never be a form of art, because it ‘never regards either the nature or reason of that pleasure to which she devotes herself, but goes straight to her end’.

Plato and his successors, however, failed to appreciate something that the French food writer Jean Anthelme Brillat-Savarin captured pithily in The Physiology of Taste (1825): ‘Animals feed; man eats; only the man of intellect knows how to eat.’ Brillat-Savarin drew a distinction between mere animal feeding, which is the ingestion of food as fuel, and human eating, which can and should engage more than just our most basic carnal desires. Eating is a complex act. Simply gathering the ingredients takes thought, since what we buy not only requires planning but affects the wellbeing of growers, producers, animals and the planet. Cooking involves knowledge of ingredients, the application of skills, the balancing of different flavours and textures, considerations of nutrition, care for the ordering of courses or the place of the dish in the rhythm of the day. Eating, at its best, brings all these things together, adding an attentive aesthetic appreciation of the end result.

Eating illustrates how the difference between higher and lower pleasures is not what you enjoy but how you enjoy it. Wolfing down your food like a pig at a trough is a lower kind of pleasure. Preparing and eating it using the powers of reflection and attention that only a human being possesses turns it into a higher pleasure. This form of higher pleasure need not be intellectual in the academic sense. An accomplished chef might be judging the balance of flavours and textures intuitively; a home cook might simply be thinking about what his guests are most likely to enjoy. What makes the pleasure higher is that it engages our more complex human abilities. It expresses more than just the brute desire to satisfy a craving.

For every pleasure, it should not be difficult to see that the how matters more than the what. Furthermore, the highest pleasures do not merely use our distinctively human capacities, they use them for a valuable end. Someone who goes to the opera to be seen in a new dress is not experiencing the higher pleasures of music but indulging the lower pleasures of vanity. Someone who reads Dr Seuss with a careful ear for language gets a higher pleasure than someone who mechanically recites The Waste Land (1922) without any understanding of what T S Eliot was doing.

Even sex, perhaps the most primal human pleasure of all, can be appreciated in higher and lower ways. To adapt Brillat-Savarin, animals copulate, humans make love. In the intensity of sexual arousal and orgasm, it might not seem that our evolved human capacities are doing much work. But sex is highly contextual, and changes its nature depending on whether it is part and parcel of a genuine relationship between two human beings, however brief, or merely the satisfaction of a brute urge.

Mill was therefore right to believe that pleasures come in higher and lower forms but wrong to think that we could distinguish them on the basis of what we take pleasure in. What matters is how we enjoy them, which means that higher and lower pleasures are not two discrete categories but form a continuum. I think the persistence of the bogus form of the higher/lower pleasures distinction is a result of the fact that some things are more obviously amenable to richer appreciation than others. Art is typically enjoyed in mind-engaging ways, food all too often consumed in an animalistic one. This has led us to mistake association for identity.

The mistake also betrays a false view of human nature, which sees our intellectual or spiritual aspects as being what truly makes us human, and our bodies as embarrassing vehicles to carry them. When we learn how to take pleasure in bodily things in ways that engage our hearts and minds as well as our five senses, we give up the illusion that we are souls trapped in mortal coils, and we learn how to be fully human. We are neither angels above bodily pleasures nor crude beasts slavishly following them, but psychosomatic wholes who bring heart, mind, body and soul to everything we do.

Let’s bring back the Sabbath as a radical act against ‘total work’


<p><em>Bryan Mills/Flickr</em></p>

 

As a boy in late-1940s Memphis, my dad got a nickel every Friday evening to come by the home of a Russian Jewish immigrant named Harry Levenson and turn on his lights, since the Torah forbids lighting a fire in your home on the Sabbath. My father would wonder, however, if he were somehow sinning. The fourth commandment says that on the Sabbath ‘you shall not do any work – you, your son or your daughter, your male or female slave, your livestock, or the alien resident in your towns’. Was my dad Levenson’s slave? If so, how come he could turn on Levenson’s lights? Were they both going to hell?

‘Remember the Sabbath day, and keep it holy.’ The commandment smacks of obsolete puritanism – the shuttered liquor store, the cheque sitting in a darkened post office. We usually encounter the Sabbath as an inconvenience, or at best a nice idea increasingly at odds with reality. But observing this weekly day of rest can actually be a radical act. Indeed, what makes it so obsolete and impractical is precisely what makes it so dangerous.

When taken seriously, the Sabbath has the power to restructure not only the calendar but also the entire political economy. In place of an economy built upon the profit motive – the ever-present need for more, in fact the need for there to never be enough – the Sabbath puts forward an economy built upon the belief that there is enough. But few who observe the Sabbath are willing to consider its full implications, and therefore few who do not observe it have reason to find any value in it.

The Sabbath’s radicalism should be no surprise given the fact that it originated among a community of former slaves. The 10 commandments constituted a manifesto against the regime that they had recently escaped, and rebellion against that regime was at the heart of their god’s identity, as attested to in the first commandment: ‘I am the Lord your God, who brought you out of the land of Egypt, out of the house of slavery.’ When the ancient Israelites swore to worship only one god, they understood this to mean, in part, they owed no fealty to the pharaoh or any other emperor.

It is therefore instructive to read the fourth commandment in light of the pharaoh’s labour practices described earlier in the book of Exodus. He is depicted as a manager never satisfied with his slaves, especially those building the structures for storing surplus grain. The pharaoh orders that the slaves no longer be given straw with which to make bricks; they must now gather their own straw, while the daily quota for bricks would remain the same. When many fail to meet their quota, the pharaoh has them beaten and calls them lazy.

The fourth commandment presents a god who, rather than demanding ever more work, insists on rest. The weekly Sabbath placed a hard limit on how much work could be done and suggested that this was perfectly all right; enough work was done in the other six days. And whereas the pharaoh relaxed while his people toiled, Yahweh insisted that the people rest as Yahweh rested: ‘For in six days the Lord made heaven and earth, the sea, and all that is in them, but rested the seventh day; therefore the Lord blessed the Sabbath day and consecrated it.’

The Sabbath, as described in Exodus and other passages in the Torah, had a democratising effect. Yahweh’s example – not forcing others to labour while Yahweh rested – was one anybody in power was to imitate. It was not enough for you to rest; your children, slaves, livestock and even the ‘aliens’ in your towns were to rest as well. The Sabbath wasn’t just a time for personal reflection and rejuvenation. It wasn’t self-care. It was for everyone.

There was a reason the fourth commandment came where it did, bridging the commandments on how humans should relate to God with the commandments on how humans should relate to one another. As the Old Testament scholar Walter Brueggemann points out in his book Sabbath as Resistance (2014), a pharaonic economy driven by anxiety begets violence, dishonesty, jealousy, theft, the commodification of sex and familial alienation. None of these had a place in the Torahic economy, which was driven not by anxiety but by wholeness, enoughness. In such a society, there was no need to murder, covet, lie, commit adultery or dishonour one’s parents.

The Sabbath’s centrality to the Torahic economy was made clearer in other laws building upon the fourth commandment. Every seventh year, the Israelites were to let their fields ‘rest and lie fallow, so that the poor of your people may eat; and what they leave the wild animals may eat’. And every 50th year, they were to not only let their fields lie fallow, but forgive all debts; all slaves were to be freed and returned to their families, and all land returned to its original inhabitants. This was a far cry from the pharaonic regime where surplus grain was hoarded and parsed out to the poor only in exchange for work and loyalty. There were no strings attached; the goal wasn’t accumulating power but reconciling the community.

It is unknown if these radical commandments were ever followed to the letter. In any case, they are certainly not now. The Sabbath was desacralised into the weekend, and this desacralisation paved the way for the disappearance of the weekend altogether. The decline of good full-time work and the rise of the gig economy mean that we must relentlessly hustle and never rest. Why haven’t you answered that email? Couldn’t you be doing something more productive with your time? Bring your phone with you to the bathroom so you can at least keep busy.

We are expected to compete with each other for our own labour, so that we each become our own taskmaster, our own pharaoh. Offer your employer more and more work for the same amount of pay, so that you undercut your competition – more and more bricks, and you’ll even bring your own straw.

In our neo-pharaonic economy, we are worth no more than the labour we can perform, and the value of our labour is being ever devalued. We can never work enough. A profit-driven capitalist society depends on the anxious striving for more, and it would break down if there were ever enough.

The Sabbath has no place in such a society and indeed upends its most basic tenets. In a Sabbatarian economy, the right to rest – the right to do nothing of value to capital – is as holy as the right to work. We can give freely to the poor and open our homes to refugees without being worried that there will be nothing left for us. We can erase all debts from our records, because it is necessary for the community to be whole.

It is time for us, whatever our religious beliefs, to see the Sabbatarian laws of old not as backward and pharisaical, but rather as the liberatory statements they were meant to be. It is time to ask what our society would look like if it made room for a new Sabbath – or, to put it a different way, what our society would need to look like for the Sabbath to be possible.

Overlooked Biomarker May Predict Cancer Immunotherapy Response


Hi. I’m David Kerr, professor of cancer medicine from the University of Oxford.

As you know, I’ve believed for some time that ploidy (the number of sets of chromosomes in a cell) measurements have been largely overlooked in terms of the relative importance of prognostic markers for the whole range of different cancer types. One of my friends and colleagues, Prof Håvard Danielsen, from the University of Oslo, has established what I consider one of the best assays in the world for measuring ploidy and DNA content in tumors, and characterizing it from paraffin-embedded tissue. ‘It’s a very available system.

New Data on an Overlooked Biomarker

To this end, a really interesting study was recently reported in Science by Teresa Davoli and colleagues,[1] who looked at ploidy across a whole range of tumor types and tried to relate ploidy measurements to the hallmarks of cancer. A ploidy is also known as somatic copy number alterations (SCNAs), and [the authors] refined the definition of ploidy a little, into [SCNAs] that were predominantly focal or [SCNAs] that mainly correlated with whole-arm ploidy, or changes in DNA content in that way.

This was a fascinating study, in which they found that ploidy was indeed associated with prognosis, but also with signatures associated with proliferation, increased expression of the gene’s enzymes involved in control of proliferation and cell cycle—this was mainly for the focal SCNAs. The larger, long-arm, and chromosomal ploidy tended to be associated with reduced expression of immune signature and immune infiltration.

This is an important first step in showing that ploidy does correlate with drivers or hallmarks of cancer. There are some subtle differences that lead you toward increased proliferation or increased immune invasion, both of which work in terms of establishing the cancer.

The researchers then retrospectively analyzed ploidy levels in melanoma tumor specimens saved from two large trials using immune checkpoint inhibitors. What they showed was that aneuploid tumors (eg, elevated levels of SCNA) were indeed more resistant to immune blockade.

It’s a really fascinating new potential use of ploidy, which has been around for decades and has been much overlooked. Not only is it a prognostic marker and therefore gives us important information about the biological behavior of our patients’ tumors, but it may also be a predictive factor in that aneuploid tumors may be relatively resistant to immune checkpoint blockade.

[Because this study was conducted] retrospectively, there’s much work yet to be done. [However, it offers] a really interesting insight for a marker, which I think could be delivered relatively easily in a sophisticated way in every pathology lab in the world. It surprises me that we don’t measure ploidy more. [It is] another interesting insight—some beautiful basic science uncovering the subtle differences in ploidy, how it links to the different hallmarks of cancer, and how it may aid us in selecting patients who may benefit less from immune checkpoint inhibitors.

Thank you for listening. It will be really keen for you to have a look at the Science paper and post any comments that you may care to talk about. This is an unfinished story but one that must be followed up prospectively.

For all book lovers please visit my friend’s website.
URL: http://www.romancewithbooks.com

Oral Edoxaban May Be an Alternative to Dalteparin for Cancer-Related VTE


Hello. I am David Kerr, professor of cancer medicine from the University of Oxford, in England. I want to talk about a study published in the February 15 edition of the New England Journal of Medicine.[1] This was a beautifully well-designed and conducted randomized trial that compared edoxaban, a novel oral anticoagulant, with dalteparin in patients with cancer who had a venous thromboembolism (VTE).

The trials group calls itself the Hokusai Group. For those of you who don’t know Hokusai, he was an important Japanese painter who created many woodblock prints and was a member of the school of ukiyo-e, painters of passing, or everyday, life. There is something about the ephemerality of their art that has always attracted me. Among the more famous paintings are different views of Mount Fuji. My apologies if I am being a smarty pants, a clever clogs. But some of these paintings, particularly The Great Wave, are absolutely beautiful.

This trials group randomly assigned just over 1000 patients to receive oral edoxaban (after 5 days of low-molecular-weight heparin) or subcutaneous dalteparin. It was a noninferiority trial; treatment was given for a minimum of 6 months and a maximum of 12 months after the initial venothrombotic or embolic event. The composite endpoint, which is being used more and more in these trials of novel oral anticoagulants, was the recurrence rates of VTE and major bleeding incidents. The trial showed that edoxaban is not inferior to subcutaneous dalteparin.

Within the composite endpoint, there were fewer further thromboembolic events in the edoxaban arm but more bleeding events in the edoxaban arm. They evened each other out in terms of the noninferiority.

This was quite a useful study. It is an important first step in being able to show that we can substitute useful oral treatment for daily subcutaneous dalteparin. Patients don’t like dalteparin. We’ve all had patients who self-administer dalteparin during chemotherapy, and they are covered in bruises; they are sore. It’s a nuisance and it’s necessary, but if we find that we can substitute edoxaban, which is given orally and is well tolerated, then this is quite an important landmark study.

The major bleeds were predominantly in the upper gastrointestinal (GI) area. Quite a number of the patients who had GI bleeding had previously undergone GI surgery of some sort. Interpret that as you will.

This is an important study—well designed, well conducted, well reported—that tells us that we have a possible alternative to discuss with patients, offering them edoxaban instead of subcutaneous dalteparin.

Thank you for listening. Thank you for allowing me to segue into stories about Hokusai and the painters of ukiyo-e. Think about the passing life, the ephemerality. W.H. Auden called life the gallop to the grave; there’s some truth in that.

For all book lovers please visit my friend’s website.
URL: http://www.romancewithbooks.com

Is Aspirin the New (Old) Immunotherapy?


Hello. I’m David Kerr, professor of cancer medicine from the University of Oxford.

For those of you who follow me on Medscape and WebMD, you know that I don’t like aspirin: I love it. I think it’s a wonderful drug. There’s a lot of work going on just now looking at its molecular pharmacology.

There’s a great recent paper published by Dr Tsuyoshi Hamada and colleagues[1] looking at the role of aspirin as an immune checkpoint blockade inhibitor. It’s a lovely study. Using part of a retrospective sample collection, they were able to look at the impact of post-primary treatment use of aspirin in patients with resectable colorectal cancer.

They hypothesized that patients who had tumors with low expression of programmed cell death ligand 1 (PD-L1) would be more sensitive to the beneficial effects of aspirin. They looked at just over 600 patients. [The study used] a beautiful statistical analysis that stratified [findings] and accounted for all of the other contributory factors that might be tied up with aspirin’s use: PIK3CA mutations, [CDX2 expression], and even tumor-infiltrating lymphocytes. It’s what you would expect from a research group of this quality. The analysis was done very carefully indeed.

At the end of the study, they showed that their hypothesis was correct. Patients with tumors with relatively low expression of PD-L1 (also known as CB274) did better than those patients who had tumors that expressed high levels of PD-L1, for which aspirin seemed to have no benefits at all.

This all fits in with the link-up between the prostaglandin E2 pathway and immune suppression. It suggests that aspirin may be yet another potential partner drug that may enhance the activity of the huge excitement around the drugs which block the PD-L1, PD-1, the whole immune checkpoint pathway just now.

It was a really nice, very carefully conducted study. The results were quite compelling in terms of the survival benefits accrued to postsurgical use of aspirin in patients with low levels of PD-L1 expression. It again shows the importance of the microenvironment in determining the outcome of tumor behavior. This gives some potential therapeutic insight into why aspirin might be a very useful companion drug to give in combination with these rather more expensive, more complex immune blockade inhibitors.

Aspirin wins again. There’s yet more plausible biological mechanism supporting its use.

 

For all book lovers please visit my friend’s website.
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If We Can See the Outcome, We Can Change the Outcome


Tom Lee: This is Tom Lee, and I’m pleased to be chatting with Roy Rosin, a very interesting and effective Chief Innovation Officer at Penn Medicine. A bunch of organizations have chief innovation officers these days. I think Penn’s program is among the most robust in the country, and they’ve got one of the most interesting leaders. Roy, you came from outside health care to be a chief leader of innovation at Penn. What were you doing before, and why did you make this move?

Roy Rosin: It’s great to talk to you, Tom. It was fun to have an opportunity to do something like it in health care when I did. I had spent many years at Intuit, which a lot of people know as the maker of TurboTax or Quicken or QuickBooks, and it’s just a fantastic company out in Silicon Valley. I had been there quite a long time, had built some of the software businesses like Quicken, but back in 2003 — my wife is from Philadelphia and wanted to move home to be near family, so I made that transition with her. I sometimes say I never really left Intuit, I just wanted to stay married, and I needed to go back and rethink what I wanted to do.

Intuit was fabulous. They gave me an opportunity to stay with the company. In fact, I stayed for another 9 years working remotely, and in those 9 years what I was able to do was think about enterprise, scale, innovation. How do you get new things going and turn ideas into actions and outcomes, and how do you get a lot of new things off the ground that actually have some impact? So we did that. We built these programs over the course of 9 years. I could do it remotely because we had new businesses starting all over the place, and we learned a tremendous amount.

Intuit was a learning organization, and after 9 years it was a lot of travel. I had kids, going back and forth, and I had started talking with Kevin Volpp who I know you know well. He’s an old friend of mine from college, and Kevin had started an innovation center at Penn that also was doing just fascinating work in behavior changes applied to health care.

Some of what we had done at Intuit was . . . thinking about, how do you get people to make different and better decisions? A lot of what we did was for profit at Intuit, but some of it worked so well that you start to wonder, well, gee, how can I do this for purely a social mission to provide some meaningful difference in the world? So talking to Kevin got me fascinated. And then seeing about what was happening in health care, [in terms of] moving toward value-based plans and into value-based care, all of a sudden I realized this was a fascinating time to be going after social missions that I could be part of as a nonclinical person. That’s what led to my leaning into it and coming over and starting to work with Penn.

Lee: I’ve been following along and in just a few years, if memory serves me, you guys have launched like 90 or so projects. That’s a lot. It’s an overwhelming number. How is it going? Is 90 too many? Is 90 not enough? How are you thinking about the overall scale of what you’re doing?

Rosin: Yeah. It is a lot of projects. Now, to be fair, some of them are very light-touch. Sometimes we’re just advising or just consulting on a project and we meet with somebody a couple of times a month and it doesn’t take up a tremendous amount of time. [But] some of the projects we’re leading in a much deeper dive, so it’s a little bit hard to get a picture. But we’ve done 90 over about 5 years. And it’s going really well.

One of the things that I absolutely love to see are outcomes, measurable outcomes, where we’re defining, what is the needle we want to move. We want to move 30-day readmissions or an infection rate or something that is important and that we’re able to do so. And we find that we can. Those projects were across a lot of different areas. They cross new care models, models about how do you get people with uncontrolled hypertension to be normotensive, new models around how do you treat women who have had a miscarriage so they don’t end up in the ER or the OR, even models like IMPaCT, just a wonderful program that has to do with how do you treat vulnerable populations where the normal care design isn’t working well and they end up being what’s often called superutilizers in the wrong setting of care and the wrong cost and not being treated well. And from those new models to technology interventions to — Kevin and David [Asch] spent a lot of time developing connected health interventions, so seeing and knowing things we never saw or knew before, things that are going on in the home or in different settings that could determine the health outcomes, and as we start see those, we can change the outcome — to all kinds of technology interventions. It’s a broad, broad range of work that we’ve been able to do, and overall I’m happy with the way it’s been going.

Lee: When I’ve spoken with you, you told me that everywhere you look you see low-hanging fruit and I’m sure it’s true, but with so much opportunity to improve, how do you prioritize, how do you choose what to do and what not to do?

Rosin: It’s a blend. We try to stay aware of what the system’s priorities are. David Asch — he’s my co-conspirator — and I, we’ll often go on listening tours and spend time with the CEOs of the entities and the chief medical officers and chief nursing officers. We will try to plug into some of the operating mechanisms where the senior leadership is talking about system priorities. Of course, we’re aware of big changes in our environment like when an area becomes bundles and all of a sudden you’re responsible in a different way than you have been before. [For example,] we just signed a fairly public big deal with Independence Blue Cross where we’re now responsible for all 30-day readmissions and not being paid for 30-day readmissions, so those certainly set some of our priorities, but I think what’s an important insight is that the way innovation works is that you have to find passion. You have to find people who really want to make a change. Innovation doesn’t work well as an assignment where you go and say hey, I want you to work on this and please go do it.

What you’re looking for are clinical champions and care teams who are engaged, who want to work on the problem, and I always say they’re pulling instead of us pushing, so we are a blended tops-down and bottoms-up model. We also will do bottoms-up work that may involve a fascinating idea, or a new idea from a clinical or administrative leader or somebody on the front lines, that doesn’t necessarily seem fully aligned with some of the system priorities just because there’s a lot of energy and passion, and it might be off our radar, and those are exciting, too. We do have a blend, and it’s a portfolio of projects that we pay attention to. We stay mostly aligned with the top priorities in the health system.

Lee: Is the goal making money for Penn, or making money for innovators, or is the top priority changing Penn’s health care?

Rosin: We have a fairly lucky position, I’d say, in that we do get to spend time [doing] what I call “de-risking” more future models. We see the world moving toward more risk-bearing contracts. We see an increasing focus on value-based care. And we have a tremendous number of colleagues across Penn who are innovating, frankly, who are changing the way we work and doing good work. We’re certainly not the only people who are innovating care, and in many cases what we try to do is enable and create infrastructure where every team can go faster and do better work.

But our work has often stayed focused on where things become a little bit more risk-bearing and the future where we expect to be pretty soon. Now, we will certainly do operations projects so we’re looking for economic wins, we’re looking for places that our work can have a measurable economic impact on what Penn is doing, but we’re also in some areas that don’t.

A good example might be [that] when we started off we did work on some benefit redesign. We have 30,000 employees and they’re self-insured, so the cost of health care just makes bottom line. Doing work there that made our own employees better off and healthier saved a tremendous amount of money and it bought us the right to work on things like hypertension, where David had a strong desire to look at our folks who had uncontrolled hypertension to try to get it normal blood pressure.

If you’re perfect there, you don’t save or make any money in the near term, but it’s, as you know, a critically important area of health. We try to keep our eye out to a balance of both long and short term as well as things that are system priorities, tops-down and bottoms-up.

Lee: It sounds like you’re amassing political capital and using it as well as financial capital. But now, have you had disappointments that bug you? Things that you think should’ve worked and they fell short, they couldn’t move any needle, at least so far for reasons that you hadn’t anticipated or you haven’t figured out how to surmount yet?

Rosin: The ones I put in that bucket haven’t not worked, they’re maybe what I call stalled. When we do our work, we often will do small pilots with a small sample size because we are trying to get things ready before we scale them. That’s one of the big changes in an innovation approach — that you don’t scale until you figure out what works and you can validate a lot of the hypotheses that you may have about a new intervention or a new care model. We had a long list of successes at the pilot stage, but to the extent that I feel frustrated is how quickly some of those moved into a scaled model. Real wins and real success for us are scale of impact, things that help lots and lots of people, millions or an entire population.

And what we love is when we do work that gets taken even beyond Penn’s walls and applied in other locations. So the pace of getting from a successful pilot to a scaled win is probably the thing that’s been frustrating. It’s a solvable problem.

We have a new CEO at the Hospital of the University of Pennsylvania, a woman named Regina Cunningham who came up as a nurse and a chief nursing officer, and we had a great meeting with Regina the other day where we had a couple of important successful pilots. One was around people who are discharged on IV antibiotics — a  high-risk, high–readmission rate population — and another was the liver population, cirrhosis and liver transplant.

In both cases the teams had done extraordinarily good work cutting that readmission rate, and in the case of liver, dramatically reducing the cost of the intervention from $1,000 a person down to $50 a person, so cutting 95% of the cost out. And even with those kind of results sometimes the pilot would stay sort of in this middle ground of no man’s land.

We were always smart enough not to throw it over the wall. We know that us doing pilots and then going to find a champion doesn’t work. We have certainly done a pretty good job of engaging operations and moving them upstream and trying to stay in tight contact with the operational leaders of the system and have good partnerships, but I love what Regina did. In this meeting she said, “Look, here’s what we have to do. You guys have to do a better job of thinking of the budget cycles and getting in front of my leadership team. Here’s the setting I’m providing to you, here is the timing [for how] we’re going to do it. Here’s the story that you need to sell and the analysis that we need to have.”

And so, making sure we’re absolutely clear on who will operationalize and how good is good enough, what is that economic argument that we need, and making sure we have the audience set up early before it’s time to do a handoff. We’re getting better at that, and that’s what is getting me around some of the things that I might otherwise call disappointments. With hindsight, I think about an intervention very early [on] that turned into a success but wasn’t for a long time. It was the early days of connected health, and you already saw this at Partners with Joe Kvedar, and Kevin and David were already doing a wonderful job talking about automated hovering and talking about we need to stay connected once people leave the hospital. We have done a version of that in the CHF population, and working with one of our physicians we ended up with zero preventable readmissions, which was probably better than anyone expected. Again, a fairly small sample size.

Everyone saw this, and the analysis was done that it was successful and financially important. We decided to scale it. And a whole year went by, I mean a full year passed without forward motion, and what we realized is that organizationally, there wasn’t anybody who owned at that time — this was many years ago now — who owned the job of preventing readmissions, of keeping someone healthy and out of the hospital. The executive team created a structure called, basically our service line, so now you were not just focused on inpatient and separately on outpatient, but more focused on patient populations, and it was remarkable what happened after the organizational change.

All of a sudden, now somebody had this job and was accountable for keeping people healthy and out of the hospital, and then they were looking for a tool that essentially did what we had figured out how to do — all of a sudden it was adopted. The problem wasn’t a technology problem or a, say, can you come up with some kind of service model that works — it was actually, gosh, I need an organizational approach that embraces and wants it. That was interesting to see that when the org[anization] changed the innovation became successful, became adopted, and became scaled.

Lee: Let me close by asking a question that may be impossible because we can’t ask someone which child you love the most, but is there any particular innovation that you bring up as one that as among those that you love the most?

Rosin: It is hard to say your favorite child. I certainly love Shreya Kangovi’s IMPaCT program because of how completely she rethought the use of community health workers and how they’re hired and identified, trained, deployed, and get out the extraordinarily difficult problems of social determinants. [That] would be one. And she’s seeing a few dollar return for every dollar invested, which I think is phenomenal.

If I could tell a single story right now, it might be a program we call Heart Safe Motherhood. Heart Safe Motherhood is a neat program. It grows out of that same connected health approach of seeing and knowing about things we never used to see and know about.

In this case it was postpartum preeclampsia and that was the number one driver of both 7-day readmissions and morbidity in the maternal population. And the team had done a whole bunch of work, good work, and yet it wasn’t moving the needle. There were free walk-in clinics. We called people and tried to follow up. They weren’t answering the phone or returning our calls and [were] not showing up to the free walk-in clinic.

And what the team did was led by two doctors . . . and at first they realized that the preferred modality was texting, because in many cases this population . . . they didn’t want to talk to us maybe ever, certainly not at any particular point in time, and we would send the women home with a blood pressure cuff. One of the interesting insights early on was that it wasn’t high-tech. It wasn’t one of these wireless cuffs that would automatically broadcast. It was actually a low-tech off-the-shelf at a Walmart or CVS because they could just text us the number and that addressed connectivity and wireless issues. They started to iterate and play with the texting, can I get these blood pressure values.

Around the same time, ACOG, the American College of OB-GYN, created a standard that said, look, to keep this population safe you need two blood pressure values, that first week after discharge, one around 3 days, one around 7 days. And in all of the top systems, including Penn, we had that for nobody. We were at 0%, and by sending women home with these blood pressure cuffs and beginning the texting protocol, that team ended up going from 0% to 82% of coverage, where we have the information, the blood pressure information we needed to keep the women safe.

But why I like the program so much is [that] it wasn’t just about this automated hovering, it wasn’t just about having that information. The real outcome you’re trying to change is could you avoid the morbidity and the readmissions and the bad outcomes, bad outcomes both for the patient and for the health system. And they were able to do that. The numbers are growing, and they moved a couple hundred patients through the system now and it has zero readmissions.

It went from the highest, 7 day readmissions, to so far no readmissions, which [is] the real impact that we’re looking for, and then you get scale, because this program is now being adopted not only in other settings across Penn, but even in other cities and in other places. When we can get that kind of endorsement and support from, for example, the National Preeclampsia Foundation and others, and see the stuff start to scale and go to other places to have a population effect, I get really happy. That’s probably it.

Lee: That is a great story, Roy. It’s a lovely one and it also shows that innovation really has to occur at that disease level. It can’t happen across the board for all readmissions. But you have a lot to be proud of and I know a lot more great work’s going to come out. The approaches you’re using I think will be instructive for all the other folks out there listening. I want to thank you for taking the time to share your insights with the NEJM Catalyst audience today.

Artificial Intelligence Will Show Us Our True Selves


Garry Kasparov doesn’t believe machines are here to replace us. They are going to show us who we really are.

“AI will force us to be more human,” Kasparov says. Automation, by his reckoning, will make us focus on the traits that humanity can do better than artificial intelligence, like creativity and imagination. We’ll leave the rest to machines.

The former chess world champion, who two decades ago traded victories in matches with IBM’s supercomputer Deep Blue, recently told Inverse those impossible-to-automate, uniquely human traits will stay that way.

Computers can be entrusted with just about any mental labor that reduces to calculation and logic, but the initial spark of human inspiration will likely always have to come from a human mind, Kasparov says.

Garry Kasparov
IBM Deep Blue

“Many of the white-collar jobs will move into the machines’ domain.”

“I think in the next few years we’ll see a dramatic regrouping in the corporate world,” Kasparov says, predicting that new jobs will be built around compensating for A.I.’s creative shortcomings. “There are those who think it’s a diminishing job for humans, because we will be stuck with very small territory. To the contrary, I think it could have much bigger impact.”

Human imagination will be especially important as A.I. moves out of the closed systems that have historically been its territory. To pick an example of a closed system with which Kasparov is intimately familiar, consider chess.

With all due respect to Anatoly Karpov and Vladimir Kramnik, Kasparov’s most famous opponent will always be Deep Blue. That machine’s digital mind was narrowly engineered to accomplish its task of competing with a grandmaster, but that wouldn’t necessarily mean it could transfer that reasoning power to some other problem. That’s where humans come in.

“Many of the white-collar jobs will move into the machines’ domain, and it’s not the end of the world. We should start thinking of ourselves more as humans to make unique contributions to the machine-human collaboration.”

Chess Match

Lynne Parker, an A.I. and robotics researcher and the director of the Distributed Intelligence Laboratory at the University of Tennessee, agrees: the future of work isn’t in removing humans from the equation, but rather zeroing in on our most irreplaceable traits.

“There are some types of humans skills that are going to be extraordinarily difficult to do any sort of automation, and creativity is a good example,” she tells Inverse. “Judgment and common sense are things that we do that quite well, but A.I. systems? Not so much.”

As A.I. becomes more advanced, it may become less about programming and more about having the imagination to know what questions to ask the machine.

“People worry about their jobs going away, and I think the thing is jobs consist of a lot of sub-tasks, and some of those tasks might get automated,” Parker posits. “That might mean the mix of things we do in our jobs changes, but we’ll still have lots of value as people.”

“Judgment and common sense are things that we do that quite well, but A.I. systems? Not so much.”

Google Home Mini

Machines have only become more formidable opponents in the two decades since Kasparov’s series with Deep Blue. Consider AlphaGo Zero, a creation of Google’s DeepMind A.I. subsidiary, which last year became the greatest Go player in history with zero human input beyond the initial parameters. AlphaGo Zero won 100 straight matches against its predecessor algorithm AlphaGo, which in turn had defeated the world’s top-ranked human player.

But to focus on those vanquished champions is to pay attention to the wrong humans. AlphaGo Zero may have taught itself Go without human assistance, but its ability to play the game in the first place was the gift of its human programmers.

“That’s a phenomenal result that tells you that as long as we can secure the borders, the limits of a system, so to define a framework, machines can do the rest,” says Kasparov. “So we are now reaching a point where the very concept of human-machine collaboration could be a thing.”

“We are now reaching a point where the very concept of human-machine collaboration could be a thing.”

Garry Kasparov

Isaac Asimov

Another Russian émigré foresaw all this more than six decades ago. In his 1956 short story “Jokester,” Isaac Asimov describes the omniscient supercomputer Multivac, a machine able to solve every conceivable problem. But it takes a rare breed of people, selected for insight shaped not by logic but by indefinable insight, to pull those answers out of this computational leviathan.

“Early in the history of Multivac, it had become apparent that the bottleneck was the questioning procedure,” Asimov writes. “Multivac could answer the problem of humanity, all the problems, if — if it were asked meaningful questions. But as knowledge accumulated at an ever faster rate, it became ever more difficult to locate those meaningful questions. Reason alone wouldn’t do. What was needed was a rare type of intuition.”

As we fast approach the future Asimov imagined 62 years ago, Kasparov says not just asking questions but also recognizing the answers when they come is what will make us the most useful collaborators with A.I. — and, with that, it will let us find our most human selves.

“A machine will never recognize the concept of diminishing returns,” he says. “If you let a machine operate, the most powerful machines, the most inventive machines, to operate in the open-ended system, it will never stop, because it’s still about actually recognizing what is the end of the story.”

A.I., for all its brilliance, can only ever think inside its parameters, inside the box. No matter how big that box gets, it falls to us who can think outside it to guide machines as partners.

It makes sense that this would be Garry Kasparov’s vision. After all, consider what Asimov called those rare, uniquely inventive minds he imagined as Multivac’s collective imagination.

He called them grandmasters.

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