We may earn commission if you buy from a link. Just when experts thought they knew every moai on Rapa Nui, otherwise known as Easter Island, a dried-up lakebed kept them on their toes. These statues—largely made of a stone formed from volcanic ash and dust called tuff—pepper the island, with more than 1,000 already found and logged. “There have been no moai found in the dry bed or in what was previously a lake, so this is a first.” Created by the Rapu Nui people, moai have a mythical legend attached to them and have gained worldwide renown for their appearances. Some believe these moai were given special powers to walk across land and end up in their resting place. Whether or not the legend has legs, there are many theories regarding how these statues moved from building sites to various locations. Each one is unique, created by carvers to represent the characteristics of the person it resembled, often a chieftain or key leader. Even though experts thought they knew the locations of all of these moai homes, finding this new, small one in the lakebed proves some had remained a complete mystery. Tim Newcomb is a journalist based in the Pacific Northwest. He covers stadiums, sneakers, gear, infrastructure, and more for a variety of publications, including Popular Mechanics. Archaeology Students Dug Up a Mass Viking Grave Scientists Found the Oldest Tools in North America Experts Found a Lost City Hidden Under the Desert Messages Found on the Walls of Last Supper Site One Man Thinks He Found a Legendary Viking Burial A Man and His Daughter Discovered Ancient Rock Art

Researchers at UC San Francisco have identified a biological process that may explain why exercise sharpens thinking and memory. Their findings suggest that physical activity strengthens the brain's built in defense system, helping protect it from age related damage. As people grow older, the blood-brain barrier becomes more fragile. Over time, however, it can become leaky, allowing damaging compounds to enter brain tissue. Several years ago, the research team discovered that exercising mice produced higher levels of an enzyme called GPLD1 in their livers. GPLD1 appeared to rejuvenate the brain, but there was a mystery. The scientists found that GPLD1 influences another protein known as TNAP. When mice exercise, their livers release GPLD1 into the bloodstream. Researchers searched for tissues containing proteins that could serve as targets and suspected that some of these proteins might accumulate with age. Cells in the blood-brain barrier stood out because they carried several possible GPLD1 targets. Young mice genetically modified to produce excess TNAP in the blood-brain barrier showed memory and cognitive problems similar to those seen in older animals. "We were able to tap into this mechanism late in life, for the mice, and it still worked," said Gregor Bieri, PhD, a postdoctoral scholar in Villeda's lab and co-first author of the study. The findings suggest that developing medications capable of trimming proteins such as TNAP could offer a new strategy to restore the blood brain barrier, even after it has been weakened by aging. "We're uncovering biology that Alzheimer's research has largely overlooked," Villeda said. Materials provided by University of California - San Francisco. Note: Content may be edited for style and length. The “Most Effective” Treatment for Osteoarthritis May Be Less Helpful Than Thought Low Dose Skin Cancer Treatment Delivers Shockingly Better Results The Southern Indian Ocean Is Losing Salt at an “Astonishing” Rate Stay informed with ScienceDaily's free email newsletter, updated daily and weekly. Or view our many newsfeeds in your RSS reader: Keep up to date with the latest news from ScienceDaily via social networks: Tell us what you think of ScienceDaily -- we welcome both positive and negative comments.

The most remarkable individual discovered in the pit was a man whose height, at 6 feet 5 inches, was so far above average for his time that he would have been considered a giant. “Before we uncovered the first remains, our best find was a 1960s Smarties lid,” said archaeology undergraduate student Olivia Courtney in a statement. “I had never encountered human remains on a dig, and I was struck by how close yet distant these people felt. Around 874, the Viking Great Army sacked the town, and Cambridgeshire was subsequently incorporated into a Viking-ruled kingdom of East Anglia. The burial pit was probably a result of that conflict, given that all the remains in it were those of young men. The mass grave was a mix of complete and dismembered remains, ranging from skulls without clear accompanying bodies, a stack of legs, and four complete skeletons. Some of the remains were even found in positions suggesting that they had been tied together. Experts believe the young men were tossed into the pit without ceremony, likely after a battle or a mass execution. A one-inch-diameter hole in his skull points to a trepanation procedure, which was believed at the time to relieve migraines and seizures. “The individual may have had a tumor that affected their pituitary gland and caused an excess of growth hormones,” Trish Biers, curator of the Duckworth Collections at the university, said in a statement. Some of the men had traces of combat injuries, including one who had chop marks on his jaw, indicating that he was beheaded. The way that parts were tossed haphazardly into the pit, including ribs, a pelvis, and legs stacked together on top of corpses, suggested that the burial followed some sort of mass execution. “Those buried could have been recipients of corporal punishment, and that may be connected to Wandlebury as a sacred or well-known meeting place,” said the university's Oscar Aldred. “It may be that some of the disarticulated body parts had previously been displayed as trophies and were then gathered up and interred with the executed or otherwise slaughtered individuals.” However, apart from signs of beheading, there isn't much evidence that the body parts were chopped up. “We suspect the pit may relate to these conflicts.” A Cambridge team will go to work on bone analysis, including ancient DNA and isotopic work, to investigate health, kinship, and ancestral links. The team may also attempt “refitting” to see if they can piece the remains back together to get a more accurate count of buried individuals. “I would never have expected to find something like this on a student training dig,” said Grace Grandfield, a Cambridge undergraduate, of the literally giant discovery. “It was a shocking contrast to the peaceful site of Wandlebury.” Tim Newcomb is a journalist based in the Pacific Northwest. He covers stadiums, sneakers, gear, infrastructure, and more for a variety of publications, including Popular Mechanics.

You are using a browser version with limited support for CSS. Ukrainian soldiers test drones in Donetsk, Febuary 2025.Credit: Serhii Mykhalchuk/Global Images Ukraine via Getty At their two-day summit in June 2025, all but one of the 32 North Atlantic Treaty Organization (NATO) member countries agreed to spend 5% of gross domestic product (GDP) on defence and security by 2035, in response to “profound security threats and challenges” — chiefly perceived threats from Russia and from terrorism. If achieved, this would be an enormous escalation in spending. But nations have considerable leeway to decide what falls under this umbrella, which can include research and development (R&D) funding. Spain, for example, which opted out of the 5% target, has called for a broader view of defence spending, to encompass areas such as quantum computing. What impact, if any, will defence-spending pledges have on research budgets? In the Organisation for Economic Co-operation and Development (OECD) countries, public R&D spending on health declined by 11.5% from 2020 to 2024, while spending on defence R&D rose by 17%4. Government spending in the OECD on ‘general advancement of knowledge' has also started to decline. Nature's careers team spoke to more than ten researchers working on science, peace and defence. Evidence suggests that admitting more international graduate students leads to economic benefits, yet Canada, the United States, the United Kingdom and Australia are among those countries making it harder for international students to secure visas. “There's been a rise of nationalism, and scientific cooperation has been influenced by that,” says Caroline Wagner, a public-policy researcher at Ohio State University in Columbus. Nevia Vera, an international-relations researcher at the National University of the Center of Buenos Aires Province in Tandil, Argentina, dates this trend to 2018, when the United States launched its China Initiative to counter potential espionage in US laboratories and businesses. Sino–US co-authored papers in the main Web of Science databases dropped by more than 10% between 2018 and 2024, according to Li Tang, a science-policy researcher at Fudan University in Shanghai, China. But the collaborations haven't ended entirely, which echoes previous ups and downs in international research. In 1984, Bill Foster started working as a physicist at the Fermi National Accelerator Laboratory near Chicago, Illinois. Even during the cold war, Foster says, there were Russian physicists working well alongside US ones — even though “you always knew that there was a KGB person”, he adds. A NATO summit with Ukrainian leader Volodymyr Zelenskyy in the Hague, Netherlands, June 2025.Credit: Emmi Korhonen/Sipa US/Alamy Live News He argues that this “will simultaneously kick the legs out from under Russian President Vladimir Putin's war effort — to lose some of the best and brightest” Russians — and “do something that will be of permanent value to the United States”. Sylvia Schwaag Serger, an economic historian at Lund University in Sweden, thinks that it would take years, if not decades, to reverse the overall decline in international research collaborations. But she also speculates that international research career moves could lose some of their lustre in the longer term. “Whereas before, international experience often was generally considered positive,” she notices that in some countries, “researchers are reconsidering whether it's actually helping their career”, she says. Although overall collaboration between scientists of different nations might decrease, some expect this to be more of a splintering effect, with researchers collaborating increasingly within regional blocs or geopolitical alliances. For instance, while their country's relationship with the United States has cooled in the past few years, Chinese researchers have increased their collaborations with colleagues in Africa, Asia and Latin America. Although the geopolitical situation is more complex now than during the cold war, scientists in many nations could again feel pressed to align with one set of countries or another. A report by United Nations secretary-general António Guterres details how the R&D benefits of military spending tend to pool in a few countries6, disadvantaging low-income nations where the military spends little on R&D. “Technology advances so quickly that countries cannot catch up” to scientific superpowers such as the United States, the European Union and China, Vera thinks. Some AI researchers have warned that this type of technological–military competition could spill over into conflict7. US brain drain: the scientists seeking jobs abroad amid Trump's assault on research US brain drain: the scientists seeking jobs abroad amid Trump's assault on research Subscribe to Nature Briefing: Careers, an unmissable free weekly round-up of help and advice for working scientists. The Security We Need: Rebalancing Military Spending for a Sustainable and Peaceful Future (UN, 2025). Pavel, B. et al. How Artificial General Intelligence Could Affect the Rise and Fall of Nations (RAND, 2025). RFK Jr cancelled mRNA research — but the US military is still funding it AI weapons: Russia's war in Ukraine shows why the world must enact a ban ‘Armed groups entered the lab': Sudan's researchers flee violent military conflict US repeals key ‘endangerment finding' that climate change is a public threat The funding system needs fixing — but it's not a ‘waste of time and money' Science journalism on the ropes worldwide as US aid cuts bite The funding system needs fixing — but it's not a ‘waste of time and money' Umeå University, Sweden, is inviting applications for two two-year Postdoctoral Scholarships focused on advancing our insight of marine biology LSMU seeks four Group Leaders in Kaunas-Kiel Microbiome & Precision Medicine Center to lead independent research groups with strong support. RFK Jr cancelled mRNA research — but the US military is still funding it AI weapons: Russia's war in Ukraine shows why the world must enact a ban ‘Armed groups entered the lab': Sudan's researchers flee violent military conflict An essential round-up of science news, opinion and analysis, delivered to your inbox every weekday. Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

The physics behind it is more complex than you'd think The reason we slip and slide on ice—a phenomenon central to figure skating, curling and other Winter Olympic events—is a centuries-old physics mystery that may have finally been cracked By Kendra Pierre-Louis, Sushmita Pathak, Fonda Mwangi, Marta Hill & Alex Sugiura Kendra Pierre-Louis: So we're out here today in lower Manhattan ice-skating. There are lots of kids skating around, dudes in hockey skates, and I'm here getting my inner Michelle Kwan on. If you're enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today. And whenever I go skating I can't help but think about the Winter Olympics, like the ones that are happening right now in Italy. [CLIP:NBC Olympics commentator Sloane Martin discusses a mixed doubles curling competition on February 6: “Welcome inside the Cortina Curling Olympic Stadium. Pierre-Louis: And watching the Olympics I started to realize that if you really think about it, so many of the Winter Olympic sports are just about controlled slipping on ice, like bobsledding, the luge, curling. And yet scientists still don't really know why ice is slippery. But scientists mostly agree that those theories aren't the full picture. The slipperiness of ice is actually still a mystery. Paulina Rowińska: It's such a simple question that should have been answered centuries ago. But turns out all the stuff we learned in school, it's not fully correct, like with many, many other things. There are at least three long-standing scientific theories that try to explain what makes ice slippery. It comes from a Scottish engineer named James Thomson, the older brother of famous physicist Lord Kelvin. And it involves the pressure that an object exerts on ice. But then pressure changes this—changes the properties of water. She's a science journalist at Quanta Magazine, and she wrote an article in December that dug into the competing theories about why ice is slippery. Rowińska: It's freezing out there, but we are getting closer to the melting temperature, so we might be melting, like, the surface layer of ice. Pierre-Louis: Thomson came to this idea—that pressure on the ice basically creates a liquid layer—by studying glaciers, says Martin Müser. Martin is a theoretical physicist in the Department of Materials Science at Saarland University. Martin Müser: Glaciers, there is a heavy, heavy load that sits on the points of contact, and we know that when we are a little below the freezing point and we squeeze on ice, it becomes liquid. So [Thomson] argued that ice liquefies because of the pressure. Pierre-Louis: But there's a problem with the pressure hypothesis—a big one, according to Daniel Bonn, a professor of physics at the University of Amsterdam. Daniel Bonn: You would need 10 elephants resting on a single skate in order to get a decent amount of melting due to the pressure. Pierre-Louis: Given that humans do not weigh as much as 10 elephants and we still manage to slip on ice, pressure alone does not seem to be why ice is slippery. So another theory emerged—and this one is especially popular among tribologists, scientists who study friction, lubrication and wear between moving surfaces. Müser: When you talk to a tribologist, in particular in the field of ice friction, they would come up with an explanation that was proposed by Frank Bowden. Daniel's team did experiments where they measured the friction on ice over a very large temperature range, from -100 degrees C, or -148 degrees F, to the freezing point of water. Bonn: And then all kinds of interesting things happen. At very low temperatures—you probably don't want to be ice-skating anyways at -100 [degrees C], but it's actually impossible to ice-skate because the friction's very high. Pierre-Louis: Daniel and his colleagues found that the friction decreased until a temperature of roughly -7 degrees C, which is about 20 degrees F. But when they went closer to the melting point of ice the friction went up again. Bonn: And this is something that you've experienced if you do ice-skating: if the ice is too warm, it actually becomes mushy and you leave traces in the ice, which—this is what we call plowing friction. Pierre-Louis: These experiments reinforced for Daniel that the answer to what makes ice slippery lies beyond friction. Sure, frictional heating might be responsible for melting the ice in our wake—that is, melting the ice behind us—but as we all know ice is slippery before you've even stepped on it, before friction has even occurred. Bonn: As you know it's difficult to remain standing on the ice, even at zero speed, yeah? Pierre-Louis: So if it's not pressure or friction, could ice be slippery because there's already a pre-melted layer of water on top? Paulina says that's what a third hypothesis suggests. Rowińska: So this has to do with how ice is structured. So we have water molecules, but they are structured in a very ordered way, so they form bonds, and they—it's kind of like a nice lattice. In a liquid, like liquid water, the molecules are kind of moving freely, and the structure is much looser. It was first proposed by English chemist and physicist Michael Faraday, Martin explains. Müser: He basically saw that from putting two ice cubes together, and when they were fresh they would slide, but if he would wait a bit longer time, they were stuck. So a single, basically, interface would form, and he said, “Well, they are slippery because there must be a very thin lubricating layer.” And in the last 30, 40 years there was a lot of experimental effort proving the existence of this layer. And a very thin layer, even if the viscosity of the liquid is as small as that of water, would still give quite noticeable friction. Two, friction heats the ice, causing us to slip. And three, ice has a thin layer of pre-melted water that, again, causes us to slip. On the one hand all of these theories have flaws. On the other hand computer simulations run by a group of European scientists a few years ago suggest that it might not be any one of these theories but all of them together. You might be asking yourself, “Why does any of this matter? Does it really matter if we know why?” For Daniel, who is Dutch, it's actually a matter of national pride. Pierre-Louis: But it also matters if you're not Dutch, he says. And so things that are extremely slippery are extremely interesting because friction is responsible for an estimated 25 percent of the world energy consumption, yeah? And so the friction on ice is roughly an order of magnitude lower than friction on all other materials. If scientists could figure out why, they might be able to mimic its behavior for use in other applications, like train tracks or motorized energy. But let's come back to the eternal question of why ice is slippery. Rowińska: So a new hypothesis came out last year in a paper, and the idea is: it's not really about melting. It's about, almost, like, a mechanical moving of atoms and molecules on the surface. So you know how when we step on ice, we kind of destroy the structure because there are some almost, like, electrostatic attraction—it's not exactly electrostatic, but it's, like, an attraction between molecules of our shoe and of ice. Pierre-Louis: And it was Martin's team that published this theory in the journal Physical Review Letters. He said that to understand the idea imagine stacking a bunch of egg cartons. Müser: You put them perfectly in parallel, of course they're going to stick. And very much to my surprise did I see that if I put two misaligned ice crystals in contact, even if they go extremely, extremely close to absolute zero, would I see amorphization right away. Pierre-Louis: In other words instead of the crystalline structure one might expect ice to have, the surface structure starts to fall apart a little bit and become more disordered. Müser: So we saw this very fast amorphization at 10 kelvin, and then we said, “Hey, now let's look what happens at -10 degrees C,” or in Fahrenheit—I don't know, roughly, it's about 10 [degrees] F or 12 [degrees] F. And we did see that the water also liquefied. Pierre-Louis: To understand what Martin is getting at it helps to understand the difference between an ordered and a disordered solid. An ordered solid is when all of the atoms are arranged in a precise, repeating 3D structure—think about a phalanx of Roman soldiers all lined up. Those structures can handle a lot of stress. The structures can be more random, less repeating. When water becomes ice the outer layers are disordered; their structure looks like an open honeycomb. When we step on that surface with, say, a sneaker or ice skate we break up that structure, introducing stress into the system. Müser: Sometimes people ask me if people accept the answer and I always say, “I hope not,” because any [Laughs], any good, nontrivial, correct scientific answer is met by a lot of skepticism. Pierre-Louis: So the next time you go ice skating or wipe out on an icy sidewalk you'll at least have a clearer idea of why it might have happened. Tune in on Monday for our weekly science news roundup. Science Quickly is produced by me, Kendra Pierre-Louis, along with Fonda Mwangi, Sushmita Pathak and Jeff DelViscio. Shayna Posses and Aaron Shattuck fact-check our show. Our theme music was composed by Dominic Smith. Subscribe to Scientific American for more up-to-date and in-depth science news. She has worked for Gimlet, Bloomberg News and Popular Science. She previously worked at NPR and was a regular contributor to The World from PRX and The Christian Science Monitor. Fonda Mwangi is an award-winning multimedia editor at Scientific American and producer of Science Quickly. She previously worked at Axios, the Recount and WTOP News. Marta Hill is the spring 2026 multimedia intern at Scientific American. Her work has appeared in Smithsonian Magazine, The Transmitter, Eos and elsewhere. He has worked on projects for Bloomberg, Axios, Crooked Media and Spotify, among others. If you enjoyed this article, I'd like to ask for your support. Scientific American has served as an advocate for science and industry for 180 years, and right now may be the most critical moment in that two-century history. I hope it does that for you, too. If you subscribe to Scientific American, you help ensure that our coverage is centered on meaningful research and discovery; that we have the resources to report on the decisions that threaten labs across the U.S.; and that we support both budding and working scientists at a time when the value of science itself too often goes unrecognized. In return, you get essential news, captivating podcasts, brilliant infographics, can't-miss newsletters, must-watch videos, challenging games, and the science world's best writing and reporting. There has never been a more important time for us to stand up and show why science matters. I hope you'll support us in that mission. 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You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. There is a need to quantify the benefits and harms of colorectal cancer (CRC) screening using primary colonoscopy or fecal immunochemical testing (FIT) compared with usual care with no screening. Guidelines recommend screening in individuals aged 50–75 years using colonoscopy or FIT, and many screening programs use one-sample biennial FIT. Here we compare incidence of diagnosed CRCs and gastrointestinal and cardiovascular events between screening and usual care during the diagnostic phase of the SCREESCO trial. A randomized block method (no masking) assigned 278,280 individuals aged 60 years to once-only colonoscopy, 2 rounds of two-stool FIT with a low cutoff (10 μg g−1 feces) or usual care (control group) in a ratio of 1:6 for colonoscopy versus control and 1:2 for FIT versus control. In the analysis, 31,113 individuals were in the primary colonoscopy arm and 60,267 were in the FIT arm, and there were 186,671 primary colonoscopy controls, of whom 120,521 were also controls for comparison with the FIT arm. After a median follow-up of 4.8 years, the incidence rate of CRC was 107.9 in the colonoscopy arm and 99.9 in controls per 100,000 person-years (incidence rate ratio (IRR): 1.08, 95% confidence interval (CI): 0.91–1.28) and 96.0 in the FIT arm and 103.9 in controls (IRR: 0.92, 95% CI: 0.81–1.05). Rates of stage I–II CRC were higher in the colonoscopy arm (IRR: 1.38, 95% CI: 1.09–1.74) and in the FIT arm (IRR: 1.19, 95% CI: 0.99–1.43) versus controls. Rates of cardiovascular and gastrointestinal events were slightly higher in the intervention arms during the first year and were subsequently more similar to controls. Our findings of an increase in CRC detection implies a benefit of screening while the increase in adverse events suggests some initial harm. To inform health policy in early detection and removal of CRC and precancerous lesions, there is a need to quantify the benefits and harms from CRC screening. The American College of Gastroenterology and the European Society of Gastrointestinal Endoscopy recommend CRC screening in individuals aged 50–75 years by colonoscopy or FIT, where colonoscopy is performed only in those with increased risk indicated by a higher fecal hemoglobin level1,2. Several countries have implemented FIT-based organized screening often with a similar age range and biennial testing but with cutoffs for a positive test ranging between 8.5 μg hemoglobin per g feces and 120 μg hemoglobin per g feces3,4. In Sweden, screening by use of a one-sample biennial FIT has been ongoing in the Stockholm-Gotland region since 2015 in individuals aged 60–69 years and since 2020 in individuals aged 60–74 years, with a cutoff of 40 μg hemoglobin per g feces for women and 80 μg hemoglobin per g feces for men5,6. A national biennial FIT-based screening program with the same cutoffs and age range began its rollout in 2021 with full implementation planned for 2026. There are several trials of colonoscopy screening, but few have examined FIT compared to usual care7,8,9,10,11,12,13,14. The Spanish randomized controlled trial (RCT) COLONPREV recently found similar CRC incidence in the FIT arm and the primary colonoscopy arm at 10 years but did not include any control arm15. Colonoscopy may cause serious adverse events, although the reported rates have been low8,16. There is also limited evidence from RCTs on the impact of screening using primary colonoscopy and FIT on CRC incidence and adverse events compared to usual care. The RCT SCREESCO trial (Screening of Swedish Colons; ClinicalTrials.gov: NCT02078804) in Sweden includes a primary colonoscopy screening arm, two rounds of a two-stool FIT screening arm with an unusually low cutoff (10 μg g−1 feces) and a control arm with individuals not invited to screening but following usual care17. By adding extensive information from Swedish healthcare registers, we now report a comparison of the diagnostic yield, in terms of total CRCs diagnosed, and of adverse events occurring in all participants in the trial—screening versus control arm—during the diagnostic phase (from 2014 to 2020, when all interventions occurred) on an intention-to-screen basis. The aim of the present study was to assess if the randomization has resulted in the three arms being similar in terms of baseline demographic variables and medical history and to assess if the screening approaches resulted in a higher rate of diagnosis of CRC during the diagnostic phase, especially stage I–II CRC, compared to usual care. It also aims to assess potential harms of screening approaches in terms of an increased rate of cardiovascular and gastrointestinal events in general and short-term all-cause mortality during the diagnostic phase. The present analysis extends previous trial information, which was limited to screen-detected CRCs and adverse events in screening colonoscopies17. Between 11 February 2014 and 1 March 2016, 201,000 individuals turning 60 or aged 60 were randomized to one of three arms: primary colonoscopy, two rounds of two-stool FIT (FIT×2) or controls. Because of low participation in the primary colonoscopy arm, an additional 77,280 individuals were randomized to primary colonoscopy or control between 30 May 2017 and 25 May 2018. A total of 278,280 individuals were randomized. Due to administrative lag in registration, 159 individuals who died and 70 individuals with prevalent CRC before the date of randomization were identified only after randomization and were excluded. Another two control individuals were excluded because they were not identifiable in any register (Fig. There were 278,051 unique individuals included in the final analyses, 31,113 in the primary colonoscopy arm, 60,267 in the FIT×2 arm and 186,671 primary colonoscopy controls (randomized 2014–2018), of whom 120,521 were also controls for comparison with the FIT×2 arm (that is, FIT×2 controls, randomized in 2014–2016). Number of randomized, excluded and included individuals. Most individuals (92%) did not have any prior gastrointestinal or cardiovascular event. Men (35%) participated slightly more often than women (33%) in the primary colonoscopy arm, whereas more women (59%) participated in the FIT×2 arm than men (52%) (Supplementary Table 1). Individuals who did not participate in colonoscopy in the primary colonoscopy arm or in fecal testing in the FIT×2 arm (that is, non-participants) had lower educational level, originated more often from another country and exhibited slightly more comorbidity. The incidence rate of diagnosed CRCs during the diagnostic phase was 107.9 per 100,000 person-years (160 individuals/148,337 person-years) in the primary colonoscopy arm and 99.9 (889 individuals/889,774 person-years) in the control arm (incidence rate ratio (IRR): 1.08, 95% confidence interval (CI): 0.91–1.28) and 96.0 (330 individuals/343,703 person-years) in the FIT×2 arm and 103.9 (715 individuals/687,048 person-years) in the FIT×2 control arm (IRR: 0.92, 95% CI: 0.81–1.05) (Table 2). Figure 2 shows that the incidence rates and IRRs peaked around year one after randomization in both the primary colonoscopy arm and the FIT×2 arm as compared to respective control arms. Yearly incidence rate (per 100,000 person-years) and IRRs of CRCs in total and by stage in the primary colonoscopy arm and FIT×2 arm as compared to respective control arms (reference). CRCs include both screen detected and those diagnosed outside of SCREESCO in a usual care setting. The incidence rate of diagnosed stage I–II CRCs in the primary colonoscopy arm was 58.7 per 100,000 person-years compared to 42.5 in the control arm (IRR: 1.38, 95% CI: 1.09–1.74) (Table 2 and Fig. Cumulative incidence proportions were higher in the intervention arms compared to controls throughout most of the study period (Extended Data Fig. The rate of diagnosed stage III–IV CRCs was somewhat lower in the primary colonoscopy arm than in the control arm (IRR: 0.86, 95% CI: 0.67–1.11) and lower in the FIT×2 arm than in the FIT×2 control arm (IRR: 0.71, 95% CI: 0.58–0.86) (Table 2 and Fig. Cumulative incidence proportions in the intervention arms were initially similar to those in controls but became lower than controls after around 4 years after randomization (Extended Data Fig. Of CRCs diagnosed in the primary colonoscopy arm and in the FIT×2 arm, 32% and 38%, respectively, were screen detected (Table 2). Few CRCs were diagnosed outside of the trial in individuals who had undergone a screening colonoscopy in the primary colonoscopy arm and in the FIT×2 arm (nine (0.03%) and eight (0.01%) individuals, respectively) during the diagnostic phase. Two of the 170 previously reported CRCs detected within the trial were, after a review of medical charts, deemed not to be CRC. Stage disagreed in three (1.7%) and was missing in nine (5.1%) of these CRCs (Supplementary Table 2). Compared to women, men had a higher rate of CRC in the FIT×2 arm (IRR men / IRR women: 1.29, 95% CI: 0.99–1.67) and especially of stage III–IV CRC in both intervention arms (Supplementary Table 3). Incidence rates of gastrointestinal or cardiovascular events were slightly higher in the intervention arms compared to the control arms during the first year of follow-up but were subsequently more similar (Fig. At the end of follow-up, the incidence rate of cardiovascular events was similar in all arms—that is, 1,475.8 per 100,000 person-years in the primary colonoscopy arm and 1,475.8 per 100,000 person-years in the control arm (IRR: 1.00, 95% CI: 0.96–1.05), although the rate of venous thromboembolism was 60.1 in the FIT×2 arm compared to 43.3 in corresponding controls (IRR: 1.39, 95% CI: 1.16–1.66) (Table 3 and Supplementary Table 4). The rate of gastrointestinal events was somewhat higher in the FIT×2 arm compared to the control arm also at the end of follow-up, primarily iatrogenic bleeding (IRR: 1.18, 95% CI: 1.05–1.32) and unspecified gastrointestinal bleeding (IRR: 1.14, 95% CI: 1.04–1.26). Yearly incidence rates (per 100,000 person-years) and IRRs of deaths, gastrointestinal events and cardiovascular events in the primary colonoscopy arm and the FIT×2 arm as compared with respective control arms (reference). We previously showed that the proportion of serious adverse events directly linked to screening colonoscopies during the trial was 0.2%, including two bowel perforations and 15 major bleedings17. Death (from any cause) was similar in all arms, with a rate of 554.6 per 100,000 person-years (825 deaths) in the primary colonoscopy arm and 579.0 per 100,000 person-years (5,163 deaths) in the control arm (IRR: 0.96, 95% CI: 0.89–1.03) and 577.1 (1,989 deaths) in the FIT×2 arm and 601.8 (4,145 deaths) in the FIT×2 control arm (IRR: 0.96, 95% CI: 0.91–1.01) (Table 3 and Fig. We previously reported one death in the FIT group on day 15 after the colonoscopy, which followed a pulmonary embolism in a man with metastatic cancer17. Men had a similar rate of cardiovascular events, a somewhat lower rate of gastrointestinal events and a higher rate of death than women (Supplementary Table 5). In this assessment of the diagnostic phase of the SCREESCO trial, there was an increase of stage I–II CRC incidence in the intervention arms compared to usual care, particularly during the first year after randomization when most of the screening colonoscopies were performed. More stage I–II and fewer stage III–IV CRCs were diagnosed in the intervention arms compared to controls after a median follow-up of almost 5 years. Similarly, we found similar incidence rates of death and gastrointestinal or cardiovascular events in all arms, except a slightly higher rate of gastrointestinal and cardiovascular events in particular during the first year after randomization. The only ongoing RCTs other than the SCREESCO trial, involving both primary colonoscopy and FIT, are the Spanish trial COLONPREV16 and the American trial Colonoscopy vs. Fecal Immunochemical Test in Reducing Mortality from Colorectal Cancer (CONFIRM)7,13, neither of which has a control arm. SCREESCO provides a comparison of screening effectiveness between invitation to FIT screening and usual care. In the FIT arms of COLONPREV and CONFIRM, a single stool sample with a higher cutoff was used compared to SCREESCO, which used two stool samples. CONFIRM recruited individuals from Veterans Affairs Medical Centers, where the majority of the population were men7. Similar to the Nordic-European Initiative on Colorectal Cancer (NordICC) RCT, we found in intention-to-screen analyses a higher rate of CRC during the first years since randomization to primary colonoscopy compared to usual care, but the rates were similar later on9. Screening using primary sigmoidoscopy has also been shown to reduce CRC incidence in RCTs compared to usual care18,19,20 and lead to a stage shift toward lower stage, particularly for screen-detected CRCs20. Similar evidence for FIT-based screening compared to usual care is lacking. COLONPREV reported similar rates of screen-detected CRC in the two screening arms16. Previous RCTs on screening using repeated fecal occult blood (FOB) followed by colonoscopy after positive FOB test found an initial increase in CRC incidence and a stage shift toward lower stage, especially in screen-detected CRCs21,22,23,24. In the present study, the rates of stage I–II cancer were higher in both intervention arms compared to controls, in particular during the first years of follow-up when most of the screening colonoscopies were performed. This excess risk decreased with time, and the incidence of stage III–IV simultaneously decreased after around 4 years, particularly in the FIT arm compared to controls. The duration of the trial is likely too short to detect a net benefit of the prevention in terms of a lower CRC incidence in the intervention arms compared to controls and/or to determine if a part of the early-stage CRC excess risk in the intervention arms represents an overdiagnosis of clinically insignificant CRCs25. Taken together with the detection and removal of adenomas, our findings suggest a possible future reduction in CRC incidence and CRC mortality in the intervention arms in the subsequent follow-up of SCREESCO (to be reported with follow-up until 31 December 2030)26. We previously showed that the rate of serious adverse events directly linked to screening colonoscopies in SCREESCO was low17 and in line with other studies8,16,27,28. The present study indicates that the potential harms of colonoscopy in terms of deaths and gastrointestinal or cardiovascular events were generally similar in individuals invited to screening involving colonoscopy at some step in a routine clinical setting and in non-invited individuals following usual care on a population-based level. Individuals who underwent screening colonoscopy in the FIT×2 arm more often had precancerous lesions needing therapeutic intervention compared to the primary colonoscopy arm; hence, the slightly increased risk of gastrointestinal events (that is, bleeding) is expected. The rate of venous thromboembolism was also higher in the FIT×2 arm than in controls, speculatively because anticoagulant users may have a higher risk of positive FIT and pause their treatment during colonoscopy. We are not aware of any other studies reporting gastrointestinal or cardiovascular events in general on an intention-to-treat level comparing primary colonoscopy or FIT followed by colonoscopy to usual care. Our findings motivate further studies on complications related to therapeutic interventions and use of medications. This large RCT has several strengths. It had a unique design using two FIT samples instead of one, an unusually low cutoff (10 μg hemoglobin per g) for the maximum of the two FIT values, two rounds of screening 2 years apart and a control arm following usual care. Thirty-three hospitals and 146 endoscopists were involved, which reflects routine care in Sweden. This study also has some limitations. Although around half of the invited individuals in the FIT arm participated, which was higher than the COLONPREV study15, most with a positive FIT participated in colonoscopy. Participation in the primary colonoscopy arm was lower than initially expected but similar to, or higher than, that in many other countries31 and similar to the NordiCC study8 (outside Norway) and the COLONPREV study15. The increase in CRC incidence during the diagnostic phase was likely lower than what would be expected in settings with higher participation in screening. Some gastrointestinal and cardiovascular events may not have been registered in the Swedish Patient Register, and some may have been re-registered at subsequent hospital visits, potentially underestimating or overestimating incidence rates, although we expect the coverage to be similar in all arms and, thus, less likely to influence IRRs. Our study was restricted to individuals aged 60 years and does not inform on the tradeoffs between benefits and harms of the interventions in younger or older individuals32,33. In conclusion, we found that a program of screening, by primary colonoscopy or two rounds of two-stool FIT using a low cutoff, detects more lower-stage CRCs than usual care. Rates of gastrointestinal or cardiovascular events were higher in the first year and later on more similar to usual care. The increase in CRC detection implies a benefit of screening while the increase in adverse events suggests some initial harm. Subsequent follow-up of SCREESCO will report CRC mortality (not reported here). This study has trial number NCT02078804 and is registered with ClinicalTrials.gov at https://clinicaltrials.gov/study/NCT02078804. We performed an individual RCT with a study base population from 18 out of 21 regions in Sweden17 comprising 74.5% of the total national population where CRC screening had not previously been offered (Stockholm, Gotland and Västernorrland regions were not included). Residents aged 60 years of age or who turned 60 in the year of randomization were identified from the Total Population Register maintained by the Swedish Tax Agency34. Individuals who had a previous diagnosis of CRC or anal cancer or who had participated in the NordICC trial were excluded8. Individuals assigned as controls were not informed about study participation. The Swedish Ethical Review Authority waived the need for informed consent for accessing pseudonymized register-based data (2022/01946-02 and 2022/06863-2). Between 11 February 2014 and 1 March 2016, a randomized block method was used to assign 201,000 individuals born 1954–1956 without prior CRC diagnosis to once-only primary colonoscopy, two rounds of FIT 2 years apart (FIT×2) or a usual care control arm with no organized program of screening activity (controls). All controls were intended for use in the separate comparisons of primary colonoscopy versus control and of FIT×2 versus control. A list of all eligible individuals within each randomization block, defined by year of randomization, region of residence and sex, was obtained to randomly allocate individuals to the three arms. The target number of randomized individuals within the strata was determined based on the distribution of sex and county among 60-year-old individuals in Sweden (excluding the counties that did not participate in SCREESCO) in 2012. Because of low participation in the primary colonoscopy arm, an additional 77,280 individuals were randomized to primary colonoscopy or control between 30 May 2017 and 25 May 2018. We call the subgroup of controls randomized in 2014–2016 (120,600 controls) ‘FIT×2 controls' because they are appropriate for use in the comparison against FIT×2 (also randomized in 2014–2016). All 186,840 controls were available for comparison against primary colonoscopy (randomized 2014–2018). All invitees in the primary colonoscopy and FIT×2 arms were sent a letter describing the study and a leaflet about CRC and screening. A reminder was sent after 8 weeks. No contact was made with individuals allocated to the control arm. Individuals assigned to the FIT×2 arm were sent a set of kits for two stool samples each screening round. One central laboratory performed all FIT analyses using a single OC-Sensor DIANA automated analyzer (Eiken Chemical). A fecal hemoglobin concentration of ≥10 μg g−1 feces in either of the stool samples was deemed positive, triggering a colonoscopy invitation. All individuals in the FIT×2 arm, except those requiring colonoscopy surveillance after adenoma removal or after a CRC diagnosis, were offered a repeat FIT after 2 years, irrespective of participation in the first FIT screening round or the results of the first FIT. Colonoscopies were performed at 33 hospitals by 146 endoscopists, with a background training as gastroenterologists, surgeons or endoscopy nurses17. In Sweden, all citizens have access to public healthcare35. A very small minority of individuals have private healthcare insurance on top of this (only 0.6% of Swedish healthcare is funded through insurance). During the study period, there was no national screening. Screening was performed in the Stockholm-Gotland healthcare region but not in the regions where SCREESCO was performed. In usual care, the main driver of colonoscopies is symptoms. During the study period, FIT has been introduced as an intermediate step in the investigation of symptoms to an increasing extent, where elevated hemoglobin in the fecal sample in a FIT taken because of symptoms triggers a colonoscopy. Individuals who are under surveillance due to increased CRC risk (that is, previous CRC diagnosis, inflammatory bowel disease or hereditary/familial CRC syndromes) may undergo colonoscopy during surveillance. Individuals may also be under surveillance after polypectomy of adenomatous colorectal polyps. The ultimate primary endpoint of SCREESCO, for which the power and sample size calculations were performed, is CRC mortality (intervention versus control) at 15 years, and it will be reported later with follow-up until 31 December 2030. CRC incidence was listed as a primary endpoint in the study protocol, but this is formally a secondary outcome of the trial, along with an analysis of compliance, and exploratory outcomes include analyses of health economy, of colonoscopy quality and of the microbiome in feces. The study protocol was amended after new power calculations due to an observed 35% participation in the colonoscopy arm (in Swedish, 10 March 2017; translated to English, 29 April 2021). The study protocol was amended after the Scientific Committee decided on a last date of follow-up based on new power calculations. It was also decided that the previously described interim analysis would not be performed. A summary of changes to the study protocol and statistical analysis plan was added. Weblinks under ‘Head Secretariat' were updated. The statistical analysis plan was amended after new power calculations due to an observed 35% participation in the colonoscopy arm. The statistical analysis plan was amended on 4 November 2024 after the Scientific Committee decided on a last date of follow-up based on new power calculations. It was also decided that the previously described interim analysis would not be performed. Power calculations were performed for CRC mortality at 15 years alone. The initial study protocol and the current study protocol state, however, that the main research questions of SCREESCO are to investigate (1) if screening has an effect on the mortality from CRC, (2) if screening has an effect on the incidence of CRC and (3) what method should be used in Sweden regarding the effect according to (1) and (2). The Scientific Committee found a need for a timely assessment of baseline findings (diagnosed CRCs and adverse events during the diagnostic phase of the trial) that also includes the control arm (usual care) and diagnoses/events occurring in general (not only those directly related to SCREESCO screening colonoscopies). Note that CRC mortality is not assessed in the present study and that this main outcome of the trial will, instead, be presented in the final report of the trial with follow-up until 31 December 2030. Note that this study does not constitute the interim analyses mentioned of CRC mortality at 5 years and 10 years of follow-up in the original study protocol and statistical analysis plan. An additional power calculation (statistical analysis plan version 3; Table 3) showed that there would be limited power to detect differences in CRC mortality at 10 years (follow-up until 31 December 2024) or earlier. Based on the calculation, the Scientific Committee decided that interim analyses of CRC mortality should not be performed. The present study focuses on early CRCs and adverse events during the diagnostic phase and is listed as a planned analysis of the study. It builds upon a previous baseline assessment of screen-detected CRCs and adverse events in screening colonoscopies of SCREESCO17 and can be considered an extended baseline report or a 5-year interim analysis of diagnosed CRCs and adverse events occurring during the intervention phase. It includes extended information from Swedish health registers regarding CRCs diagnosed and adverse events in general in both screening arms and in the control arm during the diagnostic phase of SCREESCO when screening FITs and colonoscopies were performed. The endoscopy units reported serious adverse events that occurred within 30 days of the colonoscopy. A study nurse, together with A.F., checked the case report forms for completeness or inconsistencies and obtained additional information from the screening units if needed. Subsequent monitoring was, and will be, facilitated by follow-up using healthcare registers. In the present analysis of the diagnostic phase of SCREESCO, the outcomes were diagnostic yield of screening and usual care, in terms of CRC diagnoses (overall and by stage), and adverse events (cardiovascular and gastrointestinal). We also assessed death from any cause as a measure of overall health and a potential harm of screening. Data on date of and stage at CRC diagnosis were extracted from the Swedish Cancer Register, to which registration is mandated by law29. Additional data on CRC stage were obtained from the Swedish Colorectal Cancer Register that, during 2008–2015, had a completeness of 98.5% for colon cancer and 98.8% for rectal cancer36. We defined CRC according to relevant International Classification of Disease (ICD) and Systematized Nomenclature of Medicine (SNOMED) codes registered in the Swedish Cancer Register. We used any of the following ICD 10th revision (ICD-10) codes for CRC: C18 (except C181), C19 and C20. We additionally included CRCs registered in the Swedish Colorectal Cancer Quality Register36. The date of CRC diagnosis was defined as the first date of a CRC diagnosis in either of the two registries. Medical charts for individuals with CRC registered in SCREESCO, individuals who after a screening colonoscopy required further investigation or treatment (for example, computed tomography scan) and individuals whose polyp samples were sent to pathology were reviewed to assess the correctness of the CRC diagnosis and to extract additional information on stage. CRCs were considered screen detected if detected at colonoscopy (primary or secondary after a positive FIT) performed within SCREESCO. Data on stage of CRCs detected at screening colonoscopy within SCREESCO were extracted from the SCREESCO database. Data on stage were also extracted separately for all individuals with a CRC diagnosis in the Swedish Colorectal Cancer Quality Register and/or the Swedish Cancer Register. We allowed for some administrative lag and included all entries in the Swedish Colorectal Cancer Quality Register and the Swedish Cancer Register occurring within 90 days from the first date of CRC diagnosis in either of the two registers. The TNM stages were obtained from the Swedish Colorectal Cancer Quality Register if the CRC was registered there and available (not missing) and, otherwise, from the Swedish Cancer Register if available. Stage (I–II versus III–IV) was graded similarly to the American Joint Committee on Cancer system, which is based on the TNM classification, with stage I–II if T(any or missing)N0M0, T(0–4)N0M(0/missing) or T(0–1)N(0/missing)M0 and stage III–IV if N1, N2 or M1. Stage was considered unknown if it did not fulfil any of the above. Data on cardiovascular and gastrointestinal events (events related to colonoscopy—for example, bleedings and injuries) and on colonoscopies registered in an inpatient or outpatient setting were extracted from the Patient Register30. The Patient Register covers all inpatient care in Sweden, and the validity of this register has been found to be high, varying from 85% to 95% among different diseases30. The following ICD-10 codes were used to define gastrointestinal events: K922 (Unspecified gastrointestinal bleeding), S360 (Splenic injury), S365 (Colonic injury), S366 (Rectal injury), T810 (Bleeding iatrogenic) and T812 (Perforation). The following ICD-10 codes were used to define cardiovascular events: I20–I25 (Ischemic heart disease), I26 (Pulmonary embolism), I33 (Acute endocarditis), I46 (Cardiac arrest), I63 (Cerebral infarction), I74 (Peripheral artery embolism) and I81 and I82 (Venous thromboembolism). Biological sex (man/woman), year of birth, country of birth (Sweden versus other), region of residence, educational level, Charlson Comorbidity Index, a drug comorbidity index and history of any cardiovascular or gastrointestinal event and type of event (within 10 years prior to randomization) were used to describe individuals by arm. The Charlson Comorbidity Index was calculated based on the Patient Register in the last 10 years before inclusion, and the drug comorbidity index was calculated based on drug prescriptions registered up to 1 year before date of inclusion in the Prescribed Drug Register38,39,40. Country of birth was extracted from the Total Population Register, and educational level and region of residence were extracted from the Swedish Longitudinal Integrated Database for Health Insurance and Labor Market Studies (LISA). A priori, the study was powered to detect a 17.5% decrease in CRC mortality at 15 years in individuals invited to colonoscopy compared to the control arm and a 15% decrease in individuals invited to FIT compared to the control arm, based on an anticipated 1% cumulative CRC mortality between 60 years and 75 years of age. The original sample size target was 201,000 individuals. Because of lower participation (35%) in the primary colonoscopy arm than expected (50%), new power calculations were performed to determine the additional number of randomized individuals needed to achieve acceptable power, and two additional age cohorts (born 1957 and 1958) were randomized to primary colonoscopy or control in a ratio of 1:6 (hence the deviation from the initially intended allocation ratio). In the revised study protocol, we assumed a 15% disease-specific mortality reduction by 15 years of follow-up as a minimal clinically important effect in those invited to FIT×2 compared to the control arm, based on a participation rate of 50%, and a 17.5% disease-specific mortality reduction in those invited to colonoscopy compared to the control arm, based on a 35% participation. To allow these absolute risk reductions to be detected at a two-sided 2.5% significance level with 80% power for the comparison of FIT×2 versus control and 73% power for the comparison of primary colonoscopy versus control, the revised target sample size was 278,280 participants. In total, 31,140 individuals were randomized to the primary colonoscopy arm; 60,300 individuals were randomized to the FIT×2 arm; and there were two control groups: 186,840 controls to the primary colonoscopy arm, out of which 120,600 individuals also were controls to the FIT×2 arm (FIT×2 controls). An additional power analysis was performed to determine when, in calendar time, the main analysis of SCREESCO would be performed because this was not clearly stated in the initial study protocol. The Scientific Committee decided that 31 December 2030 would be the last date of follow-up for the main analysis because power was not expected to meaningfully increase after this date. In an intention-to-screen analysis, we report the number, proportion and incidence rate per 100,000 person-years of all screen-detected CRCs within SCREESCO and all other CRCs diagnosed in regular clinical practice during the diagnostic phase of SCREESCO, in total and by stage (I–II or III–IV). We similarly report incident cardiovascular and gastrointestinal events diagnosed in regular clinical practice and death from any cause. We compare each intervention arm with the corresponding control arm concerning each of the outcomes using incidence rates and IRRs using Poisson regression models with 95% CIs. Analyses were also performed separately in men and women, and a Poisson regression model with interaction between sex and study arm was used to compare the IRR in men versus the IRR in women under the null hypothesis of no difference (two-sided test of the interaction term). Note that only the FIT×2 controls (individuals randomized 2014–2016, during which individuals could be allocated to FIT×2) were used in the comparison of FIT×2 versus control in this study, whereas all controls (randomized 2014–2018, including the FIT×2 controls) were used in the comparison of primary colonoscopy versus control. The full follow-up of up to a maximum of almost 7 years was used in the above analyses. In a complementary analysis, we also computed incidence rates and IRRs at each year of follow-up. Individuals were censored if and when they migrated out of Sweden. Individuals were similarly not considered at risk after their date of death. We assessed potential violations of equidispersion for each regression model and computed alternative CIs by use of robust standard errors. Because there were no signs of meaningful underdispersion or overdispersion and results were virtually identical, we did not report these analyses. In a complementary analysis, we computed competing risk cumulative incidence curves of CRC (overall and by stage) where death from any cause was considered a competing risk. We report baseline characteristics in participants and non-participants of the intervention arms along with diagnosed CRCs and cardiovascular and gastrointestinal events that occurred during the intervention phase. Individuals in the primary colonoscopy arm were considered to be participants if they underwent a screening colonoscopy, and individuals in the FIT×2 arm were considered participants if they returned a FIT in any of the two rounds. Analyses were performed using R version 4.0.2. Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article. The data cannot be shared publicly because the individual-level data contain potentially identifying and sensitive patient information and cannot be published due to legislation and ethical approval (https://etikprovningsmyndigheten.se). Use of the data from national health data registers is further restricted by the Swedish Board of Health and Welfare (https://www.socialstyrelsen.se/en/) and Statistics Sweden (https://www.scb.se/en/), which are government agencies providing access to the linked healthcare registers. Selected deidentified individual participant data that underlie the results reported in this article (including in the supplementary materials) can, however, be made available to researchers after request to the SCREESCO Steering Committee. Researchers must provide a methodologically sound proposal for a project that conforms with the Swedish Ethical Review Authority permit for the project and will need to sign a data access agreement. Data will be made available at a secure remote server to achieve the aims in the approved proposal. Data will be available from 3 months after publication and until 3 years after publication of the article. Proposals regarding the data underlying this article may be submitted up to 2 years after publication. The full trial protocol and statistical analysis plan (including original and revised versions) are available in Supplementary Note 1, and the most recent version of each document is available at https://clinicaltrials.gov/study/NCT02078804. The code was written in R version 4.0.2 using RStudio and is available at https://github.com/MarcusWesterberg/CRCs-and-AEs-during-diagnostic-phase-of-SCREESCO. Săftoiu, A. et al. Role of gastrointestinal endoscopy in the screening of digestive tract cancers in Europe: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement. Shaukat, A. et al. ACG clinical guidelines: colorectal cancer screening 2021. Cardoso, R. et al. Colorectal cancer incidence, mortality, and stage distribution in European countries in the colorectal cancer screening era: an international population-based study. Young, G. P. et al. Fecal immunochemical test positivity thresholds: an international survey of population-based screening programs. Jørgensen, S. F. et al. Nordic colorectal cancer screening programmes: a comparison of organization, operation, and quality indicators. Blom, J., Saraste, D., Törnberg, S. & Jonsson, H. Routine fecal occult blood screening and colorectal cancer mortality in Sweden. A. et al. Colonoscopy vs. fecal immunochemical test in reducing mortality from colorectal cancer (CONFIRM): rationale for study design. Bretthauer, M. et al. Population-based colonoscopy screening for colorectal cancer: a randomized clinical trial. Bretthauer, M. et al. Effect of colonoscopy screening on risks of colorectal cancer and related death. Effectiveness of fecal immunochemical testing in reducing colorectal cancer mortality from the One Million Taiwanese Screening Program. Robertson, D. J. et al. Baseline features and reasons for nonparticipation in the colonoscopy versus fecal immunochemical test in reducing mortality from colorectal cancer (CONFIRM) study, a colorectal cancer screening trial. Gini, A. et al. Impact of colorectal cancer screening on cancer-specific mortality in Europe: a systematic review. Castells, A. et al. Effect of invitation to colonoscopy versus faecal immunochemical test screening on colorectal cancer mortality (COLONPREV): a pragmatic, randomised, controlled, non-inferiority trial. Quintero, E. et al. Colonoscopy versus fecal immunochemical testing in colorectal-cancer screening. Forsberg, A. et al. Once-only colonoscopy or two rounds of faecal immunochemical testing 2 years apart for colorectal cancer screening (SCREESCO): preliminary report of a randomised controlled trial. Holme, Ø. et al. Effect of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality: a randomized clinical trial. Segnan, N. et al. Once-only sigmoidoscopy in colorectal cancer screening: follow-up findings of the Italian randomized controlled trial—SCORE. Schoen, R. E. et al. Colorectal-cancer incidence and mortality with screening flexible sigmoidoscopy. Lindholm, E., Brevinge, H. & Haglind, E. Survival benefit in a randomized clinical trial of faecal occult blood screening for colorectal cancer. Kronborg, O., Fenger, C., Olsen, J., Jørgensen, O. D. & Søndergaard, O. Randomised study of screening for colorectal cancer with faecal-occult-blood test. Hardcastle, J. D. et al. Randomised controlled trial of faecal-occult-blood screening for colorectal cancer. Mandel, J. S. et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. Kalager, M. et al. Overdiagnosis in colorectal cancer screening: time to acknowledge a blind spot. Zauber, A. G. et al. Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths. Benazzato, L. et al. Colonoscopy-related adverse events and mortality in an Italian organized colorectal cancer screening program. Chandan, S. et al. Colonoscopy-related adverse events in patients with abnormal stool-based tests: a systematic review of literature and meta-analysis of outcomes. Barlow, L., Westergren, K., Holmberg, L. & Talbäck, M. The completeness of the Swedish Cancer Register – a sample survey for year 1998. External review and validation of the Swedish national inpatient register. Schreuders, E. H. et al. Colorectal cancer screening: a global overview of existing programmes. Increased post-procedural non-gastrointestinal adverse events after outpatient colonoscopy in high-risk patients. Ladabaum, U., Mannalithara, A., Desai, M., Sehgal, M. & Singh, G. Age-specific rates and time-courses of gastrointestinal and nongastrointestinal complications associated with screening/surveillance colonoscopy. Registers of the Swedish total population and their use in medical research. Moberger, P., Sköldberg, F. & Birgisson, H. Evaluation of the Swedish Colorectal Cancer Registry: an overview of completeness, timeliness, comparability and validity. The Swedish cause of death register. Westerberg, M., Garmo, H., Ludvigsson, J. F., Stattin, P. & Gedeborg, R. Discriminative ability of the Charlson Comorbidity Index for long-term mortality in a general population: nationwide, population-based study of 10 million adults in Sweden. Gedeborg, R. et al. An aggregated comorbidity measure based on history of filled drug prescriptions: development and evaluation in two separate cohorts. We are grateful for grants from the 18 Swedish regions, the Stockholm County Council, Regional Cancer Center Mellansverige, the Swedish Cancer Society, the Aleris Research and Development Fund and Eiken Chemical. We are also grateful to the 33 Swedish hospitals where the colonoscopies in this study were performed. Late Rolf Hultcrantz is acknowledged for initiating SCREESCO, securing the funding and leading the study through the entire recruitment period and first report. Late Anders Ekbom is acknowledged for his important contributions in all phases of the study. Financial support was provided by the Swedish regions (A.F. Financial support was also provided through the Regional Agreement on Medical Training and Clinical Research (A.L.F.) and by the Swedish Society of Medicine (A.F. The funders of the study had no role in study design, data collection, data analysis, data interpretation or writing of the report. Open access funding provided by Uppsala University. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden Department of Surgery, Södersjukhuset, Stockholm, Sweden Department of Clinical Science and Education, Karolinska Institutet, Stockholm, Sweden Centre for Translational Microbiome Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden Department of Radiology, Institute of Clinical Sciences at Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden Department of Radiology, Sahlgrenska University Hospital, Gothenburg, Sweden Department of Clinical Chemistry, SYNLAB Sverige, Täby, Sweden Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King's College London, London, UK Search author on:PubMed Google Scholar Search author on:PubMed Google Scholar Search author on:PubMed Google Scholar Search author on:PubMed Google Scholar Search author on:PubMed Google Scholar Search author on:PubMed Google Scholar Search author on:PubMed Google Scholar Search author on:PubMed Google Scholar Search author on:PubMed Google Scholar Search author on:PubMed Google Scholar Search author on:PubMed Google Scholar has coordinated an unrelated study on behalf of the Swedish IBD quality register (SWIBREG). That study received funding from Janssen corporation. has also received financial support from Merck Sharp & Dohme/Merck for developing a paper reviewing national healthcare registers and has ongoing research collaboration on inflammatory bowel disease. has an ongoing research collaboration on celiac disease with Takeda Pharmaceuticals and has ongoing discussions for future research collaboration on liver disease with this company. The other authors declare no competing interests. Nature Medicine thanks Kai-Feng Pan and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary Handling Editor: Ming Yang, in collaboration with the Nature Medicine team. Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Number of invited and participating individuals according to study arm. Completing risk cumulative incidence proportion of colorectal cancer with death from any cause as completing risk. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Westerberg, M., Ludvigsson, J.F., Metcalfe, C. et al. Colonoscopy and fecal immunochemical testing versus usual care in diagnostic colorectal cancer screening: the SCREESCO randomized controlled trial. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Parkinson's disease is a long term neurological condition that gradually worsens over time. Current medications and therapies can ease symptoms, but no treatment has been proven to stop or slow the disease itself. This breakdown leads to the hallmark symptoms of Parkinson's, including tremors, muscle stiffness, and slowed motion. Researchers at Keck Medicine of USC are now testing a new approach that aims to address this dopamine loss directly. In an early phase clinical trial, doctors are implanting specially engineered stem cells into the brain. These cells are designed to replace damaged neurons and generate dopamine. "If the brain can once again produce normal levels of dopamine, Parkinson's disease may be slowed down and motor function restored," said Brian Lee, MD, PhD, a neurosurgeon with Keck Medicine and principal investigator of the study. Unlike embryonic stem cells, iPSCs are made by taking adult cells, such as those from skin or blood, and reprogramming them back into a versatile state. "We believe that these iPSCs can reliably mature into dopamine-producing brain cells, and offer the best chance of jump-starting the brain's dopamine production," said Xenos Mason, MD, a neurologist who specializes in Parkinson's disease and other movement disorders with Keck Medicine and co-principal investigator of the study. After the operation, participants are closely observed for 12-15 months to track changes in symptoms and watch for potential side effects, including dyskinesia -- excess movements -- or infection. "Our ultimate goal is to pioneer a technique that can repair patients' motor function and offer them a better quality of life," said Lee. The multisite clinical trial includes 12 people with moderate to moderate-severe Parkinson's disease. The stem cell therapy, known as RNDP-001, is produced by Kenai Therapeutics, a biotechnology company focused on developing treatments for neurological disorders. Disclosure: Mason has received an honorarium payment from Kenai Therapeutics in the past. The “Most Effective” Treatment for Osteoarthritis May Be Less Helpful Than Thought The Southern Indian Ocean Is Losing Salt at an “Astonishing” Rate Stay informed with ScienceDaily's free email newsletter, updated daily and weekly. Keep up to date with the latest news from ScienceDaily via social networks: Tell us what you think of ScienceDaily -- we welcome both positive and negative comments.

Older adults who live with higher levels of air pollution are more likely to develop Alzheimer's disease, according to new research led by Yanling Deng of Emory University, U.S.A. Alzheimer's is the most common type of dementia and affects roughly 57 million people worldwide. Because these conditions are also tied to dementia, researchers have questioned whether polluted air raises Alzheimer's risk indirectly by contributing to those illnesses, or whether it harms the brain more directly. Another possibility was that existing health problems could make the brain more sensitive to pollution. The relationship was somewhat stronger among individuals who had previously suffered a stroke. In contrast, hypertension and depression did not meaningfully increase the pollution related risk. At the same time, a history of stroke appears to increase vulnerability, suggesting that certain individuals face compounded risks. The findings also point to cleaner air as a potential strategy for lowering dementia rates and protecting cognitive health in aging populations. The authors add, "In this large national study of older adults, we found that long-term exposure to fine particulate air pollution was associated with a higher risk of Alzheimer's disease, largely through direct effects on the brain rather than through common chronic conditions such as hypertension, stroke, or depression." "Our findings suggest that individuals with a history of stroke may be particularly vulnerable to the harmful effects of air pollution on brain health, highlighting an important intersection between environmental and vascular risk factors." The “Most Effective” Treatment for Osteoarthritis May Be Less Helpful Than Thought Stay informed with ScienceDaily's free email newsletter, updated daily and weekly. Keep up to date with the latest news from ScienceDaily via social networks: Tell us what you think of ScienceDaily -- we welcome both positive and negative comments.

A sweeping new investigation by the Silent Spring Institute has found dozens of potentially harmful chemicals in widely sold hair extensions, including those made from human hair. Researchers say the results add strong evidence that hair extensions may pose health risks, particularly for black women, who use these products at much higher rates. More than 70 percent of black women report wearing hair extensions at least once in the past year, compared with fewer than 10 percent of women from other racial and ethnic groups. Extensions are often worn for cultural expression, personal style, and convenience. "While prior reports have found some chemicals of concern in hair extensions, there's still much we don't know about their overall chemical makeup. We wanted to get a better picture of the extent of the problem," says lead author Dr. Elissia Franklin, a research scientist at Silent Spring Institute. "This is an industry that has long overlooked the health of black women, who should not have to choose between cultural expression, convenience, and their health." Manufacturers frequently treat these fibers with chemicals to make them flame resistant, waterproof, or antimicrobial. When extensions are heated during styling, they can also release chemicals into the air that users may inhale. To better understand what these products contain, Franklin purchased 43 popular hair extension brands from online retailers and local beauty supply stores. Among the synthetic products, 19 claimed to be flame retardant, three were labeled water resistant, nine advertised heat resistance, and three promoted "green" claims such as "no PVC" or "non-toxic." Researchers then applied a method known as non-targeted analysis to search for a broad array of chemicals, including substances not typically screened in consumer goods. Using two-dimensional gas chromatography with high-resolution mass spectrometry, they detected more than 900 chemical signatures, representing both known and previously unidentified compounds. Machine-learning tools compared those signatures with an extensive chemical database, allowing the team to identify 169 chemicals spanning nine major structural classes. The testing uncovered numerous substances associated with cancer, hormone disruption, developmental harm, and immune system effects. "These are commonly used as heat stabilizers in PVC and have been linked with skin irritation, which is a common complaint among hair extension users." Many of the detected substances are included under Proposition 65, suggesting that hair extensions may warrant clearer warnings and closer regulatory scrutiny. In New York, lawmakers have introduced legislation that would require manufacturers of synthetic braids and hair extensions to disclose all ingredients. Funding for this project was provided by a Beauty Justice Grant from the Environmental Defense Fund and charitable donations to Silent Spring Institute, including the Institute's Safer Chemicals Program. The “Most Effective” Treatment for Osteoarthritis May Be Less Helpful Than Thought The Southern Indian Ocean Is Losing Salt at an “Astonishing” Rate Stay informed with ScienceDaily's free email newsletter, updated daily and weekly. Keep up to date with the latest news from ScienceDaily via social networks: Tell us what you think of ScienceDaily -- we welcome both positive and negative comments.