The Biomedical Scientist - February 2022 by Redactive Media Group

THE BIG QUESTION

HISTORY

IBMS EVENT

THE PANDEMIC

CROHN’S DISEASE:

CONGRESS 2022

What does the future hold for COVID vaccines? p.16

The latest in our ongoing series about medical eponyms: p.28

An update with new programme additions for Congress 2022: p.39

THE BIOMEDICAL SCIENTIST

THE

FEBRUARY 2022

BIOMEDICAL SCIENTIST THEBIOMEDICALSCIENTIST.NET

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FEBRUARY 2022

20/01/2022 09:25

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19/01/2022 12:41

FEBRUARY 2022 Contents

EDITORIAL 5 The Institute’s work to futureproof biomedical science

NEWS 8 Research, funding, developments and clinical updates

CONTENTS IBMS.ORG

7 News in numbers

THE BIOMEDICAL SCIENTIST

FEBRUARY 2022

13 Product advances and launches

OPINION 14 One-to-one: Xiao Fu on computational modelling, the evolution of tumours and the implications for our knowledge of cancer progression

ADVICE 33 Education: Outlining a model to connect clinical practice and higher education 36 Celebrating exam success in 2021: Examination pass list

16 The big question: What does the future hold for COVID vaccines?

39 Congress 2022: An update with new programme additions

MY IBMS

SCIENCE

42 Institute news: The latest from the IBMS

COVER ILLUSTRATION: RUI RICARDO

18 Out for blood: COVER FEATURE The story of a US blood test that it was claimed would lead to a healthcare revolution, but ended in a multi-million dollar scheme to defraud investors

46 Journal-based learning: CPD exercises based on journal articles

25 British Journal of Biomedical Science: A brief glimpse of the articles on offer in the ﬁrst issue of 2022 28 Crohn’s disease: The second instalment of the seventh article in an ongoing series about medical eponyms

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49 Here to help: The public inquiry into the pandemic response and what it means for members

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50 Jordan Moir gives a guided tour of the blood manufacturing facilities at Scottish National Transfusion Service

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07/01/2022 11:52:19 19/01/2022 13:04

EDITORIAL David Wells

s the professional body for biomedical science, the IBMS has a responsibility that stretches beyond supporting the practice and careers of our members. We must also make sure that the government and public understand the value of what our members bring to society. Throughout the pandemic, key decisionmakers did not appear to understand the value or complexities of having an accredited workforce in a diagnostics laboratory – or how our profession ensures safety, quality, wellbeing and peace of mind for patients across the UK. However, after continually informing the press and public, we began to make headway and started meeting with policymakers. With the increased visibility that the IBMS helped to foster, things are looking better, backed up with a wave of funding. More people understand the value of what we do and how we do it but a big part of our next strategy is rightly focused on taking further action to broaden this awareness. In order to change the way government and key decision-makers think and respond to our role in society, it is essential that we start to build a body of peer-reviewed evidence. This is why the IBMS is looking to offer funding for academic research that focuses on the value of having an accredited workforce in the biomedical science professions. Many other areas of the healthcare

Institute of Biomedical Science is the professional body for the biomedical science profession. INSTITUTE OF BIOMEDICAL SCIENCE

12 Coldbath Square London, EC1R 5HL United Kingdom +44 (0)20 7713 0214 +44 (0)20 7837 9658 Email: mail@ibms.org Web: www.ibms.org

BROADENING AWARENESS IBMS Chief Executive David Wells looks at the Institute’s work to futureproof biomedical science. services are supported by such studies and we want to make sure that our profession is better represented in this regard. The IBMS is also in the process of employing a Policy Lead. This means that we will have a dedicated expert whose sole responsibility will be to build stronger bridges and increase reach with the government and the relevant healthcare, academic and industrial leaders – constantly making sure that our profession’s concerns, information and advice are reaching the right people in the right ways. The inroads made over the last couple of years by Past-President Allan Wilson and others on our Council and Specialist Panels

were hard won and we have learnt from this that the IBMS needs to establish the evidence and capability to put us on the front foot with politicians, government and policy officials going forward. While there are challenges ahead, rest assured that the IBMS is busy establishing and building upon our new strengths for the future beneﬁt and support of our members, the profession and patient care.

David Wells Chief Executive

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Debra Padgett CSci FIBMS

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EXAMINATIONS

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MEMBERSHIP

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CHARTERED SCIENTIST

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THE BIOMEDICAL SCIENTIST

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20/01/2022 09:27

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19/01/2022 12:43

NEWS In numbers

THE BIOMEDICAL SCIENTIST

SCIENCE NEWS

IN NUMBERS 86% 1.3 million An estimated 1.3 million people in the UK have long COVID, an Office for National Statistics survey suggests. Of those, 892,000 first caught the virus at least 12 weeks ago and for 506,000 it was at least a year ago. Long COVID is described as symptoms that last more than 12 weeks that cannot be explained by another cause.

The ONS survey, over four weeks in November and December 2021, suggests, of those with long COVID:

51% 37% 36% 28% have fatigue

have loss of smell

have shortness of breath

13,000 BEDS OCCUPIED NHS figures released at the start of January showed there were around 13,000 beds occupied by patients with COVID. Of these, 4850 were not classed as mainly sick with the disease. The percentage was higher in London, where 45% of patients in hospital with the virus were not primarily in hospital for the virus.

have difficulty concentrating

Approximately 86% of people living in urban areas across the globe, or 2.5 billion people, are exposed to unhealthy particulate matter levels, states a paper in The Lancet. It claims this lead to 1.8 million excess deaths in cities around the world in 2019.

Dementia in 2050

INDIA’S COVID DEATHS

A new analysis finds that by September 2021, India’s cumulative COVID deaths were 6–7 times higher than reported officially. The WHO global COVID mortality estimate was 5.4 million, as of 1 January 2022. But new research suggests that in India alone there were an estimated 3.2 million COVID deaths from 1 June 2020 to 1 July 2021.

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URBAN AIR POLLUTION

153m

More than 153 million people could have dementia by 2050, according to a new study.

The predicted rise, an increase from 57 million in 2019, is expected to be largely due to ageing and growing populations. The claim comes in a new paper that looked at 195 countries, and aims to give governments an idea of resources and support that may be needed.

20/01/2022 09:28

THE BIOMEDICAL SCIENTIST

NEWS Science

SCIENCE

NEWS IMMUNOTHERAPY

SPECTROSCOPY

IMAGE: EVGENII ZHEREBTSOV-OREL STATE UNIVERSITY

Optical biopsy system for liver cancer Researchers have developed an optical biopsy system that can distinguish between cancerous and healthy liver tissue. The new technology could make it easier to diagnose liver cancer, which is the sixth most common cancer globally. “The instrument is designed to be compatible with the needles currently used for liver biopsies,” said Evgenii Zherebtsov, a member of the research team. “It could thus one day help surgeons more precisely navigate the biopsy instrument to decrease the number of errors in taking tissue samples that are used for diagnosis.”

The researchers report that the optical biopsy system can reliably distinguish between cancerous and healthy cells in mouse models. The system also showed promise in preliminary tests conducted in people with suspected liver cancer. The new optical biopsy system combines diffuse reﬂectance spectroscopy and lifetime ﬂuorescence measurements to evaluate markers related to cellular metabolism, which differs between healthy and cancerous cells. bit.ly/3tcwnRb

MRNA INJECTION TO MAKE CAR T CELL An experimental immunotherapy can temporarily reprogramme patients’ immune cells to attack a specific target via a single injection of messenger RNA (mRNA), similar to the mRNA-based COVID-19 vaccines, according to a new study. University of Pennsylvania researchers demonstrated the new approach with an mRNA preparation that reprogrammes T cells to attack heart fibroblast cells. Heart failure is often driven in part by these fibroblast cells, which respond to heart injury and inflammation by chronically overproducing fibrous material that stiffens the heart muscle, impairing heart function. In experiments in mice that model heart failure, the reduction in cardiac fibroblasts caused by the reprogrammed T cells led to a reversal of fibrosis. The new technique is based on chimeric antigen receptor (CAR) T cell technology, which, until now, has required the harvesting of a patient’s T cells and their genetic reprogramming to recognise markers on specific cell types in the body. bit.ly/3JWL8O7

EPIDEMIOLOGY

“TRUST REDUCES CORONAVIRUS CASES” Countries where people have more trust in each other have been more successful in bringing down waves of coronavirus cases and deaths, a new study shows. Researchers found there is a “threshold effect” in nations where at least 40% of people agree “most people can be trusted”.This supported effective reduction of cases and deaths during 2020. Previous studies show levels of trust in the UK are at the

critical 40%, compared with more than 60% in Scandinavian countries. China also has high levels of trust within society. Analysing coronavirus data during 2020 the researchers found more trusting societies tended to achieve a faster decline in infections and deaths from peak levels. This is likely because behaviours vital to stopping the spread of COVID-19 – such as mask wearing and social distancing – depend on mutual

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trust to be effective. Study lead Professor Tim Lenton said: “Our results add to evidence that trust within society benefits resilience to epidemics. “Building trust within communities should be a long-term project for all nations because this will help them cope with future pandemics and other challenges such as extreme events caused by climate change.” go.nature.com/3nbg0Ri

20/01/2022 09:28

OBSERVATIONAL STUDY

IMAGES: ISTOCK/SHUTTERSTOCK/SCIENCE PHOTO LIBRARY

“COMMON COLD T CELLS PROTECT AGAINST COVID” A new study led by Imperial College London researchers provides the first evidence that T cells from common colds could cross-protect against infection with SARS-CoV-2. While previous studies have shown that T cells induced by other coronaviruses can recognise SARS-CoV-2, the new study examines for the first time how the presence of these T cells at the time of SARS-CoV-2 exposure influences whether someone becomes infected. The researchers also say their findings provide a blueprint for a second-generation, universal vaccine that could prevent infection from current and future SARS-CoV-2 variants, including Omicron. Dr Rhia Kundu said: “Being exposed to the SARS-CoV-2 virus doesn’t always result in infection, and we’ve been keen to understand why. We found that high levels of pre-existing T cells, created by the body when infected with other human coronaviruses like the common cold, can protect against COVID-19 infection. While this is an important discovery, it is only one form of protection, and I would stress that no one should rely on this alone.” The study began in September 2020 when most people in the UK had neither been infected nor vaccinated against SARS-CoV-2. It included 52 people who lived with someone with PCR-confirmed SARS-CoV-2 infection and who had therefore been exposed to the virus. The participants did PCR tests at the outset and four and seven days later, to determine if they developed an infection. Blood samples from the 52 participants were taken within one to six days of them being exposed to the virus. This enabled the researchers to analyse the levels of pre-existing T cells induced by previous common cold coronavirus infections that also cross-recognise proteins of the SARS-CoV-2 virus. The researchers found that there were significantly higher levels of these cross-reactive T cells in the 26 people who did not become infected, compared with the 26 people who did become infected. go.nature.com/3GfC7xc

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WHAT’S HOT AND WHAT’S NOT

NEWS Science

THE BIOMEDICAL SCIENTIST

HOT

GENE EDITING US researchers have fine-tuned a system for more efficient gene editing, using retrons – segments of bacterial DNA.

HOT

UGANDAN SCHOOLS Schools in Uganda reopened in January, almost two years after the coronavirus pandemic started. This has been one of the world’s longest school closures.

HOT

BREASTFEEDING Women vaccinated against COVID-19 transfer SARS-CoV-2 antibodies to their breastfed infants, according to University of Massachusetts Amherst research.

NOT

HEDGEHOGS Hedgehogs have been harbouring a type of the MRSA superbug since long before the use of antibiotics in humans and livestock, research suggests.

NOT

ASTHMA Interventions aimed at promoting physical activity in people with asthma could improve symptoms and quality of life, claims a study from the Asthma UK Centre for Applied Research.

NOT

VIDEO GAMES Research that surveyed 2159 UK adults found those who engaged with video games, music, television and films tended to have lower happiness and higher anxiety levels than those who did not.

20/01/2022 09:29

BIOMEDICAL 10 THE SCIENTIST

NEWS Science

VACCINATIONS

NANOPARTICLES DELIVERING PAYLOADS

UNDER THE MICROSCOPE

This month: niclosamide What is niclosamide? It’s an oral antihelminthic drug that is used to treat parasitic infections in millions of people worldwide. So, are we talking tapeworms this month? Actually, no – niclosamide could be a promising prophylactic/preventative

STEM CELL DEVELOPMENT

Precision surveillance of colorectal cancer Some of the mechanisms by which polyps develop into colorectal cancer, setting the framework for improved surveillance for the cancer utilising precision medicine, have been revealed. A new study describes ﬁndings from a single-cell transcriptomic and imaging atlas of the two most common colorectal polyps found in humans: conventional adenomas and serrated polyps. They determined that adenomas arise from expansion of stem cells that are driven by activation of WNT signalling, which contributes to the development of cancer, while serrated polyps derive into cancer through a different process called gastric metaplasia. The ﬁnding about metaplasia, an abnormal change of cells into cells that are non-native to the tissue, was surprising, the researchers said. “Cellular plasticity through metaplasia is now recognised as a key pathway in

nasal spray and early treatment throat spray for COVID-19. What’s the story? Materials science professor David Needham has shown that a slight increase in pH might be all it takes to turn the metabolic inhibiting drug into a COVID nasal spray. Can you give me some context here? Since 1958, niclosamide has been used to treat gut parasite infections. Delivered as oral

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cancer initiation, and there were pioneering contributions to this area by investigators here at Vanderbilt,” said Ken Lauone, corresponding author. “We now have provided evidence of this process and its downstream consequences in one of the largest single-cell transcriptomic studies of human participants from a single centre to date.” They performed single-cell RNA sequencing, multiplex immunoﬂuorescence and multiplex immunohistochemistry on the samples, which were collected from diverse sex, racial and age groups. The cells from serrated polyps did not exhibit WNT pathway activation nor a stem cell signature. Moreover, the researchers observed that these cells had highly expressed genes not normally found in the colon, leading them to hypothesise that metaplasia plays a role in how serrated polyps become cancerous. bit.ly/3HQgofT

tablets, the drug kills the parasites on contact by inhibiting their crucial metabolic pathway and shutting down their energy supply. In recent years, however, researchers have been testing niclosamide’s potential to treat a wider range of diseases, such as many types of cancer, metabolic diseases and arthritis. How does niclosamide work? It acts upon host cell’s mitochondria to prevent the cell from producing its main energy molecule, adenosine 5’-triphosphate.

IMAGES: ISTOCK/SHUTTERSTOCK/SCIENCE PHOTO LIBRARY

Johns Hopkins Medicine researchers have developed a colour-coded test that quickly signals whether newly developed nanoparticles – ultra-small compartments designed to ferry medicines, vaccines and other therapies – deliver their cargo into target cells. The new testing tool, engineered specifically to test nanoparticles, could advance the search for next-generation biological medicines. The technology builds upon nanoparticles currently used against cancer and eye disease, and in vaccines for viruses. The researchers report details of the tool, which was tested in mouse cells grown in the lab and in living mice. “Many of the current assessment tools for nanoparticles only test whether a nanoparticle reaches a cell, not if the therapy can successfully escape the degradative environment of the endosome to reach inside the cytosol of the cell, which is where the medicine needs to be located for performance,” says Jordan Green, a Professor of Biomedical Engineering. The new tool was created to track location and nanoparticle release. The team designed a screening tool that assesses hundreds of nanoparticle formulations on their ability to not just reach a cell, but also how efficiently the nanoparticle can escape with its cargo to reach a cell’s interior. bit.ly/3F8TdLX

Without this, the virus has trouble replicating viable copies of itself to cause further infections. What does adjusting the pH achieve? In a new paper Needham demonstrates that raising the alkalinity of the solution might be enough to get through the mucous barrier and into the cells where a COVID-19 infection first takes hold. Where can I read more? You should visit bit.ly/3HRjeB8

20/01/2022 09:29

NEWS Science

THE BIOMEDICAL SCIENTIST

PAEDIATRICS

Climate change and kidney stones Rising temperatures due to climate change will lead to an increase in cases of kidney stones over the next seven decades, according to a new study by researchers at the Children’s Hospital of Philadelphia. Based on data from South Carolina, the study found the increase will be steeper if no action is taken, but an uptick will occur even with mitigation actions. Kidney stone disease is a painful condition caused by hard deposits of minerals that develop in concentrated urine and cause pain when passing through the urinary tract. The incidence of the condition has

increased in the last 20 years, particularly among women and adolescents. Prior research has demonstrated that high ambient temperatures increase the risk of developing kidney stone disease. Paediatric urologist Gregory E Tasian said: “While it is impossible to predict with certainty how future policies will slow or hasten greenhouse gas emission and anthropogenic climate change, and to know exactly what future daily temperatures will be, our analysis suggests that a warming planet will likely cause an increased burden of kidney stone disease on healthcare systems.” go.nature.com/3faFXvH

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04/10/2021 19/01/2022 11:12 12:44

NEWS Technology

THE BIOMEDICAL SCIENTIST

TECH

NEWS LUMIRADX

LIFE SCIENCE GROUP

CRP TEST CE MARK

CELL SHIPMENT

LumiraDx, a next-generation point-of-care diagnostics company, has announced its C-reactive protein (CRP) test has achieved CE marking. The LumiraDx CRP Test is a small, portable, fully automated, microfluidic immunoassay test used for the quantitative determination of CRP with results within four minutes. The measurement of CRP provides important information for the detection and evaluation of infection, and inflammation. lumiradx.com

A new product developed by Life Science Group and Coventry University has the potential to transform the delivery of cell and gene therapy and make cuttingedge, personalised treatments more accessible, it is claimed. CellShip is a cell shipment and storage medium. It is a sterile, xeno-free alternative to cryopreservation for the transport and short-term storage of cells and contains a non-toxic additive to maintain membrane integrity. lifescienceproduction.co.uk

Enhanced liver fibrosis markers ELF & PIIINP • NPEX result reporting • Rapid automated immunoassay service • Clinical interpretation service

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MIELE

SUSTAINABILITY REPORT Increasing the use of recycled materials in the manufacture of laboratory glasswashers and washer disinfectors is one of Miele’s goals to become more sustainable. The brand, which makes commercial dishwashers, washing machines and washer disinfectors, suitable for use in a laboratory and medical setting, has published a detailed sustainability report. Miele plans to reduce CO2 by 50% by 2030 and is working to make its equipment easier to repair to increase each appliance’s life cycle. miele.com

rajvindergarcha@nhs.net www.bcpathology.org.uk 0121 507 5348 Clinical Biochemistry, City Hospital Dudley Road, Birmingham B18 7QH @BCPathology

BCPathology

Black Country Pathology TV News

20/01/2022 09:31

BIOMEDICAL 14 THE SCIENTIST

OPINION One-to-one

IMAGES: SCIENCE PHOTO LIBRARY/SHUTTERSTOCK

nderstanding how cancerous tumours evolve spatially and over time using real tissue is a complex process; it requires repeatedly taking multiple biopsies from various parts of a tumour. A computational model, however, developed by researchers at the Francis Crick Institute, the Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, has identiﬁed links between tumour growth and shape, and how quickly a patient’s cancer might progress. The study used mathematical modelling, combined with detailed clinical, molecular, histological and radiological data from 66 real-life tumours from the TRACERx Renal study to understand how tumours come about and evolve. Cross-referencing their mathematical model with the other data, the researchers examined two types of tumour growth in kidney cancers. In the “volume growth model”, growth is consistent throughout the tumour, whereas in the “surface growth model”, growth is restricted to the tumour’s surface. They found that different rates of real-world tumour progression corresponded to different computational growth models. Tumours that rapidly progressed matched the scenario in the volume growth model where a single “ﬁt” group of cells – which had gained an advantage through mutations that make them more likely to survive and divide even with low nutrient or oxygen levels – was present early on.

MODELLING BEHAVIOUR

Computational modelling has “provided a window into the evolution of a tumour”. Biological physicist Xiao Fu explains what this means for our knowledge of cancer progression.

Impact of tumour growth on shape Tumours that did not progress appeared to demonstrate that the original group of parental cancer cells remained dominant rather than a “ﬁt” group forming – another scenario of the volume growth model. Extensive genetic diversity was found in the surface growth model of tumour progression, with different

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20/01/2022 09:32

OPINION One-to-one

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what sort of growth a tumour is undergoing, for example, if radiological imaging of an early tumour shows bulges this means it’s more likely to be undergoing surface growth. This information could help inform medical teams and treatment decisions.”

Impact of necrosis on tumour growth The study followed a 2018 paper that reported the evolutionary features of renal cell carcinomas in the TRACERx renal study, including varying structures of phylogenetic trees reflective of distinct modes of tumour evolution. “We were wondering what could be the driving mechanism for those,” says Fu, who was trained in biological physics, focusing on building computational models to study diseases including liver diseases caused by paracetamol overdoses and eye diseases including diabetic retinopathy, during his PhD study. “As a computational modeller, from my background, what I was really curious about was how the growth in a spatial context could lead to observation of distinct evolutionary features. Specifically for renal cell carcinoma, we were really interested in asking whether spatial growth patterns could influence the evolutionary trajectories [of tumours] and patterns [of clonal diversification] given all the other variables and parameters.” The model was also used to analyse how necrosis affected the tumour’s evolution. Under the surface growth model, the tumours quickly developed more “fit” groups of genetically distinct cells. This could provide insight into the future trajectory of tumour growth. “We were really excited to see the computational model under the necrotic condition, where we could clearly see a collapse or reduction of clonal diversity at a later stage of the simulation,” Fu says. “This provides unique

XIAO FU 2008-12, BSc, physics, Nanjing University, China 2012-17, PhD, physics, Indiana University Bloomington, US 2013-17, Research Assistant, Biocomplexity Institute, US 2017-present, Postdoctoral Training Fellow, Biomolecular Modelling Laboratory and Tumour Cell Biology Laboratory, The Francis Crick Institute

insights when we think about the static evolutionary snapshot of certain tumours.”

Next steps Fu says the findings are “just the start of what we hope to uncover,” and further collaboration is needed with the radiomics team at the Institute of Cancer Research to have a more comprehensive characterisation of any possible correlation between tumour shape and evolutionary pattern. “This will potentially extend the existing computational model to study more diverse patterns,” he adds. Fu is also looking at slightly different computational models to study the evolution of lung cancers. “The computational field is moving in the direction of incorporating the impact of spatial context, spatial structure and spatial growth in tumours. Our work is adding to various other perspectives to show how the spatial growth could influence the measured or observed evolutionary trajectories, even without assuming a single cell-level difference.” He concludes: “It’s exciting to see how modelling can potentially help from a quantitative perspective in cancer research.”

IMAGE: THE FRANCIS CRICK INSTITUTE/DAVE GUTTRIDGE

groups of “fit” cells forming on the tumour’s surface. This suggests the creation of a competitive environment in which different groups of cells are pushed to evolve more rapidly. The model also provided insights into how different types of growth in tumours have an impact on their shape. Volume growth tumours grew outwards in a more consistent shape, while surface growth tumours showed bulges on the surface where the “fitter” groups of cells were forming. “While investigating these two distinct growth patterns, we noticed a clear difference between the morphologies of the tumour surface, such as the budding structures in the surface growth model in contrast with the volume growth model,” says Dr Xiao Fu, first author of the study. “When we split the entire patient cohort into rapid [cancer] progression versus attenuated progression it matched what we would expect from the surface growth and volume growth. That part of the analysis was the most surprising and exciting,” he adds. “One particular point that’s really interesting and also opens doors for future research opportunities is the coupling of tumour morphology and evolutionary features such as the clonal diversification. By simulation we were able to actually simulate in a single evolutionary history of a particular simulated tumour how the clonal diversity could evolve over time.” “More research is needed but [this structural information about tumours] could be used to help determine

THE BIOMEDICAL SCIENTIST

20/01/2022 09:32

BIOMEDICAL 16 THE SCIENTIST

OPINION The big question

THE BIG QUESTION THIS MONTH WE ASK

What does the future hold for COVID vaccines?

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20/01/2022 09:33

OPINION The big question

Sally Cutler Professor of Medical Microbiology University of East London

IMAGE: GETTY

accination has been heralded as our major weapon to beat COVID, but initial hopes that we could control SARS-CoV-2 infection through a robust and durable immunity derived through vaccination and/or prior infection have been challenged by the Omicron variant. Our turbulent learning curve has shown us that we can reduce disease severity and hospitalisations, but have been less successful at reducing community transmission. Short-term vaccine goals should include ensuring vaccine equity, as we cannot control a global disease threat with only wealthy nations having access to vaccines; and we need to follow the logical developmental progression from monovalent to multivalent vaccine. Longer-term goals need to protect from serious disease and tackle community transmission. Vaccine redesign to stimulate a robust mucosal protective immunity could offer further benefits and might open up different vaccine delivery options. Furthermore, we need to work on scientific communication to combat the wave of misinformation resulting in vaccine hesitancy. Future reduced engagement with vaccination efforts could be a ticking time bomb for the future, such as that seen with measles infections through hesitancy with MMR vaccinations. Living with COVID will most likely be paralleled by living with flu – regular vaccination of vulnerable individuals, but certainly not ignoring COVID. We will hopefully reach a balance between health, societal and economic needs.

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Dr Christopher Ring Senior Lecturer in Microbiology Middlesex University

he approval of the ﬁrst COVID-19 vaccine for emergency use within a year of the initial reports of the disease is a massive achievement and our current vaccines are highly effective at protecting us from severe disease, hospitalisation and death. However, they are far from perfect. Boosters help maintain protection from serious symptoms, but we face a rapidly evolving foe and we need to update our vaccines to keep up with new variants, such as Omicron, that can evade some of the immune responses triggered by current vaccines. We need to modify our vaccines to include other viral proteins, that will also help broaden our protection against new variants. We hope to develop “pan-coronavirus” vaccines, utilising common antigens, with the aim of protecting us from all new variants. Current vaccines do not protect us against re-infection, nor do they prevent transmission to others, meaning that the virus can continue to spread and evolve. More effective control of viral replication in the airways, and subsequent transmission to others, may be achievable by delivering vaccines directly to the respiratory tract and the triggering of local immunity. Such a vaccine would also be easier to administer, as would oral vaccines that are also in development, and would assist delivering these desperately needed vaccines to the world. Vaccines have proved to be very effective. Let’s see if we can make them even better.

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Sarah Pitt Principal Lecturer School of Pharmacy and Biomolecular Sciences, Brighton University

he vaccines that we have against the SARS-CoV-2 virus are a miracle of modern science. I was as surprised and delighted as anyone that it turned out to be possible to produce safe and effective vaccines within 12 months. In the current pandemic phase, the vaccines are needed to serve two functions. The ﬁrst is protecting individuals from serious disease and death. All the vaccines that we have in use across the world at the moment are very good at this. The second is to help reduce the transmission of the virus. This can only be achieved in conjunction with other measures to stop the virus being passed between people. The virus will not be under control until every country in the world has vaccination rates of 85–90%. All the vaccines currently available are of the type that stimulate an immune response, which only gives short-lived cover. It is also known that natural infection with coronaviruses does not lead to a lasting lifelong immunity. Both these factors suggest that, once the pandemic is under control, regular vaccinations might be a feature of our lives. It is to be hoped that the virus will settle down and stop the regular drastic mutations – though it is very unclear how long that might take. It is technically possible to change the formulation of the vaccines so that they target prevailing variants. So, in the long term, we might see an annual vaccine designed to provide cover against several variants of SARS-CoV-2 in one dose.

20/01/2022 12:21

BIOMEDICAL 18 THE SCIENTIST

SCIENCE Cover feature

The story of a US blood test that it was claimed would lead to a healthcare revolution, but ended in a multi-million dollar scheme to defraud investors.

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of dollars and the many patients who had put their faith in the test results had been told they were in fact worthless. After a high-proﬁle trial in San Francisco, Holmes has been found guilty on four counts of fraud and now faces a long prison sentence.

Revolutionise healthcare delivery The rise of Theranos began in 2003 when the 19-year-old Holmes, then studying at the School of Engineering at Stanford University, spent her internship at the Genome Institute of Singapore working with SARS test samples. This experience seeded the idea to develop a test that could ﬁnd the evidence of a range of

ILLUSTRATION: RUI RICARDO

t sounded too good to be true. A blood test that could detect the markers for dozens of different health conditions from the merest pinprick of ﬂuid taken from the tip of a ﬁnger. No need for big needles stuck in the arm, no need for multiple samples and no need to wait days for the results, which could be processed accurately in a matter of hours by a single bespoke device. Of course, it was too good to be true. The science underpinning these claims was lacking. But it took more than a decade to uncover the truth about Theranos, the company fronted by Elizabeth Holmes, by which time investors had lost hundreds of millions

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SCIENCE Cover feature

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THE BIOMEDICAL SCIENTIST

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BIOMEDICAL 20 THE SCIENTIST

SCIENCE Cover feature

health issues using just a single drop of blood and mucus. At the same time, Holmes began working on a patent for a skin patch that would apply and adjust doses of medication, such as antibiotics. Believing she was on to something with the potential to revolutionise the delivery of healthcare, Holmes attempted to enlist the support of Stanford academic luminaries. A few bluntly told her it would not work. Among them was Phyllis Gardner, a professor of medicine, who felt Holmes’ ideas betrayed a fundamental lack of understanding about how blood samples and antibiotics worked. Undeterred, but with the vital backing of the dean of Stanford’s School of Engineering, Holmes dropped out of the following year in order to set up a medical technology company and pursue her vision. The name she settled on was Theranos – a composite of “therapy” and “diagnosis”. She quickly secured her ﬁrst $1m of seed investment from a family friend who happened to be a venture capitalist. She rented a lab, she took on employees, and she continued to pitch the idea of a technological breakthrough. By the time 2006 rolled round, she had close to $30m.

Hype and hustle During these early years, Holmes and Theranos operated in stealth mode – no company website, no press releases, no ﬁgures, no nothing. While this was not unusual for a Silicon Valley tech start-up, it was not normal for the healthcare sector, where solid data tends to translate as solid gold. But the story of Theranos and how it managed to attract so much investment based on so little evidence cannot be told without some reference to Holmes’ character and style. She played the largely male Silicon Valley game of hype and hustle by taking on the guise of a female Steve Jobs – she adopted the Apple founder’s trademark black roll-neck jumpers, his presentation style and his direct

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manner, along with her intent gaze and striking baritone voice. Whether all this was entirely natural, as she claimed, or a carefully crafted persona, it certainly caught the attention of investors and other backers, including political heavyweights, including Henry Kissinger, George Schultz and James Mattis, big family investment concerns, such as Bechtel, DeVos and Walton, and even the normally wily Rupert Murdoch. At its peak in 2014, Theranos had attracted $400m worth of investment and was valued at a staggering $9bn, though it remained hard to see exactly what it had done to attract such a

“She played the Silicon Valley game of hype and hustle by taking on the guise of a female Steve Jobs”

valuation. Beyond the sheen of selfpromotion, the company’s fortunes rested on the proprietary devices it said it was developing to deliver the allimportant tests. The key tasks for these tools were to automate the analysis of the tiny sample sizes. The ﬁrst was called the “nanotainer”, which, as its name suggests, was a small container barely the size of a pill that was used to collect no more than couple of drops of blood taken from the patient’s ﬁnger. This sample, held in its nanotainer, would then be transferred to a Theranos lab and the analysis machine itself, which Holmes christened the “Edison”. The idea was that the Edison would take instructions over the internet from doctors and patients on what tests to run, communicate the results, and then retest or specify follow-up tests.

Bargain-price revolution While Theranos still refused to share any data or speciﬁcs of the technology, it would sooner or later have to provide some real-world evidence that its devices

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IMAGES: ALAMY/SHUTTERSTOCK/ISTOCK/GETTY

SCIENCE Cover feature

did indeed work. It took its ﬁrst steps towards doing this in 2013 with an agreement with Walgreens, the operator of the second largest pharmacy chain in the US, to host blood sample collection services in its stores in Phoenix, Arizona. This process would involve no clinics, no appointments and seemingly no more hassle than going to the local chemist to print off a few digital photos. If successful, it would be rolled out nationwide to some 8,000 stores. To give users a helping hand, Theranos published a menu of tests that they could order, along with the pricing. It started with a urinalysis at $1.55 then cycled through more than 250 other entries until ﬁnishing with a hepatitis C virus genotype test at $117.96. In between you could choose to test your cholesterol ($2.99), uric acid levels ($3.11), insulin levels ($7.86), for any traces of cocaine, ecstasy, marijuana ($10), vitamin B-12 ($10.36), various cancer antigens ($14.31), HIV ($16.56) and tuberculosis ($42.60). The healthcare revolution had begun – and at great prices. But stubbornly resisting the revolution

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ELIZABETH HOLMES FACTFILE Born on 3 February 1984 in Washington DC Her father, Christian Rasmus Holmes IV, was a vice president at Enron (an energy company that later went bankrupt after an accounting fraud scandal) Her mother, Noel Anne, worked as a Congressional committee staffer Before the collapse of Theranos, Holmes received widespread acclaim In 2015, she was appointed a member of the Harvard Medical School Board of Fellows and named one of Time magazine’s “Time 100 most influential people”. Holmes was ranked number 73 in Forbes 2015 list of “the world’s most powerful women” A year later Fortune named Holmes in its article on “The World’s 19 Most Disappointing Leaders”.

THE BIOMEDICAL SCIENTIST

was the science. As Phyllis Gardner had warned 10 years earlier, blood samples simply don’t work like that. For a start, any blood taken from the fingertip is likely to contain as much tissue fluid as blood, and the levels of vital molecules, such as proteins, are bound to be compromised. In fact, the only way to guarantee good, uniform levels of molecules that can give a clear picture of what’s happening is by taking the blood in the tried and tested manner – from a vein. Tony Cambridge, Lead Biomedical scientist at University Hospitals Plymouth NHS Trust, argues that the pinprick approach was simply not feasible: “The challenge of producing accurate and reproducible results for so many tests from such a low volume of blood was always too great. Any lab scientist will know that reducing sample size is usually accompanied by a loss in sensitivity.” Just as ominous for Theranos, and impossible to separate from the issue of the blood samples themselves, was its seeming inability to get the Edison machine to work. The problem here for outside observers was that nobody beyond a handful of insiders had any idea what the technology was. Any number of existing small devices in a lab can conduct multiple blood tests, but they had all gone down the route of being properly evaluated and verified. Holmes and the company persisted in maintaining a high wall of secrecy around the Edison and any data available for peer review was conspicuously absent.

Media attention The wider science community looked on with increasing suspicion. In February 2015 Professor John Ioannidis, again from Stanford, published a short piece in The Journal of the American Medical Association (JAMA) entitled “Stealth Research: Is Biomedical Innovation Happening Outside the Peer-Reviewed Literature”. If ever a question was loaded to prompt an answer of an emphatic “no”, it was

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this one. Ioannadis says Theranos offered him the opportunity to work on a new paper with Holmes if he recanted the JAMA article – he declined. Then in May 2015, Dr Eleftherios Diamandis at the Mount Sinai Hospital in Toronto published a piece called “Theranos phenomenon: promises and fallacies” in Clinical Chemistry and Laboratory Medicine. Diamandis had been prompted to investigate by hospital bosses, who were wondering just how Theranos was able to provide tests at a tenth of their usual cost. Having surveyed the available evidence, he concluded that the company’s “claims of superiority over current systems and practices are speculative, at best”. Theranos’ edifice of secrecy would face an even sterner test as it began to draw more media attention. With a young and striking innovator at the helm of company worth billions, the press was suddenly all over Holmes, likening her to Elon Musk and Jeff Bezos. Forbes, Fortune and The New Yorker all ran lavish profiles. Though it had held off much scientific scrutiny, Theranos was about to find that examination under the media lens was much harder to evade. One journalist paying close attention was John Carreyrou of The Wall Street Journal. Through a chain of contacts who were growing increasingly sceptical of the

“Remember to believe the science and the data, not the sales pitch or concept” Holmes’ bandwagon, Carreyrou found himself talking to a former Theranos lab worker, who had joined the company after graduating from Stanford in 2013 but quit in acrimony just eight months later in April 2014. The whistleblower told Carreyrou that he had left the company after he had discovered unethical behaviour and on raising the issue directly with Holmes had been hit with an aggressive response from her partner and Theranos president Sunny Balwani. The former employee’s concerns had centred around the troubled Edison devices – he claimed that not only

FAST FACTS: THE TEST MENU

+240 $1.55 Theranos’ test menu included more than 240 tests

The cheapest was urinalysis at $1.55

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$117.96 The most expensive was a hepatitis C virus genotype test at $117.96.

were the machines failing Theranos’ own quality control tests (the benchmark for accuracy results was 95%, the Edison was hitting just 65%), the company was also doctoring the wildly varying results to make them look better. The ongoing struggles to get the Edison to work also meant the lab had to bring in validated third-party devices to process the actual blood tests. Carreyrou’s article appeared in October 2015. Holmes tried to shut down the piece down by appealing directly to Rupert Murdoch, Theranos investor and owner of The Wall Street Journal, but was rebuffed. In another twist, it transpired that Carreyrou’s whistleblower was Tyler Schultz, grandson of George Schultz who was on the Theranos board of directors.

The downfall From this point, having spent more than a decade building the promise of a new era of healthcare that would be cheaper and more accessible, all the while struggling to develop the tech that would fulﬁl that promise, the downfall of Holmes and Theranos was swift. The Food and Drug Administration (FDA) inspections found that Theranos’ quality management systems were

20/01/2022 09:35

SCIENCE Cover feature

severely lacking and that the nanotainer, which had gone unregulated via a legal loophole, was “not validated under actual or simulated use conditions”. From a UK perspective it appears odd that the regulators took so long to intervene in any meaningful way, especially as the system of regulation here, including the requirements for registered scientists, along with the demands of the UKAS and EQA structures, would never have allowed the situation to develop as it did. Finally, in the wake of the FDA findings, the company suspended its test and Holmes announced she would finally publish data, but it was all too little too late (and still the data failed to materialise). Throughout 2016, Federal and state medical authorities circled. Investigations, sanctions and suspensions followed. The company’s lab in Newark, California was condemned as posing “immediate jeopardy to patient safety”. In June 2016, Walgreens terminated its partnership with Theranos and in October the embattled company laid off hundreds of staff. In January 2017 the lab in Scottsdale, Arizona also failed an inspection and was closed. The company fired hundreds more employees and found itself fending off bankruptcy and lawsuits from Walgreens and the Arizona Attorney General. Worse was to follow in 2018 – criminal proceedings. The US Department of Justice accused Holmes and Balwani of engaging “in a multi-million dollar scheme to defraud investors, and a separate scheme to defraud doctors and patients” and charged them with two counts of conspiracy to commit fraud and nine counts of fraud. Just a few months later Theranos was

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wound up and its high-proﬁle investors were writing off their losses. Amid the wreckage were thousands of unsuspecting patients who had put their trust and blood samples in the hands of Theranos and now had to pick their way through the rubble of potential false negatives, false positives and interventions based on inaccurate results.

Importance of rigour “Their business model was built around an unproven concept where they were trying to create the technology as they went,” says Tony Cambridge. “Remember to believe the science and the data, not the sales pitch or concept.” For the biomedical science community, time will tell if the Theranos saga has left investors, regulators and the public wary of legitimate diagnostic breakthroughs. The upside is that it has reaffirmed the vital importance of a rigorous scientific method. “Science is about setting a hypothesis and having it challenged by peer review,” says Dr David Ricketts at Health Services Laboratories. “Getting this right makes much better sense, which is a lesson learnt from recent events.” Where Theranos failed, diagnostic innovations with firmer scientific foundations are still making progress. The NHS-Galleri trail, for example, began last September collecting blood samples from 140,000 volunteers at mobile testing clinics across England. This test works by finding chemical changes in fragments of genetic code – cell-free DNA (cfDNA) that leak from tumours into the bloodstream – it can detect more than 50 types of cancer before symptoms appear. NHS chief executive Amanda Pritchard says: “The test is particularly effective at finding cancers that are typically difficult to identify early. This could mark the beginning of a revolution in cancer detection and treatment.”

THE BIOMEDICAL SCIENTIST

TIMELINE

2003

Holmes drops out of university and launches what will become Theranos Inc

2007

Theranos is valued at an estimated $197m

2010

Another fundraising round boosts Theranos’s valuation above $1bn

2013

Theranos begins offering blood tests to the public in Arizona and California

2014

Theranos’s valuation rises to $9bn

2015

The Wall Street Journal publishes its first article exposing shortcomings with Theranos’s technology

2016

Theranos closes its medical lab operations amid regulatory scrutiny

2018

Criminal fraud charges are brought against Holmes and Balwani

JAN 2022

Holmes is convicted on three counts of fraud and one count of conspiring to defraud private investors in the company

MAR 2022

The trial of Balwani is scheduled to begin on 9 March

SEP 2022

Holmes is due to be sentenced on 26 September.

20/01/2022 12:09

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02/11/2021 19/01/2022 11:39 12:46

SCIENCE Journal synopsis

THE BIOMEDICAL SCIENTIST

Top. 3D visualisation of SARS-CoV-2 Bottom. 3D illustration of sperm approaching the ovum

THE BRITISH JOURNAL OF BIOMEDICAL SCIENCE ISSUE 1 2022 – A SYNOPSIS Deputy Editor Guy Orchard provides a brief glimpse of the articles on offer in the ﬁrst issue of 2022.

ollowing on from the journal’s productive 2021 publications, we see a number of changes in 2022. These include a new publisher in Frontiers, and the fact that the journal has now transferred entirely online. We have also seen the appointment of Anthony Rhodes as the new Editor of the journal. So there are lots of changes ahead as we steer into the new world of online journal publications.

IMAGES: SHUTTERSTOCK

COVID-19 In Issue 1 of 2022 let’s begin with COVID-19 infections. COVID-19 has produced a universal crisis, devastating health organisations across the globe. Genetic risk factors may be related to the infectivity and severity of the SARS-CoV-2 contagion. Angiotensin-converting enzyme 2 (ACE 2) and host transmembrane serine protease (TMPRSS2) play a key role

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in viral cell entrance and priming. Assessing single nucleotide polymorphisms (SNPs) on 147 health controls and 299 COVID-positive patients, Abdelsattar et al. concluded that ACE2 rs 2285666 and TMPRSS2 rs 12329760 SNPs, in addition to lymphocyte count, C-reactive protein (CRP), D-dimers, ferritin and patient hypertension, are predictors of COVID-19 disease severity.

Andrology Semen analysis and the use of andrology techniques is a growing area of laboratory investigations. In this issue the Long and Kensworthy paper provides a guide for laboratories and clinicians in its use. Rounds cells in seminal ﬂuid are deﬁned as either lymphocytes or immature germ cells. Although publications exist that

discuss the possible clinical relevance of these cells in infertility, the methods employed to differentiate between these two cell populations can be difficult for some diagnostic laboratories. The paper provides guidance on how to assess such cell populations to aid in their identification and interpretation. Keeping with a cytology background, Zhai et al. discuss the impact of thyroid tissue status on the cut-off value of lymph node fine needle aspiration (FNA) thyroglobulin measurements in papillary thyroid cancer. Studying a reasonably large cohort, it was concluded that the influential factors of FNA-Tg were still controversial and the optimal cut-off value of FNA-Tg can be based on the presence or absence of thyroid tissue.

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BIOMEDICAL 26 THE SCIENTIST

SCIENCE Journal synopsis

Right. Dividing cancer cell metastasis division as a disease anatomy concept

Chronic hepatic cirrhosis Moving on to liver disease, Neamatallah et al. assessed vitamin D derivatives (VDRs) employing SNPs to VDRs, in a substantive cohort of patients with chronic hepatic cirrhosis. It was postulated that SNPs in VDRs have a potential role to play in the outcome of patients with hepatitis C virus infection (HCV). A paper by Khalil et al. assessed the value of bile acids in diagnosing hepatitis C virus-induced liver cirrhosis in hepatocellular carcinoma (HCC). Using ultra-performance liquid chromatography, coupled with mass spectrometry, 14 bile acids were assessed in patients with non-cirrhotic posthepatitis C virus disease, cirrhotic post-hepatitis C virus disease and those with HCC, along with a control group. It was concluded that serum bile acids are associated primarily with liver cirrhosis and are not valuable in predicting progression of cirrhotic disease to HCC.

Mutations in cancer Murugan and Alzahrani assessed isocitrate dehydrogenase IDH1 and IDH2 mutations in human cancers. The study revealed that IDH1 and IDH2 are often mutated in a tissue-speciﬁc manner and most commonly in gliomas. The authors went on to state that these genes could be promising therapeutic targets and also strong biomarkers in gliomas. There are also a number of papers employing techniques to study microRNAs (MiRNAs). Li et al. looked at genetic variants miR-126, -146a, -196a2 and -499 in polycystic ovary syndrome (PCOS). It was noted that all four of the miRs were strongly linked to PCOS and could be useful predictors of the disease. Jaafar et al. employed miR-27a (rs895819), miR-423 (rs6505162) and miR-124-1 (rs531564) in an assessment of 440 women (220 cases and 220 controls) to conclude that only miR-27a and miR-423 were linked to endometriosis. Finally, a paper by Hefnawy employed miR-93 and miR-152

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“We ﬁnish with a review – a fascinating insight into the molecular diagnostics of ciliopathies” in assessments of 160 patients with type 2 diabetic conditions, 80 of which had diabetic retinopathy (DR). It was found that both miR-93 and miR-152 could be used to differentiate patients with other diabetic conditions from those with DR and could, therefore, be used as potential biomarkers for DR. Whilst on the subject of DR, Keshavarz investigated the E23K polymorphism of KCNJ11 in Caucasian patients with DR. The KCNJ11 gene has a key role in insulin secretion. Looking at the rs 5219 polymorphism in an Iranian population with DR it was concluded that it was not associated with DR in type 2 diabetes mellitus patients. Looking at indicators for cancer risk, Moghanibashi et al. report on the signiﬁcant association of variable number tandem repeat (VNTR) polymorphism rs 58335419 in the miR-137 gene, with the risk of both gastric and colon cancers. It was found that increasing the copy of VNTR in the miR-137 gene would increase the risk of both types of cancer and could serve as a marker for susceptibility too. Breast cancer is a multifactorial disease

whose genetic susceptibility is related to polymorphic variants of cell proliferation and migration pathways. In a study by Rosales-Reynoso et al., genotypes and haplotypes in the AXIN2 and TCF7L2 genes, which have been associated with several different cancer types, were assessed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) on over 202 patients with breast cancer. The data revealed that there was a link between AXIN2 rs 2240308 and TCF7L2 rs 7903146 and rs 12255372 variants in breast cancer. Again, postulating this may be an important link in understanding pathogenesis in this disease.

Ciliopathies We ﬁnish with a review by Modarage et al. on a fascinating insight into the molecular diagnostics of ciliopathies, which provide an insight into novel developments in diagnosing this rare group of diseases. Ciliopathies arise from mutations in cilia that result in abnormal formation or function. The study looks at the techniques including next-generation sequencing (NGS) in an attempt to overview the current diagnostic techniques relevant to this group of diseases and highlights the applications and limitations associated with the techniques employed. For more information and to access all the journal papers, visit frontierspartnerships.org/journals/ british-journal-of-biomedical-science

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BIOMEDICAL 28 THE SCIENTIST

SCIENCE History

MEDICAL EPONYMS PT. 7(2):

CROHN’S DISEASE

This is the second instalment of the seventh article in a series of short biographies of persons whose names are directly used for diseases, conditions or syndromes familiar to those in clinical pathology laboratories.

I IMAGE: SUPPLIED BY NATIONAL INSTITUTES OF HEALTH

n the previous article on Crohn’s disease (CD), published in the January issue of the Biomedical Scientist, the main focus was to brieﬂy review advances in knowledge of CD from around the 16th century to the 1980s. Here we review more recent developments in our knowledge of clinical features, aetiology, investigations and treatment options.

Current perspectives CD is an idiopathic chronic regional enteritis commonly affecting the terminal ileum in 40–50% of cases, with 30–40% affecting small intestine and colon. There is transmural thickening and inﬂammation of discontinuous sections of intestine and in some cases non-necrotising granulomas with epithelioid histiocytes.

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Patients may present with a history of cramping abdominal pain, diarrhoea with intestinal ﬁstula and intramural abscesses. A pattern of periods of remission and relapses when symptoms ﬂare may become apparent. A differential diagnosis between CD and ulcerative colitis is essential due to the choice of treatment options available. This involves an understanding of clinical, radiological, endoscopic, and pathological features of CD.

Epidemiology There is a wide range of prevalence of around 26-199 cases/100,000 persons. CD is more common in white people living in Western industrialised countries. There is a steady increase in cases of unknown cause and although CD may occur at any age it is more common in

two age groups – between 13 and 20 years and 60 and 70 years, with a slight increase in females.

Aetiology Even 90 years after Crohn’s landmark publication, the exact cause of CD is not known but a number of risk factors have been identified, such as family history, smoking, diet and ethnicity. It has been proposed that there are multifactorial causes, notably that the immune response of the intestinal mucosa becomes defective and there are possible changes in the balance of bacteria in the gut flora. Professor John Hunter at Addenbrooke’s Hospital suggests that there is a reduction in lactobacilli and bifidobacteria with an increase in facultative anaerobes. In addition, abnormal fermentation of food digests may damage the intestinal

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SCIENCE History

THE BIOMEDICAL SCIENTIST

Left. Dr Burill Crohn Below. X-ray of the intestines of a patient with Crohn’s disease.

CD is an idiopathic chronic regional enteritis commonly affecting the terminal ileum in 40–50% of cases, with 30–40% affecting small intestine and colon

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BIOMEDICAL 30 THE SCIENTIST

SCIENCE History

mucosa causing inﬂammation, ulceration and bleeding and immune system factors may attack and destroy healthy gut microbiota in genetically susceptible individuals.

immunosuppression can be an important treatment option and infers those changes in mucosal immunity and immunoregulation are signiﬁcant factors in CD development and progression.

Genetics

Clinical complications

It has been established that first-degree relatives have a 13-18 % increased risk of CD and consequently there is a nonMendelian polygenic mode of inheritance. Molecular linkage studies of affected families identified NOD2 (nucleotide binding domain 2) as an affected gene in CD and the protein product may prevent excessive immune activation and may also have antibacterial properties. However, it is important to note that only around 10% of CD cases are due to a mutation of NOD2 and genomic screening has shown linkage to at least four chromosomes – 3, 7, 12 and 16. A number of other genes such as autophagy-related 16 (ATG16LI) and immunity related GTPaseM (IRGM) may be involved whilst interleukin receptor 23 has a role in immune activation in the intestinal mucosa. This is a rapidly developing field of research and the interested reader will find helpful the excellent 2014 review by Jimmy Liu and Carl Anderson from the Wellcome Trust Sanger Institute, Cambridge.

This may include fissures, fistulas and abscesses, post-prandial “bloating”, constipation and bowel obstruction. Chronic mucosal inflammation may lead to fissures with resultant abscesses and fistulas and the latter are more common post-surgery. Non-intestinal complications may affect the mouth (e.g. ulcers), eyes, skin and joints. Patients with Crohn’s colitis are at increased risk for high-grade dysplasia and colonic adenocarcinoma. Those with extensive colonic disease from a young age require endoscopic surveillance for eight years after the onset of symptoms then every one to two years.

Mucosal immune response and epithelial damage Several defects in epithelial function have been identiﬁed, notably affecting junction barrier transport and associated proteins. The polarisation of T cells to T-helper cell type 1 is a well-known feature of CD and TH17 cells may also be involved. Some studies have shown that neutrophil dysfunction may alter innate immunity in the development of CD. It has also been proposed that the inﬂammation may be due to an unrestrained immune response to luminal bacteria. As shown later,

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Diagnosis This is based on clinical examination and assessment, essential imaging, histology and laboratory evidence. A variety of imaging modes are available. Contrast imaging, such as barium meal or enema, can be used to assess the extent of disease, severity, potential complications and treatment strategy. A plain X-ray of the abdomen can reveal gut inﬂammation, swelling of the bowel and complications such as perforations. More complex techniques

such as magnetic resonance enterography can detect ulceration, abscesses or the presence of a fistula. Colonoscopy can be used to allow visual examination of the colon using a fibre-optic telescope to assess disease activity and to obtain biopsy tissue. Whilst other conditions need to be considered, such as drug-induced colitis and diverticular disease, once eliminated the main focus is to differentiate CD from ulcerative colitis as surgery is better tolerated in the latter. CD is characterised by skip lesions, granulomas, transmural lymphocyte aggregates, fissures and occurrence in any part of the gastrointestinal tract. Ulcerative colitis is limited to the colon, patchy areas may mimic skip lesions and only the mucosal layer is affected. Differentiation remains challenging and it is estimated that around 30% remain undetermined. The quality of the biopsies taken at colonoscopy is crucial to diagnosis.

Histology Biopsy microscopy results in CD can be highly variable but classic features may include areas of chronic inﬂammation with

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SCIENCE History

THE BIOMEDICAL SCIENTIST

Left. Small intestine in Crohn’s disease. Centre. Immune response to inflammatory bowel disease, illustration.

can increase the risk of carcinogenesis and longer exposure to immunosuppressant therapy may promote the risk. Steroids are not indicated for maintenance therapy due to the increased risks of osteoporosis, cataracts and diabetes. If medical therapy is not effective and severe symptoms continue, with supporting imaging evidence, resection of inﬂamed bowel is required, but due to risks and consequences is only undertaken when strictly necessary. A number of anti-diarrhoea agents can be effective in CD, such as loperamide and bile acid binders, but there is a risk of toxic megacolon with an expanded colon, which may be life-threatening.

Prognosis

IMAGES: SCIENCE PHOTO LIBRARY/SHUTTERSTOCK/ISTOCK

“The exact cause remains unknown and there is concern about increasing incidence” increased lymphocytes and patchy neutrophilic inflammation. Transmural inflammation with plasma cells, neutrophils and aggregates of lymphocytes are also typical. Granulocytes may be only present in around 50% of cases and are a non-specific finding and may be seen in ulcerative colitis. However, microscopic skipping of lesions can be diagnostic. With the increased risks of small bowel cancer, colorectal cancer and lymphoma the presence of intraepithelial neoplasia is significant. Immunohistochemistry has a limited role in CD, but stains for cytomegalovirus may be helpful if there is a relapse of severe symptoms when on immunosuppressive therapy to exclude a new or reactivated viral infection.

Treatment Objectives for adult patients include the best possible control of inﬂammation, achieving stable and best possible life-style with minimal adverse side effects of

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treatment. For children, the promotion of growth and adequate nutrition are essential. There are two main lines of treatment medication, but the mode of use can vary between a step-up approach in mild CD commencing with less aggressive agents, such as antibiotics, to more potent agents, notably corticosteroid immunosuppressants, typically methotrexate or azathioprine. In more severe CD a step-down approach including biological agents, such as infliximab and steroids or biological agents combined with immunosuppressants, may be effective. The more recent introduction of biological agents is to target and inhibit tumour necrosis factor (TNF) activity as TNF is a key inflammatory cytokine and moderator of intestinal inflammation that is overexpressed in inflammatory bowel disease. Their use is not without risk, with some severe adverse reactions reported, most notably different forms of leukaemia. There is also some evidence that alteration to the immune system over a long period

Even with successful surgery it has been reported that careful endoscopic followup has shown that around 90% of cases develop further disease and probably during the next decade will require further surgery. Unlike ulcerative colitis, if a speciﬁc area of disease only is resected then a stoma is not always required. Poor prognostic indicators include diagnosis at a young age, perianal disease and perforating disease. The removal of any part of the main intestinal tract by surgery may have consequences, notably malabsorption and resection of ileum can lead to B12 and folate malabsorption, which may cause chronic fatigue, anaemia and potential damage to the nervous system, in addition the failure to reabsorb bile salts may cause their leakage into the colon and cause diarrhoea. Appetite may be affected and dietary advice should be sought, when necessary, the remaining bowel may adapt to recover absorptive capacity and allow a relatively normal diet. However, there is a reduced capacity for fat absorption and a reduction in dietary fat may help. If fat malabsorption continues, the fat-soluble vitamins A and D, along with essential

20/01/2022 09:37

BIOMEDICAL 32 THE SCIENTIST

SCIENCE History

minerals, notably calcium and magnesium, become depleted with clinical consequences. Treatment with immunosuppressants may lead to abscess formation, which may require drainage, and ﬁstulae, which may connect with other organs such as the bladder and require corrective surgery.

Haematology Anaemia may occur in CD by a gradual loss of blood into the gastrointestinal tract, chronic inflammation and malabsorption. This is usually iron deficiency anaemia and can be treated with oral iron, but if the haemoglobin is <10 g/dL, parenteral administration is required. Mean cell haemoglobin and mean cell volume are reduced with hypochromia and microcytosis. Serum ferritin is low and is a sensitive marker of iron deficiency in the absence of inflammation. Other findings include low transferrin saturation, a low serum iron and low iron-binding capacity. Other causes of anaemia should be considered – effective treatment and management is necessary as anaemia in CD is a common cause of hospitalisation. White cells and platelets may be raised in the presence of active inflammation and infection.

Clinical chemistry A range of assays are required to monitor CD, which reflects the impact of reduced intestinal function and response to inflammatory bowel disease. Serum urea and electrolytes are measured to assess salt imbalance and water loss in periods of severe diarrhoea. Serum proteins, notably albumin, are lowered in CD in severe ulceration and it has been proposed from an admittedly relatively small study of 71 patients that the reduction is associated with the response to oxidative stress. Liver function tests may be raised transiently due to inflammation or chronically in sclerosing cholangitis. There is an increased risk of

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AntiSaccharomyces cerevisiae antibodies (ASCA) are most often found in CD

gallstones and obstructive jaundice in CD. Other abnormalities include deficiencies in iron, folate and B12 and serum calcium and magnesium. Acute inflammatory markers, such as high-sensitivity serum C-reactive protein or erythrocyte sedimentation, can be helpful during relapse phases and the risk of recurrence. Faecal calprotectin is a relatively new sensitive marker of inflammation. Calprotectin is present in high concentrations in neutrophils and in active disease neutrophils migrate into the gastrointestinal tract. Faecal levels exceeding 150 μg/g indicate significant bowel inflammation and correlate well with endoscopic examination.

Microbiology Faecal samples should be tested for the presence of white blood cells, occult blood, parasites and Clostridioides difficile toxin, which may be responsible for relapse and

certainly before commencing immunosuppressant therapy.

Serology Anti-Saccharomyces cerevisiae antibodies (ASCA) are most often found in CD and it has been observed that positive results have an increased risk of early surgical intervention. Other markers, such as perinuclear anti-neutrophil cytoplasmic antibody and Pseudomonas ﬂuorescens (ant-12), are less speciﬁc.

Immunosuppressant therapy with azathioprine To detect and minimise adverse side effects of this more aggressive therapy, a full blood count and chemistry panel for renal and liver function are required. It is essential to measure the activity of thiopurine methyl transferase in red blood cells as low levels, such as <1 mg/kg have an increased risk of severe myelosuppression and haematopoietic toxicity. Monitoring of haematology and chemistry should be performed monthly and then every three months.

Concluding comments This short review describes some of the progress made in understanding Crohn’s disease, however, the exact cause still remains unknown and there is concern about the increasing incidence and prevalence worldwide and for individual patients the often serious impact on their lifestyle. Treatment hopes may rely on the use of genetic markers to predict risk and novel drug targets. Stephen Clarke is a retired IBMS fellow. To read this article with full references, visit thebiomedicalscientist.net The first instalment of this article was be published in January’s Biomedical Scientist and can be read online at bit.ly/3JMjNyc

20/01/2022 09:38

ADVICE Education

THE BIOMEDICAL SCIENTIST

CONNECTING CLINICAL PRACTICE

AND HIGHER EDUCATION

Ian Davies and Paul Orsmond outline a model for progressive degree apprenticeship education in biomedical sciences.

ocusing on the workforce changes and challenges COVID-19 has presented, in last June’s issue of the Biomedical Scientist, we highlighted a developing trend in biomedical science – addressing the new progressive NHS Long Term Plan demands a more agile workforce. To meet this transformational change, we have asserted that the false dichotomy between university and practice-based biomedical education needed to be reconﬁgured. Our experiences delivering degree apprenticeship education has allowed us to conceptualise learning as occurring within a community of practice, where learning is understood as developing a professional identity. In this way an autonomous practitioner biomedical scientist can develop enduring learning practices to meet fresh challenges with agility, moral and ethical responsibility. In this second article we present a model to encapsulate the changes to biomedical scientist education that degree apprenticeships bring. The model consists of domains of learning that are captured within a four-stage Community Personalised Learning Framework (CPLF) (Figure 1, overleaf ).

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20/01/2022 09:38

ADVICE Education

PROGRESS REVIEWS AND PROGRESSION EXPLORE ACADEMIC SKILLS

Peer-to-peer interaction

ACHIEVE

Workplace mentor

Academic delivery

SUPPORT AND WELLBEING

Stage 2. Learning domain through participation in targeted academic and pastoral support:

FIGURE 1: CPLF

Tutor interaction

Weekly engagement with blended modular learning material provides ample space for negotiation of meaning within four domains: (1) tutor interaction, (2) academic delivery, (3) peer-to-peer interaction and (4) workplace mentoring. These four domains of practice form the community of practice for apprenticeship students. Monitoring of weekly engagement and understanding is supported by signposted opportunities for discussion, differentiation and feedback, enabling theory to be applied in practice.

ASPIRE

Stage 1. Direct domain of learning participation:

LIBRARY SERVICES

BIOMEDICAL 34 THE SCIENTIST

DIGITAL CAPABILITY EXTEND

Targeted and self-referred intervention by other university communities of practice, such as support services, digital services and subject librarians provides an academic and pastoral scaffold to support wellbeing, engagement, and learning. This domain supports immediate one-to-one guidance with online and personalised support to develop learners’ academic practice and professional identity, providing a rich opportunity for developing interdependence as a learner.

Regular progress reviews triangulate learning domains such as workplace and academic experiences, developing the workplace learning environment and set targets for progression. Close, historical liaison between module tutors, academic mentors, work-based education officer and course leader identify students with community learning progression, or at-risk, marginalised community learners.

Stage 3. Learning domain through academic community mentorship:

Learning principles underpinning the CPLF:

This contributes to continual cross-modular and longitudinal mentorship by an academic mentor, where students and mentors negotiate meaning. This will support the transition to higher education (explore), before building the professional and academic identities for university-level study (achieve). These will be enhanced to develop appropriate discipline-stretch (extend), and the professional identities needed for career progression (aspire).

Learning is an experience of meaning. Meaning is achieved through negotiation with others in a community or network. In this way learning is a social process, and all learners are interdependent. Thus, learning is a negotiating process, and it is through developing students’ ability to negotiate that we develop enduring learners with the capacity to meet current learning and professional needs but who have the capability to master further learning challenges when required. In this way, learner identity changes as practitioners make sense of new experiences. Through negotiating new meanings in ongoing

Stage 4. Learning domain through monitored progress, review, and oversight:

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practice, students’ knowledge changes. This is referred to as knowledgeability. The CPLF illustrates several community examples of where negotiated meaning can occur. For example, in Stage 1, learning occurs in the dynamic “jigsaw” at the centre of the framework, allowing negotiated meaning between peer-topeer interactions, engagement with tutors or in workplace mentoring. Once such learning is occurring, students can move and use Stage 2 of the CPLF, where cross community learning occurs as students interact with members of the support service community to enhance their individual practice. Stages 1 and 2 occur throughout the period of apprenticeship study, giving learning an historical context and developing the negotiating process as interdependence and independence evolves. As autonomous learners negotiating individual meaning, students interpret the course differently; ﬁnding their own knowledge of importance. That is “personalised” learning, and by integrating experiences from the workplace and university, the CPLF model shapes the identity change needed for careerlong agile learning.

20/01/2022 09:38

ADVICE Education

The CPLF also allows for a longitudinal approach to apprenticeship study to be investigated, and provides opportunities for speciﬁc practices to be participated in. Stage 3 considers a speciﬁc aspect of participation that occurs between students and academic mentors, and highlights key themes: explore, achieve, extend, and inspire. A longitudinal presentation of Stage 3 can be shown over four years of study, with suggested topics for consideration:

IMAGES: SHUTTERSTOCK

Year 1. Explore – Support for individual student transition into higher education (HE), with an emphasis on translating (not transferring) existing professional practices, including competences, into new learning through HE experiences. Here, identifying and signposting support mechanisms to enable learner autonomy is important. Encouraging reﬂections on changing student identities, for example the change in identities before apprenticeship study and on transition into HE, provides a good way to introduce personalised learning. Year 2. Achieve – Reﬂection on the community learning practices built during Year 1 reminds students that knowledge changes because a person participates in ongoing practice. Students need to recognise those new negotiating practices that they are developing and with whom. Such practice can encompass workplace competences, but with the emphasis on negotiating meaning and the development of academic and professional identities necessary to progress through higher levels of academic study. Personalised learning can be achieved in several ways: guiding the learner to recognise what is important to them in terms of content and emphasising learning as a social process of becoming a member of a community of practice; expanding the dialogue of the social learning to integrate the values,

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“Learning is a social process, and all learners are interdependent” beliefs, and practices of the community of biomedical scientists, and ﬁnally, developing responses to feedback and acknowledging that feedback can have both immediate and delayed value in developing new practices. Year 3. Extend – Utilising personalised approaches to learning develops professionals who can critique and, where necessary, challenge long-held values and beliefs of a community. This is imperative in creating the new, agile workforce. Development of academic and professional identities further strengthens the critically evaluative skills needed to demonstrate the higher levels of understanding during the ﬁnal years at university and consolidates feedback as a way of developing new knowledge. As well as having immediate value in enhancing grades, feedback then feeds forward into an evaluative approach to continuing autonomous practice. Year 4. Inspire – Years 1–3 provide sound preparation for the transition from undergraduate study into professional practice as fully autonomous practitioners and career-long learners. This year allows consideration of onward career journey, including career structures, creating opportunities and mentoring.

THE BIOMEDICAL SCIENTIST

The development of new academic and professional identities allows students ownership to face and resolve community concerns that are not obvious to non-community members – using their newly developed skills and knowledge to identify and solve unmet needs. Negotiation provides opportunities for critical dialogue between community members and focuses on leadership, its development and implementation. This enables students to advance the boundaries of the community of practice of biomedical scientists in their onward careers. Stage 3 of the CPLF provides a rich learning culture requiring review and oversight and that is provided at Stage 4. Stage 4 monitors learners progressing and identiﬁes those at risk and not progressing (not learning). At-risk students may be understood as those not being able to negotiate meaning, hence no learning occurs. It is important to understand non-progression as community marginalisation, and not an individual event. Non-progression affects the whole community. Understanding non-progression in this way means that resolution of non-progression requires application of a community approach and not just, for example, further assessment opportunities within a decontextualised context. By reconsidering and reshaping the integration of work and university learning in the context of identity development in a community of practice, the ability to develop a highly agile, evaluative and autonomous biomedical science workforce is ampliﬁed. Ian Davies is a Biomedical Scientist and Healthcare Science Course Leader at Staffordshire University. Paul Orsmond is a member of the Staffordshire Centre of Learning and Pedagogic Practice. To read more about their work, visit blogs.staffs.ac.uk/ConnectedPathology

20/01/2022 09:38

BIOMEDICAL 36 THE SCIENTIST

ADVICE Qualifications

CELEBRATING SUCCESS IN 2021 The individuals listed here have all been awarded an IBMS Diploma of Expert Practice, Higher Specialist Diploma or Advanced Specialist Diploma in recent months.

eriodically we rightly take a moment to reflect and celebrate the achievements of members. In July 2021 we published details of those who passed the Higher Specialist Diploma (HSD) exams held in February 2021 and we are now pleased to congratulate those who have obtained various IBMS qualifications since then. In addition to the names stated below, 192 individuals were successful in achieving the Certificate of Expert Practice (CEP) in Leadership and Management, Molecular Pathology, Quality Management, Pointof-Care Testing or Training during 2021. The qualifications encourage critical thinking, questioning attitude, reflective practice and the development of greater autonomy, all of which are essential skills for leaders. They are both developed and assessed by IBMS expert practitioners and academics from IBMS-accredited universities in collaboration with, where appropriate, colleagues from the Royal College of Pathologists (RCPath). The qualifications provide value for money, helping organisations to support their staff with qualifications that are specifically designed for those who are working in laboratory settings. They represent a considerable commitment of both time and effort by

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“The qualifications encourage critical thinking, questioning attitude, reflective practice and greater autonomy” the individual concerned. Those who pass will have demonstrated to the examiners a comprehensive understanding of complex scientific, technical and managerial subjects and that they can apply their knowledge, competence and personal autonomy, as well as transferable skills and qualities in their chosen discipline. Successful individuals will find that their

new qualiﬁcation provides both peer and wider professional recognition and that it puts them in a strong position to obtain senior positions. Achievement of the HSD, or any Advanced Specialist Diploma (ASD) qualiﬁcation, enables individuals who do not already have it eligibility for upgrade to the highest level of IBMS membership, Fellowship (FIBMS) status.

20/01/2022 09:39

ADVICE Qualifications

THE BIOMEDICAL SCIENTIST

EXAMINATION PASS LIST Higher Specialist Diploma (HSD) The following individuals passed the HSD exams that were held in September 2021.

Cellular Pathology Olivia Hendry – Basildon University Hospital

Clinical Chemistry Cristina De Matteis – Hinchingbrooke Hospital Rachel Doherty – Glasgow Royal Infirmary Rachael McNair – Royal Alexandra Hospital, Paisley Matthew Nicholas – Doncaster Royal Infirmary Amanda Wright – Royal Alexandra Hospital, Paisley

Haematology Alison Butler – Ulster Hospital Anne Callow – Noble’s Hospital, Isle of Man Ronan Davies – Noble’s Hospital, Isle of Man Elizabeth Handley – Queen’s Medical Centre, Nottingham Richard Main – Freeman Hospital, Newcastle Lisa Morrison – Borders General Hospital Eva Nkansah – Princess Alexandra Hospital, Harlow Peter Strong – Royal Victoria Infirmary, Newcastle Steven Terry – Queen’s Medical Centre, Nottingham

Leadership and Management Simon Davison – University Hospitals Coventry and Warwickshire Jason Pope – University Hospitals Coventry and Warwickshire

Medical Microbiology

Cytology

Katy Dallow – Southampton General Hospital Carly James – Prince Charles Hospital, Merthyr Tydfil Rehanara Khatun – Royal Blackburn Hospital Meerani Munasinghe – Colchester General Hospital Paola Peralta – Queen’s Medical Centre, Nottingham Alexandra Ralston – University Hospital of North Durham Sharon Thomas – Glangwili General Hospital, Carmarthen

The following individuals were successful in passing the written and microscopy exams held in 2021.

Transfusion Science Michele Armour – 205 Field Hospital Vinay Bheekha – NHS Blood and Transplant, Tooting Luke Groves – Colchester General Hospital Emily McNeill – Freeman Hospital, Newcastle Matthew Meek – Peterborough City Hospital Georgina O’Connor – NHS Blood and Transplant, Birmingham Philip Russell – Health Services Laboratories (HSL) Helen Senior – Huddersfield Royal Infirmary Carol Stenning – St Richard’s Hospital, Chichester Abbit Tervit – Queen’s Medical Centre, Nottingham Richard Ullaytt – Noble’s Hospital, Isle of Man Jasmine Walker – Medway Maritime Hospital Chloe Wilkes – Queen’s Medical Centre, Nottingham Nicola Young – Western General Hospital, Edinburgh

P36-37 Exam Pass List_February 2022_Biomedical Scientist.indd 37

Diploma of Expert Practice (DEP) in Non-Gynaecological Cytology Claire Chadwick – The Royal Liverpool Hospital Joy Emmanuel – Queen’s Hospital, Romford Lois McPolin – Craigavon Area Hospital Andrea Taibi – Southmead Hospital, Bristol Richard Turner – Royal Devon and Exeter Hospital

Advanced Specialist Diploma (ASD) in Non-Gynaecological Cytology Caroline Murphy – Craigavon Area Hospital Sarah Reeves – William Harvey Hospital, Ashford Leonie Wheeldon – Royal Cornwall Hospital

ASD in Cervical Cytology Monika Bhardwaj – New Cross Hospital, Wolverhampton Sarah Ferris – Manchester University Royal Infirmary Maria Manalo Nwachuku – Ashford and St Peter’s Hospitals Foundation Trust

Histopathology Reporting To achieve this qualification

candidates have passed the Stage A, B and C portfolios and exams at stages A and C.

ASD in Histopathology Reporting – Gastrointestinal Pathology Emma Gilchrist – Norfolk and Norwich NHS Trust Joanne Motte – Gloucestershire Hospitals NHSFT Iain Sheriffs – Norfolk and Norwich NHS Trust

ASD in Histopathology Reporting – Gynaecological Pathology Karen Ezard – Kettering General Hospital Maalaviya Kumanan – Barking, Havering and Redbridge University Hospitals NHS Trust Kathryn McDermott – Queen Alexandra Hospital, Portsmouth Sue Mehew – Royal Infirmary of Edinburgh Poonam Singh – Addenbrooke’s Hospital, Cambridge

20/01/2022 09:39

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10/03/2021 08:48:47 19/01/2022 12:49

ADVICE Congress

CONGRESS

2022

THE BIOMEDICAL SCIENTIST

HIGHLIGHTS Politics and Pathology NHS England Lord Bethell UKAS – new standards Deputy Chief Medical Officer – Prof. Sir Jonathan Van-Tam

Not yet booked your place at Congress? It’s time to think again, because we have added more than 30 new presentations and speakers.

We have added a whole new programme in addition to the extremely popular Quality Management, Education and Training, and Cellular Pathology Workshop. Our latest programme “Politics and Pathology” opens with a talk from Lord Bethell, who will be talking on how the UK IVD industry responded to the pandemic. He will be followed by NHS England, who will be delivering a wholeafternoon lecture programme covering: Pathology Quality Assurance Dashboard Maturity of Networks in NHS pathology Future strategy and long-term planning requirements Pathology GIRFT report Digital programme – investment in LIMS, interoperable systems and digital pathology – aspirations for pathology networks Workforce planning tool development.

Tuesday 15 March: UKAS – new ISO 15189 standards NHS England will be repeating two of its most popular sessions between 9am and 10am for those who were unable to attend for the Monday afternoon. The remainder of the morning will be an extended UKAS session of three presentations to take delegates through the new ISO 15189 standards that are being launched this year, and what they mean for clinical laboratories.

P39 Advice-Congress 2022_February 2022_Biomedical Scientist.indd 39

Plenary Programme – Prof. Sir Jonathan Van-Tam The latest addition to our Plenary programme is Professor Sir Jonathan Van-Tam, who will be well known to all through his COVID-19 brieﬁngs. JVT, as he has become known, will be talking on Managing the UK response to the COVID-19 pandemic – lessons learned and he will be followed by Prof. Jo Martin speaking on the COVID-19 response from pathology.

Exhibition Hall Seminar Programme The Exhibition Hall Seminar Programme is three days of seminars that run parallel to the main lecture programme, and which are free to all to attend. The programme will cover safety and risk – with Vin Poran of the Health and Safety Executive, education and training – registration and Institute qualiﬁcations, laboratory IT and clinical informatics and green pathology – sustainability for laboratories. Essentially, there is something for everyone at Congress.

Tuesday 15 March: Safety and Risk The risk of not having a meaningful risk register The importance of a thorough complaints procedure New ISO risk and safety standards COVID-19: considerations of safety and risk associated with diagnostic testing and vaccine responses.

Wednesday 16 March: IBMS professional qualifications – here to help Preparing to pass the HSD Study skills for self-directed learning On-line learning – how to make it work for you Planning and delivering laboratory training The IBMS Registration Training Portfolio – everything you need to know Portfolio evidence: the good, the bad and the totally avoid Modules: a new approach to Specialist Portfolio training

Thursday 17 March: Professional qualifications, Informatics and Laboratory IT, Molecular Pathology and Genomics Diploma of Expert Practice in Histological Dissection Expert practice is more than just dissection: ICC and electron microscopy DEPs Clinical informatics and the biomedical scientist Going green: how to make labs more environmentally sound The increasing incorporation of molecular science into routine pathology

ℹ

For all the latest information, full programme and speakers, visit the Congress website at ibms.org/congress

IMAGE: SHUTTERSTOCK

Monday 14 March: Politics and Pathology

20/01/2022 12:09

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BIOMEDICAL 42 THE SCIENTIST

MY IBMS News

MY IBMS NEWS

OBITUARY

Christopher Wall: Goodbye to an extremely intelligent, caring and respected man

t is with sadness that Northwest Region IBMS reports the death of Chris Wall, Manchester Branch and Northwest Region committee member and Treasurer. Christopher James Wall died in hospital on 29 October. For those who knew him, Chris was a straighttalking no-nonsense type of person, but there was also another fun-loving, extremely caring side to him. He was an extremely intelligent and respected man, who valued people, friendships and valued life. After leaving school he worked in a bank, but soon got bored of that, so he applied to train as a lab technician at Black Notley in Essex. The pay as a trainee lab technician wasn’t too good, so Chris decided to sign up to the medical corps of the army, where he could complete his training with better pay and various postings followed. After returning from Cyprus, Chris and his family felt it time to put some roots down and create some stability. Chris got a job in a lab in Carlisle, but quite quickly got promoted and took the role of Chief Scientiﬁc Technical Officer at Crumpsall Hospital. A further promotion saw him transfer to Hope Hospital in Salford, which is now Salford Royal Hospital, here he rose to become the Principal MLSO. Chris dedicated a large amount of his time not only to work, but also to lecturing and setting up and running the

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Clinical Biochemistry discipline on the BSc and MSc programmes in Biomedical Science at Manchester Metropolitan University. During the 1970s Chris’s input signiﬁcantly improved the pass rate for the IBMS Fellowship course in Clinical Chemistry, prior to the inception of the postgraduate programmes in 1986. He also performed duties for both the Manchester Branch and Northwest Region (IBMS), where he was highly respected. When he reached retirement age, he did retire, but

then went back for a few years to work within the lab and continued his role as regional treasurer. Chris enjoyed pub quizzing, football (he was an ardent supporter of Manchester United), skiing holidays, going to the Halle and the theatre (Les Miserable was a favourite) and of course canal holidays and the odd tipple of whisky. Chris will be sorely missed by those whose lives he touched. Joyce Overfield Northwest Region IBMS Committee (rtd) D.W. Eccleston Chairman Northwest Region IBMS

20/01/2022 09:40

MY IBMS News

COUNCIL ELECTIONS: YOUR CHANCE TO SHAPE THE FUTURE OF THE IBMS The IBMS prides itself on being a professional body that is run by its members for its members. It is currently looking for corporate members who will use their professional knowledge, leadership skills and experience to set the strategic direction of the Institute, shaping its future and ensuring it continues to meet its members’ needs. The role of a Council member is hugely rewarding but requires significant personal commitment and skills, strategic thinking, financial understanding, passion for the work of the Institute and the ability to be a role model for the profession. Council members are high calibre leaders of the profession and candidates should be active in the profession at the time of standing for election, have experience of the work that the Institute does in terms of its examinations, and membership and ready to commit time and energy to supporting, progressing and promoting Biomedical Science. Nominations for corporate members to participate in the 2022 elections to Council are now invited, as there are vacancies for two National and five Regional members as follows:

NATIONAL MEMBERS Two vacancies - three-year term

REGIONAL MEMBERS Five vacancies - three-year term Irish Region Scotland South West West Midlands Yorkshire Find out more about becoming a Council member of the Institute by visiting the IBMS Council elections page where full details on this important role and eligibility criteria can be found as well as a link to the online application form. www.ibms.org/councilelections/ Deadline for return of nomination forms: 5.00 pm on Thursday 10th March 2022.

THE BIOMEDICAL SCIENTIST

PROFESSION

WELCOME TO THE NEW IBMS PRESIDENT Debra Padgett is now in post as the IBMS President, after taking over from Allan Wilson at the start of the year. Debra is passionate about promoting and recognising excellence in all IBMS members. In her eight years as an IBMS Council member, she has advocated, listened, represented and addressed the issues that are most important to the IBMS membership at national, regional and local levels. She started her career as a Medical Laboratory Assistant in microbiology and has successfully worked her way through the career grades to her current role as Clinical Pathology Lead at Northumbria Healthcare NHS Foundation Trust. This means that she understands the many routes to achieve a senior management position within the profession, and how management decisions affect every member of the laboratory. Her post encompasses provision of leadership and management with accountability for the delivery of cost-effective, high-quality, safe and sustainable services across the Northumbria health economy. These responsibilities give her a strategic insight to deliver operational priorities both for her own trust and those of national programmes. Debra has recorded a short video introducing herself to IBMS members. It can be viewed at bit.ly/3GiRtRQ

EVENTS

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IBMS CONGRESS: NEW SPEAKERS AND SESSIONS ADDED TO THE PROGRAMME With Congress a month away, more than 30 new presentation and speakers have been added to the already packed line-up. Among the additions are a plenary session by Professor Sir Jonathan Van-Tam, who will be well known to all through his regular television briefings throughout the COVID-19 pandemic.

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A new “Politics and Pathology” programme will open with a talk from Lord Bethell, who will be discussing the UK IVD industry’s response to the pandemic. Congress will take place on 14–17 March at The International Convention Centre in Birmingham and the programme theme is “Linking learning to the laboratory”.

Delegate fee includes admission to all lecture sessions, scientific posters, the exhibition, lunch, morning and afternoon refreshments and a copy of the Biomedical Science Congress Handbook. For more in formation on IBMS Congress 2022, programme updates and to book your tickets, visit congress.ibms.org

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MY IBMS News

AWARD

NOMINATE FOR PRESTIGIOUS PRIZE IBMS members are invited to enter nominations for the Buchanan Medal – the Royal Society’s ﬂagship prize in biomedical sciences. The medal is awarded for distinguished contributions to the biomedical sciences. The award was created from a fund to the memory of the physician George Buchanan FRS, former Chief Medical Officer of the UK, and was ﬁrst awarded in 1897. The medal is made of silver gilt, is awarded annually and is accompanied by a gift of £2000. The Royal Society stated: “The Buchanan medal is open to UK, Commonwealth, Irish Republic citizens or those who have been residents for three or more years. There are no restrictions on career stage and nominations will remain valid and shall be considered by the award

selection committee throughout three nomination cycles. Teams or groups may now be nominated for this award. We are happy to receive nominations for the other medals and awards that have opened this year. Further details on the awards that are currently open for nomination can be found here. “Nominations can be made through the Royal Society website and the nomination will go to the awards committee for deliberation as part of our 2022 medals and awards cycle. Nominators and nominees do not need to be fellows to either nominate or

receive any of the Society’s awards.” The Royal Society is hoping to encourage a greater pool of nominators to nominate their peers and colleagues, but also to encourage group nominations for all awards. If you think you, a colleague or a working group within your trust or organisation has made an outstanding contribution to the ﬁeld, the IBMS recommends submitting an application for this prestigious award. Nominations must be submitted by the deadline of 3pm on 25 February 2022. For more information and to view a list of past winners, visit bit.ly/3JXy7Up

OMICRON

Testing guidance for Omicron IBMS Fellow and Virology Panellist Sarah Pitt wrote a brief guide breaking down COVID-19 testing following the spread of the Omicron variant. She covered the range of tests to detect the SARS-CoV-2 virus and how useful it is to understand what the results can and cannot tell you, especially in relation to the Omicron variant. The piece says that each new variant of SARS-CoV-2 has some mutations in the N gene sequence, but so far these changes do not seem to affect LFD results. For all variants of the virus – including Omicron – LFDs have very good reliability, though they are lower in accuracy than PCR tests. The guidance goes on to state that PCR kits

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that tag the genetic code in three separate places – the ORF, S and N regions – are used regularly in UK laboratories. Changes in Omicron’s spike protein mean that certain primers are unable to find the place they are designed to “tag” or attach to in the genetic sequence. This is because these sections of genetic code are no longer present in the Omicron variant – a factor which could lead to the delivery of a strange PCR result. Sarah adds that scientists are considering using results with S gene target failure as “probable Omicron”. For more information and to read the guide, visit bit.ly/3FgcQSt

ANNUAL MEETING

NORTH STAFFS BRANCH AGM The IBMS North Staffs branch has scheduled its annual general meeting for Wednesday 6 April. The event will start at 6.30pm on the Staffordshire University Leek Road campus For further details, email aimee. pinnington@staffs.ac.uk

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19/01/2022 12:59

BIOMEDICAL 46 THE SCIENTIST

MY IBMS Continuing professional development

JOURNAL-BASED LEARNING EXERCISES Please select your choice of correct answers and complete the exercises online at: www.ibms.org/cpd/jbl

DEADLINE WEDNESDAY 4 MAY 2022 Effects of rotational thromboelastometry-guided transfusion management in patients undergoing surgical intervention for postpartum hemorrhage: An observational study. Tsang Y, Kurniawan AR, Tomasek O et al. Transfusion 2021; 61 (10): 2898–905. doi: 10.1111/trf.16637. Assessment No: 020222

Traditional coagulation tests such as prothrombin time (PT) and activated partial thromboplastin time (APTT) lack sensitivity in predicting the severity of PPH and in guiding management.

Multiparity and Caesarean deliveries were less common in the post-ROTEM cohort.

A review of randomised, controlled trials of ROTEM-guided transfusion management in cardiac surgery had shown no reduction in the need for blood products and reduced morbidity.

Slightly more patients in the pre-ROTEM cohort received a PRBC transfusion compared with the post-ROTEM cohort.

Information from a FIBTEM is typically available within 15 minutes and has been used to guide fibrinogen replacement in PPH.

For patients delivering via Caesarean section, there was no difference in rates of PRBC transfusion between the pre- and post-ROTEM groups.

The study was conducted in a 600-bed general hospital providing obstetric care for more than 7000 births per year in Melbourne, Australia.

Although there was an increase in post-ROTEM patients receiving cryoprecipitate transfusions, the results were considered not statistically significant.

For the study, PPH was defined as estimated blood loss (EBL) within the first 24 hours of greater than 1000 mL following vaginal delivery, or greater than 1750 mL following Caesarean section.

In conclusion, there was no difference in PRBC transfusion rates pre- and post-ROTEM in patients who delivered by Caesarean section and these findings were similar to previously published observational studies in PPH.

The primary outcome included the proportion of patients in each cohort receiving PRBC transfusion during admission.

The study supports the role of ROTEM for early detection and management of fibrinogen depletion in PPH.

Secondary outcomes were proportions of patients receiving transfusions of platelets, FFP, and cryoprecipitate, total and average volumes of each blood product transfused, proportion of patients requiring hysterectomy, and proportion of patients requiring intensive care.

The study concluded that proactive management of PPH in the later period had possibly led to earlier administration of PRBC on the labour ward and contributed to a greater percentage of patients receiving a PRBC transfusion in the post-ROTEM cohort.

Obstetric risk factors known to increase risk of bleeding only included the country of birth, birthweight, body mass index (BMI), and the presence of placental adhesive disorder.

A potential source of bias in the study was that only 23% of eligible patients in the post-ROTEM group received a ROTEM test.

The patient population experienced low rates of suspected or confirmed coagulopathy, with less than 4% in both pre- and post-ROTEM groups receiving FFP, platelets or cryoprecipitate.

The study concluded that ROTEM has a more useful role when guiding coagulopathy management in established or severe PPH, rather than being used as a screening tool for its early detection.

The pre-ROTEM cohort consisted of 400 consecutive patients treated from July 2015 to May 2016.

Post-ROTEM patients were treated from September 2017 to April 2018.

REFLECTIVE LEARNING 01

The study determined that ROTEM may be used firstly as a screening tool to exclude coagulopathy and secondly as a tool to identify coagulation deficiencies. Do you agree with these findings, what evidence is provided within the text to support this theory, and how could this be tested?

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The ROTEM in this study was situated within the theatres. Many point-of-care instruments, such as ROTEM, are placed within the laboratory. Can you list any advantages or disadvantages to the analyser being situated within the theatre rather than the laboratory?

20/01/2022 09:41

MY IBMS Continuing professional development

THE BIOMEDICAL SCIENTIST

DEADLINE WEDNESDAY 4 MAY 2022 PD-L1 and HER2 expression in gastroesophageal cancer: a matched case control study Beer A, Taghizadeh H, Schiefer AI et al. Pathol Oncol Res 2020; 26 (4): 2225–35. doi: 10.1007/s12253-020-00814-2. Assessment No: 020722

Immunotherapy with check-point inhibitors serves as a promising treatment strategy in patients with upper gastrointestinal (GI) tumours.

Previous studies have shown that dual inhibition of HER2 and PD-L1 improves survival of this selected patient population.

Gastric cancer is the fifth most commonly diagnosed cancer and the third most common cause of cancer-related deaths worldwide.

Five-year survival for advanced or metastatic gastric, gastroesophageal junction (GEJ) or oesophageal cancer (together upper GI tumours) is approximately 25%, with a median overall survival (OS) of about three years.

Epstein-Barr virus-positive (around 9%) gastric cancers are generally characterised by some distinct genetic features including increased number of tumour infiltrating lymphocytes and programmed cell death ligand 1 (PD-L1) positivity.

PD-L1 is a 60-kDa transmembrane protein that is activated in many cancer types and thereby leads to an immunosuppressive tumour microenvironment.

The average age of HER2-positive patients was 66.

97% of patients within the study had adenocarcinoma.

Although trastuzumab does not extend the survival of HER2positive patients, these patients typically develop treatment resistance, and second-line treatment options are limited.

Specimens in which PD-L1 staining was observed in ~1% of tumour cells or immune cells were considered PD-L1 positive.

CPS was calculated by dividing the number of PD-L1-positive tumour cells, lymphocytes and histiocytes by the total number of vital tumour cells and then multiplying the result by 100.

In patients with advanced gastroesophageal cancer (20 in both groups), overall survival was not significantly different with positive and negative HER2 status.

HER2 positivity was significantly associated with better outcome in patients with advanced disease, whereas significant association was observed in the localised group despite a tendency towards higher survival rates for HER2positive patients.

Implementation of anti-HER2 treatment with trastuzumab prolonged the survival of patients with advanced gastroesophageal tumours; however, after some time treatment resistance occurred in almost all patients.

The assessment of PD-L1 staining in immunohistochemistry was done based on four different scores: i) PD-L1 expression in tumour cells in terms of tumour proportion score, ii) PD-L1 expression in tumour-associated immune cells, iii) combined positive score, and iv) PD-L1 expression in interface pattern.

Up to 20% of gastric tumours overexpress human epidermal growth receptor 2 (HER2).

In patients with localised gastroesophageal cancer (n = 39 in both groups), overall survival was not significantly different in HER2-positive and -negative patients, although there was a tendency towards lower survival rates in HER2-positive patients.

PD-L1 expression levels in gastroesophageal cancer patients were reported within the range 34–69%.

The correlation of different PD-L1 assessments with one another was moderate and sometimes not even present, which again emphasises the fact that the variation of the PD-L1 assessment is extensive.

The relation of MSI to HER2 is very interesting, since both large TCGA and Memorial Sloan Kettering Cancer Center cohorts of gastroesophageal cancer tumours do show a complete negativity of MSI in HER2-positive tumours, indicating a different driver molecule mechanism of these markers.

REFLECTIVE LEARNING 01

Critically review the actions for the teams within your hospital who would be involved in the implementation of PD-L1 assessment and treatment in upper GI cancers.

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Critically review how good quality would be maintained in implementing PD-L1 assessment in your own laboratory. What quality factors might preclude implementation?

20/01/2022 09:42

BIOMEDICAL 48 THE SCIENTIST

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RECRUITMENT For recruitment advertising contact our Sales Team +44 (0)20 7880 7621

18/01/2022 19/01/2022 09:48 13:02

MY IBMS Here to help

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he Prime Minister recently announced that the Government will hold an independent public inquiry in relation to the Government and public sector response to the COVID-19 pandemic. The purpose of the inquiry is to provide transparency to the public and ensure that lessons are learned. Discussions are ongoing, but the devolved administrations will support the UK Government’s inquiry – with those involved in an independent public inquiry trying to ensure that their objectives will align with the planned four nations inquiry. Our members must anticipate that the inquiry will require the disclosure of a considerable number of records relating to the key issues arising and decisions made before and during the pandemic. It is possible that the scope could also include some post-pandemic decisions relating to the restoration of services. Currently, the full scope of the inquiry is unclear. However, most of our members involved in COVID-19 testing have now been instructed by their trusts to retain all documents, correspondence, notes, emails, and all other information that contains or may contain content pertaining to the response to the COVID-19 pandemic, or the key decisions made as part of the recovery. A “document” means anything in which information of any description is recorded. This includes paper and electronic documents, emails, models and datastores, text messages, social media, WhatsApp, voicemail, audio and visual recordings and “metadata” on computer systems, which contain information including details of authorship and the date or modiﬁcation of documents. A document can be held on computers or

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HERE TO HELP

COVID-19 PUBLIC INQUIRY The public inquiry into the pandemic response and what it means for members. portable devices (including memory sticks and mobile phones). Examples of such information may include (but are not limited to): 1. Reports, PowerPoint presentations, records, brieﬁngs, minutes, notes and correspondence by email or otherwise, Teams “chats”, action logs 2. Models and Sitreps and related data histories 3. Material relevant to key policy decisions or submissions 4. Materials relevant to policy or legislative development 5. Training materials

THE BIOMEDICAL SCIENTIST

6. Materials relating to contracts, procurements, other commercial arrangements, data management, recruitments, secondments and appointments (paid or not) or requests and arrangements for support from other public sector agencies 7. Any other documents relating to the organisation’s response or communications with patients, the system, industry or other stakeholders 8. Personal diaries/calendars if these are potentially relevant to the proposed inquiry. It is best to err on the side of caution and preserve anything that may relate to the public inquiry. Do not delete any documents that are potentially relevant. Suspend any routine document destruction policies you have in place. If you are asked to do so, you should seek advice to ensure your records are retained. This includes making sure that ﬁles are not autodeleted or that you know how to access archived data before it is archived. In due course it will be necessary to search for and identify all relevant records so it is essential that all records are appropriately saved and available for access – including after any staff holding these have left the organisation. All records must be retained in accordance with the COVID-19 record management requirements.

Legal helpline for IBMS members The public inquiry has not been established to determine civil or criminal liability. However, if you are concerned about your legal standing in any matter pertaining to you or your workplace’s involvement in the COVID-19 response please remember that all IBMS members have access to free 24/7 legal advice via IBMS Additions in the members’ area of our website.

20/01/2022 09:42

BIOMEDICAL 50 THE SCIENTIST

MY LAB Jordan Moir

MY LAB

THE MANUFACTURING LABORATORY Specialist Biomedical Scientist Jordan Moir gives a guided tour of the blood manufacturing facilities at the Scottish National Blood Transfusion Service.

he headquarters of the Scottish National Blood Transfusion Service (SNBTS) are based at the Jack Copland Centre (JCC) in Edinburgh. The JCC is the only Scottish blood, tissues and cells facility for processing, testing, supply, research and development. This article offers insight into the journey of blood in the manufacturing and dispatch labs. Our labs are operated 24/7, 365 by a friendly hardworking team made up of 16 biomedical scientists and 40 biomedical support workers together with a team of section and senior managers. The laboratories are strictly regulated by the MHRA and are GMP-compliant to ensure the quality, safety and efficacy of our blood products. The manufacturing lab is a Grade D facility. All whole blood, platelet and plasma donations from our volunteer donors across Scotland are received here. Over 136,000 whole blood donations were collected and processed in 2021. Donations are reconciled on receipt and the type of product entered into the laboratory information management system. Up to three blood products can be produced from each donation. For example, red cell concentrate, buffy coat (used for platelet pool production) and a

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clinical plasma product, such as fresh frozen plasma (FFP) or cryoprecipitate intermediate (which are pooled to produce pooled cryoprecipitate). All blood packs are ﬁltered to remove more than 90% of leucocytes, which reduces the risk of immune reactions during transfusion. This process is called leucodepletion. Donations are then centrifuged to separate the whole blood into different parts and then placed onto automated Macopress Blood Separators. The lines on the red cell blood packs are then stripped and segmented for use in crossmatch and phenotyping. Blood products are then weighed and component type (CT) labelled. These labels contain details of the volume and storage requirements. Clinical plasma is then frozen quickly at −80oC, to make FFP and cryoprecipitate using Freezematic devices. Blood products are placed into quarantine storage until

donation testing is complete. We work closely with our donor testing laboratories (as featured in a My Lab article in June 2021). Once donor testing is complete, each blood product is labelled with the speciﬁed results. Reconciliation of all products is undertaken prior to products being shelved in carefully regulated and monitored cold rooms, freezers and incubators. Our dispatch lab serves hospitals across Scotland, including the Islands. A hub lab supplies hospitals in the West of Scotland. All blood products are electronically issued for traceability and receipted by hospital blood banks. Our department also produces paediatric red cells, neonatal platelets and plasma, specialist products for speciﬁc patients, which include units for exchange transfusion, intrauterine transfusion (IUT), washed red cells, washed platelets and granulocytes. Some products are irradiated, depending on patient requirements, to prevent transfusionassociated graft-versus-host disease. Like all labs, we have experienced the challenges of the pandemic, but we have still managed to maintain our 24/7, 365 service. I hope this article gives you an insight into the work that takes place in a blood-processing lab. Here’s a short video from our lab youtu.be/vPsXM22Yq_Y

20/01/2022 09:43

Are you setting up a Community Diagnostic Hub? Here’s how to measure a lab quality D-dimer in ~20 minutes and a lab quality NT-proBNP in ~10 minutes Radiometer’s AQT90 FLEX immunoassay analyser provides a diverse repertoire of point-of-care tests which may help you meet many of the recommendations set out in Appendix 8 of Sir Mike Richard’s Report of the Independent Review of Diagnostic Services for NHS England.[1]

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TAKE SAMPLE

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Reportable range

Standard of traceability

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10 – 25,000 ng/L

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