Features

Technology that turns low-cost mobile phones into sophisticated stethoscopes could save thousands of lives in poor countries.

The kit, developed by Oxford University and South African researchers, enables people to record and analyse their own heart sounds using a mobile phone microphone. Patients then send the recordings to medics who can remotely monitor their condition.

The idea came from a conversation between Dr Thomas Brennan of Oxford University’s Department of Engineering Science and Professor Bongani Mayosi of the University of Cape Town about how to reduce the numbers of people dying of tuberculous pericarditis: a condition affecting up to 1-2% of TB patients where the lining of the heart becomes infected. 

‘About 40% of people die post-diagnosis, largely because the onset of symptoms is insidious and they can't get into the clinic before it's too late and they die of cardiac arrest,’ Thomas tells me.

‘We discussed various ideas of being able to remotely monitor their heart in a low-cost way to pick up early signs of deterioration. The idea of using the phone's microphone as a stethoscope to analyse and record heart sounds came after seeing the iPhone app iStethoscope, and I wondered if we could do something similar using low-cost phones.’

As half of all Africans own a mobile phone the number of patients who could potentially benefit was enormous.

Thomas teamed up with Dr Gari Clifford of Oxford’s Institute for Biomedical Engineering (IBME) who had worked with Katherine Kuan, a student at MIT, on listening technology for smart phones. They extended that work to enable low-cost phones to effectively capture and analyse the resultant phonocardiogram (PCG) recordings to assess the feasibility of the project.

‘The original idea was that a person could use their own phone to record their heart sounds,’ Thomas explains ‘and that any phone would be able to make an adequate heart sound recording at little or no cost using readily available objects, from which heart rate and abnormal heart sounds could be detected.’

Before they could create a device a number of technical challenges had to be overcome: low-cost phones are designed for voice so they had to deal with distortion introduced by the phone, signal processing techniques were needed to identify a poor recording and ask the user to try again, and algorithms had to be developed that could reliably identify heart rate and heart sounds.

‘The biggest challenge was in assessing the feasibility of the device,’ Thomas comments. In partnership with Professor Mayosi and Dr Jens Hitzeroth, the team conducted a clinical trial, in which Professor Mayosi was principal investigator and Drs Hitzeroth and Brennan were co-investigators, between January and April at the Department of Cardiology at Groote Schuur Hospital in Cape Town to compare two mobiles - a Nokia 3110 Classic and an iPhone 3G - with the £400 3M Littmann Electronic Stethoscope.

They collected phonocardiograms from 150 volunteers with a range of cardiac conditions using the Littmann, the iPhone, and the Nokia 3100 Classic. The trial showed that the Nokia actually out-performed the Littmann in estimating heart rate, although it had to discard more low signal quality recordings.

After these promising results the team are pressing ahead with the next stage of the project:

‘Alongside a MSc student, David Springer - who worked with me in developing the algorithms - we're developing an Android application to record and process the heart sounds recordings,’ Thomas tells me.

‘The next step is to expand the scope of the device to see if it can be used as a screening tool for patients with heart disease, particularly rheumatic heart disease, which has a particularly high prevalence in southern Africa.’

The genomes of 18 different and varied strains of the thale cress, Arabidopsis thaliana, have been sequenced by an international group lead by Oxford University scientists.

Arabidopsis is standard in plant genetics labs in the same way that other scientists might study E. coli, yeast and fruit flies as models from which they can draw general lessons about the way genes and biological pathways work. And the genome of the thale cress was decoded in 2000 to act as a reference for studies in plant genetics.

Oxford Science Blog asked lead researcher Professor Richard Mott of the Wellcome Trust Centre for Human Genetics about the current study providing 18 new genomes, and what it offers the field.

The research is published in Nature and also included Oxford scientists from the departments of Plant Sciences and Statistics.

Oxford Science Blog: Why is Arabidopsis so important in understanding plant genetics?
Richard Mott: Arabidopsis has become the standard model for much of plant genetics research.

It is small and grows quickly, it has an accurately sequenced reference genome that is relatively compact and there is a wealth of molecular tools with which to probe gene function.

Arabidopsis is a brassica – that is, a member of the cabbage family. But most of its genes are similar to those found in other plants, including important crops. It is generally much easier to figure out the functions of genes in Arabidopsis and apply this knowledge to other species.

OSB: I thought its genome had been sequenced already. What does this new study add?
RM: Arabidopsis is a highly variable species, at both the genetic and phenotypic [observable characteristic] level.

Several recent studies have begun to catalogue this genetic variation. Our study differs in that rather than interpret this variability in relation to the reference genome sequence (called Col-0), we have assembled 18 Arabidopsis genomes very accurately, so that we could determine the gene content of each.

What we found was quite surprising. If we had simply lifted over the genes annotated in the reference Col-0 onto each genome, then we would have predicted that about a third of the genes were severely altered (or even non-functional) in at least one of the 18 genomes.

But because we also collected gene expression data (essentially the sequences of the protein-coding genes), we could see that in many cases the gene structures changed in a way that mitigated these effects.

This means that we need to move from a view of Arabidopsis where we interpret the effects of variation relative to the reference, to one where each genome is treated on an equal footing. It will be interesting to see if this also applies to other species.

OSB: What has been learned about the genetic variation between different strains of this species?
RM: Along with several other recent studies, we found there is a lot of variation in this 119 Mb genome, not only single-letter changes in the DNA code (about 3 million) but also many insertions and deletions (over 1 million).

We also found about 100,000 ‘imbalanced substitutions’, where a stretch of reference genome was replaced with an entirely difference sequence of a different length. Only about 7% of genes were completely conserved between the genomes.

OSB: What does this tell us?
RM: One important reason for studying these particular 18 genomes is that they are the progenitors of a much larger population of over 700 inbred lines, called ‘MAGIC’. (MAGIC stands for Multi-parental Advanced Generation InterCross).

The MAGIC lines are being used in a number of labs around the world to study a wide range of phenotypes, such as growth and disease resistance.

Each MAGIC genome is a mosaic of the genomes we sequenced, so by stitching together these genomes in the right way, we can predict the genome sequences of a much larger population. In effect we have sequenced the genomes of all these lines for the price of sequencing 18.

OSB: Are the findings relevant for other plants?
RM: Arabidopsis is primarily used to understand fundamental mechanisms in plants. This includes the response to the environment. For example, the most variable genes in our study are those whose function relates to response to the biotic environment – disease-resistance genes and so on. This is going to be relevant to studies on disease resistance in the MAGIC lines.

It is expected that lessons learned in Arabidopsis will translate to crops. In fact, there similar populations of MAGIC lines being made in crops such as wheat. But the wheat genome is about 80 times larger than the Arabidopsis genome and much harder to assemble, so the work we have done here may inform studies in these other populations.

Marine algae that turn carbon dissolved in seawater into shell will produce thinner and thinner shells as carbon dioxide levels increase.

The algae, called coccolithophores, have floated in our oceans for over 200 million years Hoovering up carbon and turning it into coccoliths - overlapping plates of calcium carbonate.

Predicting how these algae, an important part of the carbon cycle, will react to rising CO2 levels has always been a puzzle. Now a team including Ros Rickaby from Oxford University’s Department of Earth Sciences, has found strong evidence that as CO2 concentration in seawater increases so calcification decreases and coccolith mass declines.

The findings, reported in a recent Nature paper, suggest that entire communities of marine organisms, such as coral, are threatened by rising CO2 and ocean acidification.

The new evidence comes from studies of half a million coccoliths from hundreds of seawater samples and ancient marine sediments cores taken from all over the world.

The research shows much greater variations in coccolith mass than previous lab-based studies, as, in the ocean, rising CO2 causes populations of algae to favour smaller, lightly calcified species over heavily calcified ones.

Further work is now needed to understand how the algae will respond to the changing marine environment and what impact a rise in thinner-shelled species will have on our oceans and the planet.

In reproductive warfare sperm is a male’s ultimate weapon to decide who fathers the next generation.

But a new Oxford University study involving feral chickens has revealed that females fight back: hens are able to eject sperm directly following copulation and, when they do, on average 80% of the ejaculate is expelled.

‘Sperm ejection can be an effective way for females to bias a male’s chance of successful fertilization,’ Rebecca Dean, of Oxford University Department of Zoology explains. This female counter-measure has also been found in worms, insects, and even primates.

The experiments, which involved analysing the physical characteristics of different cockerels, enabling them to mate with hens, and then collecting the sperm hens eject, tell a complex tale, the researchers report in this month’s American Naturalist.

Whilst large ejaculates suffered a higher risk of ejection, a larger proportion of smaller ejaculates were ‘dumped’ leaving less sperm to fertilise an egg. ‘Sperm ejection imposes on males an evolutionary dilemma,’ Rebecca tells me.

‘This trade-off between ejection risk and amount of sperm ejected could generate opposing selection on the evolution of sperm allocation strategies in males.’

Yet when it comes to having their sperm dumped females don’t treat all males equally: hens were found to be more likely to eject sperm after successive matings, favouring their first partners to the detriment of later ones. They also ejected a larger proportion of the sperm of socially subordinate males, giving more dominant males an advantage.

The results show that promiscuous females can have a strong and predictable influence on the battle between sperm from rival partners. So, even in animals such as chickens - where males can force females to mate - females can nevertheless retain control over the paternity of their offspring. 

Take a step back from the messy everyday world and you find intriguing patterns and structures in everything from shells to drips of paint.

In his new three-part series The Code, which starts on BBC Two tonight at 9pm, Oxford University's Marcus du Sautoy explores the mathematical stories behind these patterns and how they influence every aspect of our lives.

I asked Marcus about the making of the series and how he set out to bring mathematical ideas to the small screen...

Oxford Science Blog: What was the inspiration for the series?
Marcus du Sautoy: The series grew out of the success of The Story of Maths, my four part series on the history of maths, for BBC4 and the two Horizons I did on maths with comedian Alan Davies on BBC2.

Natural history or astronomy are subjects that translate easily to the screen but the abstract world of mathematics is a much tougher challenge. I think the programmes I have made to date gave the BBC courage that we really can do a major series for BBC2 on mathematics.

OSB: What mathematical ideas did you most enjoy bringing to TV?
MdS: It was fun to meet some of my mathematical heroes. For example meeting the cicadas that use prime numbers for their evolutionary survival was exciting.

The Nautilus shell is one of the iconic images of the mathematical world but I'd never actually come face to face with the strange creature that lives inside the shell. It was also exciting to visit Pixar studios and to discover how many mathematicians they employ to create the fractal landscapes in their films. The company was founded by a guy who read Mandelbrot's book on fractals and realised they were the key to modern animation.

OSB: How are online and social media getting viewers involved?
MdS: TV has been trying to crack how to make the experience of watching telly interactive. With this new series I think we've come up with a unique concept to engage viewers in the ideas of the programme. We are running a mathematical treasure hunt in parallel with the series which challenges viewers to crack puzzles, look for clues in the programmes and play addictive online games.

We wanted to create a Code Community who are working together to crack the Challenge so twitter and Facebook are powerful tools for bringing together people who are watching the series. We have a community challenge to collect photos of all the primes from 2 to 2011 which has really galvanised the community.

OSB: What are your favourite moments from filming the series?
MdS: Filming in Jackson Pollock's studio was fascinating. You can still see all the paint splattered around the studio. We made our own Pollock using a chaotic pendulum. I'm hoping to sell it on eBay for a few million. It can help fund the new maths department for Oxford.

OSB: What do you hope viewers will take away from it?
MdS: I want viewers to see the world they live in through the eyes of a mathematician. To realise how much pattern and structure can be found in our messy chaotic world if you translate it into the code of mathematics. And also to see mathematics in a new light as a subject full of great stories with huge influence on our modern world.

Marcus du Sautoy is Professor of Mathematics and Simonyi Professor for the Public Understanding of Science at Oxford University.