One hundred thousand knee replacement surgeries are carried out in the UK every year. Most of these operations take place to treat pain related to osteoarthritis. Unfortunately, each year, around 20,000 people who have knee replacement surgery to relieve their pain find that they have moderate to severe pain three months or longer after their operation, which impacts on their everyday lives.

The study found the STAR care pathway (Support and Treatment After joint Replacement) reduces pain severity, the amount pain interferes with people’s lives and is cost-effective. The new treatment could potentially save the NHS up to £14 million per year through reduced inpatient admissions.

The study found patients who received the STAR care pathway had:

• Less pain severity and impact on daily life at both six and 12 months after treatment (nine and 15 months after surgery)
• Half the number of hospital re-admissions
• Reduced length of hospital stay for any inpatient admissions three months after surgery
• Less unpaid time off work

The aim of the five-year STAR programme was to find ways to improve the care and support that people with ongoing pain receive. The programme, funded by the National Institute for Health Research (NIHR), designed and tested a new treatment in a randomised controlled trial in eight UK hospitals.

The programme looked at how likely patients are to get ongoing knee pain after their operation and discovered why patients don’t seek help. The research team developed a new treatment — a care pathway — for patients and compared how patients did on the STAR care pathway when compared with a control group who had the usual care.

STAR care pathway:

• Three months after surgery patients attended an hour-long clinic, ran by specially trained health care professionals
• Detailed pain questionnaires were filled out and X-rays were taken as well as a blood test for infection. If needed patients were referred for further ongoing treatment
• Patients received up to six ‘phone calls over the next 12 months, making sure they had their referral, and to check how they were doing

Rachael Gooberman-Hill, lead researcher for the STAR programme, Professor of Health and Anthropology and Director of Bristol’s Elizabeth Blackwell Institute, said: “People have a knee replacement to relieve their pain and it’s immensely disappointing if they find that they have long-term pain afterwards. Unfortunately, one in five people who have knee replacement have long-term pain afterwards — that is around 20,000 people each year in the UK alone.

“As a research team we wanted to do something that would help. We found that our new STAR care pathway had a positive impact on people’s pain. People who had long-term pain after their knee replacement and who were given STAR had less pain and the pain interfered less with their lives one year later. People told us that STAR helped them to feel supported, to find out more about their pain and STAR meant that they were able to get further treatment that was tailored to their pain. We are enormously pleased with our research findings because it should make a real difference to people who find that they have pain after their knee replacement.”

Brenig, a participant on the STAR trial, explained: “As part of the STAR trial, you have tailored physiotherapy appointments. At my three-month review with a STAR physiotherapist, I was having a problem not being able to straighten my leg out. She gave me some simple exercises, which worked and straightened the leg out. Occasionally I have problems at the back of the knee, then I do the exercises and it goes back to normal. So that was a very positive side of what we actually did.

“I felt that being part of the STAR trial gave me access to a specialist physiotherapist. Her knowledge was far, far superior and specific to my issue. Some mornings I get up and feel on top of the world and then the following day I have leg pain. Eventually you get to accept it, but doing the exercises helps.”

The study has benefited greatly from Bristol’s Musculoskeletal Research Unit’s patient involvement group, PEP-R (Patient Experience Partnership in Research) who worked closely with the STAR research team to develop the design of the programme.

Dr Vikki Wylde, Associate Professor in Musculoskeletal Health at Bristol Medical School (THS), and co-author, added: “The new STAR care pathway provides benefit to people with pain at three months after knee replacement, but we still need more research to understand how we could prevent people from developing this pain. High-quality research to pre-operatively identify patients at high risk of developing pain after their operation is needed. These patients could be offered treatments to increase their chance of a good outcome after knee replacement.”

Nick Howells, Consultant Orthopaedic Knee Surgeon at NBT and Honorary Senior Lecturer at Bristol Medical School: THS, continued: “Knee replacement surgery is a great operation that changes the lives of many people suffering with knee osteoarthritis, improving pain, function and quality of life, however, a proportion of people are left with ongoing pain. To have developed an intervention which has been shown to make a difference for some of these people is really satisfying for our team and a great step forward in treatment.

“We have now successfully introduced the STAR care pathway into our NHS clinical care pathway at North Bristol and hope it will be adopted in other centres across the NHS in the future.”

The intranasal vaccine contributed to multifaceted immune responses, leading to robust cross protection against influenza in mice. The vaccine consists of PEI-HA/CpG nanoparticles. PEI (polyethyleneimine), a robust and versatile delivery system, can simultaneously carry antigens (hemagglutinin, HA) that induce an immune response in the body, and adjuvants (CpG) that enhance the body’s immune response to an antigen for optimal immunoenhancement.

These comprehensive immune responses and cross protection were long lasting, exhibiting defense from influenza virus over six months after immunization. The findings are published in the journal ACS Applied Materials & Interfaces.

Intranasal vaccination is an ideal approach for infectious respiratory diseases such as influenza. Seasonal influenza vaccines generally induce narrow immune responses that rapidly decline, which leaves populations vulnerable to novel influenza strains. Advancements in influenza vaccine technology are needed to protect against a wide range of influenza viruses. Intranasal vaccination can improve local mucosal immune responses by preventing influenza infection at the portal of virus entry.

In the influenza virus, HA is a protein that plays a crucial role in the early stages of virus infection. Influenza HA has a head region and stalk region. Current influenza vaccines elicit immune responses against the HA head, but this head region is highly changeable and accounts for lowered efficiency against different strains. The HA stalk region is more conservative across different strains of influenza viruses.

Protein antigens that are administered intranasally are usually less able to provoke an immune response, so adjuvants are needed to have highly efficient intranasal vaccines. Adjuvants, such as CpG, can enhance and manipulate immune responses, thus improving the potency and breadth of protection.

“The PEI-HA/CpG nanoparticles show good potential as a cross-protective influenza vaccine candidate,” said Dr. Baozhong Wang, corresponding author of the study and a professor in the Institute for Biomedical Sciences at Georgia State. “The combination of PEI and CpG in the PEI-HA/CpG nanoparticle group contributed to the multifaceted immune responses, leading to vigorous cross protection. The incorporation of CpG and antigens into the same nanoparticle enhanced cellular immune responses.

“Our results revealed that the nanoparticles significantly enhanced HA immunogenicity, or the ability to provoke an immune response, providing cross protection against different influenza virus strains. The conserved HA stalk region induced substantial antibodies in the nanoparticle immunization groups.”

“Nanoparticle platforms have shown intriguing characteristics and great potentials in the development of next-generation cross-protective influenza vaccines,” said Dr. Chunhong Dong, the first author of the study and a postdoctoral fellow in the Institute for Biomedical Sciences. “However, challenges exist to the successful research and development of nanoparticle vaccines. Though no apparent adverse effects were observed in the study, a more comprehensive safety evaluation of the nanoparticle adjuvant system is needed before clinical trials.”

Co-authors of the study include Baozhong Wang, Chunhong Dong (first author), Ye Wang, Wandi Zhu, Yao Ma, Joo Kim, Lai Wei and Gilbert X. Gonzalez.

The study was funded by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health.

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In a new study published in the journal Biogeosciences, a team of researchers from Dalhousie University in Halifax, Canada and the GEOMAR Helmholtz Centre for Ocean Research Kiel in Germany have now, for the first time, measured the flow of oxygen into the deep ocean interior that is carried by these deep currents. It is the oceanographic equivalent of measuring oxygen transport in our bodies through the main artery or aorta.

From one sea to many oceans

Jannes Koelling, lead author of the study, explains, “We wanted to know how much of the oxygen that is breathed in each winter actually makes it into the deep, fast-flowing currents that transport it across the globe.”

The deep mixing of oxygen in the central Labrador Sea is only a first step in the deep ocean’s life support system. Deep, boundary currents then distribute the oxygen to the rest of the Atlantic Ocean and beyond. This way, oxygen that is ‘inhaled’ in the Labrador Sea can support deep ocean life off Antarctica and even in the Pacific and Indian Oceans.

Koelling explained, “The newly inhaled oxygen was clearly noticeable as a pulse of high oxygen concentration that passed our sensors between March and August.”

Compelling insights over two years

The team unravelled the connection between oxygen uptake from the atmosphere and its onward transport into the interior using dissolved oxygen sensors that were mounted for two years on anchored cables which reached from the seafloor to near the surface. The sensors were deployed at depths of about 600m, where the scientists expected water to propagate from the deep mixing region in the centre of the Labrador Sea (the lung).

The new measurements revealed that about half of the oxygen taken up from the atmosphere in the central Labrador Sea in winter was injected into the deep boundary current over the following 5 months. While some of the remaining oxygen may have been consumed locally by fish and other organisms, the bulk most likely took an alternative route out of the deep mixing region.

Findings could impact the climate model

The study and the new ability to monitor oxygen transport becomes highly relevant, given that climate model projections suggest an increased supply of freshwater — from melting glaciers and other climate-changes in the Arctic — could reduce the depth of wintertime mixing in the Labrador Sea in coming decades. This would make the Labrador Sea’s ‘breathing’ shallower and reduce the life-supporting supply of oxygen to the deep sea.

“This is an example of how monitoring enabled by the latest ocean technology can help us fill in knowledge gaps in this important region,” says Dariia Atamanchuk, who leads the oxygen programme at Dalhousie.

Koelling concludes: “The circulation of the Labrador Sea is complex, and we’ve only focused, so far, on the most direct export route. Some oxygen-rich water may be transported eastwards, instead of to the southwest, and it may enter the boundary current off Greenland before returning southwards, over a longer time-period.” These other pathways, shown as dashed lines in the map, are being investigated with further studies, using additional oxygen sensors mounted on more moorings.

The new findings are the result of a collaboration supported by the Ocean Frontier Institute, a transatlantic research organisation that connects researchers from several major institutions in Canada, Europe and the USA in a common focus on the climate-sensitive Northwest Atlantic Ocean.

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J Calvin Coffey, Foundation Chair of Surgery at UL’s School of Medicine in Ireland, whose major discovery led to the reclassification of the mesentery as a new organ in 2016, has published new research on the makeup and structure of the abdomen.

In a research paper published in the Nature Portfolio journal Communications Biology, Professor Coffey’s team has detailed the development and structure of the mesentery. In doing this, they uncovered a new order by which all contents of the abdomen are organised or arranged — or the “fundamental order of the abdomen.”

The importance of these findings on the mesentery and the impact these have on our understanding of the abdomen have been further explained in a review article just published in the Lancet Gastroenterology and Hepatology.

“Since 2016, Kevin Byrnes, Dara Walsh and members of the team been looking at the development and structure of the mesentery,” explained Professor Coffey, who is also Head of Department of Surgery, Consultant General and Colorectal Surgeon at UL Hospitals Group.

“We showed how the mesentery is a single and continuous organ in and on which all abdominal digestive organs develop and then remain connected to throughout life.

“These findings revealed a simplicity in the abdomen that was not apparent in conventional descriptions of anatomy,” he explained.

In an international collaboration, Professor Coffey’s team used a variety of state of the art techniques to clarify how the mesentery develops and the shape it has in adults.

The conclusion of the work revealed that the organisation of the abdomen has a remarkably simple design. This design is summarised in a description called the ‘Mesenteric Model of Abdominal Anatomy’.

“The abdomen is not the dauntingly complex collection of separate organs it was previously thought to be,” said Professor Coffey.

“Instead, all digestive organs are neatly packaged and arranged by the mesentery into a single digestive engine. That simplicity lay hidden until clarification of the nature of the mesentery.”

The model itself was described by the team in the most recent edition of Gray’s Anatomy. The supportive evidence was published in Communications Biology and the clinical importance was explained in the review in The Lancet Gastroenterology and Hepatology.

“The most important finding here was the discovery of the fundamental order of the abdomen. At the foundation level, all contents of the abdomen are simply organised into one of two compartments,” explained Professor Coffey.

“The fundamental order of any structure is of considerable importance, in particular when it comes to diagnosing patients with illness and treating their disease. The fundamental order is the foundation from which all science launches and clinical practice is based.

“The organisational simplicity of the abdomen now immediately explains the behaviours of viral and bacterial infections, cancer, inflammatory bowel disease, obesity, diabetes and many others,” he added.

Better understanding of the mesentery and its functions has already led to improvements in surgery and the new research builds on those advances. There are also exciting areas for future investigation, Professor Coffey outlined.

“Patients are already benefiting from what we now call mesenteric-based approaches to the diagnosis and treatment of most abdominal conditions. The Mesenteric Model of Abdominal Anatomy — or the description of the order of the abdomen — is being incorporated into numerous reference curricula at this moment,” he said.

“Regarding the future, it is being argued that we are seeing a paradigmatic shift from old to new order. Already, intriguing questions are emerging that we can call ‘legitimate or admissible’ in the strictest scientific sense. Science can approach numerous questions in a new light. Clinicians can design diagnostic and treatment approaches based on a new foundation,” Professor Coffey concluded.

The protein, known as histone H3.3, organizes the spool-like structures around which DNA is wrapped in plants, animals and most other organisms. Histones enable DNA to be tightly compacted, and serve as platforms for small chemical modifications — known as epigenetic modifications — that can loosen or tighten the wrapped DNA to control local gene activity.

The study, which appeared Dec. 27 in Nature Cell Biology, examined H3.3’s role in blood stem cells, also known as hematopoietic stem cells (HSCs), that are a major focus of efforts to develop stem-cell-based medicine. Normally most HSCs stay in a stem-like, uncommitted state where they can survive long-term, slowly self-renewing, while some HSCs mature or “differentiate” to produce all the different lineage-specific blood cell types. The study found that H3.3 is crucial for both processes; deleting the protein from HSCs led to reduced HSC survival, an imbalance in the types of blood cell produced by the HSCs and other abnormalities.

“How hematopoietic stem cells coordinate their self-renewal and differentiation into various blood cell types in a balanced way has been a mystery to a great extent, but this study helps us understand those processes much better at the molecular level and gives us many new clues to pursue in further investigations,” said study co-senior author Dr. Shahin Rafii, director of the Ansary Stem Cell Institute, chief of the Division of Regenerative Medicine and the Arthur B. Belfer Professor in Genetic Medicine at Weill Cornell Medicine.

The study was a collaboration that also included co-first and co-senior authors Dr. Ying Liu and Dr. Peipei Guo, who are senior instructors in the Rafii Laboratory; co-senior author Dr. Duancheng Wen, assistant professor of reproductive medicine research in obstetrics and gynecology; and co-author Dr. Steven Josefowicz, assistant professor of pathology and laboratory medicine and a member of the Sandra and Edward Meyer Cancer Center, all of Weill Cornell Medicine.

HSCs are among the most studied stem cells because of their importance in health and disease, and their potential in regenerative medicine. A single HSC can give rise to all blood cell types, from red blood cells and platelets to T cells, B cells and pathogen-engulfing macrophages. A more precise understanding of how HSCs work could lead to many applications including lab-grown blood for transfusions, and better HSC transplants for cancer patients. In addition, understanding how HSCs, upon acquiring aberrant mutations, give rise to leukemias could lead to development of new therapies for these often-refractory malignant diseases.

H3.3 also has been a major focus of interest for biologists in recent years, as evidence of its importance in HSCs and other stem cells — and its role in various cancers when mutated — has mounted. But just what histone H3.3 does in HSCs, and in other cell types where it appears, has been far from clear.

“Added to the complexity of this project, is that two different genes (H3.3A and H3.3B) code for the same H3.3 protein. Therefore, we had to painstakingly delete both genes in mice by genetic engineering, a herculean task that required a great deal of genetic manipulation of stem cells,” Dr. Wen said.

“Our powerful mouse model allows inducible and complete deletion of the H3.3 protein in all organs, or specific types of organs, at selected developmental stage of a mouse,” said Dr. Liu, who is also a research associate in Dr. Rafii’s lab. “Employing this approach, we showed that H3.3’s absence in adulthood primarily causes a depletion of the long-term, self-renewing HSCs on which future blood-cell production depends. At the same time, affected HSCs differentiated into mature blood cell types with an abnormal skew or bias towards certain types of white blood cell, including granulocytes and macrophages.

“Most importantly, we found evidence that H3.3 has its effects on HSCs in part by anchoring several key epigenetic marks at developmental genes and endogenous retroviruses (ERVs),” she added, “which are remnants of viruses that once inscribed themselves into our distant evolutionary ancestors’ DNA.”

“One intriguing observation was that H3.3’s deletion caused the loss of epigenetic marks that normally suppress ERVs, which led in turn to the activation of an inflammatory response in affected cells, and then drove the cells’ skewed production of blood cell types — a skew that is similar to what is seen in some leukemias,” said Dr. Guo, who is also a research associate in Dr. Rafii’s laboratory.

“H3.3 appears to be acting as a master regulator of self-renewal and differentiation in HSCs — which is wild, and hints at a very broad potential as a therapeutic target someday,” said co-author Andrew Daman, a Weill Cornell Graduate School of Medical Sciences doctoral candidate in the Josefowicz lab.

“Our take-home message is that normal blood cell development requires the proper epigenetic regulation provided by H3.3,” Dr. Liu said.

The team now plans further studies, in HSCs and other cell types, to understand in more detail how H3.3 exerts its effects and what happens when it is absent. More importantly, developing approaches to monitor the H3.3 command of the epigenetic landscape could enable them to more effectively increase blood production. “Finally, our team is investigating how H3.3 controls the function of the nurturing niche cells, such as blood vessels that orchestrate stem cell self-renewal and possibly block the emergence of malignancies such as leukemias,” said Dr. Rafii, who is also a member of the Meyer Cancer Center.

“It has been widely accepted that traditional superconductors result from electrons interacting with phonons, where the phonons pair two electrons as an entity and the latter can run in a material without resistance,” said Yao Wang, assistant professor of physics and astronomy at Clemson University.

However, in cuprates, strong repulsions known as the Coulomb force were found between electrons and were believed to be the cause of this special and high-temperature superconductivity.

Phonons are the vibrational energy that arise from oscillating atoms within a crystal. The behavior and dynamics of phonons are very different from those of electrons, and putting these two interacting pieces of the puzzle together has been a challenge.

In November 2021, writing in the journal Physical Review Letters, Wang, along with researchers from Stanford University, presented compelling evidence that phonons are in fact contributing to a key feature observed in cuprates, which may indicate their indispensable contribution to superconductivity.

The study innovatively accounted for the forces of both electrons and phonons together. They showed that phonons impact not only electrons in their immediate vicinity, but act on electrons several neighbors away.

“An important discovery in this work is that electron-phonon coupling generates non-local attractive interactions between neighboring electrons in space,” Wang said. When they used only local coupling, they calculated an attractive force an order of magnitude smaller than the experimental results. “This tells us that the longer-range part is dominant and extends up to four unit cells,” or neighboring electrons.

Wang, who led the computational side of the project, used the National Science Foundation (NSF)-funded Frontera supercomputer at the Texas Advanced Computing Center (TACC) — the fastest academic system in the world — to replicate experiments carried out at the Stanford Synchrotron Radiation Lightsource and presented in Sciencein Sept. 2021 in a simulation.

The results relied not only on Frontera’s super-fast parallel computing capabilities, but on a new mathematical and algorithmic method that allowed for far greater accuracy than ever before.

The method, called variational non-Gaussian exact diagonalization, can perform matrix multiplications on billions of elements. “It’s a hybrid method,” Wang explained. “It treats the electron and phonon by two different approaches that can adjust with each other. This method performs well and can describe strong coupling with high precision.” The method development was also supported by a grant from NSF.

The demonstration of phonon-mediated attraction has a significant impact even beyond the scope of superconductors. “Practically, the results mean we’ve found a way to manipulate Coulomb interactions,” Wang said, referring to the attraction or repulsion of particles or objects because of their electric charge.

“If superconductivity comes from Coulomb forces only, we cannot easily manipulate this parameter,” he said. “But if part of the reason comes from the phonon, then we can do something, for instance, putting the sample on some substrate that will change the electron-phonon interaction. That gives us a direction to design a better superconductor.”

“This research gives new insights into the mystery of cuprate superconductivity that may lead to higher temperature superconducting materials and devices,” said Daryl Hess, a program director in Division of Materials Research at NSF. “They may find their way into future cell phones and quantum computers. A journey started by human creativity, clever algorithms, and Frontera.”

Wang and collaborator Cheng-Chien Chen, from the University of Alabama, Birmingham, also applied this new approach and powerful TACC supercomputers to study laser-induced superconductivity. They reported these findings in Physical Review X in November 2021. And working with a team from Harvard, Wang used TACC supercomputers to study the formation of Wigner crystals in work published in Nature in June 2021.

As is the case in many fields of science, supercomputers are the only tool that can probe the quantum behavior and explain the underlying phenomena at play.

“In physics, we have very beautiful frameworks to describe an electron or an atom, but when we’re talking about real materials with 10²³ atoms, we don’t know how to use these beautiful frameworks,” Wang said.

For quantum or correlated materials in particular, physicists have had a hard time applying ‘beautiful’ theory. “So instead, we use ugly theory — numerical simulation of the materials. Although we don’t have a well-established quantum computer for now, using classical high performance computers, we can push the problem forward a lot. Ultimately, this will guide experiment.”

Wang is currently working with IBM and IonQ to develop quantum algorithms to test on current and future quantum computers. “Supercomputing is our first step.”

When it comes to big future developments in technology, Wang believes computational studies, in conjunction with experiment, observation and theory, will help untangle mysteries and achieve practical goals, like tunable superconducting materials.

“A new algorithm can make a difference. More numerical precision can make a difference,” he said. “Sometimes we don’t understand the nature of a phenomenon because we didn’t look closely enough at the details. Only when you push the simulation and zoom in to the nth digit will some important aspect of nature show up.”

All-polymer blend solar cells are formed by combining two polymer solutions that solidify into a film on an electrode with in the form of interpenetrating networks, a kind of “phase-separation.” The introduction of solvent additives to the polymer solution has been shown to increase the efficiency of all-polymer blend solar cells. However, the exact process underlying this improvement has not been fully understood. Now, in a study recently published in ACS Applied Polymer Materials, researchers from Nara Institute of Science and Technology have investigated the performance enhancement mechanism using photoconductive atomic force microscopy (PC-AFM). Their findings are expected to help accelerate the widespread application of polymer-based solar cells.

“The empirical nature of solvent additive-mediated efficiency enhancement has hindered the optimization of all-polymer blend solar cell performance, so there has been an urgent need for a greater understanding of the process,” explains senior author Hiroaki Benten. “To that end, we used PC-AFM to interrogate the nanoarchitecture that underpins the performance enhancement.”

PC-AFM is an advanced microscopy technique that allows photocurrents to be visualized with nanometer-scale resolution. The researchers found that trace solvent additives improved the power conversion and photocurrent density of an all-polymer blend solar cell by a factor of up to ~3 by enhancing the ordering and crystallization of the polymer microstructure in the solar cell without damaging the phase-separated structure.

Absorption spectroscopy measurements further confirmed that the trace additives improved the ordering in the polymer microstructures. By forming a network that efficiently transports the photogenerated charges to the external electrode, the flow of photocurrent is increased.

“We found that local photocurrents were enhanced, somewhat like forming a new charge current highway, while the scale of phase separation that is critical to device functionality was retained,” says coauthor Masakazu Nakamura. “We believe that this insight will be broadly applicable to all-polymer blend solar cells, not just those based on our choice of polymers.”

The results of the study are expected to be important for optimizing the performance of all-polymer blend solar cells. By using the findings to minimize laboratory trial-and-error, it is hoped researchers can speed up ongoing bench-to-market efforts, taking us a step closer to high-performance solar cells that are environmentally sustainable and easy to produce on a large scale.

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The study, published in Nature Communications, was funded by Breast Cancer Ireland with support from Breast Cancer Now and Science Foundation Ireland.

Most breast cancer related deaths are a result of treatment relapse leading to spread of tumours to many organs around the body. When secondary breast cancer, also known as metastatic breast cancer, spreads to the brain it can be particularly aggressive, sometimes giving patients just months to live.

The RCSI study focused on genetically tracking the tumour evolution from diagnosis of primary breast to the metastatic spread in the brain in cancer patients. The researchers found that almost half of the tumours had changes in the way they repair their DNA, making these tumours vulnerable to an existing type of drug known as a PARP inhibitor. PARP inhibitor drugs work by preventing cancer cells to repair their DNA, which results in the cancer cells dying.

“There are inadequate treatment options for people with breast cancer that has spread to the brain and research focused on expanding treatment options is urgently needed. Our study represents an important development in getting one step closer to a potential treatment for patients with this devastating complication of breast cancer,” commented Professor Leonie Young, the study’s Principal Investigator.

“By uncovering these new vulnerabilities in DNA pathways in brain metastasis, our research opens up the possibility of novel treatment strategies for patients who previously had limited targeted therapy options,” said study author Dr Damir Varešlija.

The research, led by Beaumont RCSI Cancer Centre investigators Professor Leonie Young, Dr Nicola Cosgrove, Dr Damir Varešlija and Professor Arnold Hill, was carried out in collaboration with the Mayo Clinic and University of Pittsburgh, USA.

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