Features

Professor Antoine Jerusalem of Oxford University’s Department of Engineering Science explains how a better understanding of the physical mechanisms behind brain injuries can pave the way for novel therapies and new protective devices.

Blast-induced traumatic brain injury (bTBI) can lead to a range of debilitating conditions with lifelong consequences. It is a type of injury that has unfortunately seen a significant increase in recent terrorist attacks or conflicts such as in Syria, Iraq and Afghanistan, where improvised explosive devices have proved to have devastating effects on armed forces personnel and civilians.

While these conditions can clearly manifest themselves as neurodegenerative and neuropsychiatric disorders, the specific mechanisms that link the blast wave physics to the subsequent biological alterations in the brain have remained elusive.

Our research group seeks to understand the physical mechanisms governing brain tissue damage eventually leading to cognitive disorders, to develop better head protection against such blasts.

Through a unique collaboration with Prof. Shi from Purdue University in the US, our group has constructed computer models of rat and human brains to observe how a shockwave damages soft tissue, and how such damage correlates with post-injury oxidative stress distribution in brain tissues. In order to calibrate and validate these models, novel in vivo experiments coupling blast expositions to cognitive tests were conducted in Purdue.

This approach was then applied to a human head model where the prediction of cognitive impairments was shown to match up with the injuries that individuals have been observed to incur.

This novel approach has already created new opportunities. In particular, the mechanical insights from this work have been directly leveraged to propose a new design for helmets, filed as a patent.

The full paper, ‘Cognition based bTBI mechanistic criteria; a tool for preventive and therapeutic innovations,’ can be read in the journal Scientific Reports, in open access. The resulting computer models are also made available.

Researchers at the University of Oxford and the Chinese Academy of Sciences have discovered a new gene that improves the yield and fertilizer use efficiency of cereal crops such as wheat and rice.

The worldwide 20th century ‘Green Revolution’, which saw huge year-by-year increases in global cereal grain yields, was fueled by the development by plant breeders in the 1960s of new high-yielding dwarfed varieties known as Green Revolution Varieties (GRVs).

These dwarfed GRVs remain predominant all over the world in today’s wheat and rice crops. Because they are dwarfed, with short stems, GRVs devote relatively more resources than tall plants to growing grain rather than stem, and are less susceptible to yield losses from wind and rain damage. However, growth of GRVs requires farmers to use large amounts of nitrogen-containing fertilizers on their fields. These fertilizers are costly to farmers and cause extensive damage to the natural environment. Development of new GRVs combining high yield with reduced fertilizer requirement is thus an urgent global sustainable agriculture goal.

A major new study published in the journal Nature, led by Professor Xiangdong Fu from the Chinese Academy of Sciences’ Institute of Genetics and Developmental Biology, and Professor Nicholas Harberd from the Department of Plant Sciences at the University of Oxford, part-funded by the BBSRC-Newton Rice Initiative, has for the first time discovered a gene that can help reach that goal.

Comparing 36 different dwarfed rice varieties, the study identified a novel natural gene variant that increases the rate at which plants incorporate nitrogen from the soil. The discovered gene variant increases the amount in plant cells of a protein called GRF4. GRF4 is a ‘gene transcription factor’ that stimulates the activity of other genes – genes that themselves promote nitrogen uptake and assimilation.

Professor Harberd said: ‘Discovering such a major regulator of plant nitrogen incorporation was exciting in itself. But we were even more excited to then discover that GRF4 has a yet broader role. Plants grow by the coordinated metabolic incorporation of matter from the environment. We discovered that GRF4 coordinates plant incorporation of nitrogen from the soil with the incorporation of carbon from the atmosphere. While such overall coordinators of plant metabolism have long been known to exist, their molecular identity had previously remained unknown, and our discovery is therefore a major advance in our understanding of how plants grow.’

In dwarf GRVs the promotive metabolic coordinating activity of GRF4 is inhibited by a growth-repressing protein called DELLA. This inhibition reduces the ability of GRVs to incorporate nitrogen from the soil, and is the reason why farmers need to use high fertilizer levels to obtain high GRV yields.

Professor Harberd said: ‘We reasoned that tipping the GRF4-DELLA balance in favor of GRF4 might reduce the need for high fertilizer levels in GRV cultivation. To our delight, we found that increasing GRF4 levels caused an increase in the grain yields of both rice and wheat GRVs, especially at low fertilizer input levels.’

The researchers say GRF4 should now become a major target for plant breeders in enhancing crop yield and fertilizer use efficiency, with the aim of achieving the global grain yield increases necessary to feed a growing world population at reduced environmental cost.

Professor Harberd added: ‘This study is a prime example of how pursuing fundamental plant science objectives can lead rapidly to potential solutions to global challenges. It discovers how plants coordinate their growth and metabolism, then shows how that discovery can enable breeding strategies for sustainable food security and future new green revolutions.’

The Antibiotics and Activity Spaces project is a survey of 4,800 villagers in Chiang Rai (Thailand) and Salavan (Lao PDR) to better understand (1) how people access healthcare and what actually counts as 'problematic' antibiotic use, (2) whether antibiotic-related information from educational activities spreads or simply evaporates in village community networks, and (3) whether there are simple 'early warning' indicators (eg specific symptoms) to detect whether people are likely to have 'problematic' antibiotic use. The project is hosted by Oxford's Centre for Tropical Medicine and Global Health.

Survey researchers Nutcha (Ern) Charoenboon, Marco J Haenssgen, Kanokporn (Joobjang) Wibunjak, Patthanan (Mind) Thavethanutthanawin, and Penporn (Yok) Warapikuptanun recently hosted a photography exhibition in Bangkok on rare and vivid narratives of healing in Northern Thailand. In today’s Science Blog the researchers reflect on these stories and the relationship between traditional medicine, modernity, and current global health crises.

A healing stone brought from Burma a generation ago lies alongside a tiger claw on Abor’s wooden table. Scraping this 'Black Stone' against a rock creates a fine grey powder, which Abor dissolves in water and applies to wounds that he had previously perforated lightly with a hammer holding small nails. Legends tell of people with broken bones who, unable to stay off work during the hospital’s recommended three-month recovery period, would convalesce within a week after receiving Abor’s treatment.

Abor’s story and the legends around the Black Stone are just one of the many fascinating tales of treatment that the Antibiotics and Activity Spaces survey team encountered during a demanding journey to 72 villages and more than 15 different ethnic groups in Northern Thailand. Tales about herbal medicine, ghost doctors, sacred books of chants, and ceremonial posts highlight that healing maintains firm though waning links to local knowledge and belief systems even in an economy and society transitioning as rapidly as Thailand’s.

The villagers who told their stories would still seek care from doctors for serious health conditions, using traditional healing often only as a secondary step when they had started to lose hope about the ability of formal healthcare to cure them. Traditional healing and medicine therefore do not necessarily compete with or substitute for formal healthcare from trained doctors and nurses. Rather, tradition blends into and complements modern forms of healing that have their own limitations.

One example of the blend of the traditional and the modern is the work of Grandma Kaew. The skills and knowledge for her work as a herbalist had been passed down to her from previous generations, enabling her to produce herbal compresses and mixtures and to blow ancient chants on to patients’ wounds. Practical reasons also require her to process herbs efficiently, owing to which she also blends sun-dried herbs and packages them in capsules for easier storage and administration. Her industrious work combines century-old traditions and knowledge with patient expectations for capsules that resemble modern pharmaceuticals.

Grandma Kaew dispenses herbal medicines to villagers.

Image credit: Patthanan Thavethanutthanawin

Incidentally, Grandma Kaew’s capsules do not only embody the knowledge and skills of past generations, but they also resemble solutions for acutely current global health policy problems: microbes’ resistance to antibiotics and other types of antimicrobial medicine is growing. Also known as drug resistance, this process makes medicine less effective, infectious diseases more difficult to treat, and it is feared to become the leading cause of death by 2050. One way to counteract this development is to preserve the effectiveness of the medicine by using it as sparingly as possible. Thai health policy follows this approach by promoting the use of herbal medicines through its Antibiotic Smart Use programme, which has equipped nurses and doctors with an alternative to antibiotics should patients expect or demand medicine for non-bacterial infections.

Reflecting on the relationship between traditional medicine and modern global health problems, project leader Dr Marco J Haenssgen argues: 'The Tales of Treatment are not only a vibrant account of Northern Thai culture and customs, but they also reveal an ironic situation in global health. Modern medicine has often discredited traditional medicine as unscientific and created a widespread dependence on Western pharmaceuticals. This dependence has quite plausibly accelerated the development of antimicrobial resistance, yet the threat of antimicrobial resistance may also entail a recognition of traditional forms of healing as a substitute for needless antimicrobial use. While we do see a co-existence of different systems of medicine in some health systems like in India and China, there is perhaps more that Western biomedicine can and should learn from local knowledge.'

The curators – Joobjang, Mind, Yok, and Ern – exhibited their work from 14-17 July at Art Gallery G23 (Srinakharinwirot University, Bangkok), welcoming enthusiastic visitors from NGOs, the United Nations, research institutes, Thai government departments and schools, and many more. The exhibition narrated 12 photographic tales that ranged from sacred healing stones via traditional herbal medicine to summoning ghosts, thereby illustrating still-existing yet fading rural lifestyles and medical treatments.

This provided an opportunity for visitors to envision the gradual blend of the 'traditional' and the 'modern', as research officer Ern Charoenboon recalls: 'It’s not only interesting to learn how villagers make sense out of modern medicine during our time in the field, but when we brought the stories from Chiang Rai to Bangkok, it was also fascinating to see how urban dwellers interpret these "traditional treatments," "old-days solutions," and "rural beliefs."'

The exhibition also shared a glimpse of early research findings from the Antibiotics and Activity Spaces project and paid tribute to the hard-working survey teams in Thailand and Lao PDR who made this work possible.

The Antibiotics and Activity Spaces project is funded by the Antimicrobial Resistance Cross Council Initiative supported by the UK's seven research councils in partnership with the Department of Health and Department for Environment, Food & Rural Affairs (grant ref. ES/P00511X/1, administered by the UK Economic and Social Research Council).

An Oxford University graduate named as one of the UK’s top black students has news for those that believe people are born smart. Revealing that you don’t necessarily have to be gifted to succeed in life, and with hard work and determination there is hope for us all – even underachievers.

Gladys Ngetich, Rhodes Scholar and Aerospace Engineering DPhil Student in the Department of Engineering, was recently named as one of the ‘UK Top 10 Rare Rising Stars’ of 2018.

Now in its tenth year, Rare Rising Stars is a celebration of the achievements of the UK's best black students. The judging panel included: Sophie Chandauka, Trevor Phillips OBE and Jean Tomlin OBE.

In addition to being recognised as a Rare Rising Star, Gladys’ time at Oxford has been memorable. Highlights include: registering a patent in collaboration with Rolls Royce Plc, being interviewed by BBC Science and also being awarded the ASME IGTI Young Engineer Turbo Expo Participation Award, which resulted in her presenting a paper at the annual American Society of Mechanical Engineers (ASME) conference.

However, despite her significant achievements, many would be surprised to know that Gladys has not always been so academically gifted. Born in Amalo, a small village in Kenya, she once performed so badly in the national Primary School exam (the Kenya Certificate of Primary Education - KCPE) that she struggled to find a High School (school age 14-18 years old) that would accept her.

She credits her mother as a key support in encouraging her to continue her education and follow her dream of becoming an Aerospace Engineer. It was this determination that motivated her to reverse the situation, and subsequently graduate from High School with the highest grades of any student in her district.

She then won a James Finlay Scholarship which enabled her to pursue her undergraduate degree (a BSc in Mechanical Engineering) at Kenya's top engineering university - Jomo Kenyatta University of Agriculture and Technology (JKUAT), graduating with distinction in 2015, winning several awards along the way and setting the scene for her hard-earned path to Oxford.

Of selecting Gladys as part of the Rare Rising Stars top 10, a Rare Recruitment spokesperson, said: ‘Rare Rising Stars like Gladys personify Rare's philosophy: that a person's ethnic or socio-economic background should not determine their future. It's important that elite universities like Oxford have recognised that too.’

Rare Recruitment also created and run Target Oxbridge, the programme that helps high-achieving black students gain places at top British universities, which recently announced plans to expand dramatically with support from Oxford University. A spokesperson for Rare Recruitment, said: ‘Having both Oxford and Cambridge's strong support for Rare's Target Oxbridge programme really demonstrates to young black school children across the country that the sky is the limit. Applications open for Target Oxbridge for talented black Year 12s this autumn - I hope that potential candidates can take inspiration from the achievements of our Rare Rising Stars.’

Gladys herself was overcome with emotion upon hearing the news that she had placed on the list, and explains: ‘I must confess that I have not recovered from mixed feelings of excitement and disbelief. I come from a very humble background and I have had to navigate a lot of challenges to get to where I am. Thus, this award means a lot to me. My hope is that it will inspire students with humble backgrounds like mine’.

A heartfelt Facebook post written after she received the award, that outlines her journey so far and includes words of encouragement to others like her, has received over 2000 comments, 8000 likes and almost 2000 shares, to date.

Gladys’ commitment to inspiring others, particularly young women like her, runs throughout everything she does. In April 2018, she was awarded the Skoll World Forum Fellowship as a budding inspirational social entrepreneur, and she is co-founder and CEO of the ILUU Organisationin Nairobi which mentors and inspires girls from rural parts of Kenya. She has also been shortlisted for the McKinsey & Company Next Generation Women Leaders Award.

Intent on encouraging the next generation of female engineers, Gladys served on the EngineerGirl Markers Panel and she is currently working with the Beyond Boundaries Project and IF Oxford Science Festival to organise exciting initiatives aimed at raising the profile of black women in engineering.

Her advice to others that aspire to reach and even exceed their potential is simple: ‘keep going, keep stretching beyond your comfort zone, and keep dreaming because no one knows what the future holds.’

The Cut Out Girl by Oxford English professor Bart van Es has been named Costa Book of the Year, after previously winning the biography category of the awards. Professor van Es triumphed ahead of literary figures including novelist Sally Rooney. Read our Q&A below with Professor van Es, whose book tells the story of Lien de Jong, a young Dutch girl hidden from the Nazis during World War II.

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The last time Lien de Jong saw her parents was in the Hague, where she was collected at the door by a stranger and taken away to be hidden from the Nazis. She was raised by her foster family as one of their own, but a falling out after the war put an end to their relationship. What was her side of the story, wondered Oxford University's Professor Bart van Es, a grandson of the couple who looked after Lien.

Professor van Es, of St Catherine's College and Oxford's English Faculty, talks to Arts Blog about the journey that led to the publication of his new book, The Cut Out Girl: A Story of War and Family, Lost and Found.

How did you discover the story of Lien de Jong?

I had always known that my grandparents had been part of the Dutch wartime resistance and had sheltered Jewish children, but I had never looked into what actually happened. Then in November 2014 my eldest uncle died and I knew that if I did not pursue the matter now this history would be lost forever. Thanks to my mother’s maintaining of an old connection, I got to meet Lien, who was by that time over 80 and living in Amsterdam. As a young Jewish girl Lien had lived in hiding with my grandparents and after the war she had continued to live with them. However, a row in the 1980s had cut her off from the family, which meant that she and I had never met. Lien was cautious when we met in late December 2014, but, once trust was established, we struck up a powerful partnership. Lien agreed to work with me and shared a wealth of materials: letters, photographs, official documents, and also a poetry book that she kept up throughout the war. Through many tens of hours of recorded interviews, Lien shared a story that was immensely moving and far more complex than I could have imagined.

Can you describe the process of researching and writing the book?

Starting out from those interviews with Lien, this became an archival research project as well as a literary journey. In January 2015 I decided to visit the places of Lien’s childhood: her parents’ home in The Hague (now a physiotherapy gym), my grandparents' old address in Dordrecht (now in a deprived area inhabited mainly by recent immigrants), and a series of other hiding addresses across the Netherlands, including my mother’s home village, where Lien spent time. These places brought their own stories, which I then began to investigate. Among other things I spent a lot of time at the Dutch National Archives looking at the prosecution material on 230 Dutch police officers who were investigated after the war for their role in the Holocaust. What I ended up with was a huge amount of material: the intimate narrative of Lien’s life from childhood to old age combined with archival evidence on resistance networks, police collaboration, and the wider history of Jews in the Netherlands. The challenge was to put this into a single book.

How easy was it to combine academic research with such a personal story?

It was challenging to combine the two kinds of material I had to hand, and I had some sleepless nights over what I was doing. After various experiments I opted for a double narrative with one strand in the first person (describing my travels and the documentary evidence I encountered) and a second strand that was much more novelistic (written in the third person, voicing the childhood experiences of Lien). I’d never written in such an emotionally intense way before. It was exciting and all-consuming. At the same time it was important to remain academically objective: there could be no factual errors about what happened in the war and afterwards, both because of its historical importance and because there were real, still-living people involved.

Are there any moments from your conversations with Lien that particularly stand out?

The things that stand out for me are the documents that Lien has kept with her. For example, there is the letter that Lien’s mother wrote to my grandparents in August 1942, in which she gave up her child in the hope that Lien would survive the war even if the rest of the family could not. There is also the last letter that Lien ever wrote to her mother, which was not delivered because her parents were already in Auschwitz by the time it would have been sent via the secret post. Also very powerful are the wider stories of resistance activity that came to me in the course of my research. In one case a group of young Dutch women decided that the only way in which they could save Jewish babies would be to claim them as their own illegitimate children, fathered by German soldiers. This brought absolute safety to the babies, but also, of course, terrible shame to the women themselves.

In the book I try to answer some big questions, including:

• Why was the Netherlands so compliant with the Nazis, so that 80% of the country’s Jews were killed, a far higher percentage than elsewhere in the West?
• What was it that made some brave people (such as my grandparents) resist the Nazis?
• What were the psychological consequences for survivors and rescuers?
• And, most pressingly as far as The Cut Out Girl story is concerned, how could my grandmother (who rescued Lien and brought her up as her own daughter after the war) have ended up quarrelling with the person she saved from the Holocaust? How could she have sent her a letter, in July 1988, that cut Lien out of her life?

Answering those questions will, I hope, give a new perspective on what happened in World War II.

The Cut Out Girl by Bart van Es is published by Fig Tree, 2 August, priced £16.99.