Can Doctors Predict Which Children with Pneumonia Will Develop Mild or Severe Disease? (Medicine)

Study points to need for objective, evidence-based tools to predict severity of community-acquired pneumonia in children

Currently, there are no evidence-based rules that help physicians in the Emergency Department (ED) predict if a child with community-acquired pneumonia will have a mild disease course that can be treated at home or a more severe illness that requires hospitalization. A recent study published in the journal Pediatrics found that the predictive accuracy of clinical judgement was generally fair, but clinicians were least accurate when predicting progression to severe disease in children initially classified as having “low to moderate” risk, which accounts for a large portion of children presenting with pneumonia.

Community-acquired pneumonia is one of the most common infections in children. Although most children with pneumonia fully recover after a mild illness, around 5 percent become severely sick and develop serious complications.

“In our study, physicians relying on clinical judgement to predict the risk of complications from pneumonia performed well, but there is room to improve,” said senior author Todd Florin, MD, MSCE, Director of Research in Emergency Medicine at Ann & Robert H. Lurie Children’s Hospital of Chicago and Associate Professor of Pediatrics at Northwestern University Feinberg School of Medicine. “Our study establishes the need for objective, evidence-based tools to augment, and possibly improve upon, individual clinician’s judgement, so that physicians can more accurately identify children that require earlier treatments to prevent development of severe disease.”

Dr. Florin is leading efforts to provide one of the first evidence-based, risk-scoring tools for pediatric community-acquired pneumonia, to be used in conjunction with and improve ED physicians’ ability to risk stratify children with this disease. At this stage, he and colleagues developed the tool and validated it at a single center. Their work was published in November 2020.

“Our next step is to externally validate this pediatric tool in a multi-center study before it can be broadly implemented,” said Dr. Florin.

Research at Ann & Robert H. Lurie Children’s Hospital of Chicago is conducted through the Stanley Manne Children’s Research Institute. The Manne Research Institute is focused on improving child health, transforming pediatric medicine and ensuring healthier futures through the relentless pursuit of knowledge. Lurie Children’s is ranked as one of the nation’s top children’s hospitals by U.S. News & World Report. It is the pediatric training ground for Northwestern University Feinberg School of Medicine. Last year, the hospital served more than 220,000 children from 48 states and 49 countries.


Reference: Florin TA, Ambroggio L, Lorenz D, Kachelmeyer A, Ruddy RM, Kuppermann N, Shah SS. Development and Internal Validation of a Prediction Model to Risk Stratify Children with Suspected Community-Acquired Pneumonia. Clin Infect Dis. 2020 Nov 7:ciaa1690. doi: 10.1093/cid/ciaa1690.


Provided by Lurie Children’s Hospital of Chicago

Anti-inflammatory Nanotherapy Improves Outcomes After Urethral Surgery (Medicine)

In the first study to evaluate the effects of anti-inflammatory nanofibers on wound healing following urethral surgery, scientists from the Stanley Manne Children’s Research Institute at Ann & Robert H. Lurie Children’s Hospital of Chicago found that this innovative therapy promotes faster and complete healing, preventing prolonged or excessive inflammation that commonly leads to the need for more surgery. Their results were published in the journal Macromolecular Bioscience.

Urethral reconstruction surgery is needed to correct congenital anomalies, such as hypospadias, which results in disruption of normal urethral formation and affects one in every 150-300 live male births. Surgery is also used to treat urethral strictures, an acquired pathology resulting in blockages, that may affect one in 1,000-10,000 men. 

“Protracted post-surgical inflammation leading to complications is a persistent problem in urethral reconstruction,” said senior author Arun Sharma, PhD, Director of Surgical Research at the Manne Research Institute at Lurie Children’s and Research Associate Professor of Urology and Biomedical Engineering at Northwestern University Feinberg School of Medicine and McCormick School of Engineering. “Using a rat model, we implanted during surgery a biological scaffold coated with nanomolecules that carry an anti-inflammatory peptide, which is a tiny portion of a protein. This treatment reduced the excessive pro-inflammatory immune response while increasing recruitment of pro-regenerative, anti-inflammatory immune cells. The result was faster wound healing and increased blood flow, without the common complications of urethral reconstruction.”

Research at Ann & Robert H. Lurie Children’s Hospital of Chicago is conducted through the Stanley Manne Children’s Research Institute. The Manne Research Institute is focused on improving child health, transforming pediatric medicine and ensuring healthier futures through the relentless pursuit of knowledge. Lurie Children’s is ranked as one of the nation’s top children’s hospitals by U.S. News & World Report. It is the pediatric training ground for Northwestern University Feinberg School of Medicine. Last year, the hospital served more than 220,000 children from 48 states and 49 countries.


Reference: Chan, Y. Y., Bury, M. I., Fuller, N. J., Nolan, B. G., Gerbie, E. Y., Hofer, M. D., Sharma, A. K., Effects of Anti-Inflammatory Nanofibers on Urethral Healing. Macromol. Biosci. 2021, 21, 2000410. https://doi.org/10.1002/mabi.202000410


Provided by Lurie Children’s Hospital of Chicago

UoM Medicine Performs Two Successful Lung Transplants on Patients with COVID-19 Lung Damage (Medicine)

Two patients who were near death after COVID-19 destroyed their lungs, survived and are thriving due to state-of-the-art care and double-lung transplants by University of Maryland School of Medicine (UMSOM) surgeons at the UM Medical Center (UMMC).

John Micklus, 62, of La Plata, Md., had healthy lungs before the coronavirus disease struck, but soon, doctors at one hospital said nothing could help him and told him it was time to get his affairs in order. Another Maryland man, Anthony (who asked not to reveal his last name), already had an underlying lung condition, but COVID-19 sparked an overwhelming struggle to breathe and he didn’t think he would survive.

The COVID-19 pandemic, with more than 32 million cases and more than 580,000 deaths in the United States so far, prompted some hospitals to pause organ transplantation as specialists scrambled to learn more about the pre- and post-transplant effects of COVID-19. UMMC has continued to perform organ transplantation throughout the pandemic, carefully balancing both the care of hospitalized COVID patients and the needs of patients awaiting transplant. Several UMMC patients who had recovered from COVID received kidney or liver transplants, but their need for transplantation was unrelated to the coronavirus.

“The learning curve for lung transplantation in COVID-19 patients has been particularly challenging because the infection is centered in the lungs,” said transplant surgeon Daniel G. Maluf, MD, Professor of Surgery at UMSOM and Director of the Program in Transplantation, which is a joint program between UMSOM and UMMC. “Add to that, we need to suppress the body’s immune system to help an organ survive after transplant and reduce the chance of rejection. Immunosuppression also turns down the body’s ability to fight infections. What happens if the coronavirus disease attacks the transplanted lungs, which are already quite fragile?”

‘A Different Ballgame’

Despite his underlying lung condition, Anthony was able to move around and exercise with little or no supplemental oxygen before getting infected with COVID-19. “After COVID, it was a different ballgame,” he said. He required higher and higher levels of oxygen but it became clear that he couldn’t survive on a ventilator. He was placed on a transplant wait list, and, to buy time, his care team put him on ECMO (extracorporeal membrane oxygenation), which works like the heart and lungs to remove carbon dioxide and return oxygen-filled blood back to the tissues. Then, on Feb. 6, Anthony became the first COVID-related lung transplantation patient at UMMC.

COVID-19 was also a different ballgame for the UMMC lung transplant team, which routinely performs 25-30 lung transplants each year. Unique to COVID is the rapid ebb and flow of symptoms. Within a matter of months, the two men were sick with COVID-19, then seemingly recovered from their initial infection only to get sick again, the second round producing significant lung deterioration. This contrasts with other lung conditions that may lead to transplant, such as chronic obstructive pulmonary disease (COPD) or pulmonary fibrosis (scarring of the lungs), which typically worsen gradually over many years.

Robert M. Reed, MD
Robert M. Reed, MD © University of Maryland School of Medicine

In addition, lung transplant timing is a function of COVID-19 risk. “You cannot perform the transplant too early, because you have to be sure the patient is cleared of the COVID virus. But you cannot do it too late, because at that point, patients may be so weak they cannot survive the operation and meaningfully participate in rehabilitation,” said Robert M. Reed, MD, Professor of Medicine, UMSOM, and Associate Medical Director of the Lung Transplant Program at UMMC.

The ebb and flow for John Micklus began with flu-like symptoms around Christmas 2020. A test result on New Year’s Eve showed he was COVID-positive. By early January, he was admitted to a local hospital not affiliated with the University of Maryland Medical System for 10 days. He felt better at first after discharge, but within a week he was back in the same hospital, with severe shortness of breath. After another 7-10 days, doctors said they could do nothing more for him. His wife desperately called several physicians, and eventually learned that UMMC had recently completed Anthony’s transplant. After a series of tests at UMMC, Micklus was listed for a transplant.

“I was lucky enough to be a match for a lung donor that the doctors felt was suitable for me within a few days,” said Micklus, who was discharged from UMMC on March 30.

The two cases provided an important COVID insight for the transplant team, said Reed. Despite failing lungs, the rest of their bodies were sufficiently intact to move forward with transplant and expect a good result. “The key message: this option of lung transplant is definitely not for every patient with COVID. It’s for the patients who are still strong otherwise, but have lungs that have been devastated by COVID.”

Alexander S. Krupnick, MD
Alexander S. Krupnick, MD © University of Maryland School of Medicine

One thing is clear, according to Alexander S. Krupnick, MD, Professor of Surgery, UMSOM, and Vice Chief, Thoracic Surgery and Director, Lung Transplant Program, UMMC. Hospitalized COVID-19 patients should be seen early by lung specialists. “When a COVID patient is referred to us, we assess the lungs and if we think the lungs will recover, we’ll explore a number of treatment options. Or, if we think the lungs will not recover, our treatment will include steps to get the patient ready for transplant. Many patients will be able to leave us with their own lungs. By no means is transplant the preferred option.”

Infectious Disease Strategies

As pulmonologists, surgeons and intensive care physicians weighed whether both men could withstand the stresses of lung transplantation, UMMC infectious disease specialists focused on balancing the interval between the initial bout with SARS-CoV-2, the virus that causes COVID-19, and a virus-free status that could optimize the benefits of transplant.

Among the questions: “Is there a chance the patients may still actually have some viral persistence? Are they truly fully recovered and is it safe to proceed?” said Kapil K. Saharia, MD, MPH, Assistant Professor of Medicine at UMSOM, and Chief, Solid Organ Transplant Infectious Diseases Service at UMMC. “If there is any viral persistence, the concern would be that the new lungs could become infected. You’d be right back where you were before.”

Performing lung transplants in those recovering from COVID-19 has the added complication of the rejection-infection balancing act that is key to the survival of transplanted lungs.

Aldo T. Iacono, MD
Aldo T. Iacono, MD © University of Maryland School of Medicine

“Lung transplantation holds the promise of extending the lives of people with debilitating lung disease, but chronic rejection, with its resulting decline in function, can wipe out that hope. Patients are often as sick as they were before the transplant,” said Aldo T. Iacono, MD, the Hamish S. and Christine C. Osborne Distinguished Professor in Advanced Pulmonary Care at UMSOM and Medical Director, Lung Transplant Program, UMMC.

Katya Prakash-Haft, MD
Katya Prakash-Haft, MD © University of Maryland School of Medicine

Katya Prakash, MD, Assistant Professor of Medicine at UMSOM and an infectious disease specialist at UMMC, said the immediate concern for these two patients was that a dampened immune system could open the door to COVID replication. The solution? Mild immunotherapy that protects key virus-destroying immune cells. “For Anthony, for example, we did not give him a high level of induction for transplant. We gave him just steroid induction instead of anything that would be T cell-depleting, because we know that T cells are very important for fighting the virus.”

E. Albert Reece, MD, PhD, MBA
E. Albert Reece, MD, PhD, MBA © University of Maryland

“COVID-19 has presented new challenges across the field of medicine,” said UMSOM Dean E. Albert Reece, MD, PhD, MBA, University Executive Vice President for Medical Affairs and the John Z. and Akiko K. Bowers Distinguished Professor. “The thoughtful deliberations that led to lung transplants for these two patients illustrate the value of a multidisciplinary approach as we rise to meet the individual care needs of our patients in the COVID era.”

For more than 50 years, UMMC’s transplant team has provided patients with world-class surgical and medical expertise, performing more than 400 transplant surgeries each year.

Watch a related Video >

Featured image: Daniel G. Maluf, MD © University of Maryland School of Medicine


Provided by University of Maryland School of Medicine


About the University of Maryland Medical Center

The University of Maryland Medical Center (UMMC) is comprised of two hospital campuses in Baltimore: the 800-bed flagship institution of the 13-hospital University of Maryland Medical System (UMMS) — and the 200-bed UMMC Midtown Campus, both academic medical centers training physicians and health professionals and pursuing research and innovation to improve health. UMMC’s downtown campus is a national and regional referral center for trauma, cancer care, neurosciences, advanced cardiovascular care, women’s and children’s health, and has one of the largest solid organ transplant programs in the country. All physicians on staff at the downtown campus are clinical faculty physicians of the University of Maryland School of Medicine. The UMMC Midtown Campus medical staff is predominately faculty physicians specializing in diabetes, chronic diseases, behavioral health, long term acute care and an array of outpatient primary care and specialty services. UMMC Midtown has been a teaching hospital for 140 years and is located one mile away from the downtown campus. For more information, visit www.umm.edu.

About the University of Maryland School of Medicine

Now in its third century, the University of Maryland School of Medicine was chartered in 1807 as the first public medical school in the United States. It continues today as one of the fastest growing, top-tier biomedical research enterprises in the world — with 45 academic departments, centers, institutes, and programs; and a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of Medicine and the National Academy of Sciences, and a distinguished two-time winner of the Albert E. Lasker Award in Medical Research. With an operating budget of more than $1.2 billion, the School of Medicine works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic and clinically based care for nearly 2 million patients each year. The School of Medicine has more than $563 million in extramural funding, with most of its academic departments highly ranked among all medical schools in the nation in research funding. As one of the seven professional schools that make up the University of Maryland, Baltimore campus, the School of Medicine has a total population of nearly 9,000 faculty and staff, including 2,500 student trainees, residents, and fellows. The combined School of Medicine and Medical System (“University of Maryland Medicine”) has an annual budget of nearly $6 billion and an economic impact more than $15 billion on the state and local community. The School of Medicine, which ranks as the 8th highest among public medical schools in research productivity, is an innovator in translational medicine, with 600 active patents and 24 start-up companies. The School of Medicine works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visit medschool.umaryland.edu

UK To Play Vital Role In Creating the World’s Most Powerful Neutrino Beam (Physics)

The Science and Technology Facilities Council, or STFC, has signed an agreement with Fermi National Accelerator Laboratory, in the United States, designating how the two organizations will collaborate to build one of the world’s most powerful linear accelerators.

Based at the U.S. Department of Energy’s Fermilab, the PIP-II accelerator, currently under construction, is an essential upgrade to the accelerator complex — and once complete, will enable the world’s most powerful high-energy neutrino beams.

This will allow physicists to study the elusive neutrino particle — known for having very little mass, traveling at nearly the speed of light and possibly holding the secrets to some of the biggest unanswered questions in physics.

The U.K. and the PIP-II accelerator

Today’s agreement sets out how the U.K. will contribute to the PIP-II accelerator project, which provides the engine for the highly-anticipated global science experiment, the Deep Underground Neutrino Experiment, or DUNE, hosted by Fermilab.

DUNE is an international flagship science experiment designed to study neutrinos. Results from studies looking at the neutrino particle could potentially revolutionize our understanding of the universe.

The PIP-II accelerator will also power a suite of other experiments at Fermilab. Its high-power beams can be delivered to multiple experiments at once.

The agreement was signed by STFC’s Executive Chair Mark Thomson and Fermilab Director Nigel Lockyer.

Thomson said:

“Today’s agreement further strengthens the U.K.’s collaboration with our U.S. partners in this crucial project, which sits at the heart of a new globally significant facility at Fermilab.

“STFC’s continued commitment to the Fermilab neutrino program will pave the way for fundamental discoveries into the nature of these most elusive particles, and will provide key insights into the origins and evolution of the universe.”

The U.K.’s involvement in the upgrade has been made possible through the U.K. Government’s £79-million investment in the DUNE experiment, Long-Baseline Neutrino Facility, also known as LBNF, and the new PIP-II accelerator.

This investment, delivered by STFC, has given U.K. scientists and engineers the chance to take leading roles in the management and development of the DUNE far detector, the LBNF neutrino beam targetry and the PIP-II accelerator.

International collaboration

Five nations are collaborating together with the United States to build the powerful PIP-II accelerator: France, India, Italy, Poland and the U.K.

“We are grateful for the world-class expertise and contributions of our international collaborators in building a state-of-the-art particle accelerator powering the world’s most intense neutrino beam. This upgraded technology will drive the next 50 years of global neutrino research in particle physics and the Science and Technology Facilities Council’s contributions will help make this possible,” said Nigel Lockyer, Fermilab director.

In the U.K., STFC will design, build and qualify vital elements of the 215-meter-long particle accelerator, which will accelerate the proton beam to its highest energy.

The main elements currently being developed at STFC’s Daresbury Laboratory are the superconducting cryomodules.

Cryomodules act like a large cooler, working at minus-271 degrees Celsius, to keep the instruments inside, known as radio-frequency cavities, or RF cavities, cryogenically cooled.

RF cavities store the energy needed to accelerate the proton beam, which, when fired into a carbon or beryllium target, will produce a high intensity beam of neutrinos.

By making the RF cavities from a material called niobium — which is both malleable and is superconducting at low temperatures, they become extremely efficient and need very little electrical power to achieve the powerful beam acceleration.

A powerful proton beam striking a target is critical for the study of neutrinos because neutrinos do not interact with other particles very often, which makes them hard to spot, so scientists need to produce lots of neutrinos to detect even one in the massive detectors.

Niobium is a rare metal with only a few sources and suppliers around the world. It is also not an easy material to work with, as it reacts with oxygen in the air at high temperatures — such as the high temperatures found in the welding process.

STFC has been working closely with industry partner The Welding Institute, or TWI, in Cambridge, U.K., which has commissioned the U.K.’s first electron beam welder able to weld in vacuum the high-purity niobium cavities.

Delivering world-class science at Daresbury

Teams of scientists, engineers and technicians at STFC’s Daresbury Laboratory, working with TWI, will construct three cryomodules, each housing six superconducting RF cavities, or SRF cavities. Before installing into the cryomodules, each cavity will be thoroughly tested using STFC’s Daresbury Laboratory SRF Lab, also known as SuRFLab, facility.

Now 18 months into the project, the STFC Daresbury Laboratory team is making its way through major milestones, including the completion of the cryomodule transport system design.

Once the cryomodules are built, each of them will need to be safely transported to Fermilab in the United States. The transport frame has to protect the cryomodule and all its high-tech components during transportation.

Peter McIntosh, PIP-II principal investigator and deputy director, ASTeC at STFC’s Daresbury Laboratory, said:

“The UK, STFC and Daresbury Laboratory in particular have a fantastic opportunity to provide cutting-edge accelerator technologies for ‘powering the heart’ of the international flagship project LBNF/DUNE in the United States.

“I am immensely proud of how the delivery team at Daresbury, along with our industry partners, have adapted to the challenges faced in developing our leading provision of superconducting cryomodules for PIP-II.”

Editor’s Notes

How does PIP-II work?

The PIP-II linear accelerator works by applying an alternating electromagnetic field to a beam of protons.

By attracting the moving particles at just the right time, it causes them to gain speed.

Particles are accelerated under high vacuum in special structures called cavities. Due to the significant amount of power required to accelerate the beam to high energies, even good electrical conductors like copper are unsuitable for use as cavities in this type of machine as they would convert too much power to heat.

Making cavities from superconducting materials such as niobium, significantly increases the machine’s efficiency as superconductors offer virtually zero electrical resistance to the power source. These materials only become superconducting at very low temperatures and must therefore be cryogenically cooled.

The cavities are housed in protective vessels called cryomodules. These insulating devices provide a sealed envelope for the SRF cavities, allowing them to be cooled down to 2 Kelvin or minus-271 degrees Celsius.

Imagery with captions and credits: https://ukri.box.com/s/tooux3op677em2x69a4ndzuiyl344cxp


Featured image: STFC Executive Chair Mark Thomson and Fermilab Director Nigel Lockyer sign the agreement detailing how the organizations will collaborate to build one of the world’s most powerful linear accelerators. Photo: STFC


Provided by Fermilab


About the Science and Technology Facilities Council

The Science and Technology Facilities Council, or STFC, is part of UK Research and Innovation — the U.K. body that works in partnership with universities, research organizations, businesses, charities and government to create the best possible environment for research and innovation to flourish. For more information visit U.K. Research and Innovation.

STFC funds and supports research in particle and nuclear physics, astronomy, gravitational research and astrophysics, and space science and also operates a network of five national laboratories, including the Rutherford Appleton Laboratory and the Daresbury Laboratory, as well as supporting U.K. research at a number of international research facilities including CERN, Fermilab, the ESO telescopes in Chile and many more. Visit https://stfc.ukri.org/ and follow @STFC_Matters for more information.

About Fermilab

Fermilab is America’s premier national laboratory for particle physics research. A U.S. Department of Energy Office of Science laboratory, Fermilab is located near Chicago, Illinois, and operated under contract by the Fermi Research Alliance LLC. Visit Fermilab’s website at https://www.fnal.gov and follow us on Twitter @Fermilab.

The DOE Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time. For more information, visit https://science.energy.gov.

Which Neutrino Is The Heaviest? (Physics)

The question may seem simple, but physicists don’t yet know the answer. New measurements aim to change that.

Neutrinos are the featherweights of the subatomic world. These extremely plentiful, rarely interacting particles are at least 500,000 times lighter than electrons. They are produced in the sun, in exploding stars, and in decay processes on Earth—even ones in your own body. But they interact so infrequently with other matter that you’d hardly know there are so many of them around.

For decades physicists thought these ghostly particles were massless. But experiments revealed that neutrinos do have mass. In fact, there are three types of neutrinos and three different masses. 

Scientists have yet to measure the exact value of any of these masses. But even finding out which neutrino is the heaviest would be a huge leap in our understanding of both neutrinos and the physics that govern our universe. A lot rides on the answer to this puzzle, known as the “neutrino mass hierarchy” or “neutrino mass ordering.”

Neutrinos floating through the sun, sky and earth
Illustration by Sandbox Studio, Chicago with Corinne Mucha

Sun, sky and earth

Neutrinos interact with matter as electron neutrinos, muon neutrinos or tau neutrinos, named after the partner particles they like to hang around with. And neutrinos can oscillate, meaning they shift between those three identities. 

The nuclear processes in the sun’s core generate a deluge of electron neutrinos, many of which turn into muon and tau neutrinos by the time they reach Earth. When high-energy particles strike Earth’s atmosphere, muon neutrinos are created; they may oscillate to electron or tau neutrinos before being detected.

But the three types of neutrinos do not correspond directly to the three masses. Instead, there are three “neutrino mass states” numbered 1, 2 and 3, each with different likelihoods of interacting with matter as an electron neutrino, a muon neutrino or a tau neutrino.

Knowing the rates at which neutrinos oscillate from one type to another allows scientists to make some inferences about the relationships between the three mass states. Careful measurements of solar neutrinos show that the second mass state is only slightly heavier than the first. Measurements of the oscillations of atmospheric and accelerator-made muon neutrinos indicate a large difference in mass between the third mass state and the other two. 

But so far scientists have been unable to determine whether mass state 3 is much heavier or much lighter than states 1 and 2. 

To distinguish between the “normal mass hierarchy” (the order 1, 2, 3) and the “inverted mass hierarchy” (3, 1, 2), researchers fire beams of neutrinos through hundreds of kilometers of solid rock in what are called “long-baseline” neutrino experiments. 

“When a neutrino is traveling, the electron neutrino part of it wants to interact with the electrons in the Earth, and the muon and tau neutrino parts are unaffected,” says Zoya Vallari, a postdoc at Caltech. “This extra impact affects how much oscillation will happen.”

The current leading long-baseline experiments—the NOvA experiment in the United States and the T2K experiment in Japan—have helped refine scientists’ understanding of oscillation. But their measurements of the mass hierarchy so far remain inconclusive.

Illustration of three silhouettes of neutrinos on podiums
Illustration by Sandbox Studio, Chicago with Corinne Mucha

A key puzzle piece

Whether the third neutrino is the lightest or the heaviest carries massive implications (pun intended) for our understanding of these abundant particles. For instance, the source of neutrinos’ mass remains unknown. Determining if it is akin to the Higgs mechanism, which is responsible for other particles’ mass, depends in part on figuring out the hierarchy.

Also, since neutrinos have no electric charge, they could theoretically be their own antimatter particles. Knowing the mass ordering will guide experiments that are testing this hypothesis, a gateway to deep questions about the entire universe.

In pursuit of an answer to the neutrino hierarchy question, the NOvA experiment sends beams of neutrinos and antineutrinos about 500 miles from Fermilab in Illinois to a detector in Ash River, Minnesota. The T2K experiment sends them about 190 miles from J-PARC in Tokai, Japan, to a detector under Mount Ikeno.

Scientists at the experiments compare the rate of neutrino oscillations to the rate of antineutrino oscillations. Any differences between them could help scientists figure out what’s going on with neutrino masses. It could also help them discern why matter won over antimatter in the early universe. We might owe our existence to neutrinos, but we can’t be sure yet.

NOvA currently does not see a strong asymmetry between neutrino and antineutrino oscillations. The T2K experiment has reported tantalizing evidence that neutrinos may oscillate differently than antineutrinos. T2K is currently undergoing an upgrade, and NOvA will continue collecting data through the middle of the decade.

Between the two possibilities, the inverted hierarchy would make several future experiments easier. “So if I could choose, I would choose the inverted hierarchy, but apparently it’s not up to me,” says Pedro Machado, a theorist at the US Department of Energy’s Fermi National Accelerator Laboratory. “And without experimental results, theory doesn’t go forward.”

For Vallari, too, the inverted hierarchy would be more “fun,” but “if I had to place a bet, I would do it on the normal hierarchy,” she says.

Illustration: A path appears in game show board and scientists check it out
Illustration by Sandbox Studio, Chicago with Corinne Mucha

An answer within reach

Unlike many mysteries in particle physics, the neutrino mass hierarchy has a clear path toward resolution. The answer lies well within the capabilities of the next generation of experiments.

The Deep Underground Neutrino Experiment, an international experiment hosted by Fermilab and scheduled to come online in the late 2020s, will send neutrinos on an about 800-mile journey from Illinois to South Dakota—60% farther than NOvA, providing more matter for the neutrinos to interact with. Both experiments receive support from the DOE Office of Science and other funding agencies.

Such a long voyage will amplify the Earth’s influence on neutrino oscillations, enabling researchers to tease out the mass hierarchy, says Vallari, who is part of the DUNE and NOvA collaborations. In Japan, the planned Hyper-Kamiokande upgrade to the T2K experiment should also yield an answer within a few years of data collection.

“I feel pretty confident in saying that in the early 2030s, we should have a definitive measurement of the mass hierarchy from at least one of the experiments,” Vallari says. 

Even then, we will know only the differences between the three neutrino masses—the overall magnitude of the masses will remain a mystery.

Featured image: Illustration by Sandbox Studio, Chicago with Corinne Mucha


Provided by Symmetry

Argonaut Project Launches Design Effort For Super-cold Robotics (Astronomy)

The Argonauts of Greek mythology braved sharp rocks, rough seas, magic and monsters to find the fabled Golden Fleece. A new robotics project at the Department of Energy’s Fermi National Accelerator Laboratory will share that same name and spirit of adventure.

Argonaut’s mission will be to monitor conditions within ultracold particle detectors by voyaging into a sea of liquid argon kept at minus-193 degrees Celsius — as cold as some of the moons of Saturn and Jupiter. The project, funded in March, aims to create one of the most cold-tolerant robots ever made, with potential applications not only in particle physics but also deep space exploration.

Argon, an element commonly found in the air around us, has become a key ingredient in scientists’ quests to better understand our universe. In its liquid form, argon is used to study particles called neutrinos in several Fermilab experiments, including MicroBooNEICARUSSBND and the next-generation international Deep Underground Neutrino Experiment. Liquid argon is also used in dark matter detectors like DEAP 3600ARDMMiniCLEAN and DarkSide-50.

Liquid argon has many perks. It’s dense, which increases the chance that notoriously aloof neutrinos will interact. It’s inert, so electrons knocked free by a neutrino interaction can be recorded to create a 3D picture of the particle’s trajectory. It’s transparent, so researchers can also collect light to “time stamp” the interaction. It’s also relatively cheap — a huge plus, since DUNE will use 70,000 tons of the stuff.

But liquid-argon detectors are not without their challenges. To produce quality data, the liquid argon must be kept extremely cold and extremely pure. That means the detectors must be isolated from the outside world to keep the argon from evaporating or becoming contaminated. With access restricted, diagnosing or addressing issues inside a detector can be difficult. Some liquid-argon detectors, such as the ProtoDUNE detectors at CERN, have cameras mounted inside to look for issues like bubbles or sparks.

“Seeing stuff with our own eyes sometimes is much easier than interpreting data from a sensor,” said Jen Raaf, a Fermilab physicist who works on liquid-argon detectors for several projects including MicroBooNE, LArIAT and DUNE.

The idea for Argonaut came when Fermilab engineer Bill Pellico wondered if it would be possible to make the interior cameras movable. A robotic camera may sound simple — but engineering it for a liquid-argon environment presents unique challenges.

All of the electronics have to be able to operate in an extremely cold, high-voltage environment. All the materials have to withstand the cooling from room to cryogenic temperatures without contracting too much or becoming brittle and falling apart. Any moving pieces must move smoothly without grease, which would contaminate the detector.

“You can’t have something that goes down and breaks and falls off and shorts out something or contaminates the liquid argon, or puts noise into the system,” Pellico said.

Pellico received funding for Argonaut through the Laboratory Directed Research and Development program, an initiative established to foster innovative scientific and engineering research at Department of Energy national laboratories. At this early stage of the project, the team — Pellico, mechanical engineers Noah Curfman and Mayling Wong-Squires, and neutrino scientist Flavio Cavanna — is focused on evaluating components and basic design aspects. The first goal is to demonstrate that it’s possible to communicate with, power and move a robot in a cryogenic environment.

“We want to prove that we can have, at a bare minimum, a camera that can move around and pan and tilt in liquid argon, without contaminating the liquid argon or causing any bubbles, with a reliability that shows that it can last for the life of the detector,” said Curfman.

The plan is to power Argonaut through a fiber-optic cable so as not to interfere with the detector electronics. The fist-sized robot will only get about 5 to 10 watts of power to move and communicate with the outside world.

The motor that will move Argonaut along a track on the side of the detector will be situated outside of the cold environment. The camera will be inside the cold liquid and move very slowly; but that’s not a bad thing — going too fast would create unwanted disturbances in the argon.

“As we get more advanced, we’ll start adding more degrees of freedom and more rails,” said Curfman.

A 3D rendering of Argonaut, which appears to be a silver right angle on top of a black back with a lens on the front and silver studs around the lens.
To keep power requirements low and avoid disturbances in the liquid argon, Argonaut will move slowly along tracks on the side of the detector. Its main function is a movable camera, but the engineers working on it hope to add other features like extendable arms for minor electronics repair. Image courtesy of Bill Pellico, Fermilab

Other future upgrades to Argonaut could include a temperature probe or voltage monitor, movable mirrors and lasers for calibrating the light detectors, or even extendable arms with tools for minor electronics repair.

Much of the technology Argonaut is advancing will be broadly applicable for other cryogenic environments — including space exploration. The project has already garnered some interest from universities and NASA engineers.

Deep space robots “are going to go to remote locations where they have very little power, and the lifetime has to be 20-plus years just like in our detectors, and they have to operate at cryogenic temperatures,” Pellico said. The Argonaut team can build on existing robotics know-how along with Fermilab’s expertise in cryogenic systems to push the boundaries of cold robotics.

Even the exteriors of active interstellar space probes such as Voyagers 1 and 2 don’t reach temperatures as low as liquid argon — they use thermoelectric heaters to keep their thrusters and science instruments warm enough to operate.

“There’s never been a robotic system that operated at these temperatures,” said Pellico. “NASA’s never done it; we’ve never done it; nobody’s ever done it, as far as I can tell.”

Fermilab is supported by the Office of Science of the U.S. Department of Energy. The Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time. For more information, visit science.energy.gov.

Featured image: Argonaut is a robotic system being designed to monitor the interiors of liquid-argon particle detectors, which are kept at minus-193 degrees Celsius. The ProtoDUNE neutrino detector at CERN uses fixed internal cameras to look for issues like bubbles and sparks when filled with 800 tons of liquid argon. Photo: CERN


Provided by Fermilab

ICARUS Gets Ready To Fly (Astronomy)

The ICARUS detector, part of Fermilab’s Short-Baseline Neutrino Program, will officially start its hunt for elusive sterile neutrinos this fall. The international collaboration led by Nobel laureate Carlo Rubbia successfully brought the detector online and is now collecting test data and making final improvements.

When teams began cooling the ICARUS neutrino detector and filling it with 760 tons of liquid argon in early 2020, few people knew how much the world would change in the two months that the fill would take.

“In an ideal world, as soon as the filling is complete and the cryogenic plant is stabilized, then we can activate the detector and start looking for particle tracks basically immediately,” said Angela Fava, the ICARUS commissioning coordinator and deputy technical coordinator.

The ICARUS collaboration includes more than 150 scientists from 23 institutions in Italy, Mexico, Switzerland and the United States. The detector is located at the U.S. Department of Energy’s Fermi National Accelerator Laboratory, located near Chicago.

Restrictions on international travel instituted last year due to the COVID-19 pandemic meant that many European experts could not come to Fermilab in person as planned to start up the detector components. Researchers restructured their plans to get the detector up and running with much of the team working remotely.

The collaboration successfully activated ICARUS in August 2020 and recorded the first particle tracks — from cosmic rays, particles from space that constantly bombard Earth — soon after. Exposed to both the Booster and NuMI neutrino beams at Fermilab, the ICARUS detector has recorded the first muon and electron neutrinos, demonstrating the high-level detection capabilities of the liquid-argon time projection chamber technique.

The team is now working on finishing the system to identify and exclude cosmic-ray signals. They are also making final improvements to the neutrino data acquisition system to prepare the detector for its official first data collection run in fall 2021.

“We’ve been able to do our jobs with most people not moving from their local offices or homes,” said Claudio Montanari, the ICARUS technical coordinator. “Everybody contributed to the best of their ability, which was key to the success of the operation.”

Searching for stealth particles

When the ICARUS detector was originally assembled at the laboratories of the Italian National Institute for Nuclear Physics in Pavia in the early 2000s, it was the largest liquid-argon detector in the world. It began its neutrino-hunting career at Italy’s Gran Sasso National Laboratory in an experiment that ran between 2010 and 2014.

After the experiment in Italy concluded, scientists realized that the ICARUS detector could have a second life at Fermilab, searching for a new type of particle: the sterile neutrino.

An illustration labeled Short-Baseline Neutrino Program at Fermilab shows from left to right: 1) The word Target above a gray building that says protons with an arrow to neutrinos, with horn + decay pipe and 0 below. 2) SBND above a blue building with 270 tons of argon and 110 meters below. 3) MicroBooNE with an orange building and below, 170 tons of argon and 470 meters, and ICARUS with a yellow building and 760 tons of argon and 600 meters below.
ICARUS will be the largest and farthest detector in the Short-Baseline Neutrino program at Fermilab, which examines neutrino oscillations over short distances and looks for hints of elusive sterile neutrinos. Graphic: Fermilab

Scientists already know of three types, or flavors, of neutrinos. The particles are notoriously hard to catch because they interact through only two of the four known forces: gravity and the weak force. But this potential fourth kind of neutrino — if it exists — may not even be sensitive to weak interaction, making detection even trickier. Scientists will have to look carefully at how the different flavors of neutrinos morph into one another, a phenomenon called neutrino oscillation.

Previous experiments saw hints of unusual oscillation, but researchers need more data to determine if sterile neutrinos were responsible for the results. Finding evidence of sterile neutrinos would advance scientists’ knowledge about physics beyond the Standard Model, the theoretical framework that has accurately described almost all known subatomic particle interactions for over 50 years.

To make this happen the ICARUS detector’s two school-bus-size modules were shipped from Gran Sasso to CERN for upgrades. In 2017, the two modules travelled by truck and ship to Fermilab, where they will soon begin hunting for ultra-elusive sterile neutrinos.

ICARUS is one of three particle detectors at Fermilab that will look for indicators of sterile neutrinos as part of the laboratory’s Short-Baseline Neutrino Program, along with the Short-Baseline Neutrino Detector and MicroBooNE. Together, the detectors will analyze how neutrinos oscillate as they travel along their straight beamline path through these detectors.

SBND, situated 110 meters from the start of the neutrino beamline, will provide a snapshot of the neutrinos right after they’re produced. MicroBooNE, located 360 meters farther down the beamline, will provide a second look at the beam composition. The final checkpoint is ICARUS, 600 meters from the start of the beamline. If ICARUS picks up fewer muon neutrinos and more electron neutrinos than expected based on data from SBND and MicroBooNE, “the combination of these things would be the unique signature of the oscillation and therefore of the existence of the sterile neutrino,” said Fava.

Preflight checklist

Getting ICARUS ready to search for signs of sterile neutrinos at Fermilab has involved three distinct stages: installation, activation and commissioning. Installation started in 2018 and included set up of the vacuum chambers, insulation, cryostats and various electronics used to power the detector and collect data.

After electrical safety checks, making sure the vacuum chambers were leak-free and testing the components’ basic functionality, it was time to get the detector ready for activation. Technicians started up the filters, pumps and condensers for the cryogenic systems and began adding the liquid argon in early 2020.

Collaborators from CERN and INFN with historical knowledge of the detector were present for the beginning of the fill. They left with plans to return to Fermilab in April 2020 to help wrap up the process and see the detector through to activation. While they were unable to return in person, the group successfully coordinated with the Fermilab branch of the team to complete the activation last summer.

At an angle from the second floor looking down into a rectangle of multi-colored, interconnected pipes.
ICARUS was filled with 760 tons of super-pure liquid argon in early 2020 and activated in August. Photo: Lynn Allan Johnson, Fermilab

“We were lucky enough not to have any showstoppers,” said Montanari.

With the detector activated, the international collaboration turned its attention to debugging and optimizing the equipment. For example: To capture good neutrino data, the liquid argon inside the detector has to be ultra-pure. When researchers found the argon was less pure than expected, they traced the problem back to slow gaseous argon movement through the recirculation system and took steps to address the flow.

“That’s the life of a physicist — dealing with problems and finding a way of overcoming them,“ Fava said.

Since last year, ICARUS has been in the commissioning phase. The team is testing all of the subsystems to make sure they are in sync and calibrated to collect quality data with minimal noise before the start of official data collection.

Getting ready for takeoff

ICARUS began taking test data from the booster neutrino beam in December 2020. That data is now being used to refine the triggers for deciding what type of signal constitutes a particle “event” worthy of recording.

“The trigger system is one of the most critical components to commission, because it brings together all the other subsystems,” said Fava.

The trigger rate — how frequently the system records an event — must be finely tuned. If it’s too high, the researchers end up sifting through more data than they need to, wasting time and computing power. Too low, and they might miss recording particle interactions that are crucial to making a discovery. The team plans to test the next iteration of trigger logic in May.

In addition to refining the trigger, the ICARUS team will install a final set of cosmic-ray trackers. Roughly 10 cosmic rays hit the detector during each 1.6-millisecond time window used to record a potential neutrino interaction. The cosmic-ray trackers are used to sort out which signal is which.

“If there is an external signal and the timing is correct, we can reject that event on the basis that it was induced by a particle that was coming from outside,” said Montanari. Trackers on the bottom and sides have already been installed — all that’s needed now is to finish the top.

With everything expected to be in place this fall, the experiment will move into the next exciting stage: collecting high-quality data that will be used in scientists’ search for sterile neutrinos.

“I’m really looking forward to making a nice data analysis and seeing what nature is willing to tell us,” Montanari said.

ICARUS is supported by the U.S. Department of Energy Office of Science, the Italian National Institute for Nuclear Physics (INFN) and CERN, the European Organization for Nuclear Research.

Fermilab is America’s premier national laboratory for particle physics and accelerator research. A U.S. Department of Energy Office of Science laboratory, Fermilab is located near Chicago, Illinois, and operated under contract by the Fermi Research Alliance LLC.

The DOE Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time. For more information, please visit science.energy.gov.

Featured image: The ICARUS detector has been collecting test data in preparation for the official start of the physics data collection later this year. The left panel shows an electron neutrino interaction that produced a proton (top track) and an electron, which produced an electromagnetic shower with photons and electrons (bottom tracks). The right panel shows a muon neutrino interaction that produced a proton (short track, top left) and a muon (3.4-meter-long track); a cosmic-ray track independent of the muon neutrino interaction is also visible in the lower half of the image. In both panels, the neutrino beam came from left. Image: ICARUS collaboration


Provided by FermiLab

Unparallelled Insights Into How Our Bodies Develop From A Single Cell (Biology)

Knowing what happens during normal development could help us to understand genetic diseases that arise during pregnancy

New insights into how our bodies come into being from a single cell have been generated by researchers at the Wellcome Sanger Institute, the Wellcome-MRC Cambridge Stem Cell Institute and the University of Cambridge. It is the first study of its kind to describe fetal development in humans by retracing how and when mutations are acquired during pregnancy. The team found higher rates of mutation in early cell divisions, with the ‘decision’ for whether cells become the fetus or become protective tissues like the placenta occurring much earlier than previously thought.

The study, published in Nature, highlights subtle differences between human biology and that of mice, which have previously been relied upon as models for such research. It provides an important reference of mutation under normal conditions for researchers seeking to understand the causes of diseases such as childhood cancers and rare developmental disorders, which often begin in utero.

Studying development is motivated in large part by the desire to understand how our bodies, with their incredible complexity, come into being from a single cell. Understanding how this is coordinated and which cells give rise to others under normal circumstances may help us to identify how and why development can sometimes go wrong.

Tracking development forward through time can be achieved through lineage tracing, which involves ‘marking’ cells in a way that this is passed on to the offspring of a cell. This allows you to map how cells are related to each other and create a ‘family tree’. This technique requires manipulation of the developing embryo, however, so is not ethical or feasible in humans. Study of human development has therefore been limited primarily to careful microscopy, with much of our knowledge of development based on model organisms such as zebra fish and mice.

For this study, researchers at the Wellcome Sanger Institute and Wellcome-MRC Cambridge Stem Cell Institute collected eight week and eighteen week-old haematopoietic stem and progenitor cells (HSPCs) from human fetal tissue1 and grew them into 511 single-cell-derived colonies.

DNA from hundreds of these colonies underwent whole genome sequencing to identify somatic mutations that could be used to trace the lineage of blood cells back to the first division of the embryo. Looking for these ‘marker’ mutations in tiny biopsies from other tissues then allowed the researchers to see when these tissues diverged from the blood cell population.

The team found that by week eight of development, cells had acquired 25 mutations and 42 by week 18, indicating a higher rate of mutation in early cell divisions. They also timed the ‘decision’ for which cells would become the fetus and which would become extra-embryonic tissue, which includes the placenta and yolk-sac, occurred between four and 16 cells.

“The findings of this study have challenged some of our previous understanding about how the fetus grows from one cell during the earliest stages of life, such as when the embryonic and extra-embryonic tissues diverge. This kind of resolution will be essential if we are to try to pinpoint the origin of diseases that have their roots in development.”

— Dr Anna Ranzoni,a first author of the study from the Wellcome-MRC Cambridge Stem Cell Institute and Department of Haematology at the University of Cambridge

There was also evidence that the extra-embryonic mesoderm and the blood cells that deliver oxygen to the fetus in the first trimester of pregnancy arise from the hypoblast, which is generally considered an extra-embryonic tissue – a clear difference between human and mouse biology.

“Mice have been an excellent model for studying human development, but there was always the question of whether mouse biology was the same as our biology or merely similar. We found evidence that primitive human blood cells arise from the hypoblast, which is different to mice, settling a question that has been debated for decades.”

Dr Michael Spencer Chapman,a first author of the study from the Wellcome Sanger Institute

These insights into the precise biological processes involved in human development provide an essential reference of developmental dynamics under normal circumstances for those studying childhood cancers, which often begin in utero, as well as rare developmental disorders.

“Our study provides important insights into the incredibly complex biological processes at work in the earliest weeks of life, which have simply not been possible until now. This resource will be an invaluable reference for what happens under normal circumstances, so that we can start to unravel what happens when development goes wrong.”

Dr Ana Cvejic,a senior author of the study from the Wellcome-MRC Cambridge Stem Cell Institute and Department of Haematology at the University of Cambridge

More information

Notes to Editors:

1 Human tissue used in the study was provided by the Human Developmental Biology Resource, in accordance with ethical approval by the NHS Health Research Authority (HRA).

Publication:

Michael Spencer Chapman, Anna Maria Ranzoni and Brynelle Myers et al. (2021). Lineage tracing of human development through somatic mutations. Nature. DOI: https://doi.org/10.1038/s41586-021-03548-6

Funding:

This work was supported by the European Research Council, EMBO, the Medical Research Council (MRC) and Wellcome.

Featured image credit: K Hardy_CC BY 4.0


Provided by Wellcome Sanger Institute

Astronomers Presented An Algorithm Which Computes N-point Correlation Functions Faster Than Any (Cosmology / Instrumentation)

Ever wanted to do cosmology from the four-point or the five-point function? Oliver Philcox and colleagues introduced a new estimator which computes the N-point galaxy correlation functions of Ng galaxies in O(Ng^2) time, *far* faster than the naive O(Ng^N) scaling!

𝑁-point correlation functions (NPCFs), or their Fourier-space counterparts, the polyspectra, are amongst the most powerful tools in the survey analyst’s workshop. These encode the statistical properties of the galaxy overdensity field at sets of 𝑁 positions, and may be compared to data to give constraints on properties such as the Universe’s expansion rate and composition.

Most inflationary theories predict density fluctuations in the early Universe to follow Gaussian statistics; in this case all the information is contained within the two-point correlation function (2PCF), or, equivalently, the power spectrum. For a homogeneous and isotropic Universe, both are simple functions of one variable, and have been the subject of almost all galaxy survey analyses to date.

The late-time Universe is far from Gaussian. Statistics beyond the 2PCF are of importance since the bulk motion of matter in structure formation causes a cascade of information from the 2PCF to higher-order statistics, such as the three- and four-point functions (3PCF and 4PCF).

“Correlation functions form the cornerstone of modern cosmology, and their efficient computation is a task of utmost importance for the analysis of current and future galaxy surveys.”

Now, Oliver Philcox and colleagues presented a new estimator/algorithm for efficiently computing the N-point galaxy correlation functions of Ng galaxies in O(Ng^2) time, *far* faster than the naive O(Ng^N) scaling!

By decomposing the N-point correlation function (NPCF) into an angular basis composed of products of spherical harmonics, the estimator becomes *separable* in r1, r2, r3, etc. It can be computed as a weighted sum of *pairs* of galaxies, for any N.

© Oliver Philcox et al

The algorithm is included in their new code *encore*: https://github.com/oliverphilcox/encore

It is written in C++ and computes the 3PCF, 4PCF, 5 PCF and 6 PCF of a BOSS-like galaxy survey in ~ 100 CPU-hours, including applying corrections for the non-uniform survey geometry. It can also be run on a GPU!

Whilst the complexity is technically O(Ng^2), for N>3, they practically found computation-time to scale *linearly* with the number of galaxies unless the density is very large! Below figure is the measurement of a few 5PCF components:

© Oliver Philcox et al.

This will allow future surveys like Euclid, DESI, and Roman to include higher-point functions in their analyses, giving sharper constraints on cosmological parameters, and testing new physics such as parity-violation!

Featured image: Strong scaling of the encore code: dependence of runtime, 𝑇 , on the number of CPU cores on a single node for different test cases. Dashed lines indicate linear relationships, and are calibrated at the single-CPU time © Philcox et al.


Reference: Oliver H. E. Philcox, Zachary Slepian, Jiamin Hou, Craig Warner, Robert N. Cahn, Daniel J. Eisenstein, “ENCORE: Estimating Galaxy N-point Correlation Functions in O(N2g) Time”, Arxiv, pp. 1-24, 2021. https://arxiv.org/abs/2105.08722


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