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  • Pirtobrutinib Matches Ibrutinib in Phase 3

    Pirtobrutinib Matches Ibrutinib in Phase 3

    Chronic lymphocytic leukemia cells: © Mari-stocker – stock.adobe.com

    Positive topline results from the phase 3 BRUIN CLL-314 study (NCT05254743) demonstrated that pirtobrutinib (Jaypirca), a novel noncovalent BTK inhibitor, met its primary end point of noninferiority in overall response rate (ORR) compared with ibrutinib (Imbruvica) in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). This trial is notable as the first head-to-head study comparing a BTK inhibitor against ibrutinib in CLL that included treatment-naive patients.1

    The randomized, open-label BRUIN CLL-314 study enrolled 650 patients with CLL/SLL, encompassing both treatment-naive and previously treated but BTK inhibitor-naive patients. Patients received either pirtobrutinib 200 mg orally once daily or ibrutinib 420 mg orally once daily.

    While the primary end point of ORR, as assessed by a blinded independent review committee (IRC), favored pirtobrutinib, detailed ORR percentages will be announced at a medical conference later this year. Importantly, progression-free survival (PFS) data, though still immature, trended in favor of pirtobrutinib, with a formal PFS analysis anticipated in future reporting. No detriment was observed for overall survival (OS). The safety profile of pirtobrutinib in this trial was consistent with previously reported studies, reinforcing its known tolerability.

    This positive outcome marks the second successful phase 3 study for pirtobrutinib, building upon the foundation laid by the earlier BRUIN phase 1/2 trial and the phase 3 BRUIN CLL-321 trial (NCT04664421). The BRUIN CLL-321 trial previously supported the accelerated approval of pirtobrutinib for adult patients with CLL/SLL who have received at least 2 prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.2 Its approval for relapsed or refractory mantle cell lymphoma (MCL) after at least 2 lines of systemic therapy, including a BTK inhibitor, was also based on response rate data.

    Another ongoing phase 3 study, BRUIN CLL-313 (NCT05221372), is expected to yield results later in 2025. The combined data from BRUIN CLL-313 and BRUIN CLL-314 are intended to support global regulatory submissions for pirtobrutinib in broader CLL/SLL indications.1

    Pirtobrutinib is distinguished as a highly selective, noncovalent inhibitor of the BTK enzyme. Its mechanism of action allows it to bind to BTK in a different manner than covalent inhibitors like ibrutinib, potentially overcoming resistance mechanisms that emerge with irreversible BTK inhibitors. This reversible binding characteristic may contribute to its efficacy in patients who have previously been treated with, or become resistant to, other BTK inhibitors. The drug is currently available as 100 mg or 50 mg oral tablets, typically prescribed as a once-daily 200 mg dose.

    From a safety perspective, clinicians should be aware of the established adverse reactions associated with pirtobrutinib. Fatal and serious infections (including bacterial, viral, fungal, and opportunistic) have occurred, with grade ≥3 infections reported in 24% of hematologic malignancy patients (14% pneumonia) and 32% in patients with CLL/SLL (8% fatal). Prophylaxis and close monitoring for infections are crucial. Hemorrhage, including fatal and serious major hemorrhage (3% major, 0.3% fatal), has also been observed, necessitating vigilant monitoring for bleeding and consideration of dose adjustments or discontinuation if major bleeding occurs.

    Cytopenias, including neutropenia (grade 3 or 4 in 26%), thrombocytopenia (grade 3 or 4 in 12%), and anemia (grade 3 or 4 in 12%), are common and require regular monitoring of complete blood counts. Cardiac arrhythmias, particularly atrial fibrillation/flutter (3.2%, with 1.5% being grade 3/4), have been reported, emphasizing the need for appropriate monitoring and management of cardiac status. Second primary malignancies, including nonmelanoma skin cancer (4.6%), developed in 9% of patients, underscoring the importance of sun protection and ongoing skin surveillance. Hepatotoxicity, including drug-induced liver injury, has also been noted, mandating baseline and ongoing evaluation of liver function tests and potential dose modifications or discontinuation.

    REFERENCES:
    1. Lilly’s Jaypirca (pirtobrutinib), the first and only approved non-covalent (reversible) BTK inhibitor, met its primary endpoint in a head-to-head Phase 3 trial versus Imbruvica (ibrutinib) in CLL/SLL. News release. Eli Lilly and Company. July 29, 2025. Accessed July 30, 2025. https://tinyurl.com/5atx7fyc
    2. FDA grants accelerated approval to pirtobrutinib for chronic lymphocytic leukemia and small lymphocytic leukemia. News release. U.S. Food & Drug Administrations. December 1, 2023. Accessed July 30, 2025. https://tinyurl.com/44nzmehd

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  • Irvine Welsh on New Novel and Disco Album ‘Men in Love’

    Irvine Welsh on New Novel and Disco Album ‘Men in Love’

    Britain, the 1980s. Thatcher. Black Monday. Riots. Strikes. Racism. In 1984, George Orwell’s 1984 became a bestseller again, slotting right into the nightmarish dystopia it had predicted. As unemployment figures soared, heroin addiction spread, as did HIV and AIDS. It was bloody miserable.

    Then: 1988. Ecstasy, a drug promoting love and togetherness, arrived in the U.K., brought back from Ibiza — legend has it — by members of the Mancunian rock band New Order. The Second Summer of Love began. Two years later, Thatcher’s 15-year prime ministerial reign was over. Brit-pop happened. Suede. Pulp. Blur. Oasis and the Spice Girls. Four Weddings. Trainspotting. Damien Hirst. Alexander McQueen. Tony Blair! In 1996 Ben & Jerry’s released a new flavor of ice cream called Cool Britannia. Newsweek declared London “the coolest city on the planet.” It was bloody brilliant.

    It’s at the intersection of these two eras that Irvine Welsh’s new novel, Men in Love, takes place. On an uncomfortably hot day in the summer of 2025, he sits upstairs in the Parakeet, a charming pub in Camden, the hip London borough that was once home to Amy Winehouse, Pete Doherty, and the like. Smudged tattoos peering out from beneath the sleeves of his T-shirt, Welsh discusses Men in Love and its accompanying album, nine loved-up disco tunes composed in companion to the novel. We’re in a private room. Or so we thought. Suddenly the door from downstairs flies open.

    “Scotland’s finest! In ma pub!” exclaims a Scottish voice, belonging to a man staring awestruck at my interviewee. Welsh looks up from his zero-percent Guinness.

    “Is this your pub?” he asks, tones friendly. “I’m Irvine.” 

    “I know who ye are!” says the man. “I’m the manager here. This is surreal.” 

    “I live ’round the corner,” says Welsh. “I’ve come in here for a beer a few times.”

    “I’ll send ye a pint next time yir here,” the manager tells him, before pausing, lowering his eyebrows and raising a finger. “Jist the one though.” 

    He adds this caveat perhaps to guard against the possibility that Welsh might overdo it on free beer and drop an empty pint glass off the balcony onto an unsuspecting punter below, as one character does in his debut novel, Trainspotting, published in 1993 and turned into a hugely successful film by director Danny Boyle three years later. Written in a phonetically rendered Scottish accent, Trainspotting painted a visceral, hilarious but bleak image of Edinburgh in the 1980s, a time defined by unemployment, addiction, crime, and misdemeanor, following characters like Mark “Rent Boy” Renton, Simon “Sick Boy” Williamson, glass-throwing nutcase Begbie, and hopeless junkie Spud as they steal books from bookshops and fish drugs from overflowing toilets. 

    Although the novel was set in the Eighties, the film came to symbolize British culture in the 1990s, with an iconic catchphrase — choose life — that, although it was originally delivered with irony, became synonymous with the vivacity of Britain at the time. Welsh has already written two sequels, as well as a prequel and a spinoff based in the same universe, but Men in Love begins moments after Trainspotting finished, with Renton having just betrayed his friends and fled to Amsterdam with a bag of cash that they hustled for together. In the new novel, Renton and Co. grapple with varying understandings of love, brushing with prison, politics, and the porn industry along the way.

    Trainspotting the film is as famous for its soundtrack as anything else, and Welsh has helped run the extremely credible dance label Jack Said What for some time, so his foray into music-making should not come as a surprise. But think Trainspotting and you might think Iggy Pop, Underworld, or Lou Reed. And Men in Love is set at the moment acid house and rave culture exploded in Britain. 

    So why a disco album? “In uncertain times, dominated by the ascendancy of soul dead oligarchs, their corrosive technology and looting economics, the great positive constant for humanity remains our infinite capacity for love,” reads a typically poetic note from Welsh in the album’s liner notes. “Music is still the medium by which we bypass their reductive, low frequency world.… One of the greatest musical forms in delivering that ecstasy has been discotheque music.… So don’t diss the disco, let’s dance away the heartache or die trying, because nothing else makes any sense.”

    “Music hits spots that literature can’t,” Welsh adds now, nursing his boozeless beer. He explains that if pages of a book are like tiles on a wall, music is the grout that holds it together. It’s a neat paean to his career as a writer, every stage of which has pulsated to the beat of some kind of music. If there’s one thing I want to probe, it’s how much he thinks music, literature, art, and culture can truly help us, more than simply providing a soundtrack, a backdrop to a world in chaos, chaos that has only intensified since the birth of disco, the publication of Trainspotting, the rise and fall of rave, and all that has happened since. As he always seems to do, he provides a fountain of streetwise wisdom, talking warmly and engagingly on anything that’s put in front of him. Especially music. 

    Welsh was born in Leith, Edinburgh, where most of Trainspotting takes place. His father was a dockworker, his mother a waitress whose cooking Welsh once compared to waterboarding. He says he remembers dancing to the Beatles’ debut single, “Love Me Do,” as a child in 1963. When he was old enough, he discovered Bowie, Iggy, and Lou Reed. Intrigued by the rebellious image outlined in the Velvet Underground’s “Heroin,” he and a friend tried the drug in the early 1980s. He remained addicted for about a year, then kicked the habit, moved to London, and found a respectable job working for the local council. He played in various punk bands with friends, writing stories and turning them into long ballads. “We’re a punk band,” his bandmates told him. “We don’t want fucking 12 verses explaining this big fucking long story.” 

    When Ecstasy swept the U.K., Welsh was not an immediate convert. “I was very gun-shy about trying Ecstasy,” he says. “Because I’d had this heroin experience and I thought, ‘I’m done with drugs, I’m not going anywhere near them.’” In the late Eighties, he made a tentative step inside legendary DJ Danny Rampling’s South London nightclub Shoom, designed to bring Ibiza nightlife to Britain. “Do you remember that scene in Basic Instinct, [with] Michael Douglas?” asks Welsh. “When everybody’s dressed in this mad fucking leather and bondage gear and all that, and he’s got this V-neck sweater on and he’s doing this stiff-arse dance? That’s what I was like.” 

    A year later, he was at a Christmas party in Edinburgh and his friend Susan told him, “You’re taking an eckie, and you’re coming raving with us.” He ended up in the UFO Club, and once the pill hit, it was like he’d invented acid house himself. “I was like, ‘Where’s the next rave?’” He went to the Republic in Sheffield, Back to Basics in Leeds, the Hacienda in Manchester, and started living for the weekend while working his 9-to-5 job. “I was like, ‘Oh God, I can’t do this,’” he says. “I’ve got to do something … artistic, for want of a better word. And that’s when I started seriously writing Trainspotting. It gave me the impetus to do that. I’d be raving all night, and in the morning, I’d be sitting there, can’t go to bed, head still buzzing, just smashing out pages.” 

    In interviews ever since its publication, Welsh has said Trainspotting was his attempt to get the energy of acid house — 4/4 rhythm and all — into a book. Music thrums throughout the novel. In one chapter, Iggy Pop comes to play in Edinburgh, in the same month as the girlfriend of local lad Tommy is celebrating her birthday: “It was the ticket or a present for her. Nae contest. This was Iggy Pop. Ah thought she’d understand.” When the film hit screens in 1996, it opened to the sound of Iggy’s “Lust for Life,” iconically soundtracking a chase scene as Ewan McGregor legged it down an Edinburgh high street tailed by two police officers. Years later, Welsh moved to Miami, where Iggy became his friend and neighbor.

    Welsh kept up his routine — work, rave, write, repeat — until he’d written his second book, the short story collection The Acid House, which was finished before Trainspotting even reached the shelves. By 1996 he’d written four books, including another short story collection called Ecstasy: Three Tales of Chemical Romance, which bears the strongest resemblance to Men in Love of the 22 other books in his bibliography. In the third of Ecstasy’s stories, a pill-popping DJ called Woodsy confronts an outraged priest, holding a bag full of drugs and declaring: “There’s nae medium between man and god except MDMA!” 

    As if to echo the line, on the Men in Love track “Saviour,” soul powerhouse and former West End Mufasa Shaun Escoffery belts out the lyrics — written by Welsh — “Gonna tell you right, gonna tell you now, a saviour is coming.” Whether that saviour is God, love, or MDMA is left unsaid, but it offers a certain spirituality that Welsh says is missing from a culture now dominated by unromantic tech nerds incapable of talking to the opposite sex. 

    “The internet was set up for guys that couldn’t pull,” he says. “So they set up this whole stalker network. We’ve all bought into that, and it’s spiritually barren.” He says this motivated him to include fragments of poetry and prose by the Romantic greats of English literature — Wordsworth, Coleridge, Blake — at the beginning of every chapter of Men in Love

    In much the way Men in Love the novel places Welsh’s own writing in dialogue with the wordsmiths of history, the Men in Love album offers a conversation between two lovers. “What’s a man in love to do?!” cries Escoffery on Track One. “You gotta be stronger to play this game, love’s more than a weekend tease,” replies Louise Marshall, David Gilmour’s onetime backing singer, on Track Two. Both singers have immensely powerful voices, chosen in deliberate contrast to the pop sound of today. Welsh, ever the provocateur, explains why in characteristically inflammatory terms. “If you listen to mainstream commercial music, everybody’s got that kind of sub-Sean Paul, fake Jamaican, adenoidal sex-offender whine and lyrics like ‘Baby, I want to feel your body next to mine.…’” he says. “And the women have got that shrieking, Minnie Mouse-type, sex-offender-victim voice. Whereas this is like proper men, proper women, booming out songs of love and redemption and pain and hurt, which love is all about.”

    As well as writing all of the lyrics, Welsh made the album with unsung U.K. club legend Steve Mac, his co-label head at Jack Said What records. Mac says they first met about a decade ago at Amsterdam Dance Event with “both a bit pissed” on local booze. They started working together on the forthcoming Trainspotting musical. “That was a real turning point,” Mac says. “I saw Irvine as a really, really good songwriter. It was unbelievable.” 

    “I’ve got no keyboarding or fretboarding skills,” says Welsh. “But I’ve got an array of tunes in my head all the time.” He began visiting Mac at his studio in Brighton and explaining his ideas for songs, “and suddenly he’s ripped down the bass line, we’re working on the basic melody …” and it all came together. Disco’s hallelujastic mood fit Welsh’s relationship with Mac. “My books are quite dark,” Welsh adds. “But when we get together, it’s a different energy. It’s a whole joyous experience. So we thought: ‘Let’s do a disco album.’” 

    In the late Eighties, after disco morphed into house and then acid house, the Second Summer of Love filled everyone it touched with ecstasy and optimism. “I think it’s time to fall in love!” announces narrator Lloyd in Ecstasy, off his tits on a dance floor having just delivered an impassioned eulogy on the power of pills. In Men in Love, the frontman of a struggling fictional rock band called Big Tobacco stands in a sweaty nightclub as Ecstasy and kick drums pulsate through his veins. “My God, this acid house,” he thinks. “It feels like everyone in the world is full of love. I can’t think of a single person in our generation this revolution could possibly pass by.”

    The revolution did pass by, with the Criminal Justice Act of 1994 making events “characterized by the emission of a succession of repetitive beats” illegal in the U.K. and cutting the rave movement short. But Ecstasy spread to the United States and beyond. Welsh thinks its legacy remains evident. “When I grew up in Scotland, it was like a kind of sexual apartheid,” he says. “You’d go to the discotheque and the girls would dance around their handbags. The guys would sit and drink, then stagger onto the floor for the last dance and hopefully go home with one of them. Ecstasy and acid house changed that completely.” He remembers sitting in a pub in Leith, shortly after taking his first E, finding interest in his mates’ girlfriends for the first time. “Suddenly you think, ‘They’re far more interesting than my mates!’ It opened up a whole new dimension. I think I see that still existing.”

    Trainspotting the novel sold millions of copies, and the film became a cult classic. But the British utopia of the 1990s came and went. Tony Blair’s Labour Party won power in 1997, complete with an Oasis campaign song, but six years later, Blair took Britain to war in Iraq despite protests from millions around the country. Less than four years after 9/11, the 7/7 terror attacks devastated London. The 2008 financial crash happened. Oasis split up. Could a period as positive and optimistic as the 1990s ever happen again? 

    “I think it’s very difficult with the internet, because things can’t incubate on the streets,” says Welsh. “But I think there’ll be a reaction against it, not against the internet as a concept, this library that opens up to the world; against the corporations of the state farming, basically controlling you, telling you what to do. I’m hoping there will be some kind of renaissance, whereby we get back out into the streets. Sometimes you see the embers of it. Think about Brat summer. It was all like young women who were basically locked up for a couple of years under Covid.” He even thinks the sea of camera phones that dominate concert crowds might die out, citing clips of fans at a recent Iggy show being shouted down for watching the whole thing through their phone screens and comparing the reaction to that of someone fed up with having cigarette smoke blown in their face by a stranger.

    Britain, the 2020s. Brat Summer. Oasis back together. Pulp touring again. Olivia Rodrigo in Union Jack hot pants. Skepta on Playboi Carti’s new album. British actors playing Batman and Spider-Man. The Labour Party in power again. “Cool Britannia is back!” British magazine Tatler declared on its cover this month. 

    “I’m putting a lot of hope in the Oasis comeback,” Welsh says. “Because 17 million people — that’s about a third of the population — wanted to get tickets. Clearly something bigger is happening than just a band here.”

    When Danny Boyle was making Trainspotting, he asked Oasis to feature on the soundtrack, but Noel Gallagher turned it down because he reportedly thought the film was actually about trains. He later praised both Welsh and Boyle because they “didn’t care about what anyone else thought. That’s how great art is created.” He and Welsh are now friends, and Welsh says he expects to see Oasis in Edinburgh next month, even if the local council is worried about “rowdy” and “middle-aged fans” who will all be drunk (claims to which Liam Gallagher responded by tweeting: “quite frankly your attitude fucking stinks I’d leave town that day if I was any of you lot.”)

    You can see actors playing a young Oasis in Creation Stories, a biopic about the man who signed the band, with a screenplay written by Welsh. Since those punkish beginnings, Oasis have become one of the biggest bands ever, with fans paying hundreds for “dynamically priced” tickets to the reunion shows, and well-publicized partnerships with Levi’s, Burberry, and Adidas (incidentally, you’ll see the Adidas logo quite a few times in T2: Trainspotting, Boyle’s 2017 sequel). 

    “You need to choose cash in order to choose life,” says Renton in Men in Love, capturing something about the archetypal arc of a rockstar career: start with a punk spirit, make it big, then eventually give up trying to save the world in favour of simply earning as much money as you can. Is Welsh himself an exception to that archetype? 

    “Yes,” he smiles. “Mainly through incompetence.” He adds that if he’d been strategic enough he could have spun Trainspotting into a proper franchise, written in chronological order with one central character and a lucrative run of spinoff TV shows, brand-partnered merch, and a theme park. He’s been an outspoken political voice throughout his 30-year career, critical of both Trump and Harris before the last election and recently declaring that the U.K.’s current Labour government are “all a bunch of fucking wankers.” But he’s conscious of not wanting to become “that guy who can’t shut up about this issue and all that.” 

    “I’m quite cynical about artists,” he says. “I’m quite cynical about myself. Whenever I say something about a worthy cause, whether it’s climate change or Palestine, I think to myself: Am I just playing to some kind of gallery here? Is there a Machiavellian part of me that’s trying to sell books and albums? And there probably is. So I don’t trust myself to constantly be this standard bearer.” 

    He is, however, a fan of a certain Irish rap trio. “More power to Kneecap,” Welsh wrote in a recent op-ed for Face magazine, defending the band’s vocal support for Palestine during performances at Coachella and Glastonbury this year amid prosecution by the U.K. government and calls for their U.S. visas to be revoked. “When all the British state can do in response is persecute a band for this — to try to stop them from playing music and from touring internationally with these ridiculous, nonsensical charges — it really is just an embarrassment to us all,” he wrote. 

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    He says he watched Kneecap’s recent show in North London with Noel Gallagher and Paul Weller. “The show was just unbelievably good,” Welsh says. Perhaps Kneecap are proof that music can be more than just a soundtrack to the atrocities that engulf our world. Perhaps one day they’ll cash in on a multimillion-pound reunion tour complete with branded sponsorship deals and dynamic ticket prices. 

    Ecstasy and acid house never saved the world. But Irvine Welsh still goes raving. He DJ’d at a club in Ibiza earlier this month. Like the rave, like Kneecap, like Trainspotting and Men in Love, perhaps all music can do is provide an alternative to the atrocities. “It’s all we’ve got,” Welsh says. “We don’t have politicians. We don’t have institutions. They’re all lined up on the side of the billionaire class. We don’t really have anything other than the fact that we can enjoy life. Living well is the best revenge, basically.”

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  • Stand-in captain Ollie Pope hopes to finish job Ben Stokes started against India

    Stand-in captain Ollie Pope hopes to finish job Ben Stokes started against India

    Stand-in England captain Ollie Pope hopes to finish the job Ben Stokes started by sealing a series win over India.

    A badly torn shoulder muscle meant Stokes had to admit defeat in his battle to be fit for the decider at the Kia Oval, handing over the reins – and a 2-1 lead – to his deputy.

    As well as filling the leadership void, Pope will have to make up for the absence of Stokes the all-rounder. The 34-year-old picked up player-of-the-match honours in each of the last two Tests and his competitive edge will be a big miss for a side built in his image.

    Pope, who stood in for four matches last year, is a quieter and less-combative character but has his eyes on the prize.

    “It’s gutting he’s missing the final Test, he’d love to be out there. But the impact he’s had on this series with both bat and ball has been awesome,” he said.

    “When you’ve got a cricketer like Ben, you’re going to miss them, but we appreciate everything he’s done this series and hopefully we can do him proud this week.”

    Stokes’ lay-off means a first appearance for the year for Jacob Bethell, who announced himself as a rising star in New Zealand last December and has since put in some exciting performances in the white-ball arena.

    Initially seen as a rival for Pope’s spot at three, he will now slot in at six and offer some overs of left-arm spin with Liam Dawson dropped from the XI.

    “I think everyone knows the skills he’s got, everyone saw him smack it in the T20s and one-dayers,” said Pope.

    “He’s shown he can click straight into Test match mode as he did in New Zealand so that’s really exciting. With his personality he’ll be pretty excited for the opportunity to try and help us win a series.”

    Pope’s only defeat during his previous stint in charge came at the Oval – where Sri Lanka sprung a surprise in a dead rubber – and he now has the chance to put that right at his home ground.

    “I was trying to learn on the job. Last summer was pretty much the first time I’ve done it for more than one game in professional cricket,” he said.

    “I’ve got some good things to look back on, what worked well and what I could have improved on. I know this ground well and how this pitch plays.

    “It’s about using what I know about these conditions to make good cricketing decisions.”

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  • A 'vibrant oasis' of chemical-eating creatures found in the deep Pacific – Reuters

    1. A ‘vibrant oasis’ of chemical-eating creatures found in the deep Pacific  Reuters
    2. Flourishing chemosynthetic life at the greatest depths of hadal trenches  Nature
    3. New Deep Sea Creatures ‘Challenge Current Models of Life,’ Scientists Say  404 Media
    4. How life thrives in one of the most hostile environments on Earth  New Scientist
    5. See the bizarre life forms scientists discovered more than 30,000 feet under the Pacific Ocean  vox.com

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  • Compact neutrino experiment unlocks first-ever reactor mystery

    Compact neutrino experiment unlocks first-ever reactor mystery

    Scientists at the Max Planck Institute for Nuclear Physics (MPIK) have detected antineutrinos from a nuclear reactor using a 3 kg (6.6 lbs) detector. 

    The results were achieved using the CONUS+ experiment and provide an observation of Coherent Elastic Neutrino-Nucleus Scattering (CEvNS) from a reactor source at full coherence.

    “The CEvNS measurement provides unique insights into fundamental physical processes within the Standard Model of particle physics, the current theory describing the structure of our universe,” said the researchers in a press release.

    Neutrinos do not scatter off

    The experiment is situated 20.7 meters from the core of the Leibstadt nuclear power plant in Switzerland. It uses three 1 kg (2.2 lbs) germanium semiconductor detectors to identify CEvNS, a process where a low-energy neutrino interacts with an entire atomic nucleus.

    “In this process, neutrinos do not scatter off the individual components of the atomic nuclei in the detector, but rather coherently with the entire nucleus. This significantly increases the probability of a very small but observable nuclear recoil,” explained the press release.

    The process can be compared to a ping-pong ball hitting a car; the recoil of the car, though small, is the observable effect. In this case, antineutrinos from the reactor scattered off germanium nuclei in the detectors.

    Over a measurement period of 119 days between 2023 and 2024, the team recorded an excess of 395±106 neutrino signals after subtracting background and interfering signals. The position of the detector receives a flux of more than 1013 (ten trillion) neutrinos per square centimeter per second from the reactor.

    “This value is in very good agreement with theoretical calculations, within the measurement uncertainty,” remarked the press release.

    “We have thus successfully confirmed the sensitivity of the CONUS+ experiment and its ability to detect antineutrino scattering from atomic nuclei,” added Dr. Christian Buck, an author of the study.

    Neutrino detection requires large experiments

    Neutrinos are elementary particles that interact weakly with matter, and their detection has typically required very large experiments. The CEvNS effect was theorized in 1974 and first observed by the COHERENT experiment at a particle accelerator in 2017. The CONUS+ result is the first observation of the effect from a reactor at these low energies.

    The CEvNS technique may have future applications. Dr. Buck noted the potential to develop small, mobile neutrino detectors to monitor reactor heat output or isotope concentration.

    The measurement also provides data for testing the Standard Model of particle physics. According to the authors, the CONUS+ measurements have a reduced dependence on nuclear physics aspects compared to other experiments, improving the sensitivity to physics beyond the Standard Model.

    “The techniques and methods used in CONUS+ have excellent potential for fundamental new discoveries,” concluded Professor Manfred Lindner, the project’s initiator.

    “The groundbreaking CONUS+ results could therefore mark the starting point for a new field in neutrino research.”

    The experiment was equipped with improved and larger detectors in autumn 2024, with the aim of increasing measurement accuracy.

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  • Hajj policy 2026: Pakistan reduces private sector quota – ARY News

    1. Hajj policy 2026: Pakistan reduces private sector quota  ARY News
    2. Cabinet approves Hajj 2026, National AI policies  The Express Tribune
    3. Hajj packages likely in August amid pressure to meet Saudi deadlines  Dhaka Tribune
    4. Govt to Start Collecting Hajj 2026 Dues From Next Week  ProPakistani
    5. Hajj 2026: Cabinet approves new policy, what will be expected cost?  Aaj English TV

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  • Alysanne Blackwood Cast As Annie Shapero Joins

    Alysanne Blackwood Cast As Annie Shapero Joins

    EXCLUSIVE: Internet speculation has been rife in recent weeks over who will star as one of George R.R. Martin’s most fierce female fighters in the upcoming House of the Dragon Season 3.

    We can reveal that Australian-British actor Annie Shapero is playing Alysanne Blackwood in the next season, which started shooting several weeks back in the UK.

    Known as Black Aly, Blackwood plays a key role in Martin’s Fire and Blood novel. The fearless warrior is Lord Benjicot Blackwood’s aunt and fights for Queen Rhaenyra Targaryen (Emma D’Arcy) in the Dance of the Dragons before marrying Lord Cregan Stark, who is played by Tom Taylor. She becomes a legendary figure in House Stark lore and her storyline looks likely to be told in House of the Dragon Season 3.

    Blackwood is not a series regular but we are told she will appear in five of the eight episodes of Season 3, which comes out next year.

    Shapero joins an array of newcomers to HBOs hit franchise including James Norton, who plays Alicent (Olivia Cooke)’s cousin Ormund Hightower, Tommy Flanagan as Lord Roderick Dustin and Dan Fogler as Ser Torrhen Manderly.

    Shapero played American journalist Jenny in Red Skies, the Series Mania Award-winning Israeli TV show about the Second Intifada co-created by Euphoria’s Ron Leshem. She has also been in FX pilot The Border, Jacob Elordi-starrer The Narrow Road to the Deep North and has been cast in upcoming Australian horror pic Saccharine opposite Midori Francis.

    House of the Dragon has been a huge hit for HBO. Starring Matt Smith, D’Arcy and Cooke, the third season will pick up with a major escalation in the Dance of the Dragons, the war that rips apart the powerful Targaryen dynasty.

    HBO declined comment on Shapero’s casting.

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  • Shrinking Season 3, Emmy Nom and Marvel Future

    Shrinking Season 3, Emmy Nom and Marvel Future

    “Is it just me or does he look like the president of the United States?” That’s what Jessica Williams whispered to the producers of “Shrinking” while she was watching from behind the camera as her co-star Harrison Ford acted in a scene that took place at a formal event. “And they were like, ‘No, that’s just what Harrison Ford looks like in a tuxedo, and it’s insane.’”

    On this Monday morning, I’m witnessing the same phenomenon as Ford sits in a photo studio, his black bow tie hanging loose as he holds a paper cup of black coffee as if it were a tumbler of whiskey. His face, still impossibly handsome at 83, conjures up dozens of movie heroes, from Jack Ryan to Indiana Jones, Han Solo to Rick Deckard, to, yes, multiple presidents of the United States.

    Now, after amassing a box office haul of more than $12 billion as one of the highest-grossing movie stars in history, Ford is earning a reputation as a small-screen standout thanks to his performances in Taylor Sheridan’s Yellowstone prequel “1923” and “Shrinking,” where he plays Dr. Paul Rhoades, the eccentric senior member of a psychotherapy practice in Pasadena, who has been diagnosed with Parkinson’s.

    Peggy Sirota for Variety

    In typical fashion, Ford, who just received his first Emmy nomination and some of the best reviews of his career for “Shrinking,” downplays the difficulty of the performance.

    “I say the words, do the work, rinse and repeat,” he says with his trademark dry humor.

    It’s grueling work, but Ford has enjoyed one luxury that being part of a streaming series provides. “We get more time to develop a character over a season than one normally does in a film,” he says.

    Of course, Ford has revisited several of his most famous parts throughout his career, returning to play Han Solo nearly 40 years after the first “Star Wars” movie, as well as Deckard in two “Blade Runner” movies 35 years apart, and suiting up as Indiana Jones five times across four decades. He didn’t come back to those roles for the payday; Ford wanted to examine the consequences of his characters’ actions as they aged.

    So perhaps it shouldn’t be a surprise that, at a moment when many of his peers are busy collecting lifetime achievement awards, Ford continues to challenge himself artistically. In “Shrinking,” he seems looser and more vulnerable than he’s ever been.

    “He could do an absolutely amazing job caring way less,” his co-star Jason Segel says. “This guy knows his moves, but he’s not content to do his moves. He’s creating a character from scratch.” Segel points to the Season 1 episode where Ford delivers an all-out slapstick performance when Paul shows up to a party high on weed gummies; it’s evidence of Ford’s willingness to go places he’s never been. “I don’t think anybody knew that Harrison could do that,” Segel says. “There was a moment during that episode when he got a giant laugh from the crew, and he walked by me and he whispered in my ear, ‘I knew I was fucking funny.’”

    Jason Segel and Harrison Ford on “Shrinking”
    Beth Dubber/Apple Tv +

    Segel adds: “I’ve never forgotten it, because it affirmed this idea that I had, that we all have these parts of ourselves that we believe are unknown to others, and we want them to be known. I feel like, as a performer, [comedy] is this little corner of the room that Harrison hadn’t gotten to show yet.”

    The way Ford creates characters is unique, says J.J. Abrams, who worked with him on two “Star Wars” movies, as well as “Morning Glory” and “Regarding Henry.” “Harrison meets them between who he is and who the character is,” Abrams says. “It’s like he bends the will of the character to be the thing that he brings to it in a way that I don’t see other actors do quite so much.”

    As he sits across from me, Ford glances at his phone and smiles. He just got a text with the gag reel from “Shrinking,” which wrapped filming Season 3 two weeks ago. When he presses play by accident, the audio from the clip kicks in, and the room fills with the sound of his castmates cracking each other up.

    Ford comes around the table to show me: There’s a clip of him on the “Shrinking” set bursting through the door to the “Indiana Jones” theme. I don’t have to look over my shoulder to know that he’s smiling, delighted by the memory of being part of this particular ensemble.

    How does it feel to get your first Emmy nomination for “Shrinking”?

    I don’t think there’s anything competitive about creativity, and I don’t understand the need to compare and contrast one person’s work to another’s. If you like it, you like it; if you don’t like it, look at something else.

    I’m grateful, but I would have done what I did — and I’ll do what I’m doing — regardless of whether it’s deemed worthy of mention or not. Because it’s what I do. It’s what I love doing. I love telling stories. I love pretending to be somebody else.

    In the Season 2 finale, Paul delivers a speech about how grateful he is for the family that he and his colleagues have created. Has life imitated art in terms of how you feel about working with this ensemble?

    I don’t know whether life is imitating art or art is imitating life, and I don’t care. [He laughs.] But it is true that in this case, these people do have warm feelings for each other. You’re really living with these people, as well as working with them, and that familiarity either breeds contempt or not — and these people have been wisely chosen to be not contemptible.

    How did you approach playing Paul?

    It’s an additive process. One brick goes on another brick; pretty soon you have a house. But if you don’t have a firm foundation, then the whole thing is askew. You’re trying to find that place where you can use your honest experience to represent the ideas and the relationships and the elements of the personality of the character. That’s like being an item in a recipe. You’ve got to know what your job is here — am I the onion or am I the tomato?

    Peggy Sirota for Variety

    You’ve said every character you’ve played has comedic elements to it.

    I think there’s humor in everything. Sometimes it’s just God’s joke. A character that has a sense of humor is a lot more attractive than a character that doesn’t. If somebody doesn’t have a sense of humor, I don’t want to hang out with them. So I try and bring some form of a sense of humor to whatever character I play.

    What are you adding to Paul for Season 3?

    What continues to be added is fuel to the fire, and the fire in his case, right now, is in the Parkinson’s department. He knows he’s in decline. He knows that he’s facing even more difficult physical circumstances than he finds himself in at the moment. He’s entering a phase of his life which is a mystery, but he has a partner in the character that Wendie Malick plays. She’s going on the journey with him, and so are all of his other colleagues.

    Part of what I love about what I’m doing is that I don’t know what the writers are going to come up with. And normally it’s not something I would do, is take a shot like that. But I did it on “1923” and I did it on this. And it’s kind of fun to say, “Okay, I’ll figure out how to do it, even if I don’t know what it is.”

    What made you do that? For much of your career, you have developed the stories you star in, but you’ve never had much desire to be a screenwriter or producer, so why did you now decide to say, “Alright, just take me there.”

    Well, they don’t take me there. They show me where they want me to go, and then I get myself there. Sometimes I tell them, “I don’t think that works,” but not with any degree of frequency. The way they write for this character is pretty specific, but it’s not me.

    There are writers on the set, which there are not usually on a movie, unless you’re working for a writer-director. They’re there to defend their stuff from whatever threat may come, either from the director or from the actors. I call them the “Poetry Police.”

    Why that name?

    Because they’re there to protect the poetry. Comedy is delicate. You can fuck up a joke by using one word wrong in a 12-word sentence. I kind of like when it doesn’t fit my mouth and I have to make it work. It’s fun.

    Michael J. Fox joins the cast in Season 3. Was he helpful to talk to as Paul continues to deal with his illness?

    It’s been essential. Michael’s courage, his fortitude and his grace, more than anything else, is on full display. He’s very smart, very brave, noble, generous, passionate guy, and an example to all of us, whether we’re facing Parkinson’s or not. You cannot help but recognize how amazing it is to have such grace.

    So he gives me both a physical representation of the disease to inform myself with, but more than that, he allows me to believe that Paul could believe that he could be adequate to the challenge. The truth is that we can’t be fucking around with this just to make a joke or anything. Parkinson’s is not funny. And I want to get it right. It’s necessary to be correct with what we do in respect of the challenge that Parkinson’s represents, and that we don’t use it for its entertainment value.

    Do you find parts of yourself sneaking into Paul?

    I do it on purpose, looking for what matches me and the character. When you’re doing a series like this, the writers do begin to write for you, and sometimes they write for you too much. You want to say, “Stop, guys, I did this already. We’ve done this. Let’s go back to where the story starts, and instead of something that’s become a kind of easy way of getting a laugh or an easy way of getting a point across, let’s look for another way to do it.”

    You can only say, “Do you want me to pull my pants down and make my ass clap,” so many times.

    One time.

    What’s the last time you were flipping channels and came across something you starred in and thought, “Might as well revisit this”?

    Yeah, it was actually “Witness.” I was flicking through, and I saw me and watched for a minute or two.

    How’d you look?

    Young.

    Ford with Kelly McGillis in “Witness”
    Photo 12/Alamy Stock Photo

    You were nominated for an Academy Award for that performance. What was it like to make “Witness”?

    The role was fantastic. I got to work with Peter Weir. What I loved about the movie was that we had a very, very short period of preproduction. Peter knew nothing of the Amish, so he went away to learn about the Amish, and I went away to research the police. And we came back together two weeks after that and discussed what we learned. And that was included in the rewrite. I love that kind of tension that we were under — we didn’t really have the script entirely figured out, so we left a couple of big holes in it when we started. I felt really good about the film we were making, and the film was quite a success.

    To the nomination, Peter and I were working on “The Mosquito Coast” at the time, so neither of us were able to be part of the ceremony. So it’s kind of like it never happened. We watched it on TV on the boat I was living on in Belize. It didn’t matter to me whether I won, but I was pleased that the performance was recognized.

    Ford with director Peter Weir in “Mosquito Coast”
    TCD/Prod.DB/Alamy Stock Photo

    Your first on-screen role was playing a bellboy in “Dead Heat on a Merry-Go-Round.” What do you remember about your debut?

    I was under contract to Columbia Pictures at the time for $150 a week and all the respect that that implies. I was called into the office of the head of the new talent program, and he told me that I had no future in the business. Which was OK. And then he asked me to get my hair cut like Elvis Presley. That I didn’t go along with.

    And he asked you not only to get your hair cut, but also to change your name.

    He thought that “Harrison Ford” was too pretentious a name for a young man.

    He might want to reevaluate that.

    I met him later, across a crowded dining room. He sent me a card on which he’d written, “I missed my guess.” I looked around, couldn’t remember which one he was, but then he nodded at me and smiled, and I thought, “Oh yeah, I know you.”

    What made you want to be an actor?

    I’d been to college, and I hadn’t made a success of my academic career. At the beginning of my junior year, I looked for something in the course catalog that would help me get my grade point average up, and I came across drama. The first line of the paragraph that described the course said, “You read and discuss plays,” and I thought, “I can do that.” I didn’t read all the description — typical of me in those days — because the last few lines described that the course also required you to be part of the school plays for that academic year. I hadn’t ever done anything like that before, so I was shocked by that part of it.

    But I quickly recognized that I loved telling stories. I liked dressing up and pretending to be somebody else. And the people that I met had a similar bent, people that I might have overlooked. They’re people that probably hadn’t been really seen before, for who they are, for what they were — and they were storytellers.

    Did it make you feel seen?

    No, it made me feel truly unseen. Because I was able to hide behind the character, and that was the first freedom I really felt.

    Let’s talk about “American Graffiti.” It’s a small role, but a breakout performance.

    A lot of actors came out of that show, and I thought it was remarkable the way George [Lucas] used music in that film; it was a rare use of contemporary music. That movie was fun to make. It was made very, very cheaply. I do remember I was almost fired for taking two doughnuts instead of my deserved one.

    That film was the beginning of a long friendship with George Lucas. What stood out when you first met him?

    I didn’t think he could speak. He never spoke. I remember there was an interview for the part that I was eventually given, and he was the only guy in the room that didn’t talk. I later realized he didn’t like to talk very much, but he did when necessary.

    You improvised Han Solo’s famous response, “I know,” after Leia tells him she loves him in “The Empire Strikes Back.” What’s the story behind the line?

    I was supposed to say, “I love you too,” and I thought that was a little un-Han Solo-ish. I thought it was a little banal. So I said no, and [director] Irvin Kershner agreed with me. George, when he saw it, was not so sure, and made me sit next to him at the screening of the film the first time we ran it for an audience. They laughed, but it was a good laugh, so we kept it in. Thank you, George.

    Ford on the set of “The Empire Strikes Back” with Mark Hamill, George Lucas and Carrie Fisher
    AJ Pics/Alamy Stock Photo

    When did you know that Han Solo would be a character that would become something special? Was it once you got to the second film or the third film?

    I didn’t really know whether there was going to be another film when we started, and because I didn’t know whether there would be another film — and because I only had the script from the first one to consider — I didn’t sign the sequel deal, which turned out to be to all of our advantage.

    You, Carrie Fisher and Mark Hamill had a singular experience because of those films. What comes to mind when you think of them?

    I had a special relationship with both of them. Carrie had a very inspired wit and very special manner. She’s also very smart, very funny. Both of them were dear friends — are dear friends.

    Ford with Jerry Ziesmer in “Apocalypse Now”
    TCD/Prod.DB/Alamy Stock Photo

    Another early role was working with Francis Ford Coppola on “Apocalypse Now.” What was that experience like?

    I played a character that I named myself. He wore his name proudly on his uniform. The name was L-U-C-A-S, Lucas. I played a small part, an American soldier who gives Captain Willard [Martin Sheen] the assignment to kill Colonel Kurtz [Marlon Brando]. I play a very nervous guy with a funny haircut. I went down to the Philippines and shot my part of it right after one of the “Star Wars” movies, and when George Lucas first saw the movie, he didn’t know the character was me, even though he was named Lucas. An Easter egg, I now understand it to be.

    You’re one of the few actors who has worked with Spielberg, Lucas and Coppola. What was it like to be making movies in Hollywood at that time?

    You’re talking about a very exciting time in the movie business. In the late ‘70s and through the ‘80s, there was this group of young filmmakers, all of them wildly independent, both in spirit and in mind, who wanted to make their own films their own way, and they all burst upon the scene at much the same time. I was very lucky to lump in with those guys because I was of a youthful age. But I never expected to be anything more than a character actor. I never wanted to be anything more than somebody that made a living as an actor.

    Mark Mainz/Getty Images for AFI

    You shared the screen with Sean Connery in “Last Crusade.” What was his style?

    I had the best time with him. He’s not the Billy Goat Gruff that everybody thinks he is — and neither am I. He asked me to play tennis with him, and I hadn’t played tennis much before. In fact, not at all. I was able to serve the ball, but I hit him in the back two times with a serve — much to his amusement.

    But when we got into the motorcycle with the sidecar, he really began to give me trouble; he thought he was more qualified to drive than I was. I think I proved him wrong.

    You’ve played Indiana Jones five times now. What has getting the chance to complete his journey with “Dial of Destiny” meant to you?

    Well, I wanted to see him as an older man facing the consequences of the life that he had lived. But I couldn’t imagine that we were going to end up doing five of them. I didn’t expect success. In the movie business, you always go in wanting to be successful, but you don’t always expect to be.

    I did expect the first film would be wildly successful. I read it very quickly, one time. I’d been asked by George Lucas to go and meet Steven Spielberg, who I didn’t know, and he sent me a script to read. I thought it was great. And then I went to meet Steven, we spent about an hour together and suddenly I had a job.

    Another character you revisited over the years was Rick Deckard in “Blade Runner.”

    That was an extraordinary experience. We shot for 50 nights in rain — most times, we were outside. It was sort of miserable to make, but it holds its own.

    Do you have a favorite cut of “Blade Runner”?

    I like any cut without the voice-over. When we first saw the film in script form, it had a narration. I felt strongly that the narration was not right for the film — I played a detective, and I really talked about the detective part of my job, but I didn’t appear to be doing it. So Ridley, the screenwriter, a producer and I spent three weeks at my dining room table taking the information that was in the voice-overs and making it part of the scene experience.

    And then at the end of the film, Warner Bros. said, “What the hell is going on here? I don’t understand this at all. Explain it.” And the voice-over came back. I did the voice-over about six times, and nobody was ever happy with it. So I was glad that the film was finally released without it, which I think encourages the audience to be present in the story.

    Ryan Gosling and Ford in “Blade Runner 2049”
    Everett Collection

    How did you feel about coming back to work with Ryan Gosling and Denis Villeneuve on “Blade Runner 2049”?

    I enjoyed the experience of making the second “Blade Runner” — to be fair, even more than I did the first one, because it wasn’t raining and it wasn’t night all the time.

    What about when you accidentally punched Ryan Gosling?

    [We were rehearsing a fight] and we got too close and I hit him. I apologized right away. What more could I do? Can’t take back a punch. Just take it. He’s a very handsome man. He’s still very handsome.

    It’s been 10 years since your plane accident. Helen Mirren said that she felt as if you approach things differently since then.

    Did it have an impact? I suppose it did. I’ve been through a couple of big accidents that took a while to heal from. This is not something dismissed lightly, but shit happens; it was a mechanical issue that was judged to be beyond my control. If I’d been at fault, I would have taken another direction. But I don’t think it informs my life on a day-to-day basis now that I’ve recovered sufficiently from the physical effects.

    Did it change you as an actor?

    No.

    There were moments in your career where you took on very different roles, such as the Russian submarine captain in “K-19: The Widowmaker.” Was it frustrating when the audience didn’t respond?

    No. I knew they weren’t going to like that one. [He cracks up.] I always used to think, “I’ll do one for me and one for them.”

    You shot an endorsement video for Kamala Harris. You don’t usually speak about politics directly. How do you feel about having made that video?

    Fine.

    Peggy Sirota for Variety

    Now that we’re six months into the Trump presidency, what do you think about where the country is?

    The pendulum doth swing in both directions, and it’s on a healthy swing to the right at the moment. And, as nature dictates, it will swing back.

    But currently the issue is not who we are, but that we’re not who we used to be because we’ve been purposefully disaggregated into serviceable political units. And that has caused the middle to become frayed and tenuous, and the middle is where we belong. Not because it’s banal and safe, but because it’s fair. Compromise is fair and honest.

    In politics and in life, you don’t always get what you want, but you get what you get and you don’t get upset. They teach us that in kindergarten, but they also teach you to fight for what you think is right.

    Now, because we’ve been disaggregated in this way, we’re having a hard time finding commonality. But if you look at the economy, you’ll figure out where the commonality is — it’s where it always was: Rich get richer, and poor get poorer. And that ain’t exactly right.

    Where do we go from here?

    You’re asking an unqualified person. So I don’t have that answer.

    You’ve said you’re open to the idea of working with your wife, Calista Flockhart. Do you guys have any ideas?

    If we get to work together, we’d want it to be someone else’s idea. That kind of casting might not be the best way to bring people into an imagined situation, because [audiences] may say, “Oh, I know they’re married; now I’m not even thinking about the movie anymore.”

    You appeared in “Captain America: Brave New World.” Has Kevin Feige convinced you to come back to Marvel again?

    Nope.

    Will you ever retire?

    No. That’s one of the things I thought was attractive about the job of an actor, was that they need old people, too, to play old people’s parts.


    Hair: Patricia Dehaney; Makeup: Alexa Coleman 

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  • Collaboration or collapse — Why Earth observation must be a global mission

    Collaboration or collapse — Why Earth observation must be a global mission

    Around the world, international borders are hardening. Nations are competing for resources, technology and even orbits. But in Vienna this June, a different vision took center stage. One where space is shared, data is open and no satellite orbits Earth on its own.

    At the European Space Agency’s (ESA) Living Planet Symposium 2025, the “Breaking Barriers” plenary presentation delivered the powerful message that international collaboration isn’t just idealism, it’s infrastructure. Without it, Earth science, climate resilience and disaster response as we know them would fall apart.

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  • Chinese Sub Discovers Deepest-ever Creatures 10 Km Undersea

    Chinese Sub Discovers Deepest-ever Creatures 10 Km Undersea

    A Chinese submersible has discovered thousands of worms and molluscs nearly 10 kilometres (six miles) below sea level in the Mariana Trench, the deepest colony of creatures ever observed, a study revealed on Wednesday.

    The Barron’s news department was not involved in the creation of the content above. This article was produced by AFP. For more information go to AFP.com.
    © Agence France-Presse

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