A single-molecule switch that operates via destructive quantum interference has the highest on/off ratio for a device of its kind. The switch, developed by researchers at Columbia University in the US and the University of Glasgow, UK, consists of a molecule six nanometres long (similar in size to the smallest computer chips on the market) and a special central unit. It can carry currents of over 0.1 microamps in its “on” state and could allow for faster, smaller and more energy-efficient transistors.
Transistors are the workhorses of modern electronics, and their size has decreased steadily over the last half century or so, enabling more and more to be packed onto computer chips. This relentless downsizing can’t continue forever, though, and methods to make ever-smaller transistors in silicon are rapidly approaching the material’s size and performance limits. Researchers are therefore exploring new types of switching mechanisms that can be used with different materials.
Nonlinear effects
In the nanoscale structures that Latha Venkataraman and her group study at Columbia, quantum mechanical effects dominate, and electrons behave as waves rather than particles. These waves can interfere either constructively or destructively. For two constructively-interfering waves, the amplitude of the resulting wave is greater than the sum of the individual waves. In destructive interference, two waves can completely cancel each other out.
Researchers have predicted that such nonlinear effects should allow single-molecule switches to exhibit large ratios of “on” to “off” currents. However, making transistors out of these molecules is no easy task.
One major challenge is current leakage. In an ideal transistor, current flows only in the “on” state, while in the “off” state it is blocked. While real devices are not so clear-cut, Venkataraman explains that the amount of current flowing in the on- and off-states must nevertheless be very different. Otherwise, the device behaves like a leaky hosepipe in which it is hard to tell whether the valve (that is, the on-off switch) is open or closed.
Strongly supressing current in the off-state
Most previous designs for molecular transistors produced leaky devices because they used short molecules for which the difference between the on and off states was small.
In their new work, Venkataraman’s team instead used six-nanometre-long fluorene oligomer molecules synthesized by Peter Skabara and his group at Glasgow. “We observed transport across a six-nanometre molecular wire, which is remarkable since transport across such long length scales is rarely observed,” she explains. “In fact, this is the longest molecule we have ever measured in our lab.”
The molecules are also easy to trap between metal contacts, making it possible to create stable, single-molecule circuits that sustain applied voltages of more than 1.5 V. An additional central benzothiadiazole unit enhances destructive interference between different electronic energy levels in the molecules and strongly supresses current in the devices’ off state, so mitigating current leakage. This electronic structure makes the relationship between (tunnelling) current and applied voltage highly nonlinear, Venkataraman says, and produces a ratio of 104 between the on- and off-state current.
The design and development of active, stable and selective electrocatalysts for energy conversion reactions is key for the transition towards a sustainable future. Tailoring the structure of the electrochemical interface at the atomic and molecular levels allows us to understand the structure–function relations and enhance the electrocatalytic performance for renewable-energy conversion. In this webinar, Dr María Escudero-Escribano will present some recent strategies aiming to understand and engineer the interfacial structure and properties for oxygen and carbon monoxide/carbon dioxide electrocatalysis.
The first part will be focused on the oxygen reduction and evolution reactions (ORR and OER, respectively), which slow kinetics and limits the performance of proton exchange membrane fuel cells and electrolysers. She will present our work on oxygen electrocatalysis, from model studies on well-defined surfaces to the development of self-supported high-surface area nanostructured catalysts for ORR and OER (see figure, left).
In the second part, María will present our recent work on Cu single-crystalline electrodes in contact with different electrolytes aiming to understand the structure sensitivity for CO2 and CO reduction (see figure, right). We have studied the effect of pH, anion adsorption, and potential dependence of interfacial processes for CO reduction. We show how model studies are essential to understand the structure–property relationships and design efficient electrocatalysts for sustainable energy conversion.
Dr María Escudero-Escribano is an Assistant Professor of Chemistry at the University of Copenhagen, Denmark, where she leads the NanoElectrocatalysis and Sustainable Chemistry group. Her research group investigates tailored electrochemical interfaces for renewable-energy conversion and electrosynthesis of green fuels and value-added chemicals. She obtained her PhD from the Autonomous University of Madrid, Spain, in 2011, for her work on electrocatalysis and surface nanostructuring using well-defined electrode surfaces. She carried out her postdoctoral research on oxygen electrocatalysts for fuel cells and water electrolysers at the Technical University of Denmark and Stanford University, US, before moving to the University of Copenhagen in 2017. María is chair of the Danish Electrochemical Society since 2018. She was awarded a Villum Young Investigator grant from the Villum Foundation in 2018 and is a PI of the Center for High Entropy Alloy Catalysis (CHEAC) from the Danish National Research Foundation. She has received numerous national and international awards in recognition of her early-career achievements, including the European Young Chemist Award (Gold Medal) 2016, the Princess of Girona Scientific Research Award 2018, the Energy Technology Division Supramaniam Srinivasan Young Investigator Award 2018 from The Electrochemical Society, the Spanish Royal Society of Chemistry Young Researchers Award 2019, and the Clara Immerwahr Award 2019 from UniSysCat.
An international team of researchers has developed an innovative system that can sterilize medical tools using solar heat. The device could help to maintain safe, sterile equipment at low cost in remote locations, and could prove particularly valuable in developing regions of the world.
The sterilization of invasive medical equipment is a critical step in mitigating infection risks in healthcare settings. However, although common sterilization procedures using saturated steam in a pressurized chamber – known as an autoclave – are effective and standardized worldwide, they can be a challenge to use in remote areas without reliable energy sources.
In an effort to address this issue, a team of researchers at Massachusetts Institute of Technology (MIT) and the Indian Institute of Technology Bombay have developed a novel way of generating high-temperature, high-pressure steam passively by using a portable solar energy collector. This steam is used to drive a typical small-clinic autoclave. The researchers describe their system in the journal Joule.
As MIT graduate student Lin Zhao – who wrote the paper alongside MIT professors Evelyn Wang and Gang Chen, and colleagues at MIT and IIT Bombay – explains, the researchers started to work on this problem after realising that a transparent silica aerogel material they had originally developed for large-scale concentrating solar-thermal power applications could also enable a “unique solution to medical sterilization with solar energy”.
A transparent thermally insulating aerogel reduces heat loss from the solar-driven steam generator. (Courtesy: Lin Zhao)
After some research, the team found that the thermally insulating aerogel is particularly suitable because its operating temperature of around 125°C – beyond the 100°C limit of conventional passive solar water heaters, but without the complexity and cost of an active tracking system – is perfect for solar-powered sterilization applications.
“Because of [the system’s] relatively small-scale, it can also benefit greatly from a simple, modular design and it can have a high impact on people’s lives, especially in the developing regions,” says Zhao.
In a field test performed in Mumbai, the team simulated a clinical sterilization process by using a standard autoclave indicator tape – designed to change colour when sterilization conditions meet minimum exposure requirements – in a test chamber.
“The same tape is widely used in hospitals and clinics worldwide to verify the efficacy of their autoclaves,” Zhou explains. “As we showed in our paper, the tape changed colour after we completed the sterilization cycle in our device, validating the device’s sterilization efficacy.”
Next steps
Zhao points out that the device is likely to be of particular benefit for hospitals and clinics in remote locations, where electricity or fuel-powered autoclaves are too expensive or impossible to operate due to power shortages.
“Additionally, as we saw in India, centralized hospitals in big cities extend their healthcare service by setting up temporary clinics in remote villages,” he says. “Due to the lack of power sources, they have to carry sterilized equipment on every trip to the village, which limits the number of operations they can do. Our solar-powered device can help them sterilize the equipment on the spot, therefore increasing their capacity without adding more items to their packing list.”
Compared to existing solar-powered autoclaves, the new system has a number of advantages – including the fact that it is completely passive with no moving parts and its high energy efficiency, which enables it to provide more steam for a given footprint.
“Most of the components in our system are commercially available in the solar water heater industry. Once the aerogel becomes available, we expect our system can be mass-produced at low cost,” says Zhao.
The next critical step is to demonstrate feasible large-scale manufacturing of the transparent aerogel. As part of this process, AeroShield, a start-up company founded by co-author Elise Strobach, is developing a commercially viable manufacturing plan.
“After the aerogel material is available, we plan to partner with solar collector manufacturers such as AEi to produce our solar-autoclave prototypes and distribute them through local channels such as NGOs,” adds Zhou.
In the latter half of the 20th century physicists undertook a shrewd move: they began to take the entire universe as their laboratory. It was a clever manoeuvre based on real-estate values alone, but it had other advantages as well. Floor space was essentially unlimited, maintenance fees were negligible, it cost nothing to heat and cool, and no insurance policies were required. But getting through the door, or even watching through a window, was costly. Of course, astronomers and physicists have always used observations of the universe to hone their understanding of the world.
“We cosmologists,” writes Page, who studies temperature variations in the CMB, near the end of this clearly written, delectable book, “feel fortunate to have been alive in the decades when the explosion of knowledge about the universe took place.” He has made good use of these feelings to produce this enthusiastic and approachable survey of the state of cosmology today. This is hardly a surprise, as Page is an expert in observational cosmology, being one of the original co-investigators of the Wilkinson Microwave Anisotropy Probe (WMAP) project, and has won numerous awards including the 2018 Breakthrough Prize in Fundamental Physics, the 2015 Gruber Prize and the 2010 Shaw Prize.
In The Little Book of Cosmology, Page uncovers the discoveries that have led to some of the most interesting and astonishing phenomena in all of the sciences. The book touches upon the cosmological constant of empty space; the accelerating expansion of the universe; the fact that ordinary matter makes up only 1/20th of the energy density of the universe; the mysteries of dark matter and dark energy; the slight (about one part in 100,000) but exceedingly informative temperature variations of the CMB as seen across the entire sky. In truth, at 185 pages this book is more than a survey, but still something you can read without a pen in your hand and a tablet before you. The book includes forays into more advanced topics as well, though not to the same degree. Page introduces inflationary models of the very early universe, how the gravitational landscape of the early universe produces anisotropy of the CMB, gravitational lensing of the CMB, and quantum fluctuations as a basis for cosmic structure.
A heartening feature of the book is Page’s repeated emphasis on precise measurement as the best way to test ideas, theories and models. He gives examples of where this has already been done, perhaps most spectacularly with the determination of the power spectrum of the CMB as measured by the WMAP and Planck satellites. That a relatively simple cosmological model, with just six free parameters (beyond those of the Standard Model of elementary particle physics), explains this non-trivial, shapely curve is a true masterpiece of scientific achievement.
Grand scale Lyman’s book looks at the birth and formation of our universe. (Courtesy: iStock/Andreus)
The book ends with a chapter on the frontiers of cosmology, what remains to be known, and what might be known soon. Sensitive upcoming galactic surveys will see the effects of neutrinos on cosmic structure, and perhaps give more precious information about their masses, for which only limits exist today. Primordial gravitational waves may reveal secrets about the infinitesimal era of quantum gravity. Galactic and CMB surveys could reveal small deviations in the expansion rate versus time, and hence changes from predictions of an unchanging cosmological constant. Meanwhile, instruments are being designed to look for CMB radiation departures from a blackbody spectrum.
In many ways The Little Book of Cosmology reminds me, in mission and style, of Steven Weinberg’s 1977 book The First Three Minutes, which sits on my desk as I write, its matured pages smelling a bit like soap, its lower right-hand corner having been nibbled on by a mouse. Weinberg includes more numbers, but no plots. Page’s book has an exceptionally clear and direct style of writing. There are no equations in this book except for the famous little one of that Einstein fellow (which is more for show), some graphs and only a few spots that require multiplication. It avoids scientific notation until an appendix, to my chagrin as I struggled with the written number “one ten-millionth.” Surely anyone who can understand the bulk of this book can understand scientific notation from the get-go. Also, I was somewhat surprised to find Alice and Bob gallivanting across the universe, explaining inflation and other concepts – indeed, it was a bit disorienting.
I don’t think the revelations and the remaining mysteries presented in this book have yet penetrated much of the public, which is a lowdown shame
I don’t think the revelations and the remaining mysteries presented in this book have yet penetrated much of the public, which is a lowdown shame. After all, how much we have learned about the cosmos over the last 20–30 years, how precise the measurements have become, how tightly constrained the most successful model is. But yet, we still don’t know what 95% of the universe is made of. There’s something untoward about saying space is being created everywhere, and there are portions of universe constantly fading from our view. Still, those costly windows into the ultimate laboratory are providing ever clearer views. It is no place for the timorous.
I think this book can open the eyes of many motivated readers – smart high school students, university students regardless of their course of study but particularly those assigned it in an introductory astronomy class, members of astronomy clubs, physics students looking for a quick introduction to the field, and certainly anyone who reads this or any other science magazine. It’s got to be the best, most up-to-date, “little” introduction to cosmology they’re going to find.
The most precise measurement ever of the fine-structure constant has placed new constraints on theories that predict the existence of “dark sector” particles. The new value, which researchers in France measured using clouds of cold rubidium atoms, provides a stringent test of the Standard Model of particle physics while also further limiting the properties of dark matter – the substance thought to make up more than 90% of the matter in our universe.
The fine-structure constant α is a composite of several physical quantities (including e, the charge on an electron, and c, the speed of light) that, together, characterize the strength of the electromagnetic interaction. This makes α ubiquitous throughout the universe. Because it is a dimensionless number, it is in some sense more fundamental than physical constants such as the strength of gravity or Planck’s constant ħ, which change depending on the units in which they are measured.
Electromagnetic interaction is weak
The relatively low value of α – it is approximately equal to 1/137 – implies that the electromagnetic interaction is weak. The main consequence of this is that electrons orbit some distance from their atoms, so they are free to form chemical bonds and build up molecules. This property made it possible for matter and energy to form stars and planets. Indeed, some physicists have argued that we owe our very existence to the exact value of α, because if it were slightly bigger or smaller, stars might not been have able to synthesize heavier elements like carbon, and life as we know it wouldn’t exist.
Precise measurements of α make it possible to rigorously test relationships between elementary particles. These relationships are described by the equations that make up the Standard Model of particle physics, and any discrepancy between the model’s predictions and experimental observations may provide evidence of new physics.
Determining the recoil velocity of atoms
Measurements of α generally begin by determining how strongly atoms recoil when they absorb photons. The kinetic energy of this recoil (or its velocity) reveals how massive the atoms are. Next, the electron’s mass is calculated using the precisely known ratio of the atom’s mass to that of an electron. Finally, α is calculated from the electron’s mass and the binding energy of a hydrogen atom, the value of which is likewise well known from spectroscopy measurements.
In the new work, researchers led by Saïda Guellati-Khélifa at the Kastler Brossel Laboratory in Paris cooled atoms of rubidium to a few degrees above absolute zero in a vacuum chamber. They then created a quantum superposition of two states of the atoms using laser pulses. The first state corresponds to atoms that recoil when they absorb photons and the second state to atoms that do not recoil.
The two possible versions of each of type of atom propagate through the experimental chamber along different paths. The researchers then applied a second set of laser pulses to “re-join” the two halves of the superposition.
The more an atom recoils after absorbing photons, the more out of phase it will be with the version of itself that does not recoil. By measuring this difference, Guellati-Khélifa and colleagues extracted the mass of the atoms, which they then used to determine the fine-structure constant. Their result shows that α has a value of 1/137.035999206(11) – a measurement that, with an accuracy of 81 parts per trillion, is 2.5 times more exact than the previous milestone, which was made in 2018 by Holger Müller and colleagues at the University of California at Berkeley, US.
Improved experimental setup
The Paris researchers say that improvements to their experimental setup were key to the new result. By controlling effects that can create perturbations in the measurement, they were able to reduce sources of inaccuracies. For example, the researchers considered, and compensated for, the gradient in the local strength of gravity across their experimental set-up and the Coriolis acceleration created as the Earth rotates. They also meticulously characterized properties such as laser beam alignment, frequency, wave-front curvature and the second-order Zeeman effect, which account for many errors in such experiments.
The new measurement, which is reported in Nature, differs from the value obtained in the 2018 Berkeley experiment in its seventh digit. This result surprised the Paris researchers, since it implies that either one or both measurements has an error currently unaccounted for. However, the two groups’ measurements do agree closely with the value of α calculated from precise measurements of the electron’s so-called g-factor, which relates to its magnetic moment. In a related News and Views article, Müller notes that the Paris result “confirms that the electron has no substructure and is truly an elementary particle”.
The Paris researchers say they now plan to back up their results by measuring the recoil velocity of a different rubidium isotope. “We also plan to build an even more precise instrument,” Guellati-Khélifa tells Physics World.
Intuition is a funny thing. Loosely defined as the ability to know something without recourse to “conscious reasoning”, it is the notion that we can rely on “gut instinct” or the depths of our unconscious mind, to instinctively intuit knowledge. As the world we live in becomes more and more complex, knowing when to trust your gut and when to follow expert, rational discourse (especially of the scientific sort) is a difficult decision for many. Throw into that mix a subject as notoriously complicated, and often (wilfully) misconstrued, as quantum mechanics, and the brightest of human minds can be convinced that there exist connections, correlations and patterns between random events – whether or not they do.
Physicist and author Paul Halpern explores this and other themes in his latest popular-science book, Synchronicity: the Epic Quest to Understand the Quantum Nature of Cause and Effect. If you, like me, are a bit unsure as to what exactly the word “synchronicity” means, the concept is rooted in psychology, not physics. First proposed in the 1920s by famed analytical psychologist Carl Jung, synchronicity referrers to the idea that some events are meaningfully linked or related, despite having no causal relationship. Jung wanted to encompass his idea that the collective unconscious of human experience is linked to our dreams, thoughts and behaviours. Indeed, he was “hoping to establish the reality of an acausal connecting principle”, writes Halpern. Jung’s inspiration for this came from the exciting new physics of relativity and quantum mechanics, via Albert Einstein and Wolfgang Pauli.
Carl Jung’s inspiration for synchronicity came from the exciting new physics of relativity and quantum mechanics
In a letter he sent to Einstein’s first biographer Carl Seelig in 1935, Jung wrote that “It was Einstein who started me thinking of a possible relativity of time as well as space, and their psychic conditionality. More than 30 years later, this stimulus led to my relation with the physicist Professor W Pauli and to my very thesis of psychic synchronicity.” As it is neither testable nor falsifiable, it’s easy to think of synchronicity as pseudoscience – and indeed Wikipedia dubs it so. With its “spooky” correlations and possible “hidden” mechanics, it’s no surprise that quantum theory inspired Jung to dream up a reality in which the laws of cause and effect could be avoided.
Add in the complexities of the “observer effect” and the “measurement problem” – which, depending on your quantum-mechanical interpretation of choice, suggests that the mere act of conscious observation changes the outcome of a quantum experiment – and you can see why it’s a ripe playground for a psychologist. (For a detailed discussion on the subject, see the feature “Thirty years of ‘against measurement’”.) But many readers may be surprised to know that Pauli – a seemingly staunch realist – was as keen as Jung to explore the principle, and thought it a credible means of explaining a variety of so-called paranormal phenomena from entanglement to telepathy.
Apart from his significant contributions to physics, Pauli is perhaps best known for his lancing wit and brutal take-downs of people and ideas he deemed foolish or careless. It’s hard to reconcile the Pauli who once famously put down a young physicist’s paper with the phrase “not even wrong” (now synonymous with “non-falsifiable”) with the Pauli whom Halpern describes as an “emotional wreck”. By the 1930s, thanks to troubles in the physicist’s personal life, combined with mental health issues and an alcohol problem, Pauli’s father suggested he seek help, in the form of therapy from Jung. The psychoanalyst first and foremost attempted to help Pauli navigate those turbulent times through the medium of a very detailed dream journal. It was a fortuitous coincidence for Jung, who was at the time developing his idea of synchronicity (then mainly based on relativistic concepts), to be able to run his thesis past Pauli.
Influencers Wolfgang Pauli (right) and Carl Jung inspired each other’s work. (Courtesy: AIP Emilio Segrè Visual Archives, Physics Today Collection; Ortsmuseum Zollikon)
From what I’ve mentioned in this review so far, it would be fair to think that Halpern’s book is based purely on the tale of Pauli and Jung, but that’s far from the case. In fact, the dense subject matter of the duo, their relationship and their academic collaboration is all packed into three chapters out of nine in this 300-page book. The rest is devoted to everything from a detailed view of relativity and particle physics, to cosmology and modern-day quantum computing. This is simultaneously both a strength and weakness of Synchronicity. For the uninitiated, the book gives an excellent if broad look at some of the key concepts and ideas of 21st-century physics.
Halpern does fall into the seemingly too-tempting pop-sci trap of beginning his book with the ancient Greeks and their ideas of cosmology and philosophy; though it must be said that he is much more discerning in these three chapters than other authors who attempt to squeeze a couple of millennia of scientific advancement in the West into one chapter. For those of us who would much rather have delved deeper into the backgrounds of Jung and his contemporaries, and read about synchronicity, and the Jung–Pauli partnership, the book is more of a jumping-off point, rather than a treatise. Despite these quibbles, Synchronicity is an absolutely fascinating read, and Halpern is an excellent writer and researcher, despite (or perhaps indicated by) the dizzying number of names and dates in the book.
As physics stands at the precipice of a technological quantum revolution, many physicists, philosophers and even psychologists are grappling more than ever with how quantum mechanics truly reflects our everyday reality, if at all. While entanglement between photons across thousands of kilometres is an experimental reality, what this means for our ideas on cause and effect, the speed of light in the universe, and “meaningful” correlations remains unclear.
Over the course of his career, Jung described synchronicity in a number of ways – “acausal connecting (togetherness) principle”, “meaningful coincidence”, “acausal parallelism” – all of which seem vague, but maybe that’s the point. I couldn’t help but wonder why “correlation does not imply causation” wasn’t more of a guiding philosophy for the Jung (or indeed, latter-day Pauli). AsAlanis Morrissette sagely sang about chance and coincidence, “It’s like ten thousand spoons when all you need is a knife; It’s meeting the man of my dreams, and then meeting his beautiful wife; And isn’t it ironic, don’t you think?”
Workflow showing the development of the new heart model. (Courtesy: Suman Shrestha)
Improved radiotherapy techniques and technologies allow an increasing number of children diagnosed with cancer to survive long into adulthood. Unfortunately, the very treatments that save their lives are associated with several severe, life-threatening, or even fatal chronic health conditions. For example, children who received radiation therapy are at a heightened risk of developing heart disease later in life. Further improving radiation treatments to minimize this risk requires a deep understanding of the relationship between radiation exposure and heart disease that is currently lacking. A multi-institutional team of researchers in the US has enhanced a critical computational tool to enable new insights into this relationship.
Our current understanding of how radiation exposure contributes to heart disease comes from several studies of childhood cancer survivors. These studies, which correlated radiation dose to the heart with various cardiac conditions, demonstrated a positive correlation, or that risk generally increases with increasing cardiac dose. All these studies, however, considered the whole heart as a single unit.
In reality, the heart is a complex organ made up of several substructures including valves, arteries, ventricles and atria. Similarly, heart disease refers to a diverse collection of conditions, including narrowed or blocked blood vessels and heart rhythm problems, among others. Recent evidence suggests that each of these unique conditions is associated with radiation dose to specific heart substructures, rather than to the heart overall. Existing research infrastructure, however, is insufficient to elucidate these associations.
Doctoral research fellow Suman Shrestha (left) and his PhD advisor Rebecca Howell (right).
Correlating radiation therapy exposures to observed health effects requires comprehensive knowledge of the delivered treatment. Critically, studies of long-term health effects rely on historical medical records that often lack computed tomography (CT) scans of the patients. Therefore, researchers must simulate the treatments on representative patient surrogates, known as phantoms, to estimate the delivered dose.
Howell’s lab at MD Anderson performs these simulations using a computational phantom that can be scaled in size based on the patient’s age at the time of treatment. This scaling is particularly important for simulating paediatric cancer treatments because of the large variation in size from infancy to early adulthood. The heart model in this age-scalable phantom, however, represented the heart as a single structure and did not delineate its distinct substructures.
The University of Florida (UF) and National Cancer Institute (NCI) maintain a different set of computational phantoms that include 10 heart substructures, representing the most comprehensive heart model available for radiation simulations. This set of phantoms, however, only includes six distinct ages and cannot be scaled to match a particular patient’s age at treatment.
Their powers combined
The research collaboration combined the age scalability of the MD Anderson phantom with the detailed completeness of the UF/NCI phantoms to create a hybrid heart model. Their new heart model includes the 10 heart substructures represented in the UF/NCI phantoms, as well as four additional heart substructures, for a total of 14 substructures that can be scaled to any age.
The team tested the hybrid heart model in three ways and found it to be anatomically accurate across children ranging from infants to adolescents, clinically acceptable and dosimetrically viable – all crucial factors for widespread research use.
Moreover, the methods used to enhance this heart model can be applied to other organs and tissues to further improve outcomes research. “This work was paradigm shifting for our team in how we will approach organ development and validation in future studies,” says Howell. “We are using methodologies similar to those developed here to develop additional organs in our computational phantom, for example, the colon, with the ascending, transverse and descending colon substructures defined.”
The new heart model is already enabling researchers to consider the unique relationships between radiation exposures and complications associated with specific heart substructures.
“We have used the heart model developed in this study to calculate dose to [the] heart and its substructures for over 13,000 survivors in the CCSS treated with radiotherapy. Analyses are ongoing to determine relationships between specific late cardiac diseases and dose to specific substructures, for example, relationships between coronary artery disease and coronary artery dose,” says Howell.
This understanding will facilitate future studies seeking to refine radiation treatments to avoid distinct heart complications and improve the long-term quality-of-life of cancer survivors.
Since 10 March 2020, when Latvia went into lockdown, my 11-year-old daughter Vija has attended only 16 in-school sessions. It’s an understatement to say that my work as a space entrepreneur and senior scientist at the Planetary Science Institute and the University of Latvia has been impacted. I am a solo parent, and I never imagined that I would become a many-hours-per-week teacher. But while it’s not strange these days for kids to do distance learning, it is a little bit strange for children like my daughter to be learning remotely while their friends are in class – as was the case for most of this autumn.
The story of how this happened is both complex and sobering. Within two weeks of Latvia’s spring lockdown, teachers were augmenting existing electronic course materials. With broadband speeds among the best in the world – including in the countryside, where many Latvians rode out the first wave – “online everything” was relatively easy. Thanks to this and the cohesiveness of Latvian society, our management of the first wave of the pandemic was among the best in Europe. In the summer, the Latvian Investment Agency even trumpeted the country’s achievements with a series of promotional videos entitled Ahead of the Curve.
They weren’t the only ones who were optimistic. I was, too. I filled pages in my journal and created elaborate mind maps, brainstorming ways to fight the disease and improve society. Because countries all over the world were experiencing disruptions, formerly siloed groups had an incentive to listen to each other and think creatively about solutions. I cherished, especially, the Foresight Institute’s “Global Online” discussions, which took place every night at 9 p.m., Riga time, for about six weeks.
Causes for concern
From these discussions, though, I also picked up medical information about the virus that made me concerned – first for myself, a person in her late 50s who had major surgery in January, and then for my daughter, who has allergies that neither I nor her doctors fully understand. It seems that Vija may have something called mast cell activation syndrome (MCAS), which has implications for her COVID-19 risk; a leading MCAS researcher has said that some of the most severe COVID-19 infections may be rooted in undiagnosed MCAS-like conditions. This information made me extra cautious about returning her to school in the autumn, when in-person classes were due to resume.
Big plans Amara Graps’ mind map of disease-fighting strategies. (Courtesy: Amara Graps)
While I was immersed in learning more for my family’s health, Latvia had a lovely, long and relaxed summer – as long as one didn’t think about the pandemic. Latvia and the other Baltic countries, Lithuania and Estonia, formed a “Baltic Bubble” to facilitate summertime travel without quarantine or isolation. People had parties. Restaurants and gyms reopened. No-one wore masks. Social distancing disappeared. And parents who hadn’t coped well with distance learning in the spring – either because having kids at home made it challenging to manage their own work, or because they didn’t have the electronic devices they needed for their kids to follow online courses – lobbied the government to keep schools open in the future, no matter what. Faced with their strong opinions, the education minister agreed.
In the meantime, the rest of the government acted as if its pandemic work was finished. Our main infectious disease expert, who was on our airwaves constantly in the spring – explaining the science, the what, the how and the why – faded into the background. He and the experts who followed him spoke of the need to prepare for a second wave, but at the government level no serious preparations were made. And thanks to the relative ease with which our country “flattened the curve” in the spring, with minimal impact on the medical system and few deaths, disinformation and disagreement entered our formerly cohesive society.
Falling behind
The most vocal and proud among this dissenting faction stated that Latvians lived through three military occupations in the last century. Why should we be scared of a virus? People began to say that we had “done enough” already, and that masks and social distancing were not necessary. A split formed between native speakers of Russian and Latvian about the virus’s risks. Conspiracy theorists even claimed that COVID-19 was created in the US to further Bill Gates’ business interests, then brought to China during a military sports competition.
By August, infection numbers were creeping up due to holes in the “Baltic Bubble” and, later, to traditional singing excursions that proceeded without restraint. Still, schools opened on 1 September, and my daughter’s large government-funded school was among them, complete with a hand sanitizer machine at the door and a plan for pupils to spend four days a week in school and one day at home, to approximate a separation strategy. The school also provided an elaborate flu/COVID-19 symptom flowchart describing when to keep a child at home.
Yet inside my daughter’s classroom, kids were not separated by large distances. The windows were not opened regularly. Neither teachers nor students wore masks. Kids were not encouraged to wash their hands regularly. And so the super-spreader events began.
Two and a half weeks into the new semester, a bad (but normal) flu passed through Vija’s classroom. We were both ill for two weeks – an experience I considered a warning. In the next few days, my concern grew. As we were recovering from this normal flu, the novel coronavirus rode into Vija’s school on its tail. A singing excursion that a couple of the teachers took in September ended up infecting nearly half of their 60 colleagues, who tested positive in the first week of October. From there, the disease spread to students, siblings and parents. Eventually, the cluster grew to 150, including 14 of the 29 students in my daughter’s class. We thought we might be among them, especially after our cat had some symptoms (yes, cats can catch COVID-19), but on 12 October our tests came back negative. We had dodged a bullet.
Lessons (not) learned
With Vija’s school quarantined in late October and early November, a few teachers in the hospital, and a high prevalence of the virus in Latvia’s capital, Riga, I felt sure that the principal would implement distance learning. But when they polled the parents, two-thirds voted to send the younger kids back to school, overruling the rest of us. So I chose to keep my daughter at home while her classmates continued attending – until 7 December, when the Latvian government finally bowed to the inevitable, and ordered all schools to implement distance learning again.
In the past nine months, I have gone from feeling safe and happy in Riga to feeling as though people in my town want my daughter and me to die of a preventable disease. Yes, that is an exaggeration – but my winter solstice in Latvia will nevertheless be a time of reflection and emotional transition. If Latvian society follows the rules currently in place, we should be on the other side of the second-wave peak by late January 2021, with vaccinations planned to start in February. Yet the main thought on my mind is this: if the Baltic nations cannot manage a small crisis like this pandemic, what does that say about the looming existential crisis of climate change?
Inside view Kellie Gerardi returning from a successful microgravity research flight. (CC BY 4.0 Kellie Gerardi)
When the Apollo 11 astronauts landed on the Moon in 1969 the whole world stopped, just for a moment, and looked up. We stepped out into the universe and firmly entered the Space Age, which had begun with Sputnik just 12 years earlier. For many Physics World readers, the scientific and engineering exploits of those early achievements are a source of intrigue and no little excitement. From those crackled first words on the Moon, to images of the boot print in the lunar surface, or the new perspective of our world – the fragile blue marble suspended in darkness – humanity’s most impressive engineering effort has had a huge impact on our collective consciousness.
Commercial spaceflight industry professional and science communicator Kellie Gerardi was one of the many who wanted to be part of the nascent Space Age. But with a degree in film studies rather than aerospace engineering, her non-traditional path in the space industry is a key theme of her new book Not Necessarily Rocket Science: a Beginner’s Guide to Life in the Space Age. With more than 122,000 followers on Instagram, Gerardi is something of a social-media star, and her book serves as part mission statement, part witness statement and part manifesto. They say that those converted to a cause are often the most evangelical and Not Necessarily Rocket Science brims with Gerardi’s passion – not just for the science and engineering of space exploration, but also for its democratization.
The reader is greeted in the opening chapter by a whistle-stop tour of the history of space flight. Gerardi’s experience as a copywriter and communicator imbues the text with an urgency and personality that bubbles throughout the book. It is subtitled “a beginner’s guide” but even the most seasoned space reader will find nuggets in this opening chapter, which is set up to deliver the reader to where the industry is now. But it is Gerardi’s experience and insight into the space exploration of today, and tomorrow, which really set this book apart.
Gerardi conducts bioastronautics research and spacesuit evaluation in microgravity with the “Polar Suborbital Science in the Upper Mesosphere” Project PoSSUM – the first crewed suborbital research programme. Having previously worked in business development, she now also serves in an advisory role to Masten Space Systems, an aerospace-manufacturing start-up company in Mojave, California. Indeed, NASA is set to pay Masten $75.9m for the company to build and launch a lander called XL-1. It will take NASA and other customer payloads to the south pole of the Moon, in a mission scheduled for late 2022.
Gerardi recounts her experiences as part of the 149th crew rotation of the Mars Desert Research Station, a simulated Mars analogue habitat owned and operated by the Mars Society. She also talks about her numerous parabolic flights as a Suited Test Subject, flying fully pressurized in a spacesuit while carrying out microgravity experiments on fluid configuration, solid body rotation and biometrics. Gerardi’s sense of humour and passion are evident throughout, along with an interest in science fiction. Her excitement is palpable as she recounts the time when Lucasfilm turned up at Masten Space Systems to record its rocket engine sounds to use in Star Wars: Episode VII – the Force Awakens.
Gerardi’s broad and deep knowledge of the commercial space industry makes Not Necessarily Rocket Science a fascinating read, even for those for whom the words “thousands of followers on TikTok” are either meaningless or not really a selling point. Social media is often maligned, and often justifiably so, for its lack of depth or for celebrating the less salubrious aspects of humanity. Gerardi’s first foray into social-media success came as a teenager in the early days of YouTube. She filmed her father excitedly opening his Christmas present (an Xbox) and uploaded it to the then new but burgeoning video-sharing site. A family Christmas lunch later and the video had hundreds of thousands of views. These days, YouTube is awash with people unboxing tech items and make-up packages. That Gerardi turned her gaze (and those of her viewers) to science, engineering and space exploration is surely something to celebrate.
The mainstream media became aware of Gerardi when she was selected for the (now cancelled) Mars One project. The idea was to raise money from investors to send a mission to Mars with human occupants to establish a permanent base for humanity. The project was much maligned in the media and Gerardi appeared on a host of television and radio programmes to defend it. The chapters covering this experience in her book offer a fascinating insight into the process. Gerardi has a strained, if not broken, relationship with Mars One and regrets the media spotlight being on the foolishness of the idea rather than the exciting prospect of the possibilities of space flight. Her book turns the attention squarely in the right direction.
Space is no longer the preserve of all-male, all-white flight test pilots or people with PhDs in orbital mechanics
If we truly are in the Space Age then the next steps for space exploration include space tourism with Virgin Galactic and others. With that comes the need for baristas, chefs, guides and more. Space is no longer the preserve of all-male, all-white flight test pilots or people with PhDs in orbital mechanics. Space exploration will be covered by social-media stars and, in the right hands, could reach perhaps even more of humanity than those pictures of the Apollo missions did over 50 years ago. It would be something of a tragedy if the science and engineering of those missions were lost to the vacuities of social media and it is something of a relief that there are social-media stars with a depth of passion and understanding like that of Kellie Gerardi.
The clinical introduction of MR-guided radiation therapy has brought high-contrast soft-tissue imaging into the radiotherapy workflow. MRI can visualize tumour targets and surrounding organs with high accuracy, delivering the ability to “see what you treat” and, ultimately, the potential for real-time treatment adaptation based on anatomical changes observed during treatment.
But how prevalent is the need for online adaptive radiotherapy (ART)? And is the MR-linac a necessity to achieve this – or could other technologies fulfil future requirements just as well? These questions were examined at the recent ESTRO 2020 congress, where four experts debated the motion that “there is no future for ART in external-beam radiotherapy without an MR-linac”.
Optimizing advances
The first speaker, Uwe Oelfke from the Institute of Cancer Research/The Royal Marsden, argued for the motion, albeit with a more modest take: “We believe that there will be significantly less improvement for radiotherapy patients without an MR-linac,” he stated.
Uwe Oelfke.
Looking at future requirements for radiotherapy, Oelfke suggested that these will include safe hypofractionation, development of response/physiology-guided radiotherapy and, further ahead, increased application of radiotherapy for treating advanced, non-localized disease.
“For this, we urgently need new technologies,” said Oelfke. “We need ultra-hypofractionation guided by real-time ART, we need to exploit imaging signals that have a different quality of information, such as biological imaging, and we need more patient-friendly treatment schedules. Step one is the introduction of technology like the MR-linac.”
Oelfke argued that the MR-linac is key to enabling safe, anatomically-driven ultra-hypofractioned treatments, delivered in one to three fractions. By reducing the number of required hospital visits, this approach will improve both patient comfort and treatment efficiency, as well as offering overall economic benefits.
The MR-linac also removes the need for implanted fiducials, enabling surrogate-free anatomy monitoring in a few hundred milliseconds. High-quality MR images acquired at the time of treatment improve both treatment safety and quality, and simply cannot be achieved by X-ray guidance, emphasized Oelfke. Meanwhile, online dose reconstruction will provide “the ultimate treatment QA while the patient is treated,” he added.
Oelfke next considered the development of biologically-driven radiotherapy. When a radiation treatment is unsuccessful, is this failure due to missing the target, he asked, or could it be due to incorrect correlation of the dose with the underlying tissue biology? “By definition, X-ray imaging is biology blind,” he said. “Functional MRI, however, is closer to biology and can monitor physiology. Hypoxia imaging, diffusion imaging and fingerprinting are tremendous opportunities. The MR-linac is needed so that we can see these signals at the time of treatment.”
Further into the future, radiotherapy may move from being a symptom-driven technique that treats localized tumours to a mechanism-driven therapy that can tackle disseminated disease. “Currently, there is no real bridge between local radiotherapy and immunotherapy, biologically-targeted therapy and chemotherapy. The MR-linac can be part of this bridging technology,” said Oelfke.
Sensible selection
“I believe there is a future for ART without MR-linac,” declared the second speaker, Marta Scorsetti from Humanitas University.
Marta Scorsetti from Humanitas University.
Scorsetti explained that while the need for ART is increasing, it is not yet part of routine clinical practice, likely due to the challenge of performing the full planning workflow while the patient is on the couch. The MR-linac could indeed address this unmet need for daily plan adaptation and possibly also enable tumour tracking during treatment. “This should be a dream for radiation oncologists,” said Scorsetti. “But in my mind, there are some points that deserve clarification.”
One major obstacle is time. Scorsetti noted that in a centre-of-excellence in Italy using an MR-linac, the mean treatment time is 50 minutes, limiting the number of patients that can be treated each day. This contrasts with other recent radiotherapy advances that reduce beam-on times, enabling more treatments per day and lowering intrafraction motion.
By 2025, the number of radiotherapy courses needed in Europe is expected increase by 16%. And even now, not all patients that need it can get radiotherapy. “So would online adaptation really benefit patients or further reduce the ability to treat all of them?” Scorsetti asked. “We can’t treat all patients we would like to with an MR-linac, or we will not be able to treat all patients who need radiotherapy. Patient selection criteria are urgently needed.”
Scorsetti also pointed out that the MR-linac is not the only technology available for daily adaptation. For example, the new ETHOS radiotherapy system offers online ART based on cone-beam CT (CBCT). “Using ETHOS, the treatment time should be five to 10 minutes, compared with 30 to 50 minutes for the MR-linac,” she said.
But rather than focusing on which technology to use, what’s more important is defining which patients would benefit most from online adaptation and using this opportunity to make real clinical improvements. Scorsetti concluded by quoting Henry Ford: “Real progress happens only when advantages of a new technology become available to everybody,” she said.
Biological benefits
“We have been working with the 1.5T MR-linac for more than two years now,” stated Cihan Gani, a radiation oncologist at University Hospital Tübingen.
Cihan Gani.
The main advantage, Gani said, is the ability to record an MR image for every fraction and use these to create plans optimized to the anatomy of the day. The most intuitive application is adapting treatment plans for tumour shrinkage. Gani shared an example of a head-and-neck tumour that shrank with each week of treatment. He noted that while CBCT can visualize air–tumour interfaces (although these are clearer on MRI), within soft tissues, it is far harder to see tumour borders using CBCT. Here, MR imaging is the only option for tracking tumour volume.
The adaptation workflow is also far simpler with an MR-linac. Images are recorded immediately before treatment and the plan adapted accordingly, using one device. Without an MR-linac, images must be recorded on a separate scanner, at imaging times reserved in advance. Critically, as it’s not known exactly when a tumour will shrink, such pre-defined imaging sessions may miss important changes.
Another reason to employ an adaptive workflow is for treatments near organs-at-risk (OARs) with high anatomic variability. In pancreatic cancer, for example, it is beneficial to be able to adapt the treatment plan based on the current position of the small bowel, which is hard or impossible to see using CBCT.
And MRI has another advantage: functional imaging, which provides information on tumour biology and could enable biological plan adaptation. Gani described an example in which a rectal cancer patient treated on an MR-linac had diffusion-weighted imaging MR scans twice weekly. While the tumour did not shrink over the course of treatment, suggesting that it had not responded, the apparent diffusion coefficient (ADC) values increased with time, indicating tumour response. ADC maps could potentially also be used to identify areas of residual tumour to boost the dose to such regions.
“With the MR-linac, you have the possibility to adapt without relying on anatomy that was there weeks ago. Plus you have many more possibilities for novel treatments if you also include biological information,” Gani concluded. “So yes, there is a future for ART without an MR-linac, but the options are limited. It clearly depends on how the future shall look like, and it looks best if you do ART with an MR-linac.”
Cost considerations
Rounding off the debate, Stine Korreman from Aarhus University Hospital suggested that the motion under consideration was actually a little biased. “Of course MR-linacs will be part of ART in future,” she said. “Maybe the more relevant questions are whether all linacs will eventually be replaced by MR-linacs. Or will all images for ART eventually be MR images? Or will all major ART research be directed towards MR-linacs?”
Stine Korreman.
These questions address different considerations: cost effectiveness, benefit and innovation potential, respectively. Looking first at cost, Korreman noted that the MR-linac is at least four times more expensive than a CBCT-equipped linac – and cannot treat as many patients per hour. “What is gained with one MR-linac compared with the four CBCT-linacs you could get for the same price?” she asked.
Korreman next examined potential improvements in outcome, noting that the main objectives of ART are to monitor treatment response and reduce margins. Response monitoring enables adaptation of either the spatial dose distribution or the fractionation regime. “But for both these, the role of MR is not entirely clear; both are at an early stage with little clinical evidence, though there is interesting potential,” she said.
Previous studies have demonstrated that ART can reduce margins by up to 5 mm. “But removing 5 mm of high-dose volume corresponds to just 5% reduction of the integral dose to the patient,” Korreman said. Even looking at the extreme of margin reduction, such that radiotherapy approaches surgery, treatments are still limited by knowledge of what to cut out or where to aim. “Geometric margin reduction has limited potential and response monitoring seems to be premature. So the benefits don’t seem to make up for the large cost,” she said.
Looking at the potential of imaging-related developments in radiotherapy, there are many other important imaging objectives unrelated to ART – such as target and OAR identification, biological target differentiation or proton range verification. Further ahead, the introduction of techniques such as FLASH radiotherapy, grid therapy and immuno-radiotherapy may lead to completely different image guidance and adaptation needs.
“Given that cost will not be reduced enough to be competitive, there will not be enough clear benefits to balance this cost, and innovation will continue to happen at a more rapid pace for other modalities for some time to come,” said Korreman. “The conclusion must be that, in the foreseeable future, MR-linacs will not replace other modalities for adaptive radiotherapy.”
With the ESTRO congress a totally online event this year, the traditional show-of-hands vote at the end of the debate did not take place. I will leave it to the readers to make up their own minds as to how the future of ART will pan out.
Dr María Escudero-Escribano is an Assistant Professor of Chemistry at the University of Copenhagen, Denmark, where she leads the NanoElectrocatalysis and Sustainable Chemistry group. Her research group investigates tailored electrochemical interfaces for renewable-energy conversion and electrosynthesis of green fuels and value-added chemicals. She obtained her PhD from the Autonomous University of Madrid, Spain, in 2011, for her work on electrocatalysis and surface nanostructuring using well-defined electrode surfaces. She carried out her postdoctoral research on oxygen electrocatalysts for fuel cells and water electrolysers at the Technical University of Denmark and Stanford University, US, before moving to the University of Copenhagen in 2017. María is chair of the Danish Electrochemical Society since 2018. She was awarded a Villum Young Investigator grant from the Villum Foundation in 2018 and is a PI of the Center for High Entropy Alloy Catalysis (CHEAC) from the Danish National Research Foundation. She has received numerous national and international awards in recognition of her early-career achievements, including the European Young Chemist Award (Gold Medal) 2016, the Princess of Girona Scientific Research Award 2018, the Energy Technology Division Supramaniam Srinivasan Young Investigator Award 2018 from The Electrochemical Society, the Spanish Royal Society of Chemistry Young Researchers Award 2019, and the Clara Immerwahr Award 2019 from UniSysCat.
