The researchers said the results indicate that rocatinlimab has the potential to change the genetic makeup of a person’s atopic dermatitis for the long term, and possibly help sustain lasting results without continued use. Rocatinlimab inhibits OX40 — an immune molecule involved in activating inflammatory cells that play a key role in the development of atopic dermatitis and other inflammatory diseases.

“Atopic dermatitis, the most common type of eczema, is a debilitating chronic inflammatory skin disease that affects 1 in 10 Americans and millions of people worldwide,” said Emma Guttman, MD, PhD,Waldman Professor and System Chair, The Kimberly and Eric J. Waldman Department of Dermatology; Director, Center of Excellence in Eczema; and Director, Laboratory of Inflammatory Skin Diseases, at the Icahn School of Medicine at Mount Sinai. “It often develops at a very young age, causing the skin to become inflamed, red, extremely itchy, painful, and very dry — all symptoms that greatly affect a patient’s quality of life. We are very optimistic about the results of this trial and the potential for disease modification and long-lasting effects to improve patients’ quality of life.”

In this phase 2b multicenter, double-blind, placebo-controlled study, 274 patients were recruited and (rocatinlimab: n=217; placebo: n=57) randomly assigned 1:1:1:1:1 to rocatinlimab every four weeks (150 mg or 600 mg) or every two weeks (300 mg or 600 mg) or subcutaneous placebo up to week 18, with an 18-week active-treatment extension and 20-week follow-up. This trial was conducted at 65 sites within the United States, Canada, Japan, and Germany.

Percent change from baseline in the Eczema Area and Severity Index (EASI) score was assessed as the primary endpoint at week 16, and significance versus placebo was achieved with all active rocatinlimab doses (-48% to -61%) doses compared to placebo (-15%). All active dose cohorts also continued improving after week 16, and most patients maintained the response for at least 20 weeks off treatment.

The results support rocatinlimab as a safe and effective treatment for moderate to severe atopic dermatitis, with potentially long-lasting efficacy and disease modification. Adverse events reported were generally similar between rocatinlimab groups. Common adverse events during the double-blind period included fever, chills, headache, aphthous ulcers (canker sores), and nausea.

“At week 36, all participants had been on the treatment for at least 18 weeks,” added Dr. Guttman, senior author of the study. “By this time, we saw that while the drug achieved the primary endpoints in all doses versus the placebo, it’s also a drug that improves over time, which is really unusual and unique among currently available treatment options.”

Researchers plan to continue this investigation in a phase 3 program in 2023. Future studies will also include a larger study population, longer follow-up, and exploration of combination therapy (such as rocatinlimab plus topical corticosteroids).

The trial is registered on ClinicalTrials.gov (NCT03703102).

CanRisk-Prostate, developed by researchers at the University of Cambridge and The Institute of Cancer Research, London, will be incorporated into the group’s CanRisk web tool, which has now recorded almost 1.2 million risk predictions. The free tool is already used by healthcare professionals worldwide to help predict the risk of developing breast and ovarian cancers.

Prostate cancer is the most common type of cancer in men. According to Cancer Research UK, over 52,000 men are diagnosed with the disease each year and there are more than 12,000 deaths. Over three-quarters (78%) of men diagnosed with prostate cancer survive for over ten years, but this proportion has barely changed over the past decade in the UK.

Testing for prostate cancer involves a blood test that looks for a protein known as a prostate-specific antigen (PSA) that is made only by the prostate gland; however, it is not always accurate. According to the NHS website, around three in four men with a raised PSA level will not have cancer. Further tests, such as tissue biopsies or MRI scans, are therefore required to confirm a diagnosis.

Professor Antonis Antoniou from the Department of Public Health and Primary Care at the University of Cambridge said: “Prostate cancer is the most common cancer in men in the UK, but population-wide screening based on PSA isn’t an option: these tests are often falsely positive, which means that many men would then be biopsied unnecessarily. Also, many prostate tumours identified by PSA tests are slow-growing and would not have been life-threatening. The treatment of these tumours may do more harm than good.

“What we need is a way of identifying those men who are at greatest risk, allowing us to target screening and diagnostic tests where they are most needed, while also reducing the harms for those men who have low risk of the disease. This is what CanRisk-Prostate aims to do. For the first time, it combines information on the genetic makeup and prostate cancer family history, the main risk factors for the disease, to provide personalised cancer risks.”

Prostate cancer is one of the most genetically determined of common cancers. Inherited faulty versions of the BRCA2, HOXB13 and possibly BRCA1 genes are associated with moderate-to-high risk of prostate cancer, though such faults are rare in the population. In addition, there are several hundred more common genetic variants that each confer a lower risk, but in aggregate they act like ‘volume control’ that moderate or increase the prostate cancer risk.

Writing in the Journal of Clinical Oncology, the researchers — supported by Cancer Research UK — describe the development of the first comprehensive prostate cancer model using genetic and cancer family history data from almost 17,000 families affected by prostate cancer. It uses data on rare genetic faults in moderate-to-high-risk genes and a risk score based on 268 common low-risk variants, together with detailed cancer family history, to predict the future risks.

One in six men (16%) will develop prostate cancer by the time they are 85 years old. Using the model, the team found that the predicted risk was higher for men who had a father diagnosed with prostate cancer — 27% if the father was diagnosed at an older age (80 years) but as high as 42% if the father was diagnosed at a young age (50 years).

The risks were considerably higher for men with genetic faults. For example, 54% of men who carry an alteration in the BRCA2 gene would develop prostate cancer — however, among men with BRCA2 gene faults, the risks were substantially lower if they also had a small number of the low-risk variants, but much higher if they also had a large number of the low-risk variants.

In practice, say the researchers, clinicians will be able to use any combination of cancer family history, rare and common genetic variants to provide a personalised risk.

To validate their model, the team ran the risk model on an independent cohort of over 170,000 men recruited to UK Biobank, a biomedical database and research resource containing anonymised genetic, lifestyle and health information from half a million UK participants. All of these men were free from prostate cancer when they were recruited to the study, but more than 7,600 developed prostate cancer within the subsequent ten years.

When validating their model, the researchers found that 86% of the UK Biobank participants who developed cancer were in the half of men with the highest predicted risks, which suggests that it may be possible to target screening and diagnostic tests to the subgroup of the population at highest risk, among whom the majority of the cancers will occur.

Dr Tommy Nyberg from the MRC Biostatistics Unit at Cambridge said: “We’ve created the most comprehensive tool to date for predicting a man’s risk of developing prostate cancer. We hope this will help clinicians and genetic counsellors assess their clients’ risk and provide the appropriate follow-up.

“Over the next 12 months, we aim to build this tool into the widely used CanRisk tool, which will facilitate the risk-based clinical management of men seen in family cancer clinics and enable risk-adapted early detection approaches to the population at large.”

Professor Ros Eeles from The Institute of Cancer Research, London and co-author on the study said: “This is an important step forward as it will enable clinicians to have conversations with men about their individual risk of prostate cancer based on the most accurate computer model to date. This will help them in making decisions about screening.”

So far, the data used to develop CanRisk-Prostate has been from men of European ancestry. The team hope to be able to include data from men of other ethnicities as further research is undertaken.

The University of Cambridge recently launched the Early Cancer Institute with the aim of detecting cancer early enough to cure it. It is the first physical institute in the UK dedicated to early cancer. A new Cambridge Cancer Research Hospital is also planned for the near future, bringing together clinical and research expertise in a new, world-class hospital, designed in partnership with patients.

There is also an Early Detection and Diagnosis centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust where a prostate risk clinic has been established to translate these findings into targeted screening programmes.

The research was supported by the Cancer Research UK-funded CanRisk programme. Additional support for CanRisk-Prostate was provided by Prostate Cancer UK, The Institute of Cancer Research, Everyman Campaign, National Cancer Research Network UK, National Cancer Research Institute, NIHR Cambridge Biomedical Research Centre and the NIHR Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust.

The demonstration system consists of a flight laser transceiver, a ground laser transmitter and a ground laser receiver. The downlink transmitter has been installed on the Psyche spacecraft, which will travel to a unique metal asteroid also called Psyche, which orbits the Sun between Mars and Jupiter.

Malcolm. W. Wright, from the Jet Propulsion Laboratory, California Institute of Technology, will present the functional and environmental test results of the DSOC downlink flight laser transmitter assembly and ground uplink transmitter assembly at the Optica Laser Congress, 11 — 15 December 2022.

Validating deep space optical communications will allow streaming back high-definition imagery during robotic and manned exploration of planetary bodies, utilizing resources comparable to state-of-art radio-frequency telecommunications.

Transmitting into deep space

Although free-space optical communications from space to ground have been demonstrated at distances as far away as the moon, extending such links to deep space ranges requires new types of laser transmitters. The downlink flight laser must have a high photon efficiency while supporting near kilowatt peak power. The uplink laser requires multi-kilowatt average powers with narrow linewidth, good beam quality and low modulation rates.

The flight laser transmitter assembly uses a 5 W average power Er-Yb co-doped fiber-based master oscillator power amplifier laser with discrete pulse widths from 0.5 to 8 ns in a polarized output beam at 1550 nm with an extinction ratio of more than 33 dB. The laser passed verification and environmental tests before being integrated into spacecraft. End-to-end testing of the flight laser transmitter with the ground receiver assembly also validated the optical link performance for a variety of pulse formats and verified the interface to the DSOC electronics assembly.

Launching a new approach

The ground uplink transmitter assembly can support optical links with up to 5.6 kW average power at 1064 nm. It includes ten kilowatt-class continuous wavelength fiber-based laser transmitters modified to support the modulation formats. A remotely placed chiller provides thermal management for the lasers and power supplies. The uplink laser will also provide a light beacon onto which the flight transceiver can lock.

“Using multiple individual laser sources that propagate through sub-apertures on the telescope’s primary mirror relieves the power requirement from a single source,” said Wright. “It also allows atmospheric turbulence mitigation and reduces the power density on the telescope mirrors.”

Now that spacecraft-level testing is complete, the Psyche spacecraft — with the flight laser transceiver aboard — will be integrated into a launch vehicle. The DSOC technology demonstration will begin shortly after launch and continue for one year as the spacecraft travels away from Earth and eventually performs a flyby of Mars.

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One possible explanation is that a shell of dust envelops our solar system all the way out to Pluto, and is reflecting sunlight. Seeing airborne dust caught in sunbeams is no surprise when cleaning the house. But this must have a more exotic origin. Because the glow is so smoothy distributed, the likely source is innumerable comets — free-flying dusty snowballs of ice. They fall in toward the Sun from all different directions, spewing out an exhaust of dust as the ices sublimate due to heat from the Sun. If real, this would be a newly discovered architectural element of the solar system. It has remained invisible until very imaginative and curious astronomers, and the power of Hubble, came along.

Aside from a tapestry of glittering stars, and the glow of the waxing and waning Moon, the nighttime sky looks inky black to the casual observer. But how dark is dark?

To find out, astronomers decided to sort through 200,000 images from NASA’s Hubble Space Telescope and made tens of thousands of measurements on these images to look for any residual background glow in the sky, in an ambitious project called SKYSURF. This would be any leftover light after subtracting the glow from planets, stars, galaxies, and from dust in the plane of our solar system (called zodiacal light).

When researchers completed this inventory, they found an exceedingly tiny excess of light, equivalent to the steady glow of 10 fireflies spread across the entire sky. That’s like turning out all the lights in a shuttered room and still finding an eerie glow coming from the walls, ceiling, and floor.

The researchers say that one possible explanation for this residual glow is that our inner solar system contains a tenuous sphere of dust from comets that are falling into the solar system from all directions, and that the glow is sunlight reflecting off this dust. If real, this dust shell could be a new addition to the known architecture of the solar system.

This idea is bolstered by the fact that in 2021 another team of astronomers used data from NASA’s New Horizons spacecraft to also measure the sky background. New Horizons flew by Pluto in 2015, and a small Kuiper belt object in 2018, and is now heading into interstellar space. The New Horizons measurements were done at a distance of 4 billion to 5 billion miles from the Sun. This is well outside the realm of the planets and asteroids where there is no contamination from interplanetary dust.

New Horizons detected something a bit fainter that is apparently from a more distant source than Hubble detected. The source of the background light seen by New Horizons also remains unexplained. There are numerous theories ranging from the decay of dark matter to a huge unseen population of remote galaxies.

“If our analysis is correct there’s another dust component between us and the distance where New Horizons made measurements. That means this is some kind of extra light coming from inside our solar system,” said Tim Carleton, of Arizona State University (ASU).

“Because our measurement of residual light is higher than New Horizons we think it is a local phenomenon that is not from far outside the solar system. It may be a new element to the contents of the solar system that has been hypothesized but not quantitatively measured until now,” said Carleton.

Hubble veteran astronomer Rogier Windhorst, also of ASU, first got the idea to assemble Hubble data to go looking for any “ghost light.” “More than 95% of the photons in the images from Hubble’s archive come from distances less than 3 billion miles from Earth. Since Hubble’s very early days, most Hubble users have discarded these sky-photons, as they are interested in the faint discrete objects in Hubble’s images such as stars and galaxies,” said Windhorst. “But these sky-photons contain important information which can be extracted thanks to Hubble’s unique ability to measure faint brightness levels to high precision over its three decades of lifetime.”

A number of graduate and undergraduate students contributed to project SKYSURF, including Rosalia O’Brien, Delondrae Carter and Darby Kramer at ASU, Scott Tompkins at the University of Western Australia, Sarah Caddy at Macquarie University in Australia, and many others.

The past decade has seen a global surge in adolescent use of e-cigarettes/vaping, cannabis, and prescription opioids not-taken-as-prescribed. This surge has been aided, in some cases, by entirely new methods of substance use and delivery — such as cannabis edibles and vaping — as well as youths’ lower perceptions of harm, and/or greater accessibility. These substances have “invisible symptoms” to adults and, in turn, can be much harder-to-detect by parents, caregivers, and health care providers.

“What is so different today than in past generations is that parents and providers could really rely on what we traditionally think of as obvious signs to tell if kids were using. Did they come home smelling like cigarettes or cannabis? Is there alcohol on their breath? Are they slurring their speech?” said Feldstein Ewing. “While some of these things still work, where we run into trouble today is that, more and more, the substances that kids are using are just not as easy to spot. And, the signs are not as conspicuous as they once were.”

This is especially concerning when it comes to the still-developing adolescent brain. While the ways in which these substances affect the brain are under ongoing investigation, there is evidence to suggest that their use during adolescence may adversely affect long-term neural and behavioral development. Also, because their use can be hard to identify by adults, youth may be more likely to transition from experimentation to heavier, hazardous use in a manner that is often undetected by providers or caregivers until there is a substantial impact on school, work, or their personal or family relationships.

In addition to her position as a professor of psychology within URI’s College of Health Sciences, Feldstein Ewing is a child/adolescent clinician with over two decades experience working in adolescent substance use prevention and treatment.

“Families would come to me for treatment for youth engaged in heavy substance use and say, ‘I didn’t even know my kid was using.’ Parents are having a hard time and now that many states are making cannabis legal for recreational use, I think parents and providers are really feeling at a loss to navigate this,” she said.

The Viewpoint is primarily geared toward adolescent health care providers who are in a unique position to assist in detection as well as facilitating access to treatment services, due to their recurring appointments with young people. But, says Feldstein Ewing, parents and caregivers may also find the recommendations helpful. Opening the lines of communication with young people can provide adolescents a platform in which to discuss current life concerns, including substance use. One straightforward way that parents or caregivers can do this, she says, is by increasing the frequency of family dinners.

“It’s definitely hard today — families are busy with work, school, sports and other activities. But the point is, if that can be a place where you are seeing and connecting with your kids every day, it will be easier to notice small changes in behavior or other patterns. It doesn’t even have to be a dinner, it can also take the form of drives or walks — if you provide a forum to talk about ‘regular stuff’ it will be easier for them and for you to bring these things up.”

Provider use of well-validated substance use screening tools, specific for adolescents, is recommended as part of the framework — as is active listening and the use of open-ended questions. Providers may also be able to communicate things that parents can’t, such as the risks and potential longer-term effects associated with such substances. By the same token, adolescents may be more likely to open up to providers in the patient-provider context. Parents and providers may find that asking about peer use can provide helpful insights while being perceived as less intrusive to young people.

“The most important part of all this is that this is new territory — and that’s OK. The things we have done historically no longer translate well for these new forms of substances, so we need to readjust. Providers and parents often do not feel comfortable discussing topics like substance use because they are not sure what to do if teens say, ‘Yes , we are using’,” said Feldstein Ewing. “But when it comes down to it, even though we often think about teens as spending most of their time with their friends, parents still have the biggest influence on their teen’s behavior. So knowing where they are, who they are hanging out with, and being open to having these sometimes scary conversations on a consistent basis is important. And, providers have a critical role to play in supporting kids and families.”

Feldstein Ewing is Director of URI’s Adolescent Neuroscience Center for Health Resilience, which focuses on adolescent translational approaches, increasing understanding of the links between basic biological mechanisms — like the brain — and effective treatments for reducing adolescent health risk behaviors. Several of Feldstein Ewing’s trainees contributed to the piece, including lead author, Genevieve Dash, M.S., at the University of Missouri; as well as Karen Hudson, M.C.R., at URI; and her URI graduate students Emily Kenyon, Emily Carter, and Diana Ho.

Astronomers are hoping to tease out which of these origin stories is more likely by analyzing the 69 confirmed binaries detected to date. But a new study finds that for now, the current catalog of binaries is not enough to reveal anything fundamental about how black holes form.

In a study appearing in the journal Astronomy and Astrophysics Letters, MIT physicists show that when all the known binaries and their spins are worked into models of black hole formation, the conclusions can look very different, depending on the particular model used to interpret the data.

A black hole’s origins can therefore be “spun” in different ways, depending on a model’s assumptions of how the universe works.

“When you change the model and make it more flexible or make different assumptions, you get a different answer about how black holes formed in the universe,” says study co-author Sylvia Biscoveanu, an MIT graduate student working in the LIGO Laboratory. “We show that people need to be careful because we are not yet at the stage with our data where we can believe what the model tells us.”

The study’s co-authors include Colm Talbot, an MIT postdoc; and Salvatore Vitale, an associate professor of physics and a member of the Kavli Institute of Astrophysics and Space Research at MIT.

A tale of two origins

Black holes in binary systems are thought to arise via one of two paths. The first is through “field binary evolution,” in which two stars evolve together and eventually explode in supernovae, leaving behind two black holes that continue circling in a binary system. In this scenario, the black holes should have relatively aligned spins, as they would have had time — first as stars, then black holes — to pull and tug each other into similar orientations. If a binary’s black holes have roughly the same spin, scientists believe they must have evolved in a relatively quiet environment, such as a galactic disk.

Black hole binaries can also form through “dynamical assembly,” where two black holes evolve separately, each with its own distinct tilt and spin. By some extreme astrophysical processes, the black holes are eventually brought together, close enough to form a binary system. Such a dynamical pairing would likely occur not in a quiet galactic disk, but in a more dense environment, such as a globular cluster, where the interaction of thousands of stars can knock two black holes together. If a binary’s black holes have randomly oriented spins, they likely formed in a globular cluster.

But what fraction of binaries form through one channel versus the other? The answer, astronomers believe, should lie in data, and particularly, measurements of black hole spins.

To date, astronomers have derived the spins of black holes in 69 binaries, which have been discovered by a network of gravitational-wave detectors including LIGO in the U.S., and its Italian counterpart Virgo. Each detector listens for signs of gravitational waves — very subtle reverberations through space-time that are left over from extreme, astrophysical events such as the merging of massive black holes.

With each binary detection, astronomers have estimated the respective black hole’s properties, including their mass and spin. They have worked the spin measurements into a generally accepted model of black hole formation, and found signs that binaries could have both a preferred, aligned spin, as well as random spins. That is, the universe could produce binaries in both galactic disks and globular clusters.

“But we wanted to know, do we have enough data to make this distinction?” Biscoveanu says. “And it turns out, things are messy and uncertain, and it’s harder than it looks.”

Spinning the data

In their new study, the MIT team tested whether the same data would yield the same conclusions when worked into slightly different theoretical models of how black holes form.

The team first reproduced LIGO’s spin measurements in a widely used model of black hole formation. This model assumes that a fraction of binaries in the universe prefer to produce black holes with aligned spins, where the rest of the binaries have random spins. They found that the data appeared to agree with this model’s assumptions and showed a peak where the model predicted there should be more black holes with similar spins.

They then tweaked the model slightly, altering its assumptions such that it predicted a slightly different orientation of preferred black hole spins. When they worked the same data into this tweaked model, they found the data shifted to line up with the new predictions. The data also made similar shifts in 10 other models, each with a different assumption of how black holes prefer to spin.

“Our paper shows that your result depends entirely on how you model your astrophysics, rather than the data itself,” Biscoveanu says.

“We need more data than we thought, if we want to make a claim that is independent of the astrophysical assumptions we make,” Vitale adds.

Just how much more data will astronomers need? Vitale estimates that once the LIGO network starts back up in early 2023, the instruments will detect one new black hole binary every few days. Over the next year, that could add up to hundreds more measurements to add to the data.

“The measurements of the spins we have now are very uncertain,” Vitale says. “But as we build up a lot of them, we can gain better information. Then we can say, no matter the detail of my model, the data always tells me the same story — a story that we could then believe.”

This research was supported in part by the National Science Foundation.