Depression and Incident Cardiovascular Disease
JACC Asia. 2024 Apr 3;4(4):289-291. doi: 10.1016/j.jacasi.2024.02.003. eCollection 2024 Apr.
NO ABSTRACT
PMID:38660106 | PMC:PMC11035929 | DOI:10.1016/j.jacasi.2024.02.003
Study highlights increased risk of second cancers among breast cancer survivors
For the first time, the research has shown that this risk is higher in people living in areas of greater socioeconomic deprivation.
Breast cancer is the most commonly diagnosed cancer in the UK. Around 56,000 people in the UK are diagnosed each year, the vast majority (over 99%) of whom are women. Improvements in earlier diagnosis and in treatments mean that five year survival rates have been increasing over time, reaching 87% by 2017 in England.
People who survive breast cancer are at risk of second primary cancer, but until now the exact risk has been unclear. Previously published research suggested that women and men who survive breast cancer are at a 24% and 27% greater risk of a non-breast second primary cancer than the wider population respectively. There have been also suggestions that second primary cancer risks differ by the age at breast cancer diagnosis.
To provide more accurate estimates, a team led by researchers at the University of Cambridge analysed data from over 580,000 female and over 3,500 male breast cancer survivors diagnosed between 1995 and 2019 using the National Cancer Registration Dataset. The results of their analysis are published today in Lancet Regional Health – Europe.
First author Isaac Allen from the Department of Public Health and Primary Care at the University of Cambridge said: “It’s important for us to understand to what extent having one type of cancer puts you at risk of a second cancer at a different site. The female and male breast cancer survivors whose data we studied were at increased risk of a number of second cancers. Knowing this can help inform conversations with their care teams to look out for signs of potential new cancers.”
The researchers found significantly increased risks of cancer in the contralateral (that is, unaffected) breast and for endometrium and prostate cancer in females and males, respectively. Females who survived breast cancer were at double the risk of contralateral breast cancer compared to the general population and at 87% greater risk of endometrial cancer, 58% greater risk of myeloid leukaemia and 25% greater risk of ovarian cancer.
Age of diagnosis was important, too – females diagnosed with breast cancer under the age of 50 were 86% more likely to develop a second primary cancer compared to the general population of the same age, whereas women diagnosed after age 50 were at a 17% increased risk. One potential explanation is that a larger number of younger breast cancer survivors may have inherited genetic alterations that increase risk for multiple cancers. For example, women with inherited changes to the BRCA1 and BRCA2 genes are at increased risk of contralateral breast cancer, ovarian and pancreatic cancer.
Females from the most socioeconomically deprived backgrounds were at 35% greater risk of a second primary cancer compared to females from the least deprived backgrounds. These differences were primarily driven by non-breast cancer risks, particularly for lung, kidney, head and neck, bladder, oesophageal and stomach cancers. This may be because smoking, obesity, and alcohol consumption – established risk factors for these cancers – are more common among more deprived groups.
Allen, a PhD student at Clare Hall, added: “This is further evidence of the health inequalities that people from more deprived backgrounds experience. We need to fully understand why they are at greater risk of second cancers so that we can intervene and reduce this risk.”
Male breast cancer survivors were 55 times more likely than the general male population to develop contralateral breast cancer – though the researchers stress that an individual’s risk was still very low. For example, for every 100 men diagnosed with breast cancer at age 50 or over, about three developed contralateral breast cancer during a 25 year period. Male breast cancer survivors were also 58% more likely than the general male population to develop prostate cancer.
Professor Antonis Antoniou from the Department of Public Health and Primary Care at the University of Cambridge, the study’s senior author, said: “This is the largest study to date to look at the risk in breast cancer survivors of developing a second cancer. We were able to carry this out and calculate more accurate estimates because of the outstanding data sets available to researchers through the NHS.”
The research was funded by Cancer Research UK with support from the National Institute for Health and Care Research Cambridge Biomedical Research Centre.
Cancer Research UK’s senior cancer intelligence manager, Katrina Brown, said: “This study shows us that the risk of second primary cancers is higher in people who have had breast cancer, and this can differ depending on someone’s socioeconomic background. But more research is needed to understand what is driving this difference and how to tackle these health inequalities.”
People who are concerned about their cancer risk should contact their GP for advice. If you or someone close to you have been affected by cancer and you’ve got questions, you can call Cancer Research UK nurses on freephone 0808 800 4040, Monday to Friday.
Reference
Allen, I, et al. Risks of second primary cancers among 584,965 female and male breast cancer survivors in England: a 25-year retrospective cohort study. Lancet Regional Health – Europe; 24 April 2024: DOI: 10.1016/j.lanepe.2024.100903
Survivors of breast cancer are at significantly higher risk of developing second cancers, including endometrial and ovarian cancer for women and prostate cancer for men, according to new research studying data from almost 600,000 patients in England.
It’s important for us to understand to what extent having one type of cancer puts you at risk of a second cancer at a different site. Knowing this can help inform conversations with their care teams to look out for signs of potential new cancersIsaac AllenNational Cancer InstituteDoctor standing near woman patient doing breast cancer
The text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.
A simple ‘twist’ improves the engine of clean fuel generation
The researchers, led by the University of Cambridge, are developing low-cost light-harvesting semiconductors that power devices for converting water into clean hydrogen fuel, using just the power of the sun. These semiconducting materials, known as copper oxides, are cheap, abundant and non-toxic, but their performance does not come close to silicon, which dominates the semiconductor market.
However, the researchers found that by growing the copper oxide crystals in a specific orientation so that electric charges move through the crystals at a diagonal, the charges move much faster and further, greatly improving performance. Tests of a copper oxide light harvester, or photocathode, based on this fabrication technique showed a 70% improvement over existing state-of-the-art oxide photocathodes, while also showing greatly improved stability.
The researchers say their results, reported in the journal Nature, show how low-cost materials could be fine-tuned to power the transition away from fossil fuels and toward clean, sustainable fuels that can be stored and used with existing energy infrastructure.
Copper (I) oxide, or cuprous oxide, has been touted as a cheap potential replacement for silicon for years, since it is reasonably effective at capturing sunlight and converting it into electric charge. However, much of that charge tends to get lost, limiting the material’s performance.
“Like other oxide semiconductors, cuprous oxide has its intrinsic challenges,” said co-first author Dr Linfeng Pan from Cambridge’s Department of Chemical Engineering and Biotechnology. “One of those challenges is the mismatch between how deep light is absorbed and how far the charges travel within the material, so most of the oxide below the top layer of material is essentially dead space.”
“For most solar cell materials, it’s defects on the surface of the material that cause a reduction in performance, but with these oxide materials, it’s the other way round: the surface is largely fine, but something about the bulk leads to losses,” said Professor Sam Stranks, who led the research. “This means the way the crystals are grown is vital to their performance.”
To develop cuprous oxides to the point where they can be a credible contender to established photovoltaic materials, they need to be optimised so they can efficiently generate and move electric charges – made of an electron and a positively-charged electron ‘hole’ – when sunlight hits them.
One potential optimisation approach is single-crystal thin films – very thin slices of material with a highly-ordered crystal structure, which are often used in electronics. However, making these films is normally a complex and time-consuming process.
Using thin film deposition techniques, the researchers were able to grow high-quality cuprous oxide films at ambient pressure and room temperature. By precisely controlling growth and flow rates in the chamber, they were able to ‘shift’ the crystals into a particular orientation. Then, using high temporal resolution spectroscopic techniques, they were able to observe how the orientation of the crystals affected how efficiently electric charges moved through the material.
“These crystals are basically cubes, and we found that when the electrons move through the cube at a body diagonal, rather than along the face or edge of the cube, they move an order of magnitude further,” said Pan. “The further the electrons move, the better the performance.”
“Something about that diagonal direction in these materials is magic,” said Stranks. “We need to carry out further work to fully understand why and optimise it further, but it has so far resulted in a huge jump in performance.” Tests of a cuprous oxide photocathode made using this technique showed an increase in performance of more than 70% over existing state-of-the-art electrodeposited oxide photocathodes.
“In addition to the improved performance, we found that the orientation makes the films much more stable, but factors beyond the bulk properties may be at play,” said Pan.
The researchers say that much more research and development is still needed, but this and related families of materials could have a vital role in the energy transition.
“There’s still a long way to go, but we’re on an exciting trajectory,” said Stranks. “There’s a lot of interesting science to come from these materials, and it’s interesting for me to connect the physics of these materials with their growth, how they form, and ultimately how they perform.”
The research was a collaboration with École Polytechnique Fédérale de Lausanne, Nankai University and Uppsala University. The research was supported in part by the European Research Council, the Swiss National Science Foundation, and the Engineering and Physical Sciences Research Council (EPSRC), part of UK Research and Innovation (UKRI). Sam Stranks is Professor of Optoelectronics in the Department of Chemical Engineering and Biotechnology, and a Fellow of Clare College, Cambridge.
Reference:
Linfeng Pan, Linjie Dai et al. ‘High carrier mobility along the [111] orientation in Cu2O photoelectrodes.’ Nature (2024). DOI: 10.1038/s41586-024-07273-8
For more information on energy-related research in Cambridge, please visit the Energy IRC, which brings together Cambridge’s research knowledge and expertise, in collaboration with global partners, to create solutions for a sustainable and resilient energy landscape for generations to come.
Researchers have found a way to super-charge the ‘engine’ of sustainable fuel generation – by giving the materials a little twist.
orange via Getty ImagesAbstract orange swirls
The text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.
Molecular mechanism of complement inhibition by the trypanosome receptor ISG65
Elife. 2024 Apr 24;12:RP88960. doi: 10.7554/eLife.88960.
ABSTRACT
African trypanosomes replicate within infected mammals where they are exposed to the complement system. This system centres around complement C3, which is present in a soluble form in serum but becomes covalently deposited onto the surfaces of pathogens after proteolytic cleavage to C3b. Membrane-associated C3b triggers different complement-mediated effectors which promote pathogen clearance. To counter complement-mediated clearance, African trypanosomes have a cell surface receptor, ISG65, which binds to C3b and which decreases the rate of trypanosome clearance in an infection model. However, the mechanism by which ISG65 reduces C3b function has not been determined. We reveal through cryogenic electron microscopy that ISG65 has two distinct binding sites for C3b, only one of which is available in C3 and C3d. We show that ISG65 does not block the formation of C3b or the function of the C3 convertase which catalyses the surface deposition of C3b. However, we show that ISG65 forms a specific conjugate with C3b, perhaps acting as a decoy. ISG65 also occludes the binding sites for complement receptors 2 and 3, which may disrupt recruitment of immune cells, including B cells, phagocytes, and granulocytes. This suggests that ISG65 protects trypanosomes by combining multiple approaches to dampen the complement cascade.
PMID:38655765 | DOI:10.7554/eLife.88960
HSV-1 employs UL56 to antagonize expression and function of cGAMP channels
Cell Rep. 2024 Apr 22;43(5):114122. doi: 10.1016/j.celrep.2024.114122. Online ahead of print.
ABSTRACT
DNA sensing is important for antiviral immunity. The DNA sensor cGAS synthesizes 2'3'-cyclic GMP-AMP (cGAMP), a second messenger that activates STING, which induces innate immunity. cGAMP not only activates STING in the cell where it is produced but cGAMP also transfers to other cells. Transporters, channels, and pores (including SLC19A1, SLC46A2, P2X7, ABCC1, and volume-regulated anion channels (VRACs)) release cGAMP into the extracellular space and/or import cGAMP. We report that infection with multiple human viruses depletes some of these cGAMP conduits. This includes herpes simplex virus 1 (HSV-1) that targets SLC46A2, P2X7, and the VRAC subunits LRRC8A and LRRC8C for degradation. The HSV-1 protein UL56 is necessary and sufficient for these effects that are mediated at least partially by proteasomal turnover. UL56 thereby inhibits cGAMP uptake via VRAC, SLC46A2, and P2X7. Taken together, HSV-1 antagonizes intercellular cGAMP transfer. We propose that this limits innate immunity by reducing cell-to-cell communication via the immunotransmitter cGAMP.
PMID:38652659 | DOI:10.1016/j.celrep.2024.114122
Rare disease research at Cambridge receives major boost with launch of two new centres
The virtual centres, supported by the charity LifeArc, will focus on areas where there are significant unmet needs. They will tackle barriers that ordinarily prevent new tests and treatments reaching patients with rare diseases and speed up the delivery of rare disease treatment trials.
The centres will bring together leading scientists and rare disease clinical specialists from across the UK for the first time, encouraging new collaborations across different research disciplines and providing improved access to facilities and training.
LifeArc Centre for Rare Mitochondrial DiseasesProfessor Patrick Chinnery will lead the LifeArc Centre for Rare Mitochondrial Diseases, a national partnership with the Lily Foundation and Muscular Dystrophy UK, together with key partners at UCL, Newcastle University and three other centres (Oxford, Birmingham and Manchester).
Mitochondrial diseases are genetic disorders affecting 1 in 5,000 people. They often cause progressive damage to the brain, eyes, muscles, heart and liver, leading to severe disability and a shorter life. There is currently have no cure for most conditions, however, new opportunities to treat mitochondrial diseases have been identified in the last five years, meaning that it’s a critical time for research development. The £7.5M centre will establish a national platform that will connect patient groups, knowledge and infrastructure in order to accelerate new treatments getting to clinical trial.
Professor Chinnery said: “The new LifeArc centre unites scientific and clinical strengths from across the UK. For the first time we will form a single team, focussed on developing new treatments for mitochondrial diseases which currently have no cure.”
Adam Harraway has Mitochondrial Disease and says he lives in constant fear of what might go wrong next with his condition. “With rare diseases such as these, it can feel like the questions always outweigh the answers. The news of this investment from LifeArc fills me with hope for the future. To know that there are so many wonderful people and organisations working towards treatments and cures makes me feel seen and heard. It gives a voice to people who often have to suffer in silence, and I'm excited to see how this project can help Mito patients in the future."
LifeArc Centre for Rare Respiratory DiseasesProfessor Stefan Marciniak will co-lead the LifeArc Centre for Rare Respiratory Diseases, a UK wide collaborative centre co-created in partnership with patients and charities. This Centre is a partnership between Universities and NHS Trusts across the UK, co-led by Edinburgh with Nottingham, Dundee, Cambridge, Southampton, University College London and supported by six other centres (Belfast, Cardiff, Leeds, Leicester, Manchester and Royal Brompton).
For the first time ever, it will provide a single ‘go to’ centre that will connect children and adults with rare respiratory disease with clinical experts, researchers, investors and industry leaders across the UK. The £9.4M centre will create a UK-wide biobank of patient samples and models of disease that will allow researchers to advance pioneering therapies and engage with industry and regulatory partners to develop innovative human clinical studies.
Professor Marciniak said: “There are many rare lung diseases, and together those affected constitute a larger underserved group of patients. The National Translational Centre for Rare Respiratory Diseases brings together expertise from across the UK to find effective treatments and train the next generation of rare disease researchers.”
Former BBC News journalist and presenter, Philippa Thomas, has the rare incurable lung disease, Lymphangioleiomyomatosis (LAM). Her condition has stabilised but for many people, the disease can be severely life-limiting. Philippa said: “There is so little research funding for rare respiratory diseases, that getting treatment - let alone an accurate diagnosis - really does feel like a lottery. It is also terrifying being diagnosed with something your GP will never have heard of.”
Globally, there are more than 300 million people living with rare diseases. However, rare disease research can be fragmented. Researchers can lack access to specialist facilities, as well as advice on regulation, trial designs, preclinical regulatory requirements, and translational project management, which are vital in getting new innovations to patients.
Dr Catriona Crombie, Head of Rare Disease at LifeArc, says: “We’re extremely proud to be launching four new LifeArc Translational Centres for Rare Diseases. Each centre has been awarded funding because it holds real promise for delivering change for people living with rare diseases. These centres also have the potential to create a blueprint for accelerating improvements across other disease areas, including common diseases.”
Adapted from a press release from LifeArc
Cambridge researchers will play key roles in two new centres dedicated to developing improved tests, treatments and potentially cures for thousands of people living with rare medical conditions.
The new LifeArc centre unites scientific and clinical strengths from across the UKPatrick ChinneryAlexander_Safonov (Getty)Woman inhaling from a mask nebulizer
The text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.
The IRE1α-XBP1 arm of the unfolded protein response is a host factor activated in SARS-CoV-2 infection
Biochim Biophys Acta Mol Basis Dis. 2024 Apr 20:167193. doi: 10.1016/j.bbadis.2024.167193. Online ahead of print.
ABSTRACT
SARS-CoV-2 infection can cause severe pneumonia, wherein exacerbated inflammation plays a major role. This is reminiscent of the process commonly termed cytokine storm, a condition dependent on a disproportionated production of cytokines. This state involves the activation of the innate immune response by viral patterns and coincides with the biosynthesis of the biomass required for viral replication, which may overwhelm the capacity of the endoplasmic reticulum and drive the unfolded protein response (UPR). The UPR is a signal transduction pathway composed of three branches that is initiated by a set of sensors: inositol-requiring protein 1 (IRE1), protein kinase RNA-like ER kinase (PERK), and activating transcription factor 6 (ATF6). These sensors control adaptive processes, including the transcriptional regulation of proinflammatory cytokines. Based on this background, the role of the UPR in SARS-CoV-2 replication and the ensuing inflammatory response was investigated using in vivo and in vitro models of infection. Mice and Syrian hamsters infected with SARS-CoV-2 showed a sole activation of the Ire1α-Xbp1 arm of the UPR associated with a robust production of proinflammatory cytokines. Human lung epithelial cells showed the dependence of viral replication on the expression of UPR-target proteins branching on the IRE1α-XBP1 arm and to a lower extent on the PERK route. Likewise, activation of the IRE1α-XBP1 branch by Spike (S) proteins from different variants of concern was a uniform finding. These results show that the IRE1α-XBP1 system enhances viral replication and cytokine expression and may represent a potential therapeutic target in SARS-CoV-2 severe pneumonia.
PMID:38648902 | DOI:10.1016/j.bbadis.2024.167193
Recognition of nonself is necessary to activate Drosophila's immune response against an insect parasite
BMC Biol. 2024 Apr 22;22(1):89. doi: 10.1186/s12915-024-01886-1.
ABSTRACT
BACKGROUND: Innate immune responses can be activated by pathogen-associated molecular patterns (PAMPs), danger signals released by damaged tissues, or the absence of self-molecules that inhibit immunity. As PAMPs are typically conserved across broad groups of pathogens but absent from the host, it is unclear whether they allow hosts to recognize parasites that are phylogenetically similar to themselves, such as parasitoid wasps infecting insects.
RESULTS: Parasitoids must penetrate the cuticle of Drosophila larvae to inject their eggs. In line with previous results, we found that the danger signal of wounding triggers the differentiation of specialized immune cells called lamellocytes. However, using oil droplets to mimic infection by a parasitoid wasp egg, we found that this does not activate the melanization response. This aspect of the immune response also requires exposure to parasite molecules. The unidentified factor enhances the transcriptional response in hemocytes and induces a specific response in the fat body.
CONCLUSIONS: We conclude that a combination of danger signals and the recognition of nonself molecules is required to activate Drosophila's immune response against parasitic insects.
PMID:38644510 | PMC:PMC11034056 | DOI:10.1186/s12915-024-01886-1
Risks of releasing imperfect Wolbachia strains for arbovirus control
Lancet Microbe. 2024 Apr 17:S2666-5247(24)00072-7. doi: 10.1016/S2666-5247(24)00072-7. Online ahead of print.
NO ABSTRACT
PMID:38642566 | DOI:10.1016/S2666-5247(24)00072-7
Wed 15 May 13:00: Bradford Hill seminar - Is perfection the enemy of good? Challenges and opportunities for building the evidence-base to inform sexual and reproductive health policy and practice
All are welcome to our next hybrid Bradford Hill Seminar by Prof Cath Mercer of the UCL Institute for Global Health, who will discuss:
‘Is perfection the enemy of good? Challenges and opportunities for building the evidence-base to inform sexual and reproductive health policy and practice’.
This will be a hybrid event
No registration required to attend in person at:
Large Seminar Room, East Forvie Building, Forvie Site, Robinson Way, Cambridge CB2 0SRT .
Registration required to attend online
Please register in Teams in advance at https://rb.gy/4svy5i
About this talk
Poor sexual and reproductive health causes significant morbidity. Last year, nearly 400,000 new sexually transmitted infections were diagnosed in England alone. Additionally, there is increasing awareness of sexual rights, the role of sexual pleasure and wellbeing, and what these mean for a satisfying sex life and our general health and wellbeing.
Yet this critical aspect of our lives is highly sensitive and sometimes stigmatised making sexual behaviour, its drivers and consequences difficult to research. Methods are required that maximise response and minimise bias so that the resulting evidence is of sufficient quality, including for informing policy and practice.
Such methodological rigour is neither cheap nor quick, and since the COVID -19 pandemic shifted expectations around both the timelines for acquiring evidence and the public’s willingness to participate in research, do we need to re-think how we do research in challenging fields such as sexual and reproductive health? Do we need to revise in our definition of what is ‘good enough’?
About Professor Cath Mercer
Cath Mercer is Professor of Sexual Health Science at University College London. A statistician and demographer by training, Cath is internationally recognised as an expert in developing and employing robust methods that advance the scientific study of sexual behaviour, one of the most socially-sensitive disciplines, leading studies that work for – and with – marginalised communities through to the general population, in a variety of settings, employing a range of study designs and research methods.
- Speaker: Professor Cath Mercer, UCL Institute for Global Health
- Wednesday 15 May 2024, 13:00-14:00
- Venue: Large Seminar Room, East Forvie Building, Forvie Site Robinson Way Cambridge CB2 0SR..
- Series: Bradford Hill Seminars; organiser: Paul Browne.
Wed 15 May 13:00: Bradford Hill seminar - Is perfection the enemy of good? Challenges and opportunities for building the evidence-base to inform sexual and reproductive health policy and practice
All are welcome to our next hybrid Bradford Hill Seminar by Prof Cath Mercer of the UCL Institute for Global Health, who will discuss:
‘Is perfection the enemy of good? Challenges and opportunities for building the evidence-base to inform sexual and reproductive health policy and practice’.
This will be a hybrid event
No registration required to attend in person at:
Large Seminar Room, East Forvie Building, Forvie Site, Robinson Way, Cambridge CB2 0SRT .
Registration required to attend online
Please register in Teams in advance at https://rb.gy/4svy5i
About this talk
Poor sexual and reproductive health causes significant morbidity. Last year, nearly 400,000 new sexually transmitted infections were diagnosed in England alone. Additionally, there is increasing awareness of sexual rights, the role of sexual pleasure and wellbeing, and what these mean for a satisfying sex life and our general health and wellbeing.
Yet this critical aspect of our lives is highly sensitive and sometimes stigmatised making sexual behaviour, its drivers and consequences difficult to research. Methods are required that maximise response and minimise bias so that the resulting evidence is of sufficient quality, including for informing policy and practice.
Such methodological rigour is neither cheap nor quick, and since the COVID -19 pandemic shifted expectations around both the timelines for acquiring evidence and the public’s willingness to participate in research, do we need to re-think how we do research in challenging fields such as sexual and reproductive health? Do we need to revise in our definition of what is ‘good enough’?
About Professor Cath Mercer
Cath Mercer is Professor of Sexual Health Science at University College London. A statistician and demographer by training, Cath is internationally recognised as an expert in developing and employing robust methods that advance the scientific study of sexual behaviour, one of the most socially-sensitive disciplines, leading studies that work for – and with – marginalised communities through to the general population, in a variety of settings, employing a range of study designs and research methods.
- Speaker: Professor Cath Mercer, UCL Institute for Global Health
- Wednesday 15 May 2024, 13:00-14:00
- Venue: Large Seminar Room, East Forvie Building, Forvie Site Robinson Way Cambridge CB2 0SR..
- Series: Bradford Hill Seminars; organiser: Paul Browne.
Wed 15 May 13:00: Bradford Hill seminar - Is perfection the enemy of good? Challenges and opportunities for building the evidence-base to inform sexual and reproductive health policy and practice
All are welcome to our next hybrid Bradford Hill Seminar by Prof Cath Mercer of the UCL Institute for Global Health, who will discuss:
‘Is perfection the enemy of good? Challenges and opportunities for building the evidence-base to inform sexual and reproductive health policy and practice’.
This will be a hybrid event
No registration required to attend in person at:
Large Seminar Room, East Forvie Building, Forvie Site, Robinson Way, Cambridge CB2 0SRT .
Registration required to attend online
Please register in advance at https://teams.microsoft.com/registration/W-89URffB0G1Uj26AJ5ZkA,4gqNqQyPO0ORfyzDfqnrLQ,NG69L_hHNkePrbS1cdRxLA,_0aT3zeTQEa1NGghd-e_mw,nYZuQfjZLEW7X-eoyDoKsw,3BREDUKldEemm90D0KOMUQ
About this talk
Poor sexual and reproductive health causes significant morbidity. Last year, nearly 400,000 new sexually transmitted infections were diagnosed in England alone. Additionally, there is increasing awareness of sexual rights, the role of sexual pleasure and wellbeing, and what these mean for a satisfying sex life and our general health and wellbeing.
Yet this critical aspect of our lives is highly sensitive and sometimes stigmatised making sexual behaviour, its drivers and consequences difficult to research. Methods are required that maximise response and minimise bias so that the resulting evidence is of sufficient quality, including for informing policy and practice.
Such methodological rigour is neither cheap nor quick, and since the COVID -19 pandemic shifted expectations around both the timelines for acquiring evidence and the public’s willingness to participate in research, do we need to re-think how we do research in challenging fields such as sexual and reproductive health? Do we need to revise in our definition of what is ‘good enough’?
About Professor Cath Mercer
Cath Mercer is Professor of Sexual Health Science at University College London. A statistician and demographer by training, Cath is internationally recognised as an expert in developing and employing robust methods that advance the scientific study of sexual behaviour, one of the most socially-sensitive disciplines, leading studies that work for – and with – marginalised communities through to the general population, in a variety of settings, employing a range of study designs and research methods.
- Speaker: Professor Cath Mercer, UCL Institute for Global Health
- Wednesday 15 May 2024, 13:00-14:00
- Venue: Large Seminar Room, East Forvie Building, Forvie Site Robinson Way Cambridge CB2 0SR..
- Series: Bradford Hill Seminars; organiser: Paul Browne.
Wed 15 May 13:00: Bradford Hill seminar - Is perfection the enemy of good? Challenges and opportunities for building the evidence-base to inform sexual and reproductive health policy and practice
All are welcome to our next hybrid Bradford Hill Seminar by Prof Cath Mercer of the UCL Institute for Global Health, who will discuss:
‘Is perfection the enemy of good? Challenges and opportunities for building the evidence-base to inform sexual and reproductive health policy and practice’.
This will be a hybrid event
No registration required to attend in person at:
Large Seminar Room, East Forvie Building, Forvie Site, Robinson Way, Cambridge CB2 0SRT .
Registration required to attend online
Please register in advance at https://teams.microsoft.com/registration/W-89URffB0G1Uj26AJ5ZkA,4gqNqQyPO0ORfyzDfqnrLQ,NG69L_hHNkePrbS1cdRxLA,_0aT3zeTQEa1NGghd-e_mw,nYZuQfjZLEW7X-eoyDoKsw,3BREDUKldEemm90D0KOMUQ
About this talk
Poor sexual and reproductive health causes significant morbidity. Last year, nearly 400,000 new sexually transmitted infections were diagnosed in England alone. Additionally, there is increasing awareness of sexual rights, the role of sexual pleasure and wellbeing, and what these mean for a satisfying sex life and our general health and wellbeing.
Yet this critical aspect of our lives is highly sensitive and sometimes stigmatised making sexual behaviour, its drivers and consequences difficult to research. Methods are required that maximise response and minimise bias so that the resulting evidence is of sufficient quality, including for informing policy and practice.
Such methodological rigour is neither cheap nor quick, and since the COVID -19 pandemic shifted expectations around both the timelines for acquiring evidence and the public’s willingness to participate in research, do we need to re-think how we do research in challenging fields such as sexual and reproductive health? Do we need to revise in our definition of what is ‘good enough’?
About Professor Cath Mercer
Cath Mercer is Professor of Sexual Health Science at University College London. A statistician and demographer by training, Cath is internationally recognised as an expert in developing and employing robust methods that advance the scientific study of sexual behaviour, one of the most socially-sensitive disciplines, leading studies that work for – and with – marginalised communities through to the general population, in a variety of settings, employing a range of study designs and research methods.
- Speaker: Professor Cath Mercer, UCL Institute for Global Health
- Wednesday 15 May 2024, 13:00-14:00
- Venue: Large Seminar Room, East Forvie Building, Forvie Site Robinson Way Cambridge CB2 0SR..
- Series: Bradford Hill Seminars; organiser: Paul Browne.
Training AI models to answer ‘what if?’ questions could improve medical treatments
Artificial intelligence techniques can be helpful for multiple medical applications, such as radiology or oncology, where the ability to recognise patterns in large volumes of data is vital. For these types of applications, the AI compares information against learned examples, draws conclusions, and makes extrapolations.
Now, an international team led by researchers from Ludwig-Maximilians-Universität München (LMU) and including researchers from the University of Cambridge, is exploring the potential of a comparatively new branch of AI for diagnostics and therapy.
The researchers found that causal machine learning (ML) can estimate treatment outcomes – and do so better than the machine learning methods generally used to date. Causal machine learning makes it easier for clinicians to personalise treatment strategies, which individually improves the health of patients.
The results, reported in the journal Nature Medicine, suggest how causal machine learning could improve the effectiveness and safety of a variety of medical treatments.
Classical machine learning recognises patterns and discovers correlations. However, the principle of cause and effect remains closed to machines as a rule; they cannot address the question of why. When making therapy decisions for a patient, the ‘why’ is vital to achieve the best outcomes.
“Developing machine learning tools to address why and what if questions is empowering for clinicians, because it can strengthen their decision-making processes,” said senior author Professor Michaela van der Schaar, Director of the Cambridge Centre for AI in Medicine. “But this sort of machine learning is far more complex than assessing personalised risk.”
For example, when attempting to determine therapy decisions for someone at risk of developing diabetes, classical ML would aim to predict how probable it is for a given patient with a range of risk factors to develop the disease. With causal ML, it would be possible to answer how the risk changes if the patient receives an anti-diabetes drug; that is, gauge the effect of a cause. It would also be possible to estimate whether metformin, the commonly-prescribed medication, would be the best treatment, or whether another treatment plan would be better.
To be able to estimate the effect of a hypothetical treatment, the AI models must learn to answer ‘what if?’ questions. “We give the machine rules for recognising the causal structure and correctly formalising the problem,” said Professor Stefan Feuerriegel from LMU, who led the research. “Then the machine has to learn to recognise the effects of interventions and understand, so to speak, how real-life consequences are mirrored in the data that has been fed into the computers.”
Even in situations for which reliable treatment standards do not yet exist or where randomised studies are not possible for ethical reasons because they always contain a placebo group, machines could still gauge potential treatment outcomes from the available patient data and form hypotheses for possible treatment plans, so the researchers hope.
With such real-world data, it should generally be possible to describe the patient cohorts with ever greater precision in the estimates, bringing individualised therapy decisions that much closer. Naturally, there would still be the challenge of ensuring the reliability and robustness of the methods.
“The software we need for causal ML methods in medicine doesn’t exist out of the box,” says Feuerriegel. “Rather, complex modelling of the respective problem is required, involving close collaboration between AI experts and doctors.”
In other fields, such as marketing, explains Feuerriegel, the work with causal ML has already been in the testing phase for some years now. “Our goal is to bring the methods a step closer to practice,” he said. The paper describes the direction in which things could move over the coming years.”
“I have worked in this area for almost 10 years, working relentlessly in our lab with generations of students to crack this problem,” said van der Schaar, who is affiliated with the Departments of Applied Mathematics and Theoretical Physics, Engineering and Medicine. “It’s an extremely challenging area of machine learning, and seeing it come closer to clinical use, where it will empower clinicians and patients alike, is very satisfying.”
Van der Schaar is continuing to work closely with clinicians to validate these tools in diverse clinical settings, including transplantation, cancer and cardiovascular disease.
Reference:
Stefan Feuerriegel et al. ‘Causal machine learning for predicting treatments.’ Nature Medicine (2024). DOI: 10.1038/s41591-024-02902-1
Adapted from an LMU media release.
Machines can learn not only to make predictions, but to handle causal relationships. An international research team shows how this could make medical treatments safer, more efficient, and more personalised.
Yuichiro Chino via Getty ImagesComputer-generated image of human brain
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Mess is best: disordered structure of battery-like devices improves performance
Researchers led by the University of Cambridge used experimental and computer modelling techniques to study the porous carbon electrodes used in supercapacitors. They found that electrodes with a more disordered chemical structure stored far more energy than electrodes with a highly ordered structure.
Supercapacitors are a key technology for the energy transition and could be useful for certain forms of public transport, as well as for managing intermittent solar and wind energy generation, but their adoption has been limited by poor energy density.
The researchers say their results, reported in the journal Science, represent a breakthrough in the field and could reinvigorate the development of this important net-zero technology.
Like batteries, supercapacitors store energy, but supercapacitors can charge in seconds or a few minutes, while batteries take much longer. Supercapacitors are far more durable than batteries, and can last for millions of charge cycles. However, the low energy density of supercapacitors makes them unsuitable for delivering long-term energy storage or continuous power.
“Supercapacitors are a complementary technology to batteries, rather than a replacement,” said Dr Alex Forse from Cambridge’s Yusuf Hamied Department of Chemistry, who led the research. “Their durability and extremely fast charging capabilities make them useful for a wide range of applications.”
A bus, train or metro powered by supercapacitors, for example, could fully charge in the time it takes to let passengers off and on, providing it with enough power to reach the next stop. This would eliminate the need to install any charging infrastructure along the line. However, before supercapacitors are put into widespread use, their energy storage capacity needs to be improved.
While a battery uses chemical reactions to store and release charge, a supercapacitor relies on the movement of charged molecules between porous carbon electrodes, which have a highly disordered structure. “Think of a sheet of graphene, which has a highly ordered chemical structure,” said Forse. “If you scrunch up that sheet of graphene into a ball, you have a disordered mess, which is sort of like the electrode in a supercapacitor.”
Because of the inherent messiness of the electrodes, it’s been difficult for scientists to study them and determine which parameters are the most important when attempting to improve performance. This lack of clear consensus has led to the field getting a bit stuck.
Many scientists have thought that the size of the tiny holes, or nanopores, in the carbon electrodes was the key to improved energy capacity. However, the Cambridge team analysed a series of commercially available nanoporous carbon electrodes and found there was no link between pore size and storage capacity.
Forse and his colleagues took a new approach and used nuclear magnetic resonance (NMR) spectroscopy – a sort of ‘MRI’ for batteries – to study the electrode materials. They found that the messiness of the materials – long thought to be a hindrance – was the key to their success.
“Using NMR spectroscopy, we found that energy storage capacity correlates with how disordered the materials are – the more disordered materials can store more energy,” said first author Xinyu Liu, a PhD candidate co-supervised by Forse and Professor Dame Clare Grey. “Messiness is hard to measure – it’s only possible thanks to new NMR and simulation techniques, which is why messiness is a characteristic that’s been overlooked in this field.”
When analysing the electrode materials with NMR spectroscopy, a spectrum with different peaks and valleys is produced. The position of the peak indicates how ordered or disordered the carbon is. “It wasn’t our plan to look for this, it was a big surprise,” said Forse. “When we plotted the position of the peak against energy capacity, a striking correlation came through – the most disordered materials had a capacity almost double that of the most ordered materials.”
So why is mess good? Forse says that’s the next thing the team is working on. More disordered carbons store ions more efficiently in their nanopores, and the team hope to use these results to design better supercapacitors. The messiness of the materials is determined at the point they are synthesised.
“We want to look at new ways of making these materials, to see how far messiness can take you in terms of improving energy storage,” said Forse. “It could be a turning point for a field that’s been stuck for a little while. Clare and I started working on this topic over a decade ago, and it’s exciting to see a lot of our previous fundamental work now having a clear application.”
The research was supported in part by the Cambridge Trusts, the European Research Council, and UK Research and Innovation (UKRI).
Reference:
Xinyu Liu et al. ‘Structural disorder determines capacitance in nanoporous carbons.’ Science (2024). DOI: 10.1126/science.adn6242
For more information on energy-related research in Cambridge, please visit the Energy IRC, which brings together Cambridge’s research knowledge and expertise, in collaboration with global partners, to create solutions for a sustainable and resilient energy landscape for generations to come.
The energy density of supercapacitors – battery-like devices that can charge in seconds or a few minutes – can be improved by increasing the ‘messiness’ of their internal structure.
This could be a turning point for a field that’s been stuck for a little while. Alex ForseNathan PittLeft to right: Clare Grey, Xinyu Liu, Alex Forse
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Tue 04 Jun 12:00: DNA damage response control by RNA and its therapeutic potential
Abstract not available
- Speaker: Fabrizio d'Adda di Fagagna
- Tuesday 04 June 2024, 12:00-13:00
- Venue: Jean Thomas Lecture theatre, Sanger Building, Tennis Court Road.
- Series: Department of Biochemistry - Tea Club Seminars; organiser: reception.
Tue 04 Jun 12:00: DNA damage response control by RNA and its therapeutic potential
Abstract not available
- Speaker: Fabrizio d'Adda di Fagagna
- Tuesday 04 June 2024, 12:00-13:00
- Venue: Jean Thomas Lecture theatre, Sanger Building, Tennis Court Road.
- Series: Department of Biochemistry - Tea Club Seminars; organiser: reception.
Sea stack plots: Replacing bar charts with histograms
Ecol Evol. 2024 Apr 16;14(4):e11237. doi: 10.1002/ece3.11237. eCollection 2024 Apr.
ABSTRACT
Graphs in research articles can increase the comprehension of statistical data but may mislead readers if poorly designed. We propose a new plot type, the sea stack plot, which combines vertical histograms and summary statistics to represent large univariate datasets accurately, usefully, and efficiently. We compare five commonly used plot types (dot and whisker plots, boxplots, density plots, univariate scatter plots, and dot plots) to assess their relative strengths and weaknesses when representing distributions of data commonly observed in biological studies. We find the assessed plot types are either difficult to read at large sample sizes or have the potential to misrepresent certain distributions of data, showing the need for an improved method of data visualisation. We present an analysis of the plot types used in four ecology and conservation journals covering multiple areas of these research fields, finding widespread use of uninformative bar charts and dot and whisker plots (60% of all panels showing univariate data from multiple groups for the purpose of comparison). Some articles presented more informative figures by combining plot types (16% of panels), generally boxplots and a second layer such as a flat density plot, to better display the data. This shows an appetite for more effective plot types within conservation and ecology, which may further increase if accurate and user-friendly plot types were made available. Finally, we describe sea stack plots and explain how they overcome the weaknesses associated with other alternatives to uninformative plots when used for large and/or unevenly distributed data. We provide a tool to create sea stack plots with our R package 'seastackplot', available through GitHub.
PMID:38633526 | PMC:PMC11021675 | DOI:10.1002/ece3.11237
No evidence that a transmissible cancer has shifted from emergence to endemism in Tasmanian devils
R Soc Open Sci. 2024 Apr 17;11(4):231875. doi: 10.1098/rsos.231875. eCollection 2024 Apr.
ABSTRACT
Tasmanian devils are endangered by a transmissible cancer known as Tasmanian devil facial tumour 1 (DFT1). A 2020 study by Patton et al. (Science 370, eabb9772 (doi:10.1126/science.abb9772)) used genome data from DFT1 tumours to produce a dated phylogenetic tree for this transmissible cancer lineage, and thence, using phylodynamics models, to estimate its epidemiological parameters and predict its future trajectory. It concluded that the effective reproduction number for DFT1 had declined to a value of one, and that the disease had shifted from emergence to endemism. We show that the study is based on erroneous mutation calls and flawed methodology, and that its conclusions cannot be substantiated.
PMID:38633353 | PMC:PMC11022658 | DOI:10.1098/rsos.231875
Steven Barrett appointed Regius Professor of Engineering
Professor Steven Barrett has been appointed Regius Professor of Engineering at the University of Cambridge, effective 1 June. He joins the University from the Massachusetts Institute of Technology (MIT), where he is head of the Department of Aeronautics and Astronautics (AeroAstro).
Barrett’s appointment marks his return to Cambridge, where he was an undergraduate at Pembroke College, and received his PhD. He was a Lecturer in the Department of Engineering from 2008 until 2010, when he joined the faculty at MIT.
The Regius Professorships are royal academic titles created by the monarch. The Regius Professorship in Engineering was announced in 2011, in honour of HRH Prince Philip, The Duke of Edinburgh’s 35 years as Chancellor of the University.
“It’s a pleasure to welcome Steven back to Cambridge to take up one of the University’s most prestigious roles,” said Vice-Chancellor Professor Deborah Prentice. “His work on sustainable aviation will build on Cambridge’s existing strengths, and will help us develop the solutions we need to address the threat posed by climate change.”
Barrett’s research focuses on the impact aviation has on the environment. He has developed a number of solutions to mitigate the impact aviation has on air quality, climate, and noise pollution. The overall goal of his research is to help develop technologies that eliminate the environmental impact of aviation. His work on the first-ever plane with no moving propulsion parts was named one of the 10 Breakthroughs of 2018 by Physics World.
“This is an exciting time to work on sustainable aviation, and Cambridge, as well as the UK more generally, is a wonderful platform to advance that,” said Barrett. “Cambridge’s multidisciplinary Department of Engineering, as well as the platform that the Regius Professorship provides, makes this a great opportunity. I’ve learned a lot at MIT, but I’d always hoped to come back to Cambridge at some point.”
Much of Barrett’s research focuses on the elimination of contrails, line-shaped clouds produced by aircraft engine exhaust in cold and humid conditions. Contrails cause half of all aviation-related global warming – more than the entirety of the UK economy. Barrett uses a combination of satellite observation and machine learning techniques to help determine whether avoiding certain regions of airspace could reduce or eliminate contrail formation.
“It will take several years to make this work, but if it does, it could drastically reduce emissions at a very low cost to the consumer,” said Barrett. “We could make the UK the first ‘Blue Skies’ country in the world – the first without any contrails in the sky.”
“Steven’s pioneering work on contrail formation and avoidance is a key element in reducing the environmental impact of aviation, and will strengthen the UK’s position as a world leader in this area,” said Professor Colm Durkan, Head of Cambridge’s Department of Engineering. “Together with Steven’s work on alternative aviation propulsion systems, this will strengthen Cambridge’s vision of helping us all achieve net zero at an accelerated rate.”
In addition to the Professorship in Engineering, there are seven other Regius Professorships at Cambridge: Divinity, Hebrew, Greek, Civil Law and Physic (all founded by Henry VIII in 1540), History (founded by George I in 1724) and Botany (founded in 2009, to mark the University’s 800th anniversary).
An expert on the environmental impacts of aviation, Barrett joins the University of Cambridge from MIT.
MITSteven Barrett
The text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.