World's first fiber-optic ultrasonic imaging probe for future nanoscale disease diagnostics

UNIVERSITY OF NOTTINGHAM

Research News

 

IMAGE: CONCEPT ART SHOWING THE 3D MAPPING OF MICROSCOPIC OBJECTS BY THE PHONON PROBE SYSTEM. THE OPTICAL FIBRE CONTAINS A METAL LAYER ON ITS TIP AND PROJECTS RED LASER LIGHT INTO... view more 

CREDIT: DR SALVATORE LA CAVERA

Scientists at the University of Nottingham have developed an ultrasonic imaging system, which can be deployed on the tip of a hair-thin optical fibre, and will be insertable into the human body to visualise cell abnormalities in 3D.

The new technology produces microscopic and nanoscopic resolution images that will one day help clinicians to examine cells inhabiting hard-to-reach parts of the body, such as the gastrointestinal tract, and offer more effective diagnoses for diseases ranging from gastric cancer to bacterial meningitis.

The high level of performance the technology delivers is currently only possible in state-of-the-art research labs with large, scientific instruments - whereas this compact system has the potential to bring it into clinical settings to improve patient care.

The Engineering and Physical Sciences Research Council (EPSRC)-funded innovation also reduces the need for conventional fluorescent labels - chemicals used to examine cell biology under a microscope - which can be harmful to human cells in large doses.

The findings are being reported in a new paper, entitled 'Phonon imaging in 3D with a fibre probe' published in the Nature journal, Light: Science & Applications.

Paper author, Salvatore La Cavera, an EPSRC Doctoral Prize Fellow from the University of Nottingham Optics and Photonics Research Group, said of the ultrasonic imaging system: "We believe its ability to measure the stiffness of a specimen, its bio-compatibility, and its endoscopic-potential, all while accessing the nanoscale, are what set it apart. These features set the technology up for future measurements inside the body; towards the ultimate goal of minimally invasive point-of-care diagnostics."

Currently at prototype stage, the non-invasive imaging tool, described by the researchers as a "phonon probe", is capable of being inserted into a standard optical endoscope, which is a thin tube with a powerful light and camera at the end that is navigated into the body to find, analyse, and operate on cancerous lesions, among many other diseases. Combining optical and phonon technologies could be advantageous; speeding up the clinical workflow process and reducing the number of invasive test procedures for patients.

3D mapping capabilities

Just as a physician might conduct a physical examination to feel for abnormal 'stiffness' in tissue under the skin that could indicate tumours, the phonon probe will take this '3D mapping' concept to a cellular level.

By scanning the ultrasonic probe in space, it can reproduce a three-dimensional map of stiffness and spatial features of microscopic structures at, and below, the surface of a specimen (e.g. tissue); it does this with the power to image small objects like a large-scale microscope, and the contrast to differentiate objects like an ultrasonic probe.

"Techniques capable of measuring if a tumour cell is stiff have been realised with laboratory microscopes, but these powerful tools are cumbersome, immobile, and unadaptable to patient-facing clinical settings. Nanoscale ultrasonic technology in an endoscopic capacity is poised to make that leap," adds Salvatore La Cavera.

CAPTION

The optical fibre imaging sensor has a diameter of 125 micrometres, approximately the size a human hair, shown for perspective against a penny. A microscope image shows the true scale of the device, and its ability to conduct light.

CREDIT

Dr Salvatore La Cavera

How it works

The new ultrasonic imaging system uses two lasers that emit short pulses of energy to stimulate and detect vibrations in a specimen. One of the laser pulses is absorbed by a layer of metal - a nano-transducer (which works by converting energy from one form to another) - fabricated on the tip of the fibre; a process which results in high-frequency phonons (sound particles) getting pumped into the specimen. Then a second laser pulse collides with the sound waves, a process known as Brillouin scattering. By detecting these "collided" laser pulses, the shape of the travelling sound wave can be recreated and displayed visually.

The detected sound wave encodes information about the stiffness of a material, and even its geometry. The Nottingham team was the first to demonstrate this dual-capability using pulsed lasers and optical fibres.

The power of an imaging device is typically measured by the smallest object that can be seen by the system, i.e. the resolution. In two dimensions the phonon probe can "resolve" objects on the order of 1 micrometre, similar to a microscope; but in the third dimension (height) it provides measurements on the scale of nanometres, which is unprecedented for a fibre-optic imaging system.

Future applications

In the paper, the researchers demonstrate that the technology is compatible with both a single optical fibre and the 10-20,000 fibres of an imaging bundle (1mm in diameter), as used in conventional endoscopes.

Consequently, superior spatial resolution and wide fields of view could routinely be achieved by collecting stiffness and spatial information from multiple different points on a sample, without needing to move the device - bringing a new class of phonon endoscopes within reach.

Beyond clinical healthcare, fields such as precision manufacturing and metrology could use this high-resolution tool for surface inspections and material characterisation; a complementary or replacement measurement for existing scientific instruments. Burgeoning technologies such as 3D bio-printing and tissue engineering could also use the phonon probe as an inline inspection tool by integrating it directly to the outer diameter of the print-needle.

Next, the team will be developing a series of biological cell and tissue imaging applications in collaboration with the Nottingham Digestive Diseases Centre and the Institute of Biophysics, Imaging and Optical Science at the University of Nottingham; with the aim to create a viable clinical tool in the coming years.

CAPTION

(top) Conventional microscope pictures of model biological cells. (bottom) The phonon probe reproduces 3D images of the objects (colour is height). Simultaneously, the probe detected stiffness related measurements which are mapped in green on the top left image. The white scales bar are 10 micrometres long.

CREDIT

Dr Salvatore La Cavera

More information is available from Salvatore La Cavera III on salvatore.lacaveraiii@nottingham.ac.uk or Emma Lowry, Media Relations Manager (Engineering) on 0115 84 67156 or Emma.Lowry@nottingham.ac.uk.

The University of Nottingham is a research-intensive university with a proud heritage, consistently ranked among the world's top 100. Studying at the University of Nottingham is a life-changing experience and we pride ourselves on unlocking the potential of our students. We have a pioneering spirit, expressed in the vision of our founder Sir Jesse Boot, which has seen us lead the way in establishing campuses in China and Malaysia - part of a globally connected network of education, research and industrial engagement. The University's state-of-the-art facilities and inclusive and disability sport provision is reflected in its status as The Times and Sunday Times Good University Guide 2021 Sports University of the Year. We are ranked eighth for research power in the UK according to REF 2014. We have six beacons of research excellence helping to transform lives and change the world; we are also a major employer and industry partner - locally and globally. Alongside Nottingham Trent University, we lead the Universities for Nottingham initiative, a pioneering collaboration which brings together the combined strength and civic missions of Nottingham's two world-class universities and is working with local communities and partners to aid recovery and renewal following the COVID-19 pandemic.

'Pokemonas': Bacteria related to lung parasites discovered, named after Pokémon

UNIVERSITY OF COLOGNE

Research News

   

IMAGE: LIGHT MICROSCOPE IMAGE AND ILLUSTRATION OF A THECOFILOSEA AMOEBA WITH INTRACELLULAR LEGIONELLALES BACTERIA ('CA. POKEMONAS KADABRA'). THE BACTERIA WERE STAINED RED BY SO-CALLED 'FLUORESCENCE IN SITU HYBRIDIZATION'. view more 

CREDIT: MARCEL DOMINIK SOLBACH

A research team at the University of Cologne has discovered previously undescribed bacteria in amoebae that are related to Legionella and may even cause disease. The researchers from Professor Dr Michael Bonkowski's working group at the Institute of Zoology have named one of the newly discovered bacteria 'Pokemonas' because they live in spherical amoebae, comparable to Pokémon in the video game, which are caught in balls. The results of their research have been published in the journal Frontiers in Cellular and Infection Microbiology.

LEGIONARIES DISEASE

Bacteria of the order Legionellales have long been of scientific interest because some of these bacteria are known to cause lung disease in humans and animals - such as 'Legionnaires' disease', which is caused by the species Legionella pneumophila and can sometimes be fatal. Legionellales bacteria live and multiply as intracellular parasites in the cells of organisms as hosts. In particular, the hosts of Legionellales are amoebae. The term 'amoeba' is used to describe a variety of microorganisms that are not closely related, but share a variable shape and crawling locomotion by means of pseudopods. 'We wanted to screen amoebae for Legionellales and chose a group of amoebae for our research that had no close relationship to the hosts that were previously studied. The choice fell on the amoeba group Thecofilosea, which is often overlooked by researchers,' explains Marcel Dominik Solbach.

And indeed, the spherical Thecofilosea serve as host organisms for Legionellales. In Thecofilosea amoebae from environmental samples, the scientists were able to detect various Legionellales species, including two previously undescribed genera and one undescribed species from the genus Legionella. 'The results show that the range of known host organisms of these bacteria is considerably wider than previously thought. In addition, these findings suggest that many more amoebae may serve as hosts for Legionellales - and thus potentially as vectors of disease. To investigate this further, we are now sequencing the complete genome of these bacteria,' said Dr Kenneth Dumack, who led the project.

In the future, these new findings should help to better understand how Legionellales bacteria are related amongst each other, and clarify their interactions with their hosts as well as the routes of infection in order to prevent outbreaks of the diseases in humans.

The researchers named one of the genera of bacteria they discovered 'Pokemonas.' The genus name 'Pokemonas' is a play on words based on the video game franchise 'Pokémon,' which celebrates its 25th anniversary this year and which most schoolchildren, students, and their parents should be familiar with. The name alludes to the intracellular lifestyle of the bacteria in the ball-shaped Thecofilosea amoebae, because in the 'Pokémon' series games, little monsters are caught in balls, much like 'Pokemonas' in the Thecofilosea.

CAPTION

Light microscope image and illustration of a Thecofilosea amoeba with intracellular Legionellales bacteria ('Ca. Pokemonas kadabra'). The bacteria were stained red by so-called 'fluorescence in situ hybridization'. 

CUTE; KADABRA AS IN ABRAKADABRA 

POKEMON AS KADABRA

CREDIT

Marcel Dominik Solbach

 

The Lancet: Study confirms greater risk of poor COVID outcomes in minority ethnic groups in England

Study confirms greater risk of poor COVID outcomes in minority ethnic groups in England, with inequalities widening in the second wave for South Asian groups

THE LANCET

Research News

Largest study so far of more than 17 million adults in England confirms that minority ethnic groups had a higher risk of testing positive, hospitalisation, admission to intensive care units (ICU), and death from COVID-19 compared with white groups, even after accounting for other factors known to increase risk like deprivation, occupation, household size and underlying health conditions.

• Disparities for hospitalisation and death lessened for most minority ethnic groups between pandemic waves 1 (February to September 2020) and wave 2 (September to December 2020), but increased for South Asian groups.

• To tackle ethnic disparities in COVID-19 risks, the authors call for reducing structural disadvantage and inequality, improving quality of and access to healthcare, and improving uptake of testing and vaccination. They also stress the need for more intensive strategies tailored to improve outcomes in South Asian communities.

Minority ethnic groups had higher risk of testing positive for SARS-CoV-2 and of COVID-19-related hospitalisations, intensive care (ICU) admissions and death compared with white groups in England, according to an observational study published in The Lancet.

The COVID-19 pandemic is understood to have had a disproportionate impact on minority ethnic communities in the UK and beyond. This study accounted for a large number of explanatory variables such as household size, social factors and health conditions across all ethnic groups and at different stages of COVID-19, from testing to mortality. Understanding drivers of SARS-CoV-2 infection and COVID-19 in minority ethnic communities will be crucial to public policy efforts to overcome inequalities.

"Minority ethnic groups in the UK are disproportionately affected by factors that also increase the risk for poor COVID-19 outcomes, such as living in deprived areas, working in front-line jobs, and having poorer access to healthcare. Our study indicates that even after accounting for many of these factors, the risk for testing positive, hospitalisation, ICU admission and death was still higher in minority ethnic groups compared with white people in England. To improve COVID-19 outcomes, we urgently need to tackle the wider disadvantage and structural racism faced by these communities, as well as improving access to care and reducing transmission," says lead author, Dr Rohini Mathur of the London School of Hygiene and Tropical Medicine, UK. [1]

On behalf of NHS England, the research team used the new secure OpenSAFELY data analytics platform to analyse partially anonymised electronic health data collected by GPs covering 40% of England. These GP records were linked to other national coronavirus-related data sets for the first and second waves of the pandemic - including testing, hospital data and mortality records. Ethnicity was self-reported by participants in GP records and grouped into five census categories (white, South Asian, Black, other, mixed) and then a further 16 sub-groups.

Possible explanatory factors, including clinical characteristics, such as BMI, blood pressure, smoking status and conditions such as asthma and diabetes were included in the analyses alongside demographic information such as age, sex, deprivation and household size.

Of 17,288,532 adults included in the study, 63% (10,877,978) were white, 5.9% (1,025,319) South Asian, 2% (340,912) Black, 1.8% (320,788) other, and 1% (170,484) mixed. Ethnicity was unknown for 26.3% (4,553,051) people.

During wave 1, nearly all minority ethnic groups had higher relative risk for testing positive, hospitalisation, ICU admission, and death compared to white groups. The largest disparities were seen in ICU admissions, which were more than doubled for all minority ethnic groups compared with white groups, with Black people more than three times more likely to be admitted to ICU after accounting for other factors.

The proportion of people testing positive for SARS-CoV-2 in wave 1 was higher in South Asian groups (0.9% test positivity), Black (0.7%) and mixed groups (0.5%) and compared with white people (0.4%).

"Higher risks for testing positive and subsequent poor outcomes amongst minority ethnic groups suggest that people may delay seeking testing or accessing care for SARS-CoV-2. This may be due to lack of access to testing sites or conflicting health messaging. It may also suggest that some may be fearful of losing income or employment if required to quarantine after testing positive as minority ethnic groups are more likely to work in insecure jobs with poorer workplace protections. People who need to be tested as well as those who test positive must be supported better if we are to reduce disparities in COVID-19 outcomes," says Dr Mathur. [1]

Compared with wave 1, the relative risk for testing positive, hospitalisation, ICU admission, and death were smaller in pandemic wave 2 for all minority ethnic communities compared to white people, with the exception of South Asian groups. South Asian groups remained at higher risk for testing positive, with relative risks for hospitalisation, ICU admission, and death greater in magnitude in wave 2 compared to wave 1.

"Despite the improvements seen in most minority ethnic groups in the second wave compared to the first, it's concerning to see that the disparity widened among South Asian groups. This highlights an urgent need to find effective prevention measures that fit with the needs of the UK's ethnically diverse population," says Dr Mathur. [1]

After accounting for age and sex, social deprivation was the biggest potential explanatory factor for disparities in all minority ethnic groups except South Asian. In South Asian groups, health factors (e.g., BMI, blood pressure, underlying health conditions) played the biggest role in explaining excess risks for all outcomes. Household size was an important explanatory factor for the disparity for COVID-19 mortality in South Asian groups only.

"While multigenerational living may increase risk of exposure and transmission (from children or working age adults to older or vulnerable family members), such households and extended communities also offer valuable informal care networks and facilitate engagement with health and community services. In light of emerging evidence that minority ethnic groups are less likely to take up the COVID-19 vaccine, co-designing culturally competent and non-stigmatising engagement strategies with these communities is increasingly important," says Dr Mathur. [1]

The authors caution that there are some limitations to the study including an inability to capture all potential explanatory variables, including occupation, health-related behaviours, and experiences of racism or structural discrimination. They call for improving the completeness of ethnicity recording in health data to further support the conduct of high quality research into addressing health inequalities for COVID-19 and beyond.

Writing in a linked Comment, Dr Daniel Morales, University of Dundee, UK, and Dr Sarah Ali, Royal Free London NHS Foundation Trust, UK, (who were not involved in the study), said: "The pressing challenge is now ensuring that COVID-19 vaccination programmes are rolled out effectively amongst all minority ethnic groups. Key to this, will be ensuring that vaccine hesitancy is urgently addressed. There are reports of increased hesitancy in minority ethnic groups, including those working in front-line health and social care roles, who knowingly face an increased risk of contracting COVID-19. Unless vaccine hesitancy is tackled head on, differential vaccine uptake may further exacerbate health inequalities faced by minority ethnic groups."

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Peer-reviewed / Observational study / People

NOTES TO EDITORS

This study was funded by the Medical Research Council, part of UK Research and Innovation. It was conducted by researchers from London School of Hygiene and Tropical Medicine, the University of Oxford, TPP, NIHR Health Protection Research Unit in Immunisation, the Intensive Care National Audit and Research Centre, the University of Leicester, and University College London, full list at the end of the Article.

The labels have been added to this press release as part of a project run by the Academy of Medical Sciences seeking to improve the communication of evidence. For more information, please see: http://www.sciencemediacentre.org/wp-content/uploads/2018/01/AMS-press-release-labelling-system-GUIDANCE.pdf if you have any questions or feedback, please contact The Lancet press office pressoffice@lancet.com

[1] Quote direct from author and cannot be found in the text of the Article.

Vaccines bring us closer

Eurosurveillance issue marks European Immunization Week 2021

EUROPEAN CENTRE FOR DISEASE PREVENTION AND CONTROL (ECDC)

Research News

 

IMAGE: WORLD HEALTH ORGANIZATION (WHO) MEMBER STATES AFFIRMATIVELY REPORTING NATIONAL ADULT IMMUNISATION PROGRAMMES, BY WHO REGION AND WORLDWIDE, 2018 view more 

CREDIT: EUROSURVEILLANCE, WHO

Effectively and safely protecting against disease--this is what makes vaccines a vital and successful public health tool that saves lives and safeguards health and well-being. Today, vaccines shield us from more than 20 life-threatening diseases.

Each year, between 2 to 3 million lives are saved by immunisation against diseases like diphtheria, tetanus, pertussis, influenza or measles [1]. However, several vaccines such as the one against measles can only reach their full potential--protecting not just those who are immunised, but also those who might not be eligible for vaccination--if the vaccination coverage in a population is high enough [2].

Looking at immunisation programmes' successes and remaining challenges, this week's issue of Eurosurveillance is published on the occasion of European Immunization Week (EIW), from 26 April to 2 May 2021. The campaign, observed annually in the last week of April, was established by the World Health Organization (WHO) Regional Office for Europe in 2005 and aims to highlight the benefits of routine immunisation and to support national immunisation systems.

This year's EIW slogan, 'Vaccines bring us closer', embraces coronavirus disease (COVID-19) vaccines as an integral part of the response to end the ongoing pandemic and ease the physical distancing measures that have been implemented to help control it [3].

Thanks to routine vaccination--which has helped to eradicate for example smallpox and to protect against other diseases with potentially serious health consequences [4]--we know that vaccines work. Yet, WHO estimates that around 20 million children worldwide do not receive the vaccines they need or miss out on vaccination later in life [5].

Vaccines are most often administered to infants and children as part of routine national vaccination schedules. But immunisation protection reaches further than childhood and is important for people in all stages of life, from teenagers to adults and elderly people. Providing such lifelong protection poses further challenges for vaccination programmes, including ensuring equitable access to vaccines [6].

The editorial in this Eurosurveillance issue outlines the lessons learnt since the outset of the coronavirus disease (COVID-19) pandemic, with regards to rapid vaccine development, authorisation, procurement, distribution and administration in large vaccination campaigns. It looks at the key considerations for national vaccine decision-making--during a pandemic or otherwise--and the role that National Immunisation Technical Advisory Groups (NITAGs) or equivalent bodies play when they advise their governments on how to best use new vaccines or design national immunisation programmes.

Also in this issue, Williams et al. documented and quantified immunisation programmes for adults across 194 WHO Member States in order to assess existing infrastructures' suitability for COVID-19 vaccine deployment. Looking at five vaccines licensed for adult immunisation (hepatitis B, herpes zoster, influenza, pneumococcal conjugate and pneumococcal polysaccharide vaccines), the authors found that of the 194 WHO Member States, 120 (62%) reported having at least one adult vaccination programme in 2018, and that 59% of countries had adult vaccination programmes for influenza.

High- or upper-middle-income countries were found to be significantly more likely to report adult immunisation programmes, with country income serving as the most strongly associated factor overall in a multivariable analysis. Other significantly associated factors in a bivariable analysis included meeting National Immunisation Technical Advisory Group (NITAG) basic functional indicators, having introduced new or underused vaccines and having achieved paediatric vaccine coverage goals.

Based on their assessment, Williams et al. conclude that almost 40% of the assessed countries have no infrastructure for adult immunisation and that even the presence of a national adult vaccination programme does not guarantee extensive use of vaccines in the adult population [7].

One target group for adult vaccination is healthcare workers, given that they are exposed to vaccine-preventable diseases like measles, mumps, pertussis and varicella at work and can also transmit these to patients.

In their article, von Linstow et al. detected immunity gaps mainly among young healthcare workers. In addition, considerable proportions of healthcare workers in the study reported that they were unsure about their vaccination status (22-32%, depending on the disease) and possible previous infections (11% for varicella and 41% for pertussis). According to the authors, this demonstrates the need for more targeted measures like screening and a vaccine strategy to address these gaps in healthcare workers [8].

Specifically for measles and its related elimination goal, coverage and uptake of routine childhood immunisation programmes have to improve in many European countries in the same way that immunity gaps in adolescents and adults need to be addressed [9].

In their paper, Rohleder et al. examine a possible relationship between socioeconomic deprivation and measles incidence in Germany, taking into account demographic, spatial and temporal factors [10]. They conclude that the risks for measles infections are higher and more concentrated in areas with the highest socioeconomic status.

In a study of 6,423 healthcare workers in Italy who received the Comirnaty vaccine (BNT162b2, BioNTech/Pfizer, Mainz, Germany/New York, United States), Fabiani et al. found that the effectiveness of preventing SARS-CoV-2 infection was 84% (95% confidence interval (CI): 40-96) 14-21 days after receiving the first dose and 95% (95% CI: 62-99) at least 7 days after the second dose. According to the authors, these results could support the ongoing COVID-19 vaccination campaigns with evidence for targeted communication [11].

Vaccination may be receiving more attention than usual right now, as many adults worldwide are currently being vaccinated or awaiting their opportunity to receive protection against COVID-19. Topics around vaccine safety and efficacy, ethical and equity considerations, as well as logistics are being discussed more widely and more intensely. In this context, EIW serves to highlight the ongoing need to increase efforts to achieve better vaccination coverage for all vaccine-preventable diseases, in order to prevent disease and protect individuals beyond the COVID-19 pandemic.

###

References

1. World Health Organization (WHO). Vaccines and Immunization. Geneva: WHO; 2021. Available from: https://www.who.int/health-topics/vaccines-and-immunization#tab=tab_1

2. European Vaccination Information Portal (EVIP). Benefits of vaccination for the community. Stockholm: European Commission, European Centre for Disease Prevention and Control, European Medicines Agency; 2021. Available from: https://vaccination-info.eu/en/vaccination/benefits-vaccination-community

3. World Health Organization Regional Office for Europe (WHO/Europe). European Immunization Week. Copenhagen: WHO/Europe; 2021. Available from: https://www.euro.who.int/en/media-centre/events/events/2021/04/european-immunization-week

4. European Vaccination Information Portal (EVIP). Benefits of vaccination for individuals. Stockholm: European Commission, European Centre for Disease Prevention and Control, European Medicines Agency; 2021. Available from: https://vaccination-info.eu/en/vaccination/benefits-vaccination-individuals

5. World Health Organization (WHO). World Immunization Week 2021 - Vaccines bring us closer. Geneva: WHO: 2021. Available from: https://www.who.int/news-room/events/detail/2021/04/24/default-calendar/world-immunization-week-2021

6. World Health Organization (WHO). Immunization Agenda 2030: A Global Strategy to Leave No One Behind. Geneva: WHO; 2020. Available from: https://www.who.int/teams/immunization-vaccines-and-biologicals/strategies/ia2030

7. Williams S, Driscoll A, LeBuhn H, Chen W, Neuzil K, Ortiz J. National Routine Adult Immunization Programs among World Health Organization Member States: an assessment of health systems to deploy future SARS-CoV-2 vaccines. Euro Surveill. 2021; 26(17). https://doi.org/10.2807/1560-7917.ES.2021.26.17.2001195

8. von Linstow M-L, Yde Nielsen A, Kirkby N, Eltvedt A, Nordmann Winther T, Bybeck Nielsen A, Bang D, Poulsen A. Immunity to vaccine-preventable diseases among paediatric healthcare workers in Denmark, 2019. Euro Surveill. 2021; 26(17). https://doi.org/10.2807/1560-7917.ES.2021.26.17.2001167

9. European Centre for Disease Prevention and Control (ECDC). Who is at risk for measles in the EU/EEA? Identifying susceptible groups to close immunity gaps towards measles elimination. Stockholm: ECDC; 2019. Available from: https://www.ecdc.europa.eu/en/publications-data/risk-assessment-measles-eu-eea-2019

10. Rohleder S, Stock C, Bozorgmehr K. Socioeconomic deprivation is inversely associated with measles incidence: a longitudinal small-area analysis in Germany, 2001-2017. Euro Surveill. 2021; 26(17). https://doi.org/10.2807/1560-7917.ES.2021.26.17.1900755

11. Fabiani M, Ramigni M, Gobbetto V, Mateo-Urdiales A, Pezzotti P, Piovesan C. Effectiveness of the Comirnaty (BNT162b2, BioNTech/Pfizer) vaccine in preventing SARS-CoV-2 infection among healthcare workers, Treviso province, Veneto region, Italy, 27 December 2020 to 24 March 2021. Euro Surveill. 2021; 26(17). https://doi.org/10.2807/1560-7917.ES.2021.26.17.2100420

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

QUANTUM ALCHEMY

Researchers analyzed circulating currents inside gold nanoparticles

A new method facilitates accurate analysis of magnetic field effects inside complex nanostructures

UNIVERSITY OF JYVÄSKYLÄ - JYVÄSKYLÄN YLIOPISTO

Research News

 

IMAGE: THE ATOMIC STRUCTURE OF A GOLD NANOPARTICLE PROTECTED BY PHOSPHINE MOLECULES (LEFT) AND MAGNETIC-FIELD-INDUCED ELECTRON CURRENTS IN A PLANE INTERSECTING THE CENTER OF THE PARTICLE (RIGHT). THE TOTAL ELECTRON CURRENT... view more 

CREDIT: UNIVERSITY OF JYVÄSKYLÄ/OMAR LOPEZ ESTRADA

Researchers in the Nanoscience Center of University of Jyvaskyla, in Finland and in the Guadalajara University in Mexico developed a method that allows for simulation and visualization of magnetic-field-induced electron currents inside gold nanoparticles. The method facilitates accurate analysis of magnetic field effects inside complex nanostructures in nuclear magnetic resonance measurements and establishes quantitative criteria for aromaticity of nanoparticles. The work was published 30.4.2021 as an Open Access article in Nature Communications.

According to the classical electromagnetism, a charged particle moving in an external magnetic field experiences a force that makes the particle's path circular. This basic law of physics is used, e.g., in designing cyclotrons that work as particle accelerators. When nanometer-size metal particles are placed in a magnetic field, the field induces a circulating electron current inside the particle. The circulating current in turn creates an internal magnetic field that opposes the external field. This physical effect is called magnetic shielding.

The strength of the shielding can be investigated by using nuclear magnetic resonance (NMR) spectroscopy. The internal magnetic shielding varies strongly in an atomic length scale even inside a nanometer-size particle. Understanding these atom-scale variations is possible only by employing quantum mechanical theory of the electronic properties of each atom making the nanoparticle.

Now, the research group of Professor Hannu Häkkinen in the University of Jyväskylä, in collaboration with University of Guadalajara in Mexico, developed a method to compute, visualize, and analyze the circulating electron currents inside complex 3D nanostructures. The method was applied to gold nanoparticles with a diameter of only about one nanometer. The calculations shed light onto unexplained experimental results from previous NMR measurements in the literature regarding how magnetic shielding inside the particle changes when one gold atom is replaced by one platinum atom.

A new quantitative measure to characterize aromaticity inside metal nanoparticles was also developed based on the total integrated strength of the shielding electron current.

"Aromaticity of molecules is one of the oldest concepts in chemistry, and it has been traditionally connected to ring-like organic molecules and to their delocalized valence electron density that can develop circulating currents in an external magnetic field. However, generally accepted quantitative criteria for the degree of aromaticity have been lacking. Our method yields now a new tool to study and analyze electron currents at the resolution of one atom inside any nanostructure, in principle. The peer reviewers of our work considered this as a significant advancement in the field", says Professor Häkkinen who coordinated the research.

###

The authors of the article included post-doctoral researcher Omar Lopez Estrada (lead author), PhD student Elli Selenius and university researcher Sami Malola in Häkkinen's group and professor Bernardo Zuniga-Gutierrez in Guadalaraja University in Mexico. The computations were made by using the Finnish Computing Competence Infrastructure (FCCI) in University of Jyväskylä.

Link to the research in Nature Communications in 30 April 2021

Engineering T cells to attack cancer broadly

A new approach to immunotherapy arrests solid tumor growth for a variety of cancers and squashes the spread of cancer to other tissues, in mice.

VIRGINIA COMMONWEALTH UNIVERSITY

Research News

 

IMAGE: CONTROL MICE (LEFT PANEL) WITH PROSTATE CANCER SHOW LARGE AREAS OF METASTASIS IN THE LUNGS (BLUE). WHEN A SUBSET OF ANIMALS WERE TREATED WITH UNMODIFIED T CELLS (MIDDLE PANEL), THE... view more 

CREDIT: SHAWN WANG, PH.D.

Through T cell engineering, researchers at Virginia Commonwealth University Massey Cancer Center show that it's possible to arrest tumor growth for a variety of cancers and squash the spread of cancer to other tissues. This research will be published in tomorrow's print edition of Cancer Research.

The paper builds on decades of research by study co-senior author Paul B. Fisher, M.Ph., Ph.D., a member of Massey's Cancer Biology research program, who discovered a protein called IL-24 that attacks a variety of cancers in several different ways.

In this latest study, Fisher teamed up with his colleague Xiang-Yang (Shawn) Wang, Ph.D., who co-leads the Developmental Therapeutics research program at Massey, to deliver the gene coding for IL-24, which is called MDA-7, to solid tumors using T cells.

"I think the beauty of what we've been involved in is that it expands the scope of immunotherapy," said Fisher, professor and chair of the Department of Human and Molecular Genetics at the VCU School of Medicine, director of the VCU Institute of Molecular Medicine (VIMM) and Thelma Newmeyer Corman Endowed Chair in Oncology Research. "Our approach is less dependent on cancer cells expressing something specific to target."

After all, this isn't the first time T cells have been engineered for cancer immunotherapy. FDA-approved chimeric antigen receptor T (CAR-T) cell therapy - which is designed to destroy cancer cells expressing specific surface molecules - has shown tremendous success for treating advanced cancers of the blood and lymphatic systems.

But CAR-T has made limited progress on solid tumors, such as prostate cancer or melanoma, because the cells that make up those tumors aren't all the same, which blocks the engineered T cells from recognizing and attacking.

Wang and Fisher armed T cells with MDA-7/IL-24 to target cancer more broadly.

"Engineering T cells to produce MDA-7/IL-24 allows killing of cancer cells regardless of their expression of target molecules. This will help prevent cancer cells from escaping immune attack," said Wang, who is also a professor of human and molecular genetics at VCU, associate director of immunology in the VIMM and holds the Harry and Judy Wason Distinguished Professorship at Massey.

At the sub-cellular level, MDA-7/IL-24 binds to receptors on the surface of cells and instructs them to make and release more copies of the MDA-7/IL-24 protein. If the cell is normal, the protein is simply secreted and no damage occurs. But if the cell is cancerous, MDA-7/IL-24 causes oxidative stress damage and ultimately cell death, not only within the primary tumor but also among its distant metastases - the cause of death in 90% of patients.

As a result of this process, the immune system generates memory T cells that can theoretically kill the tumor if it ever comes back. At the whole tumor level, IL-24 also blocks blood vessel formation, starving tumors of the nutrients so badly needed to sustain their unchecked growth.

In mice with prostate cancer, melanoma or other cancer metastases, MDA-7/IL-24-expressing T cells slowed or stopped cancer progression better than unmodified T cells.

The researchers also discovered that arming T cells with MDA-7/IL-24 allowed them to survive better and multiply in the tumor microenvironment - the space right around the cancerous mass.

"The tumor site is often very hostile to immune cells," Wang said. "We discovered that MDA-7/IL-24 can help T cells to proliferate and outnumber cancer cells."

In the clinic, this approach would involve extracting the patient's own T cells from tumor samples, genetically engineering them to express MDA-7/IL-24, growing millions of copies of the cells in the lab and finally transplanting them back into the patient. With federally-mandated manufacturing standards, the procedure is generally safe and minimally invasive. CAR-T cells could also be engineered to express MDA-7/IL-24.

To be most effective, MDA-7/IL-24 T cells would likely be used in conjunction with other therapies.

Although it's never easy bringing a technology from the bench to the bedside, Fisher is optimistic that much of the groundwork has already been laid.

Clinical trials using different methods of delivering IL-24 are already underway for several cancers. A phase 1 trial using an adenovirus - similar to the common cold - to deliver MDA-7/IL24 to the tumor demonstrated about 44% efficacy against multiple forms of cancer and generally proved non-toxic.

"I think we have a head start and a running ramp that could be really accelerated," Fisher said.

Together, Wang and Fisher recently secured a grant from the National Cancer Institute to optimize their technology for the treatment of solid tumors and cancer metastases, in anticipation of future human trials.

CAPTION

professor and chair of the Department of Human and Molecular Genetics at the VCU School of Medicine, director of the VCU Institute of Molecular Medicine (VIMM) and Thelma Newmeyer Corman Endowed Chair in Oncology Research at VCU Massey Cancer Center

CREDIT

VCU Massey Cancer Cent

CAPTION

professor of human and molecular genetics at VCU, associate director of immunology in the VIMM and Harry and Judy Wason Distinguished Professorship at VCU Massey Cancer Center

CREDIT

VCU Massey Cancer Center

UVA engineering computer scientists discover new vulnerability affecting computers globally

Computing experts thought they had developed adequate security patches after the major worldwide Spectre flaw of 2018, but UVA's discovery shows processors are open to hackers again.

UNIVERSITY OF VIRGINIA SCHOOL OF ENGINEERING AND APPLIED SCIENCE

Research News

 

CHARLOTTESVILLE, Va. - In 2018, industry and academic researchers revealed a potentially devastating hardware flaw that made computers and other devices worldwide vulnerable to attack.

Researchers named the vulnerability Spectre because the flaw was built into modern computer processors that get their speed from a technique called "speculative execution," in which the processor predicts instructions it might end up executing and preps by following the predicted path to pull the instructions from memory. A Spectre attack tricks the processor into executing instructions along the wrong path. Even though the processor recovers and correctly completes its task, hackers can access confidential data while the processor is heading the wrong way.

Since Spectre was discovered, the world's most talented computer scientists from industry and academia have worked on software patches and hardware defenses, confident they've been able to protect the most vulnerable points in the speculative execution process without slowing down computing speeds too much.

They will have to go back to the drawing board.

A team of University of Virginia School of Engineering computer science researchers has uncovered a line of attack that breaks all Spectre defenses, meaning that billions of computers and other devices across the globe are just as vulnerable today as they were when Spectre was first announced. The team reported its discovery to international chip makers in April and will present the new challenge at a worldwide computing architecture conference in June.

The researchers, led by Ashish Venkat, William Wulf Career Enhancement Assistant Professor of Computer Science at UVA Engineering, found a whole new way for hackers to exploit something called a "micro-op cache," which speeds up computing by storing simple commands and allowing the processor to fetch them quickly and early in the speculative execution process. Micro-op caches have been built into Intel computers manufactured since 2011.

Venkat's team discovered that hackers can steal data when a processor fetches commands from the micro-op cache.

"Think about a hypothetical airport security scenario where TSA lets you in without checking your boarding pass because (1) it is fast and efficient, and (2) you will be checked for your boarding pass at the gate anyway," Venkat said. "A computer processor does something similar. It predicts that the check will pass and could let instructions into the pipeline. Ultimately, if the prediction is incorrect, it will throw those instructions out of the pipeline, but this might be too late because those instructions could leave side-effects while waiting in the pipeline that an attacker could later exploit to infer secrets such as a password."

Because all current Spectre defenses protect the processor in a later stage of speculative execution, they are useless in the face of Venkat's team's new attacks. Two variants of the attacks the team discovered can steal speculatively accessed information from Intel and AMD processors.

"Intel's suggested defense against Spectre, which is called LFENCE, places sensitive code in a waiting area until the security checks are executed, and only then is the sensitive code allowed to execute," Venkat said. "But it turns out the walls of this waiting area have ears, which our attack exploits. We show how an attacker can smuggle secrets through the micro-op cache by using it as a covert channel."

Venkat's team includes three of his computer science graduate students, Ph.D. student Xida Ren, Ph.D. student Logan Moody and master's degree recipient Matthew Jordan. The UVA team collaborated with Dean Tullsen, professor of the Department of Computer Science and Engineering at the University of California, San Diego, and his Ph.D. student Mohammadkazem Taram to reverse-engineer certain undocumented features in Intel and AMD processors.

They have detailed the findings in their paper: "I See Dead μops: Leaking Secrets via Intel/AMD Micro-Op Caches."

This newly discovered vulnerability will be much harder to fix.

"In the case of the previous Spectre attacks, developers have come up with a relatively easy way to prevent any sort of attack without a major performance penalty" for computing, Moody said. "The difference with this attack is you take a much greater performance penalty than those previous attacks."

"Patches that disable the micro-op cache or halt speculative execution on legacy hardware would effectively roll back critical performance innovations in most modern Intel and AMD processors, and this just isn't feasible," Ren, the lead student author, said.

"It is really unclear how to solve this problem in a way that offers high performance to legacy hardware, but we have to make it work," Venkat said. "Securing the micro-op cache is an interesting line of research and one that we are considering."

Venkat's team has disclosed the vulnerability to the product security teams at Intel and AMD. Ren and Moody gave a tech talk at Intel Labs worldwide April 27 to discuss the impact and potential fixes. Venkat expects computer scientists in academia and industry to work quickly together, as they did with Spectre, to find solutions.

The team's paper has been accepted by the highly competitive International Symposium on Computer Architecture, or ISCA. The annual ISCA conference is the leading forum for new ideas and research results in computer architecture and will be held virtually in June.

Venkat is also working in close collaboration with the Processor Architecture Team at Intel Labs on other microarchitectural innovations, through the National Science Foundation/Intel Partnership on Foundational Microarchitecture Research Program.

Venkat was well prepared to lead the UVA research team into this discovery. He has forged a long-running partnership with Intel that started in 2012 when he interned with the company while he was a computer science graduate student at the University of California, San Diego.

This research, like other projects Venkat leads, is funded by the National Science Foundation and Defense Advanced Research Projects Agency.

Venkat is also one of the university researchers who co-authored a paper with collaborators Mohammadkazem Taram and Tullsen from UC San Diego that introduce a more targeted microcode-based defense against Spectre. Context-sensitive fencing, as it is called, allows the processor to patch running code with speculation fences on the fly.

Introducing one of just a handful more targeted microcode-based defenses developed to stop Spectre in its tracks, "Context-Sensitive Fencing: Securing Speculative Execution via Microcode Customization" was published at the ACM International Conference on Architectural Support for Programming Languages and Operating Systems in April 2019. The paper was also selected as a top pick among all computer architecture, computer security, and VLSI design conference papers published in the six-year period between 2014 and 2019.

The new Spectre variants Venkat's team discovered even break the context-sensitive fencing mechanism outlined in Venkat's award-winning paper. But in this type of research, breaking your own defense is just another big win. Each security improvement allows researchers to dig even deeper into the hardware and uncover more flaws, which is exactly what Venkat's research group did.

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About UVA Engineering: As part of the top-ranked, comprehensive University of Virginia, UVA Engineering is one of the nation's oldest and most respected engineering schools. Our mission is to make the world a better place by creating and disseminating knowledge and by preparing future engineering leaders. Outstanding students and faculty from around the world choose UVA Engineering because of our growing and internationally recognized education and research programs. UVA is the No. 1 public engineering school in the country for the percentage of women graduates, among schools with at least 75 degree earners; the No. 1 public engineering school in the United States for the four-year graduation rate of undergraduate students; and the top public engineering school in the country for the rate of Ph.D. enrollment growth since 2015. Learn more at engineering.virginia.edu.