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Monday, September 02, 2024

 Research finds particulate pollution during pregnancy may impact newborn kidney function

In a recent cohort study published in the journal eBioMedicineresearchers investigated the potential effect of gestational exposure to particulate air pollution on cord blood cystatin C levels, a marker for kidney function.

They found that increased exposure to black carbon and fine particulate matter during pregnancy, particularly in the third trimester, was associated with higher cord blood cystatin C levels, suggesting potential negative effects on newborn kidney function.

Study: Newborn glomerular function and gestational particulate air pollution. Image Credit: Deemerwha studio/Shutterstock.com

Background

Researchers have previously hypothesized that a lower number of nephrons at birth increases the risk of hypertension, and early environmental exposures can have a long-term impact on health. Optimal kidney function is critical for maintaining body homeostasis.

However, assessing kidney function in neonates is challenging. Cystatin C, a protein produced by nucleated cells and filtered by the kidneys, has emerged as a valuable marker for glomerular filtration in newborns, as it is not influenced by muscle mass or inflammation.

Ambient air pollution, especially particulate matter of diameter <2.5 micrometers (PM2.5) and black carbon (BC), is a significant contributor to global disease, linked to cardiovascular, respiratory, and kidney issues. PM2.5 is known to cause cardiovascular problems, which are closely related to kidney health.

Maternal exposure to PM2.5 is shown to be associated with higher blood pressure and lower birth weight in newborns, potentially affecting kidney development.

While studies have shown that air pollution increases cystatin C levels and decreases glomerular filtration in adults, there is a lack of research on its effects on cystatin C levels in newborns, highlighting a gap in understanding the early-life impact of pollution on kidney function.

Therefore, researchers in the present study investigated whether cystatin C levels are altered in the cord blood plasma of neonates owing to exposure to ambient air pollution, specifically BC and PM2.5.

About the study

In the present study, medical and lifestyle data of 1,484 healthy mother-newborn pairs with singleton pregnancies between 2010 and 2020 were obtained from the ENVIRONAGE (ENVIRonmental influence ON early AGEing) birth cohort in Belgium.

Pairs lacking cord blood samples or missing data were excluded. Exposure to air pollution in the form of BC and PM2.5 was estimated using a model that integrated satellite land cover data and pollution data from monitoring stations.

Daily exposure values were averaged for the entire pregnancy and across trimesters. Cord blood samples were collected within 10 minutes of delivery, stored, and analyzed.

Cystatin C levels were measured in the samples using an accredited immune turbidimetry assay, where cystatin C binds to antibody-coated latex particles for quantification, providing insights into kidney function in newborns.

Statistical analysis involved the use of multiple linear regression analyses, distributed lag models, logistic regression analyses, and sensitivity analyses adjusting for various covariates, including age, education, smoking habits, alcohol consumption throughout pregnancy, and ethnicity.

Results and discussion

The average birth weight of newborns was 3,417.52 g, with 49.6% being girls, and the average gestational age was 39.2 weeks. Cord blood cystatin C levels averaged 2.16 mg/L. Mean exposure to BC and PM2.5 during pregnancy was found to be 1.18 μg/m³ and 12.65 μg/m³, respectively, remaining relatively constant across trimesters.

Significant associations were found between BC exposure during the entire pregnancy and elevated cord blood cystatin C levels, with a 0.5 μg/m³ increase correlating with a 0.04 mg/L rise (p<0.01). For PM2.5, a 5 μg/m³ increase was found to be associated with a 0.07 mg/L increase in cystatin C (p<0.01).

The first trimester showed associations with BC but not with PM2.5. Sensitivity analyses indicated that adjusting for additional covariates did not significantly alter effect estimates. Notably, the third trimester (beyond week 27) was identified as the most significant exposure window.

Higher exposures to PM2.5 and BC during the entire pregnancy and specifically in the third trimester increased the risk of higher cord blood cystatin C levels, with a 0.5 μg/m³ increase in BC linked to a 37% higher risk and a 5 μg/m³ increase in PM2.5 associated with an 80% higher risk.

The study is strengthened by its large, representative sample of well-characterized newborns and mothers with a prospective follow-up and high-resolution spatial air pollution model for fetal exposure estimation. However, the study lacks the use of additional markers to assess kidney function, such as creatinine.

Conclusion

In conclusion, the study shows that exposure to PM2.5 and BC during pregnancy, especially beyond week 27, is significantly linked to elevated cord blood cystatin C levels in newborns. This indicates the negative impact of particulate air pollution on kidney function since birth.

Therefore, monitoring early life exposure to particulate air pollution may be crucial for improving kidney health later in life. These findings warrant further research and aim to inform public health policy for improved outcomes in newborns.

Journal reference:


Dr. Sushama R. Chaphalkar

Written by

Dr. Sushama R. Chaphalkar

Dr. Sushama R. Chaphalkar is a senior researcher and academician based in Pune, India. She holds a PhD in Microbiology and comes with vast experience in research and education in Biotechnology. In her illustrious career spanning three decades and a half, she held prominent leadership positions in academia and industry. As the Founder-Director of a renowned Biotechnology institute, she worked extensively on high-end research projects of industrial significance, fostering a stronger bond between industry and academia.  

Science is rewriting the history of horse domestication

As they spread, horses reshaped ecology, social structures and economies at a never-before-seen scale.



Perspective by William Taylor
September 1, 2024 
THE CONVERSATION

Across human history, no animal has had a deeper impact on human societies than the horse. But when and how people domesticated horses have posed an ongoing scientific mystery.

Half a million years ago or more, early human ancestors hunted horses with wooden spears, the very first weapons, and used their bones for early tools. During the late Paleolithic era, as far back as 30,000 years ago or more, ancient artists chose wild horses as their muse: Horses are the most commonly depicted animal in Eurasian cave art.

Following their first domestication, horses became the foundation of herding life in the grasslands of Inner Asia, and key leaps forward in technology such as the chariot, saddle and stirrup helped make horses the primary means of locomotion for travel, communication, agriculture and warfare across much of the ancient world. With the aid of ocean voyages, these animals eventually reached the shores of every major landmass — even Antarctica, briefly.

Archaeologists William Taylor (left), and Aidan Marler (right) investigate an ancient horse jaw bone in western Mongolia. (Yancen Diemberger)

As they spread, horses reshaped ecology, social structures and economies at a never-before-seen scale. Ultimately, only industrial mechanization supplanted their near-universal role in society.

Because of their tremendous impact in shaping our collective human story, figuring out when, why and how horses became domesticated is a key step toward understanding the world we live in now.

Doing so has proved to be surprisingly challenging. In my new book, “Hoof Beats: How Horses Shaped Human History,” I draw together new archaeological evidence that is revising what scientists like me thought we knew about this story.

A domestication hypothesis

Over the years, almost every time and place on Earth has been suggested as a possible origin point for horse domestication, from Europe tens of thousands of years ago to places such as Saudi Arabia, Anatolia, China or even the Americas.

By far the most dominant model for horse domestication, though, has been the Indo-European hypothesis, also known as the “Kurgan hypothesis.” It argues that, sometime in the fourth millennium B.C. or before, residents of the steppes of western Asia and the Black Sea known as the Yamnaya, who built large burial mounds called kurgans, hopped astride horses. The newfound mobility of these early riders, the story goes, helped catalyze huge migrations across the continent, distributing ancestral Indo-European languages and cultures across Eurasia.

But what’s the actual evidence supporting the Kurgan hypothesis for the first horse domestication? Many of the most important clues come from the bones and teeth of ancient animals, via a discipline known as archaeozoology. Over the past 20 years, archaeozoological data seemed to converge on the idea that horses were first domesticated in sites of the Botai culture in Kazakhstan, where scientists found large quantities of horse bones at sites dating to the fourth millennium B.C.

Other kinds of circumstantial evidence had already started to pile up. Archaeologists discovered evidence of what looked like fence post holes that could have been part of ancient corrals. They also found ceramic fragments with fatty horse residues that, based on isotope measurements, seem to have been deposited in the summer months, a time when milk could be collected from domestic horses.

The scientific smoking gun for early horse domestication, though, was a set of changes found on some Botai horse teeth and jawbones. Like the teeth of many modern and ancient ridden horses, the Botai horse teeth appeared to have been worn down by a bridle mouthpiece, or bit.

Together, the data pointed strongly to the idea of horse domestication in northern Kazakhstan around 3500 B.C. — not quite the Yamnaya homeland, but close enough geographically to keep the basic Kurgan hypothesis intact.

There were some aspects of the Botai story, though, that never quite lined up.

From the outset, several studies showed that the mix of horse remains found at Botai was unlike that found in most later pastoral cultures: Botai is evenly split between male and female horses, mostly of a healthy reproductive age. Killing off healthy, breeding-age animals like this on a regular basis would devastate a breeding herd. But this demographic blend is common among animals that have been hunted. Some Botai horses even have projectile points embedded in their ribs, showing they died through hunting rather than a controlled slaughter.

These unresolved loose ends loomed over a basic consensus linking the Botai culture to horse domestication.

New tools, new questions

In recent years, as archaeological and scientific tools have rapidly improved, key assumptions about the cultures of Botai, Yamnaya and the early chapters of the human-horse story have been overturned.

In 2018, nuclear genomic sequencing revealed that Botai horses were not the ancestors of domestic horses but of Przewalski’s horse, a wild relative and denizen of the steppe that has never been domesticated, at least not in recorded history.

Next, when my colleagues and I reconsidered skeletal features linked to horse riding at Botai, we saw that similar issues are also visible in ice age wild horses from North America, which had certainly never been ridden. Even though horse riding can cause recognizable changes to the teeth and bones of the jaw, we argued that the small issues seen on Botai horses can reasonably be linked to natural variation or life history

This finding reopened the question: Was there horse transport at Botai at all?

Leaving the Kurgan hypothesis in the past

Over the past few years, trying to make sense of the archaeological record around horse domestication has become an ever more contradictory affair.

For example, in 2023, archaeologists noted that human hip and leg skeletal problems found in Yamnaya and early Eastern European burials looked like problems found in mounted riders, consistent with the Kurgan hypothesis. But such problems can also be caused by other kinds of animal transport, including the cattle carts found in Yamnaya-era sites.

So how should archaeologists make sense of these conflicting signals?


A clearer picture may be closer than we think. A detailed genomic study of early Eurasian horses, published in June in the journal Nature, shows that Yamnaya horses were not ancestors of the first clearly domestic horses, known as the DOM2 lineage. And Yamnaya horses showed no genetic evidence of close control over reproduction, such as changes linked with inbreeding.

Instead, the first DOM2 horses appear just before 2000 B.C., long after the Yamnaya migrations and just before the first burials of horses and chariots also show up in the archaeological record.

For now, all lines of evidence seem to converge on the idea that horse domestication probably took place in the Black Sea steppes, but much later than the Kurgan hypothesis requires. Instead, human control of horses took off just before the explosive spread of horses and chariots across Eurasia during the early second millennium B.C.

There’s still more to be settled, of course. In the latest study, the authors point to funny patterns in the Botai data, especially fluctuations in genetic estimates for generation time — essentially, how long it takes on average for a population of animals to produce offspring. Might these suggest that Botai people still raised those wild Przewalski’s horses in captivity, but only for meat, without a role in transportation? Perhaps. Future research will let us know for sure.

Either way, out of these conflicting signals, one consideration has become clear: The earliest chapters of the human-horse story are ready for a retelling.

The writer is an assistant professor and curator of archaeology at the University of Colorado at Boulder. This article was produced in collaboration with theconversation.com.


Sunday, September 01, 2024



‘He was in mystic delirium’: was this hermit mathematician a forgotten genius whose ideas could transform AI – or a lonely madman?

Phil Hoad
Sat 31 August 2024 

Alexander Grothendieck photographed at his home in Lassarre, France, in 2013.
Photograph: Peter Badge


LONG READ


One day in September 2014, in a hamlet in the French Pyrenean foothills, Jean-Claude, a landscape gardener in his late 50s, was surprised to see his neighbour at the gate. He hadn’t spoken to the 86-year-old in nearly 15 years after a dispute over a climbing rose that Jean-Claude had wanted to prune. The old man lived in total seclusion, tending to his garden in the djellaba he always wore, writing by night, heeding no one. Now, the long-bearded seeker looked troubled.

“Would you do me a favour?” he asked Jean-Claude.

“If I can.”

“Could you buy me a revolver?”

Jean-Claude refused. Then, after watching the hermit – who was deaf and nearly blind – totter erratically about his garden, he telephoned the man’s children. Even they hadn’t spoken to their father in close to 25 years. When they arrived in the village of Lasserre, the recluse repeated his request for a revolver, so he could shoot himself. There was barely room to move in his dilapidated house. The corridors were lined with shelves heaving with flasks of mouldering liquids. Overgrown plants spilled out of pots everywhere. Thousands of pages of arcane scrawling were lined up in canvas boxes in his library. But his infirmity had put paid to his studies, and he no longer saw any purpose in life. On 13 November, he died exhausted and alone in hospital in the neighbouring town of St-Lizier.

The hermit’s name was Alexander Grothendieck. Born in 1928, he arrived in France from Germany as a refugee in 1939, and went on to revolutionise postwar mathematics as Einstein had physics a generation earlier. Moving beyond distinct disciplines such as geometry, algebra and topology, he worked in pursuit of a deeper, universal language to unify them all. At the heart of his work was a new conception of space, liberating it from the Euclidean tyranny of fixed points and bringing it into the 20th-century universe of relativity and probability. The flood of concepts and tools he introduced in the 1950s and 60s awed his peers.

Then, in 1970, in what he later called his “great turning point”, Grothendieck quit. Resigning from France’s elite Institut des Hautes Études Scientifiques (IHES) – in protest at funding it received from the ministry of defence – put an end to his high-level mathematics career. He occupied a few minor teaching posts until 1991, when he left his home underneath Provence’s Mont Ventoux and disappeared. No one – friends, family, colleagues, the intimates who knew him as “Shurik” (his childhood nickname, the Russian diminutive for Alexander) – knew where he was.

Grothendieck’s capacity for abstract thought is legendary: he rarely made use of specific equations to grasp at mathematical truths, instead intuiting the broader conceptual structure around them to make them surrender their solutions all at once. He compared the two approaches to using a hammer to crack a walnut, versus soaking it patiently in water until it opens naturally. “He was above all a thinker and a writer, who decided to apply his genius mostly to mathematics,” says Olivia Caramello, a 39-year-old Italian mathematician who is the leading proponent of his work today. “His approach to mathematics was that of a philosopher, in the sense that the way in which one would prove results was more important to him than the results themselves.”

In Lasserre, he lived in near-complete solitude, with no television, radio, phone or internet. A handful of acolytes trekked up to the village once his whereabouts filtered out; he politely refused to receive most of them. When he did exchange words, he sometimes mentioned his true friends: the plants. Wood, he believed, was conscious. He told Michel Camilleri, a local bookbinder who helped compile his writings, that his kitchen table “knows more about you, your past, your present and your future than you will ever know”. But these wild preoccupations took him to dark places: he told one visitor that there were entities inside his house that might harm him.

Grothendieck’s genius defied his attempts at erasing his own renown. He lurks in the background of one of Cormac McCarthy’s final novels, Stella Maris, as an eminence grise who leads on its psychically disturbed mathematician protagonist. The long-awaited publication in 2022 of Grothendieck’s exhaustive memoir, Harvests and Sowings, renewed interest in his work. And there is growing academic and corporate attention to how Grothendieckian concepts could be practically applied for technological ends. Chinese telecoms giant Huawei believes his esoteric concept of the topos could be key to building the next generation of AI, and has hired Fields medal-winner Laurent Lafforgue to explore this subject. But Grothendieck’s motivations were not worldly ones, as his former colleague Pierre Cartier understood. “Even in his mathematical milieu, he wasn’t quite a member of the family,” writes Cartier. “He pursued a kind of monologue, or rather a dialogue with mathematics and God, which to him were one and the same.”

Beyond his mathematics was the unknown. Were his final writings, an avalanche of 70,000 pages in an often near-illegible hand, the aimless scribblings of a madman? Or had the anchorite of Lasserre made one last thrust into the secret architecture of the universe? And what would this outsider – who had spurned the scientific establishment and modern society – make of the idea of tech titans sizing up his intellectual property for exploitation?

* * *

In a famous passage from Harvests and Sowings, Grothendieck writes that most mathematicians work within a preconceived framework: “They are like the inheritors of a large and beautiful house all ready-built, with its living rooms and kitchens and workshops, and its kitchen utensils and tools for all and sundry, with which there is indeed everything to cook and tinker.” But he is part of a rarer breed: the builders, “whose instinctive vocation and joy is to construct new houses”.

Now his son, Matthieu Grothendieck, is working out what to do with his father’s home. Lasserre lies on the top of a hill 22 miles (35km) north of the Spanish border, in the remote Ariège département, a haven for marginals, drifters and utopians. I first walk up there one piercingly cold January morning in 2023, mists cloaking forests of oak and beech, red kites surveying the fields in between. Grothendieck’s home – the only two-storey house in Lasserre – is at the village’s southern extremity. Hanging above the road beyond are the snow-covered Pyrenees: a promise of a higher reality.

Matthieu answers the door wearing a dressing gown, with the sheepish air of a man emerging from hibernation. The 57-year-old has deeply creased features and a strong prow of a nose. Inheriting the house where his father experienced such mental ordeals weighs on him. “This place has a history that’s bigger than me,” he says, his voice softened by smoking. “And as I haven’t got the means to knock it into shape, I feel bad about that. I feel as if I’m still living in my father’s house.”

A former ceramicist, he is now a part-time musician. In the kitchen, a long, framed scroll of Chinese script stands on a sideboard, next to one photograph of a Buddha sculpture and two of his mother, Mireille Dufour, whom Grothendieck left in 1970. (Matthieu is her youngest child; he has a sister, Johanna, and brother, Alexandre. Grothendieck also had two other sons, Serge and John, with two other women.) Above Matthieu’s bed is a garish portrait of his paternal grandfather, Alexander Schapiro, a Ukrainian Jewish anarchist who lost an arm escaping a tsarist prison, and later fought in the Spanish civil war.

Even with all his wisdom and the depth of his insight, there was always a sense of excessiveness about my father. He always had to put himself in danger

Schapiro and his partner, the German writer Johanna Grothendieck, left the five-year-old Grothendieck in foster care in Hamburg when they fled Nazi Germany in 1933 to fight for the socialist cause in Europe. He was reunited with his mother in 1939, and lived the remainder of the war in a French internment camp or in hiding. But his Jewish father, interned separately, was sent to Auschwitz and murdered on arrival in 1942. It was this legacy of abandonment, poverty and violence that drove the mathematician and finally overwhelmed him, Matthieu suggests: “Artists and geniuses are making up for flaws and traumas. The wound that made Shurik a genius caught up with him at the end of his life.”

Matthieu leads me into the huge, broken-down barn behind the house. Heaped on the bare-earth floor is a mound of glass flasks encased in wicker baskets: inside them are what remains of the mathematician’s plant infusions, requiring thousands of litres of alcohol. Far removed from conventional mathematics, Grothendieck’s final studies were fixated on the problem of why evil exists in the world. His last recorded writing was a notebook logging the names of the deportees in his father’s convoy in August 1942. Matthieu believes his father’s plant distillations were linked with this attempt to explain the workings of evil: a form of alchemy through which he was attempting to isolate different species’ properties of resilience to adversity and aggression. “It’s hard to understand,” says Matthieu. “All I know is that they weren’t for drinking.”

Later, Matthieu agrees to let me look at his father’s Lasserre writings – a cache of esoterica scanned on to hard disk by his daughter. At the start of 2023, the family were still negotiating their entry into the French national library; the writings have now been accepted and at some point will be publicly available for research. Serious scholarship is needed to decide their worth on mathematical, philosophical and literary levels. I’m definitely not qualified on the first count.

I open a first page at random. The writing is spidery; there are occasional multicoloured topological diagrams, namechecks of past thinkers, often physicists – Maxwell, Planck, Einstein – and recurrent references to Satan and “this cursed world”. His children are struggling to fathom this prodigious output, too. “It’s mystic but also down to earth. He talks about life with a form of moralism. It’s completely out of fashion,” says Matthieu. “But in my opinion there are pearls in there. He was the king of formulating things.”

After a couple of hours’ reading, head spinning, I feel the abyss staring into me. So imagine what it was like for Grothendieck. According to Matthieu, a friend once asked his father what his greatest desire was. The mathematician replied: “That this infernal circle of thought finally ceases.”

* * *

The colossal folds of Mont Ventoux’s southern flank are mottled with April cloud shadow as cyclists skirt the mountain. In the Vaucluse département of Provence, this is the terrain where Alexander Grothendieck took his first steps into mysticism. Now, another of his sons, Alexandre, lives in the area. I wander up a bumpy track to see the 62-year-old ambling out of oak woods, smiling, to meet me. Wearing a moth-eaten jumper, dark slacks and slippers, Alexandre is slighter than his brother, with wind-chafed cheeks.

He leads me into the giant hangar where he lives. It is piled with amps and instruments; at the back is a workshop where he makes kalimbas, a kind of African thumb piano. In 1980, his father moved a few kilometres to the west, to a house outside the village of Mormoiron. In the subsequent years, Grothendieck’s thoughts turned inwards towards bewildering spiritual vistas. “Even with all his wisdom and the depth of his insight, there was always a sense of excessiveness about my father,” says Alexandre. “He always had to put himself in danger. He searched for it.”

Grothendieck had abandoned the commune he had been part of since 1973 in a village north of Montpellier, where he still taught at the university. From 1970 onwards, he had been one of France’s first radical ecologists and became increasingly preoccupied with meditation. In 1979, he spent a year dwelling intensely on his parents’ letters, a reflection that stripped away any lingering romanticism about them. “The myth of their great love fell flat for Shurik – it was a pure illusion,” says Johanna Grothendieck, who bears her grandmother’s name. “And he was able to decrypt all the traumatic elements of his childhood. He realised he had been quite simply abandoned by his own mother.”

This preoccupation with the past intensified into the mid-1980s, as Grothendieck worked on the manuscript for Harvests and Sowings. A reflection on his mathematical career, it was filled with stunning aphoristic insights, like the house metaphor. But, choked with David Foster Wallace-like footnotes, it was relentless and overwhelming, too – and steeped in a sense of betrayal by his former colleagues. In the wake of his revelations about his parents, this feeling became a kind of governing principle. “It was a systematic thing with our papa – to put someone on a pedestal, in order to see their flaws. Then – bam! – they went down in flames,” says Alexandre.

Although he still produced some mathematical work during this period, Grothendieck delved further into mysticism. He looked to his dreams as a conduit to the divine; he believed they were not products of his own psyche, but messages sent to him by an entity he called the Dreamer. This being was synonymous with God; as he conceived it, a kind of cosmic mother. “Like a maternal breast, the ‘grand dream’ offers us a thick and savorous milk, good to nourish and invigorate the soul,” he later wrote in The Key of Dreams, a treatise on the subject. Pierre Deligne, the brilliant pupil he accused in Harvests and Sowings of betraying him, felt his old master had lost his way. “This was not the Grothendieck I admired,” he says, on the phone from Princeton’s Institute for Advanced Study.

He became totally isolated. He was no longer in contact with nature. He had cut ties with everyone

By summer 1989, the prophetic dreams had intensified into daily audiences, “absorbing almost all of my time and energy”, with an angel Grothendieck called either Flora or Lucifera, depending on whether she manifested as benevolent or tormenting. She tutored him in a new cosmology, central to which was the question of suffering and evil in God’s greater scheme. He believed, for example, that the speed of light being close to, but not precisely, 300,000km a second, was evidence of Satan’s interference. “He was in a form of mystic delirium,” says another former pupil, Jean Malgoire, now a professor at Montpellier University. “Which is also a form of mental illness. It would have been good if he could have been seen by a psychiatrist at that point.”

In real life, he had become forbidding and remote. Matthieu spent two months in Mormoiron working on the house; during that time, his father invited him in only once. His son blew his top: “He’d lost interest in others. I could no longer feel any authentic or sincere empathy.” But Grothendieck was still interested in people’s souls. On 26 January 1990, he sent 250 of his acquaintances – including his children – a messianic, seven-page typed epistle, entitled Letter of the Good News. He announced a date – 14 October 1996 – for the “Day of Liberation” when evil on Earth would cease, and said they had been chosen to help usher in the new era. It was “a kind of remake of the most limited aspects of Christianity”, says Johanna.

Then in June 1990, as if to firm up his spiritual commitment, Grothendieck fasted for 45 days (he wanted to beat Christ’s 40), cooling himself in the heat of summer in a wine barrel filled with water. As he watched his father shrivel to an emaciated frame reminiscent of the Nazi concentration camp prisoners, Alexandre realised he may have been emulating someone else: “In some way, he was rejoining his father.”

Grothendieck almost died. He only relented when persuaded to resume eating by Johanna’s partner. She believes the fast damaged her father’s brain on a cellular level in a way impossible for a 62-year-old to recover from, further loosening his grip on rationality. Shortly afterwards, he summoned Malgoire to Mormoiron to collect 28,000 pages of mathematical writings (now available online). He showed his student an oil drum full of ashes: the remains of a huge raft of personal papers, including his parents’ letters, he had burned. The past was immaterial, and now Grothendieck could only look ahead. One year later, without warning, he moved away from his house on a trajectory known only to him.

* * *

A circular slab of black pitted sandstone, fashioned by Johanna and now smothered in wild roses, marks Grothendieck’s resting place in Lasserre churchyard. It’s almost hidden behind a telegraph post. The mathematician was alone when he died in hospital; after several weeks in their company, he had spurned his children again, only accepting care from intermediaries.

The presence of his family seemed to stir up unbearable feelings. In his writings, he evaluates the people in his life for how much they are under the sway of Satan. But, as Alexandre points out, this was also a projection of his own seething unconscious: “He didn’t like what he saw in the mirror we held out to him.”

They only discovered his whereabouts in Lasserre by accident: one day in the late 90s Alexandre signed up for car insurance, and the company said they already had an address for an Alexander Grothendieck on file. Deciding to make contact, Alexandre spotted his father across the marketplace in the town of St-Girons, south of Lasserre. “Suddenly, he sees me,” says Alexandre. “He’s got a big smile, he’s super-happy. So I said to him: ‘Let me take your basket.’ And all of a sudden, he has a thought that he shouldn’t have anything to do with me, and his smile turns the other way. It lasted a minute and a half. A total cold shower.” He didn’t see his father again until the year he died.

At least until the early 00s, Grothendieck worked at a ferocious pace, often writing up the day’s “meditation” at the kitchen table in the dead of night. “He became totally isolated. He was no longer in contact with nature. He had cut ties with everyone,” says Johanna.

He vacillated about the date of the Day of Liberation, when evil on Earth would cease. Recalculating it as late August or early September 1996 instead of the original October date, he was crestfallen at the lack of celestial trumpets. Mathematicians Leila Schneps and Pierre Lochak, who had tracked him down a year earlier, visited him the day afterwards. “We delicately said: ‘Perhaps it’s started and people’s hearts are opening.’ But obviously he believed what we believed, which was that nothing had happened,” Schneps says.

Experiencing an “uncontrollable antipathy” to his work, that he attributed to malign forces but sounds a lot like depression, he wrote in early 1997: “The most abominable thing in the fate of victims is that Satan is master of their thoughts and feelings.” He contemplated suicide for several days, but resolved to continue living as a self-declared victim.

The house was weighing on him. In 2000, he offered it to his bookbinder, Michel Camilleri, for free, deeming him the perfect candidate because he was “good with materials”. The sole condition was that Camilleri look after his plant friends. When Camilleri refused, he was outraged – seeing the hand of Satan once more. A year later, the building was nearly destroyed when his unswept stove chimney caught fire. Some witnesses say Grothendieck tried to prevent the firefighters from accessing his property (Matthieu doesn’t believe this).

The curate at Lasserre church, David Naït Saadi, wrote Grothendieck a letter in around 2005, attempting to bring the hermit into the community. But Grothendieck fired back a missive full of biblical references, saying Saadi had a “viper’s tongue” and that he should nail his reply to the church noticeboard.

By the mid-00s, his writing was petering out. The endpoint of his late meditations, according to Matthieu, is a chronicle in which his father painstakingly records everything he is doing, as if the minutiae of his own life are imbued with immanence. Matthieu finds these writings so painful to read that he kept them back from the national library donation. Grothendieck was lost in the rooms and corridors of his own mind.

* * *

In mid-April, dapper Parisians are filing out of the polished foyer of a redeveloped hotel in the seventh arrondissement, heading for lunch. The first French TV programmes were broadcast from the building; now, Huawei is pushing for a similar leap in AI here. It has set up the Centre-Lagrange, an advanced mathematics research institute, on the site and hired elite French mathematicians, including Laurent Lafforgue, to work there. An aura of secrecy surrounds their work in this ultra-competitive field, compounded by growing suspicion in the west of Chinese tech. Huawei initially refuse to answer any questions, before permitting some answers to be emailed.

Grothendieck’s notion of the toposdeveloped by him in the 1960s, is of particular interest to Huawei. Of his fully realised concepts, toposes were his furthest step in his quest to identify the deeper algebraic values at the heart of mathematical space, and in doing so generate a geometry without fixed points. He described toposes as a “vast and calm river” from which fundamental mathematical truths could be sifted. Olivia Caramello views them rather as “bridges” capable of facilitating the transfer of information between different domains. Now, Lafforgue confirms via email, Huawei is exploring the application of toposes in a number of domains, including telecoms and AI.

Caramello describes toposes as a mathematical incarnation of the idea of vision; an integration of all the possible points of view on a given mathematical situation that reveals its most essential features. Applied to AI, toposes could allow computers to move beyond the data associated with, say, an apple; the geometric coordinates of how it appears in images, for example, or tagging metadata. Then AI could begin to identify objects more like we do – through a deeper “semantic” understanding of what an apple is. But practical application to create the next generation of “thinking” AI is, according to Lafforgue, some way off.

A larger question is whether this is what Grothendieck would have wanted. In 1972, during his ecologist phase, concerned that capitalist society was driving humanity towards ruin, he gave a talk at Cern, near Geneva, entitled Can We Continue Scientific Research? He didn’t know about AI – but he was already opposed to this collusion between science and corporate industry. Considering his pacifist values, he would probably also have been opposed to Huawei’s championing of his work; its chief executive, Ren Zhengfei, is a former member of the People’s Liberation Army engineering corps. The US department of defense, as well as some independent researchers, believes Huawei is controlled by the Chinese military.

Huawei insists it is a private company, owned by its employees and its founding chairman, Ren Zhengfei, and that it is “not owned, controlled or affiliated to any government or third-party company”.

We are at the very beginning of a huge exploration of these manuscripts. And certainly there will be marvels in them

Lafforgue points out that France’s IHES, where Grothendieck and later he worked, was funded by industrial companies – and thinks Huawei’s interest is legitimate. Caramello, who is the founder and president of the Grothendieck Institute research organisation, believes that he would have wanted a systematic exploration of his concepts to bring them to fruition. “Topos theory is itself a kind of machine that can extend our imagination,” she says. “So you see Grothendieck was not against the use of machines. He was against blind machines, or brute force.” What is unsettling is a degree of opaqueness about Huawei’s aims regarding AI and its collaborations, including its relationship with the Grothendieck Institute, where Lafforgue sits on the scientific council. But Caramello stresses that it is an entirely independent body that engages in theoretical, not applied research, and that makes its findings available to all. She says it does not research AI and that Lafforgue’s involvement pertains solely to his expertise in Grothendieckian maths.

Matthieu Grothendieck is clear about whether his father would have consented to Huawei, or any other corporation, exploiting his work: “No. I don’t even ask. I know.” There is little doubt that the mathematician believed modern science had become morally stunted, and the Lasserre papers attempted to reconcile it with metaphysics and moral philosophy. Compared with Grothendieck’s delirious 1980s mysticism, there is structure and intent here. They begin with just under 5,000 pages devoted to the Schematic Elemental Geometry and Structure of the Psyche. According to the mathematician Georges Maltsiniotis, who has examined this portion, these sections contain maths in “due and proper form”. Then Grothendieck gets going on the Problem of Evil, which sprawls over 14,000 pages undertaken during much of the 1990s.

Judging by the 200 or so pages I attempt to decipher, Grothendieck put herculean effort into his new cosmology. He seems to be trying to fathom the workings of evil at the level of matter and energy. He squabbles with Einstein, James Clerk Maxwell and Darwin, especially about the role of chance in what he viewed as a divinely created universe. There are numerological musings about the significance of the lunar and solar cycles, the nine-month term of a pregnancy. He renames the months in a new calendar: January becomes Roma, August becomes Songha.

How much of this work is meaningful and how much empty mania? For Pierre Deligne, Grothendieck became fatally unmoored in his solitude. He says that he has little interest in reading the Lasserre writings “because he had little contact with other mathematicians. He was restricted to his own ideas, rather than using those of others too.” But it’s not so clear-cut for others, including Caramello. In her eyes, this fusion of mathematics and metaphysics is true to his boundary-spanning mind and could yield unexpected insights: she points out his use of the mathematics of vibration to explain psychological phenomena in Structure of the Psyche. “We are at the very beginning of a huge exploration of these manuscripts. And certainly there will be marvels in them,” she says.

Grothendieck remained hounded by evil until the end. Perhaps, shattered by his traumas, he couldn’t allow himself to forgive, and to conceive of the world in a kinder light. But his children, despite the long estrangement, aren’t the same. Matthieu rejects the idea that his father repeated the abandonment he suffered as a child on them: “We were adults, so it’s nothing compared to what he went through. He did a lot better than his parents.”

The shunning of his children wounded Johanna, but she understands that something was fundamentally broken in her father. “In his mind, I don’t think he left us. We existed in a parallel reality for him. The fact that he burned his parents’ letters was extremely revealing: he had no feeling of existing in the family chain of generations.” What’s striking is the trio’s lack of judgment about their father and their openness to discussing his ordeals. “We accept it,” says Alexandre. “It was the trial he wanted to inflict on himself – and he inflicted it on himself most of all.”

Saturday, August 31, 2024

 DECRIMINALIZE DRUGS

Cannabis and hallucinogen use among adults remained at historic highs in 2023



Vaping among younger adults and binge drinking among mid-life adults also maintained historically high levels, NIH-supported study shows



NIH/National Institute on Drug Abuse




Past-year use of cannabis and hallucinogens stayed at historically high levels in 2023 among adults aged 19 to 30 and 35 to 50, according to the latest findings from the Monitoring the Future survey. In contrast, past-year use of cigarettes remained at historically low levels in both adult groups. Past-month and daily alcohol use continued a decade-long decline among those 19 to 30 years old, with binge drinking reaching all-time lows. However, among 35- to 50-year-olds, the prevalence of binge drinking in 2023 increased from five and 10 years ago. The Monitoring the Future study is conducted by scientists at the University of Michigan’s Institute for Social Research, Ann Arbor, and is funded by the National Institutes of Health.

Reports of vaping nicotine or vaping cannabis in the past year among adults 19 to 30 rose over five years, and both trends remained at record highs in 2023. Among adults 35 to 50, the prevalences of nicotine vaping and of cannabis vaping stayed steady from the year before, with long-term (five and 10 year) trends not yet observable in this age group as this question was added to the survey for this age group in 2019.

For the first time in 2023, 19- to 30-year-old female respondents reported a higher prevalence of past-year cannabis use than male respondents in the same age group, reflecting a reversal of the gap between sexes. Conversely, male respondents 35 to 50 years old maintained a higher prevalence of past-year cannabis use than female respondents of the same age group, consistent with what’s been observed for the past decade.

“We have seen that people at different stages of adulthood are trending toward use of drugs like cannabis and psychedelics and away from tobacco cigarettes,” said Nora D. Volkow, M.D., director of NIH’s National Institute on Drug Abuse (NIDA). “These findings underscore the urgent need for rigorous research on the potential risks and benefits of cannabis and hallucinogens – especially as new products continue to emerge.”

Since 1975, the Monitoring the Future study has annually surveyed substance use behaviors and attitudes among a nationally representative sample of teens. A longitudinal panel study component of Monitoring the Future conducts follow-up surveys on a subset of these participants (now totaling approximately 20,000 people per year), collecting data from individuals every other year from ages 19 to 30 and every five years after the participants turn 30 to track their drug use through adulthood. Participants self-report their drug use behaviors across various time periods, including lifetime, past year (12 months), past month (30 days), and other use frequencies depending on the substance type. Data for the 2023 panel study were collected via online and paper surveys from April 2023 through October 2023.

Full data summaries and data tables showing the trends below, including breakdowns by substance, are available in the report. Key findings include:

Cannabis use in the past year and past month remained at historically high levels for both adult age groups in 2023. Among adults 19 to 30 years old, approximately 42% reported cannabis use in the past year, 29% in the past month, and 10% daily use (use on 20 or more occasions in the past 30 days). Among adults 35 to 50, reports of use reached 29%, 19%, and 8%, respectively. While these 2023 estimates are not statistically different from those of 2022, they do reflect five- and 10-year increases for both age groups.

Cannabis vaping in the past year and past month was reported by 22% and 14% of adults 19 to 30, respectively, and by 9% and 6% of adults 35 to 50 in 2023. For the younger group, these numbers represent all-time study highs and an increase from five years ago.

Nicotine vaping among adults 19 to 30 maintained historic highs in 2023. Reports of past-year and past-month vaping of nicotine reached 25% and 19%, respectively. These percentages represent an increase from five years ago, but not from one year ago. For adults 35 to 50, the prevalence of vaping nicotine remained steady from the year before (2022), with 7% and 5% reporting past-year and past-month use.

Hallucinogen use in the past year continued a five-year steep incline for both adult groups, reaching 9% for adults 19 to 30 and 4% for adults 35 to 50 in 2023. Types of hallucinogens reported by participants included LSD, mescaline, peyote, shrooms or psilocybin, and PCP.

Alcohol remains the most used substance reported among adults in the study. Past-year alcohol use among adults 19 to 30 has showed a slight upward trend over the past five years, with 84% reporting use in 2023. However, past month drinking (65%), daily drinking (4%), and binge drinking (27%) all remained at study lows in 2023 among adults 19 to 30. These numbers have decreased from 10 years ago. Past-month drinking and binge drinking (having five or more drinks in a row in the past two week period) decreased significantly from the year before for this age group (down from 68% for past month and 31% for binge drinking reported in 2022).

Around 84% of adults 35 to 50 reported past-year alcohol use in 2023, which has not significantly changed from the year before or the past five or 10 years. Past-month alcohol use and binge drinking have slightly increased over the past 10 years for this age group; in 2023, past-month alcohol use was at 69% and binge drinking was at 27%. Daily drinking has decreased in this group over the past five years and was at its lowest level ever recorded in 2023 (8%).

Additional data: In 2023, past-month cigarette smoking, past-year nonmedical use of prescription drugs, and past-year use of opioid medications (surveyed as “narcotics other than heroin”) maintained five- and 10-year declines for both adult groups. Among adults 19 to 30 years old, past-year use of stimulants (surveyed as “amphetamines”) has decreased for the past decade, whereas for adults 35 to 50, past-year stimulant use has been modestly increasing over 10 years. Additional data include drug use reported by college/non-college young adults and among various demographic subgroups, including sex and gender and race and ethnicity.

The 2023 survey year was the first time a cohort from the Monitoring the Future study reached 65 years of age, therefore trends for the 55 to 65 year old age group are not yet available.

“The data from 2023 did not show us many significant changes from the year before, but the power of surveys such as Monitoring the Future is to see the ebb and flow of various substance use trends over the longer term,” said Megan Patrick, Ph.D., of the University of Michigan and principal investigator of the Monitoring the Future panel study. “As more and more of our original cohorts – first recruited as teens – now enter later adulthood, we will be able to examine the patterns and effects of drug use throughout the life course. In the coming years, this study will provide crucial data on substance use trends and health consequences among older populations, when people may be entering retirement and other new chapters of their lives.”

View more information on data collection methods for the Monitoring the Future panel study and how the survey adjusts for the effects of potential exclusions in the report. Results from the related 2023 Monitoring the Future study of substance use behaviors and related attitudes among teens in the United States were released in December 2023, and 2024 results are upcoming in December 2024.

If you or someone you know is struggling or in crisis, help is available. Call or text 988 or chat at 988lifeline.orgTo learn how to get support for mental health, drug or alcohol conditions visit FindSupport.govIf you are ready to locate a treatment facility or provider, you can go directly to FindTreatment.gov or call 800-662-HELP (4357).

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About the National Institute on Drug Abuse (NIDA): NIDA is a component of the National Institutes of Health, U.S. Department of Health and Human Services. NIDA supports most of the world’s research on the health aspects of drug use and addiction. The Institute carries out a large variety of programs to inform policy, improve practice, and advance addiction science. For more information about NIDA and its programs, visit www.nida.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

About substance use disorders: Substance use disorders are chronic, treatable conditions from which people can recover. In 2023, nearly 49 million people in the United States had at least one substance use disorder. Substance use disorders are defined in part by continued use of substances despite negative consequences. They are also relapsing conditions, in which periods of abstinence (not using substances) can be followed by a return to use. Stigma can make individuals with substance use disorders less likely to seek treatment. Using preferred language can help accurately report on substance use and addiction. View NIDA’s online guide.

NIH…Turn 

Plastic surgery patients who use marijuana also have elevated nicotine levels



Nicotine may be an unsuspected risk factor for complications, reports Plastic and Reconstructive Surgery®



Peer-Reviewed Publication

Wolters Kluwer Health




August 29, 2024 — Marijuana use is common among patients considering plastic surgery and is associated with elevated nicotine levels on laboratory tests, reports a paper in the September issue of Plastic and Reconstructive Surgery®the official medical journal of the American Society of Plastic Surgeons (ASPS). The journal is published in the Lippincott portfolio by Wolters Kluwer

"We found that patients who report marijuana use also have elevated urine nicotine and cotinine levels – even those who don't smoke or use other nicotine-containing products" comments ASPS Member Surgeon Joseph A. Ricci of Hofstra University School of Medicine, Great Neck, NY. "This raises concerns that unsuspected nicotine exposure might lead to an increased risk of postoperative complications." 

First study to assess marijuana and nicotine use in plastic surgery patients 

The rising prevalence of marijuana use raises questions about potential negative effects in patients undergoing surgery. Marijuana smoke contains carcinogens and irritants similar to those in tobacco smoke, with similarly harmful effects on pulmonary health. 

Nicotine causes impaired wound healing, which is a special concern in patients undergoing plastic surgery. The rising popularity of marijuana, combined with newer nicotine delivery products such as vapes, "presents a clinical challenge for healthcare providers to identify patients who are exposed to nicotine, as patients themselves may be unaware," the researchers write. 

Dr. Ricci and colleagues examined the possible link between marijuana use and nicotine exposure in 135 consecutive patients who consulted a surgeon to discuss cosmetic plastic surgery. Ninety-two percent of patients were women; the average age was 38 years. The patients were largely Hispanic, reflecting the demographics of the area served by the clinic. 

High nicotine levels raise 'concern for unrecognized surgical risk' 

In a survey, 19% of patients reported active nicotine use while 20% reported marijuana use: marijuana alone in 7% of patients and both nicotine and marijuana by 13%. Levels of nicotine and the nicotine metabolite cotinine were compared between groups. 

The results showed elevated nicotine and cotinine levels among patients who said they used marijuana. The association was apparent not only in those who reported nicotine-containing products, but also in those who denied any type of nicotine use. 

Although marijuana users had elevated nicotine, the levels weren't as high as typically found in patients who smoke or use other forms of nicotine. Most patients who reported marijuana and/or nicotine use on the study survey did not mention these substances during their discussion with the plastic surgeon. For this group, nicotine levels were comparable similar to those in active cigarette smokers. 

"Patients may be hesitant to disclose their substance use history, possibly due to a lack of awareness about the perioperative risks associated with smoking and marijuana use," the researchers write. In 84 patients who went on to have plastic surgery, nicotine levels were lower compared to patients who did not undergo surgery.  

Although the study did not find increased complication rates among marijuana users or those with elevated nicotine levels, the findings raise concern that such risks could occur. The researchers emphasize the need for definitive studies of the effects of marijuana on surgical outcomes. Meanwhile, Dr. Ricci and coauthors conclude: "In real clinical settings, under-reporting of nicotine-containing product use, including marijuana, remains a concern for unrecognized surgical risk and affects decision on offering elective procedures." 

Read Article: Patterns of Marijuana Use and Nicotine Exposure in Patients Seeking Elective Aesthetic Procedures 

Wolters Kluwer provides trusted clinical technology and evidence-based solutions that engage clinicians, patients, researchers and students in effective decision-making and outcomes across healthcare. We support clinical effectiveness, learning and research, clinical surveillance and compliance, as well as data solutions. For more information about our solutions, visit https://www.wolterskluwer.com/en/health

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About Wolters Kluwer 

Wolters Kluwer (EURONEXT: WKL) is a global leader in information, software solutions and services for professionals in healthcare; tax and accounting; financial and corporate compliance; legal and regulatory; corporate performance and ESG. We help our customers make critical decisions every day by providing expert solutions that combine deep domain knowledge with technology and services. 

Wolters Kluwer reported 2023 annual revenues of €5.6 billion. The group serves customers in over 180 countries, maintains operations in over 40 countries, and employs approximately 21,400 people worldwide. The company is headquartered in Alphen aan den Rijn, the Netherlands.  

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29-Aug-2024ing Discovery Into Health®