Hendriks and Besse in Nature:

Chemotherapy became the standard treatment for lung cancer in the twentieth century¹. But in the past 15 years, there has been a drive to improve outcomes for people with this still-deadly disease, either through therapies that target enzymes encoded by genes harbouring cancer-driving mutations, or through immunotherapies, which activate the body’s immune system to target tumours. Writing in The New England Journal of Medicine, two groups^2,3 provide evidence that supports the use of immunotherapies to treat non-small-cell lung cancer (NSCLC) at different stages of the disease. Tumour cells evade destruction by activating signals known as immune checkpoints, which deactivate immune cells called T cells⁴. Two immune checkpoints are the proteins cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1), which are expressed by T cells themselves. Another, programmed cell death ligand 1 (PD-L1), is produced by tumour cells (Fig. 1).

Antibodies that interact with these proteins to prevent their normal activity, and so reawaken the immune system, are now used to treat metastatic NSCLC — the stage at which the cancer has spread. Antibodies that bind PD-1 or PD-L1 are sometimes successful in patients who have had treatments such as chemotherapy, but whose cancer has nonetheless progressed⁵. Alternatively, the anti-PD-1 antibody pembrolizumab can be used as a first-line treatment for metastatic NSCLC when the percentage of tumour cells that express PD-L1 is high — these patients respond better to immunotherapy than to chemotherapy⁶.

If such immune-checkpoint-targeted antibodies (ICTs) can improve outcomes for metastatic NSCLC, could they also help to tackle early-stage disease? In the first of the current papers, Forde et al.² carried out a pilot study to investigate whether the anti-PD-1 ICT nivolumab could be used to shrink tumours before surgery, which is a standard treatment for most cases of early-stage NSCLC. The authors treated 21 patients with 2 doses of nivolumab 2 weeks apart, starting 4 weeks before the planned surgery date. They showed that surgery did not need to be delayed (for example, because of an adverse event with nivolumab) for any patient. The researchers anticipated that four weeks would not be enough time for the reactivated immune system to significantly shrink the tumour. Indeed, imaging revealed significant shrinkage in tumours in only two patients before surgery. However, examination of the surgically removed tumours revealed that 45% had undergone a major response to the ICT — less than 10% of the tumour cells remained alive. ICTs, unlike chemotherapy, cause inflammation and scar-tissue formation in tumours, and can therefore sometimes cause tumour growth. However, the researchers found that even two tumours that showed such growth had undergone a strong pathological response.

More here.

Charles Krauthammer in the Washington Post:

I have been uncharacteristically silent these past ten months. I had thought that silence would soon be coming to an end, but I’m afraid I must tell you now that fate has decided on a different course for me.

In August of last year, I underwent surgery to remove a cancerous tumor in my abdomen. That operation was thought to have been a success, but it caused a cascade of secondary complications — which I have been fighting in hospital ever since. It was a long and hard fight with many setbacks, but I was steadily, if slowly, overcoming each obstacle along the way and gradually making my way back to health.

However, recent tests have revealed that the cancer has returned. There was no sign of it as recently as a month ago, which means it is aggressive and spreading rapidly. My doctors tell me their best estimate is that I have only a few weeks left to live. This is the final verdict. My fight is over.

More here.

Susan Scutti at CNN:

“Disgust evolved to protect us from disease in our ancient past. The disgust response today may, or may not, be a good guide to what might make us sick today,” said Val Curtis, lead author of the study and a professor and director of the Environmental Health Group of the London School of Hygiene & Tropical Medicine.

“It is unlikely to be a coincidence that many of the stimuli that elicit the emotion of disgust in humans are also implicated in the transmission of infectious disease,” Curtis and her co-author, Mícheál de Barra, a lecturer at Brunel University London, wrote.

To better understand disgust, Curtis and de Barra recruited more than 2,500 participants through advertisements on social media and psychology websites for an online survey. They checked IP addresses to control for the possibility of multiple survey entries from a single participant.

More here.

Yanis Varoufakis in The Guardian:

Donald Trump’s early departure, and his subsequent refusal to endorse the G7 communique, has thrown the mainstream press into an apoplexy reflecting a deeper incomprehension of our unfolding global reality.

In a bid to mix toughness with humour, Emmanuel Macron had quipped that the G7 might become the … G6. That’s absurd, not least because without the United States, capitalism as we know it (let alone the pitiful G7 gatherings) would disappear from the planet’s face.

There is, of course, little doubt that with Trump in the White House there is an awful lot we should be angst-ridden about. However, the establishment’s reaction to the president’s shenanigans, in the United States and in Europe, is perhaps an even greater worry for progressives, replete as it is with dangerous wishful thinking and copious miscalculation.

Some put their faith in the Mueller investigation, assuming that Mike Pence would be kinder to them as president. Others are holding their breath until 2020, refusing to consider the possibility of a second term. What they all fail to grasp is the very real tectonic shifts underpinning Trump’s uncouth antics.

More here.

Ed Yong in The Atlantic:

Around 1,500 years ago, shortly after the collapse of the Roman Empire, a baobab tree started growing in what is now Namibia. The San people would eventually name the tree Homasi, and others would call it Grootboom, after the Afrikaans words for “big tree.” As new empires rose and fell, Homasi continued growing. As humans invented paper money, printing presses, cars, and computers, Homasi sprouted new twigs, branches, and even stems, becoming a five-trunked behemoth with a height of 32 meters and a girth to match.

And then, in 2004, it collapsed.

The tree’s demise was sudden and unexpected. In March, at the end of the rainy season, Homasi was in full bloom. But by late June, its health had suddenly deteriorated. One by one, its stems broke off from the gargantuan trunk and toppled. The last of them fell on New Year’s Day, 2005, ending 15 centuries of life.

More here.

Pen and Ink Sketch

………………………………….. How little it takes –
a single line
……….. from
…………………………………………………………………. the
……………………………………………………… right edge
…………………………………………… downward
meeting another
……….. from the left
…………………. and there are hills –

……….. a straight line between the two,
……………………. squiggles,

……………………. now the sea.

……….. add a circle, low,
…………………… in what’s become
………………………………. the sky
…………………………………………. and dusk
falls
……………………………… .above three
………………….. quick
……….. pelican
………………….. V’s.

………………….. less
………………….. than thirty
………………….. touches
………………….. of the pen,
………………….. world floods
………………….. the page,

………………….. and these words
………………….. ………… wash
………………….. ashore.

by Nils Peterson

Scott Manley Hadley at berfrois:

Jon Fosse is also a man, though about a decade older than Knausgaard. This story collection, Scenes From A Childhood, has recently been published in the UK by Fitzcarraldo Editions. In fact, acknowledging (or ignoring) this gender bias, the publishers include an extract from a Paris Review article in the blurbs at the front of the text that compares “the four elder statesmen of Norwegian letters” to the Beatles, deciding that “Knausgaard is Paul, the cute one; and Fosse is George, the quiet one, mystical, spiritual, probably the best craftsman of them all”. This description of Fosse is certainly accurate, if the impression given by this collection is correct, as the stories included here boast a rich emotionality as well as a complex blending of reality and dream to create a powerful dissociative response. The stories that comprise this collection vary from the bizarre to the conventional, using a gentle variety of voices to show loneliness, affection, depression, anxiety, excitement, hope and loss. This is powerful work.

more here.

Chantel Tatolli at Harper’s Magazine:

By 1956, Howard had graduated more than five hundred Santas, working in department stores across the country from Macy’s in Kansas City to D. H. Holmes in New Orleans. On his fifty-acre farm just west of Albion, he opened a Christmas-themed amusement park, encircled by a miniature railroad, and home to pigs, cows, and a team of reindeer. “But he wasn’t a good businessman,” said Cheryl Mowatt, a local librarian. Howard would wave poorer families through the gates, sometimes allowing entry to six kids when they had only three tickets. Eventually, he could not pay a bill for toys, and a court put the school, suit business, and park up on the auction block in 1965.

more here.

Jeremy Bernstein at the NYRB:

The Standard Model, which is a theory of nearly everything (gravity being an exception) likes things in threes. There are, for example, three colors of quarks, just as there were three neutrinos types—until very recently: research conducted by the Mini Booster Neutrino Experiment (MiniBooNE) at the Fermi National Accelerator Laboratory in Batavia, Illinois, suggests the possible existence of a fourth type of neutrino that does not fit into any theoretical model.

Neutrinos have always been my favorite particles, ever since I learned about them in graduate school in the 1950s. They reminded me of that eccentric uncle you’ve never seen, but who you know exists because your aunt speaks of him affectionately as a slightly rogue member of the family. Even the invention of neutrinos is a bizarre tale.

more here.

Natalie Angier in The New York Times:

In advance of Father’s Day, let’s take a moment to sort out the differences and similarities between “Dad jeans” and “Dad genes.” Dad jeans are articles of sex-specific leisure clothing, long mocked for being comfy, dumpy and elastic-waisted but lately reinvented as a fashion trend, suitable for male bodies of all shapes and ages. Dad genes are particles on the sex-specific Y chromosome, long mocked for being a stunted clump of mostly useless nucleic waste but lately revealed as man’s fastest friend, essential to the health of male bodies and brains no matter the age. Yes, dear fathers and others born with the appurtenances generally designated male. We live in exciting times, and that includes novel insights into the sole chromosomal distinction between you and the women now prowling the aisles at the hardware store. (“Didn’t he say he could use a new bow saw? Or some halogen light bulbs?”)

Researchers have discovered that, contrary to longstanding assumptions, the Y chromosome is not limited to a handful of masculine tasks, like specifying male body parts in a developing embryo or replenishing the sperm supply in an adult man. New evidence indicates that the Y chromosome participates in an array of essential, general-interest tasks in men, like stanching cancerous growth, keeping arteries clear and blocking the buildup of amyloid plaque in the brain. As a sizable percentage of men age, their blood and other body cells begin to spontaneously jettison copies of the Y chromosome, sometimes quickly, sometimes slowly. That unfortunate act of chromosomal decluttering appears to put the men at a heightened risk of Alzheimer’s disease, leukemia and other disorders. “I’m quite certain,” said Lars Forsberg, an associate professor of medical genetics at Uppsala University in Sweden, “that the loss of the Y chromosome with age explains a very large proportion of the increased mortality in men, compared to women.”

Other researchers are tracing the evolution of the Y chromosome and comparing the version found in modern men with those of our close relatives, both living and extinct.

More here.

Yasmeen Serhan in The Atlantic:

Many Palestinians would disagree on political grounds with my decision to watch Fauda. In fact, some have called for a boycott of the show. “It is an anti-Arab, racist, Israeli propaganda tool that glorifies the Israeli military’s war crimes against the Palestinian people,” the Palestinian-led Boycott, Divestment, and Sanctions movement said of the show in March, adding, “By sanitizing and normalizing these crimes, Fauda is directly complicit in promoting and justifying these grave human rights violations.”

Yet the harsh reality of Israel’s continued military presence in the Palestinian territories isn’t absent from Fauda, despite this and similar criticisms. The show depicts an elderly woman being stopped at one of the many military checkpoints around and within the West Bank, where an armed Israeli soldier rummages through her bags. It also shows Israeli soldiers trashing and seizing property from a Palestinian home during a raid. And one of this season’s main plot arcs concerns a group of young Palestinian terrorists who realize that they’re more likely to gain entry into Israel proper (from which the vast majority of Palestinians are barred, except on certain holidays) if they speak Hebrew and pretend to be religious Jews from one of Israel’s West Bank settlements. These are the daily, almost mundane, images of occupation that linger in the background of Fauda.

More here.

Sheldon Lee Glashow in Inference Review:

This is the third and final essay in a three-part series. Parts one and two told of the development of the physical sciences from ancient times to the discovery of relativity and quantum mechanics in the first quarter of the twentieth century. This part begins with the challenges posed by the atomic nucleus. Two forces of nature had been recognized, gravity and electromagnetism, but two more would needed to understand nuclear phenomena: a strong force to bind nucleons into nuclei, and a weak force to explain how they decay.

In this part, I describe the Standard Model of particle physics, which encompasses three of the four forces of nature. Gravity seems to play no role in the subatomic world. The strong force results from a gauge theory based on an unbroken SU(3) symmetry called quantum chromodynamics, the weak and electromagnetic forces from a broken SU(2) × U(1) symmetry. Together they form the Standard Model of particle physics, offering a complete, correct, and consistent description of all known elementary particle phenomena. Its formulation, unlike the theories of Isaac Newton and Albert Einstein, depended on the work of thousands of physicists and engineers and the generosity of many governments. Triumph though it is, for reasons both experimental and theoretical, the Standard Model is known to be incomplete.

More here.

Reihan Salam in The Atlantic:

In 2000, Congress made the fateful decision to extend “permanent normal trade relations,” or PNTR, to China. As the economists Justin Pierce and Peter Schott have argued, the permanence of PNTR status made an enormous difference: Without PNTR, there was always a danger that China’s favorable access to the U.S. market would be revoked, which in turn deterred U.S. firms from increasing their reliance on Chinese suppliers. With PNTR in hand, the floodgates of investment were opened, and U.S. multinationals worked hand in glove with Beijing to create new China-centric supply chains. The age of “Chimerica” had begun.

PNTR was a euphemism designed to get around the fact that the traditional term for “normal trade relations” was “most-favored-nation” (MFN) tariff status, which basically meant a plain-vanilla relationship. A country could enter into a preferential trade agreement such as NAFTA, the accord between the United States, Mexico, and Canada—say, plain vanilla with chocolate sprinkles on top. But short of that, MFN status meant imports would be treated as favorably as those arriving from “the most favored nation.” Absurd as it might sound, this linguistic convention had meaningful political consequences. To argue that we ought to have normal trade relations with China was one thing. Sure, why not? To make the case that China ought to be treated as our most favored nation was a more vexing PR challenge, not least in the wake of the brutal crackdown that followed the Tiananmen Square protests in 1989.

More here.

Lionel Shriver in The Spectator:

I’d been suffering under the misguided illusion that the purpose of mainstream publishers like Penguin Random House was to sell and promote fine writing. A colleague’s forwarded email has set me straight. Sent to a literary agent, presumably this letter was also fired off to the agents of the entire Penguin Random House stable. The email cites the publisher’s ‘new company-wide goal’: for ‘both our new hires and the authors we acquire to reflect UK society by 2025.’ (Gotta love that shouty boldface.) ‘This means we want our authors and new colleagues to reflect the UK population taking into account ethnicity, gender, sexuality, social mobility and disability.’ The email proudly proclaims that the company has removed ‘the need for a university degree from nearly all our jobs’ — which, if my manuscript were being copy-edited and proof-read by folks whose university-educated predecessors already exhibited horrifyingly weak grammar and punctuation, I would find alarming.

The accompanying questionnaire for PRH authors is by turns fascinating, comical and depressing. Gender and ethnicity questions provide the coy ‘prefer not to say’ option, ensuring that being female or Japanese can remain your deep dark secret. As the old chocolate-or-vanilla sexes have multiplied into Baskin Robbins, responders to ‘How would you define your gender?’ may tick, ‘Prefer to use my own term’.

More here.