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Academics from City, University of London, believe that COVID-19 pandemic has amplified existing barriers to healthcare for ethnic minority and migrant women in England.

In their recent paper, COVID-19 Highlighting Inequalities in Access to Healthcare in England: A Case Study of Ethnic Minority and Migrant Women, Senior Law Lecturers,
Dr Sabrina Germain and Dr Adrienne Yong analyse recent research demonstrating that this marginalised group of women are disproportionately affected by a healthcare system which overlooks the intersectional barriers generated by being a woman from a migrant or ethnic minority background.

The academics also draw attention to how the pandemic has amplified these barriers and expose the manner in which the pandemic has affected the allocation of healthcare resources in England, leading to the prioritisation of COVID-19 patients, thereby suspending the equal access to healthcare services approach.

Their paper goes on to explore poorer health outcomes for women in ethnic minority and migrant communities that the disruption in provision does not solely account for, by looking at underlying barriers to access that have been amplified by the pandemic. Dr Germain and Dr Yong reflect on racialised medical perceptions, gendered cultural norms - including information barriers and stigma - and specific legal barriers.

The authors reveal that though there are no specific policies or guidance on healthcare for vulnerable migrant women, a feminist critique of barriers to accessing healthcare, "demonstrates specific barriers for women aggravated by their race and cultural associations with race, or having migrant status and being subject to hostile immigration law. We argue that these existing barriers to accessing services have been reinforced, and in some situations deepened, by the pandemic."

Dr Germain and Dr Yong also highlight how racialised medical perceptions can impact the judgment of medical professionals, and that these biases are potentially heightened in critical situations where they have to act urgently and instinctively such as during a pandemic:

"There is evidence that medical training received by healthcare professionals perpetuates unconscious biases against marginalised groups, prejudicing future diagnoses of illnesses as well as courses of treatment . Ethnic minority and migrant women are more vulnerable to these perceptions because of prejudices and racist beliefs, such as having higher pain thresholds or a greater ability to cope with illness They are often also undermined when voicing their healthcare needs."

Italy was one the countries first hit hard by the COVID-19 pandemic. In a new review presented at this weekend's Euroanaesthesia (the annual meeting of the European Society of Anaesthesiology and Intensive Care [ESAIC]) an Italian doctor on the front line of the pandemic concludes that it is not fair to use age alone as the deciding factor on whether or not someone receives intensive care treatment.

The presentation, given by Professor Ornella Piazza, University of Salerno and Salerno University Hospital, Italy, will discuss the desperate situation many Italian hospitals found themselves in when patient demand was far in excess of availability of intensive care (ICU) beds early in the pandemic.

She will also discuss the document published by The Italian Society of Anesthesia (SIAARTI), on 6 March 2020, entitled "Clinical ethics recommendations for the breakdown of intensive care treatments, in exceptional circumstances limited to resources". In this document, the principle of: "saving limited resources, which can become extremely scarce, for those who have a much greater chance of survival and life expectancy, in order to maximise the benefits for the greatest number of people" is stated.

COVID-19 outcomes in elderly patients are usually much worse than in healthy young subjects. SIAARTI, therefore, suggested that: "together with the age, comorbidity and functional status of each patient in critical condition must be carefully evaluated in these exceptional circumstances".

While praising SIAARTI for acting so quickly in creating recommendations for treating COVID, Prof Piazza says that using age alone as the deciding factor on whether or not someone receives potentially life-saving ICU care is not the right choice. She explains: "Put simply, if there is an equal need between two patients, age can be the decisive element in defining the priority of treatment according to this guidance. Lifesaving procedures, such as intubating and ventilating, would be carried out only in younger patients, reserving only less invasive or palliative treatments for the elderly."

She adds: "Following this principle, the elderly, lesser valued citizens (in these criteria), would give young people the right to play their game of life, as defined by the principle of a fair life expectancy. So, I question, is the age of the patient the right thing to determine whether they enter ICU?"

She explains: "Defining a rigid cut-off - a precise threshold of age - is, in my opinion, more a 'defensive' tool for young and inexperienced doctors, left in distress in the emergency room devastated by the epidemic. However, it is essential that these decisions, extremely distressing for both those affected and those forced to make them, are based on clinical factors related to therapeutic outcomes and not on the basis of discriminatory judgments about the value of individual lives."

And in cases where there are two patients but only one bed, Prof Piazza explains that doctors will never just 'give up' on the patient who does not get the bed. "For that patient, we evaluate alternative treatments," she explains. "Abandoning them is never an option, and we should explore any other possible ways we can help them."

The University of Oxford's CASE Gold Award winning podcast, Futuremakers, will return for its third season at the end of October. Featuring a sweeping original soundtrack, the podcast will take listeners on a narrative journey through ten significant pandemics across humanity's history, from the Siege of Athens to the 2014 Western African Ebola outbreak, via the Black Death and Spanish Flu.

Join host, Gilbert Ryle Fellow and Professor of Philosophy at Hertford College, University of Oxford, Peter Millican, as he takes a journey through ten historical outbreaks, asking what we know of what happened at the time, whether we might learn anything for today's COVID-19 pandemic, and what might be coming in the future.

Episode list:

1: Athens: the first plague?

2: The Plague of Justinian

3. The Black Death

4: The Great Plague

5: Smallpox, and Jenner

6: Cholera, and John Snow

7: The Flu Pandemic... that wasn't?

8: The Spanish Flu

9: HIV and AIDS

10: Ebola 2014

Featuring a diverse range of notable voices from the University of Oxford and across the globe on every episode, each episode reflects the conversations and global collaboration that underpins the heart of scientific endeavour.

This season follows on from two highly successful seasons covering the implications of climate change and artificial intelligence on our society and how we live, and a one-off special exploring the 'race' to develop the world's first truly scalable quantum computer.

The first five episodes of the series will be released this Sunday 29 November 2020, across a wide range of platforms including Apple and Spotify, and you can find the full list and more information about the series at https://bit.ly/TheHistoryOfPandemics

Futuremakers is produced by Ben Harwood and Steve Pritchard for the University of Oxford, with Season 3's cinematic score being composed and recorded by Richard Watts.

You can download the podcast at: http://bit.ly/futureMAKERS (AudioBoom), http://bit.ly/FUTUREmakers (Apple) or from any of the platforms listed here https://bit.ly/TheHistoryOfPandemics

To get in touch with the production team, or arrange interviews Prof. Millican or with any of the guests from the University of Oxford, contact ben.harwood@admin.ox.ac.uk

The number of patients starting anticancer therapies dropped by more than 30 per cent in April, the month following the UK's first COVID-19 lockdown, but went above pre-pandemic levels within three months, finds a new study of NHS England data co-led by UCL researchers.

The analysis, published in The Lancet Oncology, assessed the number of registrations to initiate systemic anticancer treatment recorded per month in April, May, and June 2020, against the mean number of monthly registrations in the pre-lockdown 'control period' of September 2019 to February 2020. This information is recorded on the NHS England Prior Approval system.

For April*, 2,969 registrations were recorded, representing 1,417 fewer registrations than in the control period, a 32% reduction. In May 2020, registrations increased to 3,950, representing a 10% reduction from the control period. However in June 2020, 5,022 registrations were recorded, representing a 15% increase compared with the control period.

Researchers say a major part of the return to pre-pandemic cancer treatment levels by June is the result of NHS England's 'COVID-19 rapid guidance: delivery of systemic anticancer treatments'**, approved by the National Institute of Clinical Excellence (NICE). This provided more treatment options via temporary approval of oral drug alternatives and less immunosuppressive therapies, many of these being 'off label' treatments and used in earlier stages of therapy than currently licensed.

Co-lead author, Professor Allan Hackshaw (UCL Cancer Institute), said: "Many cancer services in the UK and across the world underwent extensive changes to minimise COVID-19 exposure among patients with cancer and health-care staff.

"These changes included delayed surgery and radiotherapy, reduced outpatient visits (often replaced with telephone assessments), and where possible, switching from therapies that require intravenous administration in clinic to oral drugs that can be taken at home.

"Our study shows the positive consequences of NHS England offering clinicians and patients a wider range of treatment options including drugs that had not yet been appraised by NICE or which are off-label, but are likely to result in less risk to patients from the pandemic. These additional options contributed to the greater number of registrations for new patients starting systemic anticancer treatment in May and June, 2020."

The initial NHS England 'COVID-19 rapid guidance: delivery of systemic anticancer treatments' was published at the end of March, though guidance on most of the new drug treatment approvals were published sequentially from April.

The initial decreases in April were seen across all types of therapies and cancer types. For example, there was a 36% reduction in the number of people starting immunotherapies, and a 51% reduction in those who needed chemotherapy. The reduction in registrations was also large for breast cancer (33%), prostate cancer (57%), lung cancer (36%) and skin cancer (32%). The decreases in April were followed by rises in May and June, which were observed for all types of therapy, with the exception of neoadjuvant (pre-surgery) therapy. This pattern was also seen for most cancer types.

Co-lead author, Dr James Clark, oncologist at Imperial College London, said: "This study shows a cancer treatment service in England that reacts quickly to change; whether that is to COVID-19 in April or to the measures that the NHS rapidly put in place to increase the safety of treatment to patients. The initial reductions were largely reversed by June, 2020, when the number of treatment registrations was significantly higher than those observed during the control period. These findings can provide some reassurance to patients and clinicians that treatment delays can be minimised or avoided if health-care providers are able to quickly implement guidance on drug prescribing."

Dr Clark added: "Despite this, by June the number of cancer treatments being registered for neoadjuvant therapies for breast cancer remained significantly lower than the control period. However, we know from unpublished and recent data that registrations for neoadjuvant breast cancer therapy have now recovered."

Professor Hackshaw added: "Although cancer registrations returned to normal levels by June, a significant number of patients would have had their cancer treatments delayed during the early part of the pandemic. It will be essential to monitor these patients - particularly when cancer drugs for some advanced cancers improve survival by several months, so even a two-month delay could be an issue."

Research limitations

First, the NHS registration system records an intention to treat that might not necessarily result in treatment itself, although previous audits have shown that 92-95% of registrations result in actual treatment. Second, this analysis only covers drugs approved for use since 2016, and does not include hormone therapies or free-of-charge drugs from companies. Some cancer treatments, including those that were established before 2016, are not recorded on the databases assessed in this research.

Researchers believe this is the first study to assess how prescribing practice for anticancer treatments has changed at a national level since the pandemic began, on the basis of all drugs approved by the National Institute for Health and Care Excellence since 2016.

Scientists from Trinity College Dublin have developed a new gene therapy approach that offers promise for one day treating an eye disease that leads to a progressive loss of vision and affects thousands of people across the globe.

The study, which involved a collaboration with clinical teams in the Royal Victoria Eye and Ear Hospital and the Mater Hospital, also has implications for a much wider suite of neurological disorders associated with ageing.

The scientists publish their results today [Thursday 26th November 2020] in leading journal, Frontiers in Neuroscience.

Dominant optic atrophy (DOA)

Characterised by degeneration of the optic nerves, DOA typically starts to cause symptoms in patients in their early adult years. These include moderate vision loss and some colour vision defects, but severity varies, symptoms can worsen over time and some people may become blind. There is currently no way to prevent or cure DOA.

A gene (OPA1) provides instructions for making a protein that is found in cells and tissues throughout the body, and which is pivotal for maintaining proper function in mitochondria, which are the energy producers in cells.

Without the protein made by OPA1, mitochondrial function is sub-optimal and the mitochondrial network which in healthy cells is well interconnected is highly disrupted.

For those living with DOA, it is mutations in OPA1 and the dysfunctional mitochondria that are responsible for the onset and progression of the disorder.

The new gene therapy

The scientists, led by Dr Daniel Maloney and Professor Jane Farrar from Trinity's School of Genetics and Microbiology, have developed a new gene therapy, which successfully protected the visual function of mice who were treated with a chemical targeting the mitochondria and were consequently living with dysfunctional mitochondria.

The scientists also found that their gene therapy improved mitochondrial performance in human cells that contained mutations in the OPA1 gene, offering hope that it may be effective in people.

Dr Maloney, Research Fellow, said:

"We used a clever lab technique that allows scientists to provide a specific gene to cells that need it using specially engineered non-harmful viruses. This allowed us to directly alter the functioning of the mitochondria in the cells we treated, boosting their ability to produce energy which in turn helps protects them from cell damage.

"Excitingly, our results demonstrate that this OPA1-based gene therapy can potentially provide benefit for diseases like DOA, which are due to OPA1 mutations, and also possibly for a wider array of diseases involving mitochondrial dysfunction."

Importantly, mitochondrial dysfunction causes problems in a suite of other neurological disorders such as Alzheimer's and Parkinson's disease. The impacts gradually build up over time, which is why many may associate such disorders with ageing.

Professor Farrar, Research Professor, added:

"We are very excited by the prospect of this new gene therapy strategy, although it is important to highlight that there is still a long journey to complete from a research and development perspective before this therapeutic approach may one day be available as a treatment.

"OPA1 mutations are involved in DOA and so this OPA1-based therapeutic approach is relevant to DOA. However mitochondrial dysfunction is implicated in many neurological disorders that collectively affect millions of people worldwide. We think there is great potential for this type of therapeutic strategy targeting mitochondrial dysfunction to provide benefit and thereby make a major societal impact. Having worked together with patients over many years who live with visual and neurological disorders it would be a privilege to play a role in a treatment that may one day help many."

A new method for analysing the structure of skin using a type of radiation known as T-rays could help improve the diagnosis and treatment of skin conditions such as eczema, psoriasis and skin cancer.

Scientists from the University of Warwick and The Chinese University of Hong Kong (CUHK) have shown that using a method that involves analysing T-rays fired from several different angles, they can build a more detailed picture of the structure of an area of skin and how hydrated it is than current methods allow.

Their method is reported in Advanced Photonics Research and could provide a new tool for scientists and clinicians for characterising the properties of skin in individuals, to assist in managing and treating skin conditions.

Terahertz (THz) radiation, or T-rays, sit in-between infrared and WiFi on the electromagnetic spectrum. T-rays can see through many common materials such as plastics, ceramics and clothes, making them potentially useful in non-invasive inspections. The low-energy photons of T-rays are also non-ionizing, making them very safe in biological settings including security and medical screening.

Only the T-rays passing through the outer layers of skin (stratum corneum and epidermis) before being reflected back can be detected, as those travelling deeper are attenuated too much. This makes T-ray imaging a potentially effective way of monitoring these outermost layers. To test this, terahertz light is focused onto the skin via a prism, to align the ray in a particular focal plane. Depending on the properties of the skin, that light will be reflected back slightly differently. Scientists can then compare the properties of the light before and after it enters the skin.

There are limitations in standard THz reflection spectroscopy however, and to overcome these the scientists behind this new research instead used ellipsometry, which involves focusing T-rays at multiple angles on the same area of skin.

They successfully demonstrated that using ellipsometry they could accurately calculate the refractive index of skin (which determines how fast the ray travels through it) measured in two directions at right angles to each other. The difference between these refractive indices is termed birefringence - and this is the first time that the THz birefringence of human skin has been measured in vivo. These properties can provide valuable information on how much water is in the skin and enable the skin thickness to be calculated.

Professor Emma Pickwell-MacPherson, from the Department of Physics at the University of Warwick and the Department of Electronic Engineering at CUHK, said: "We wanted to show that we could do in-vivo ellipsometry measurements in human skin and calculate the properties of skin accurately. In ordinary terahertz reflection imaging, you have thickness and refractive index combined as one parameter. By taking measurements at multiple angles you can separate the two.

"Hydrated skin will have a different refractive index from dehydrated skin. For people with skin disorders, we'll be able to probe the hydration of their skin quantitatively, more so than existing techniques. If you're trying to improve skincare products for people with conditions like eczema or psoriasis, we would be potentially be able to make quantitative assessments of how the skin is improving with different products or to differentiate types of skin.

"For skin cancer patients, you could also use THz imaging to probe the skin before surgery is started, to get a better idea of how far a tumour has spread. Skin cancer affects the properties of the skin and some of those are unseen as they're beneath the surface."

Dr. Xuequan Chen, the study's first author and post-doctoral fellow from the Department of Electronic Engineering at CUHK, said: "T-rays have been known to be sensitive to the hydration level of skin. However, we point out that the cellular structure of the stratum corneum also reacts to the terahertz reflections. Our technique enables this structure property to be sensitively probed, which provides comprehensive information about the skin and it is highly useful for skin diagnosis."

To test their method, the researchers had volunteers place their arm on the imaging window of their T-ray equipment for 30 minutes, after acclimatising to the ambient temperature and dryness of the laboratory. By holding their skin against the surface of the imaging window, they blocked water from escaping from their skin as perspiration, a process referred to as occlusion.

The researchers then made four measurements at right angles to each other every two minutes over half an hour, so they could monitor the effect of occlusion over time. Because T-rays are particularly sensitive to water, they could see a noticeable difference as water accumulated in the skin, suggesting that the method could show how effective a product is at keeping skin hydrated, for example.

Further research will look at improving the instrumentation of the process and how it might work as a practical device.

Professor Pickwell-MacPherson said: "We don't have anything that's really accurate for measuring skin that clinicians can use. Dermatologists need better quantitative tools to use, and use easily.

"If this works well you could go into a clinic, put your arm on a scanner, your occlusion curve would be plotted and a suitable product for your skin could be recommended. We could get more tailored medicine and develop products for different skin responses. It could really fit in with the current focus on tailored medicine."

RIVERSIDE, Calif. -- On a near daily basis, the internet spews out numerous tips and tricks for exercise motivation. Now we can add smell to the long and growing list.

A research team led by a scientist at the University of California, Riverside, has found olfaction -- or smell -- may play an important role in motivating mammals to engage in voluntary exercise.

Performed in lab mice, the study may open up new areas of research and have relevance for humans. Study results appear in PLOS ONE.

Video.

"Exercise, which is essential for both physical and mental health, can help prevent obesity and other inactivity-related diseases and disorders in humans," said Sachiko Haga-Yamanaka, an assistant professor of molecular, cell and systems biology at UC Riverside and the study's lead author. "Some people like to exercise more than others do, but why this is so is not well understood."

To determine genetic contributions to voluntary exercise-related traits, Haga-Yamanaka and her team subjected mice to voluntary wheel running, or VWR, a widely studied behavior in which rodents run spontaneously when given access to running wheels.

Her collaborator and co-author Theodore Garland Jr., a distinguished professor of evolution, ecology, and organismal biology at UCR, established independent, artificially evolved mouse lines by selectively breeding mice showing high VWR activity. Regular mice -- those not genetically engineered in any way -- constituted the controls. To their surprise, the researchers found high-runner mice developed genetic differences in their olfactory system that made them perceive smells differently from the controls.

"The olfactory system became genetically differentiated between the high runner and control lines during the selective breeding process with several chemosensory receptors in specific receptor gene clusters being differentially expressed between high runners and controls," Haga-Yamanaka said. "Our results suggest these chemosensory receptors are important trait locations for the control of voluntary exercise in mice."

The implications of the findings for humans are hard to miss. In fitness centers, gyms, and team sports, people receive many olfactory stimuli from the environment and other nearby people.

"It's not inconceivable that someday we might be able to isolate the chemicals and use them like air fresheners in gyms to make people even more motivated to exercise," Garland said. "In other words: spray, sniff, and squat."

The researchers focused on the vomeronasal organ, the accessory olfactory organ in amphibians, squamates, and most mammals, including rodents. The vomeronasal organ detects pheromones -- chemical substances animals produce and release into the environment -- that trigger behavioral and physiological changes in those who receive the molecules. The signals detected by vomeronasal sensory receptor neurons are then processed in the brain's amygdala and hypothalamus, which induce behavioral responses and endocrinological changes.

The researchers found:

Receptor genes were differentially expressed between the vomeronasal organs of the high runners and control lines.
Genetic alterations resulting from selective breeding of mice for VWR produced this gene expression change, suggesting a relationship between high running activity and the function of the vomeronasal organ in high runner lines.
Individual differences of exercise habit may be accounted for by a differentiated perception of specific smells.

"Taken together, our results show vomeronasal receptors as trait locations for voluntary exercise behavior in mice," Haga-Yamanaka said. "The high runner and control lines provide a strong model for determining the contribution of genetics to voluntary-exercise related traits."

Next, the researchers plan to conduct experiments to isolate particular chemicals produced by mice, perhaps from their urine, and determine if and how these chemicals increase motivation for exercising.

Higher than normal blood pressure is linked to more extensive brain damage in the elderly, according to a new study published today (Thursday) in the European Heart Journal [1].

In particular, the study found that there was a strong association between diastolic blood pressure (the blood pressure between heart beats) before the age of 50 and brain damage in later life, even if the diastolic blood pressure was within what is normally considered to be a healthy range.

The findings come from a study of 37,041 participants enrolled in UK Biobank, a large group of people recruited from the general population aged between 40 and 69 years, and for whom medical information, including MRI brain scans was available.

The research, carried out by Dr Karolina Wartolowska, a clinical research fellow at the Centre for Prevention of Stroke and Dementia, University of Oxford, UK, looked for damage in the brain called "white matter hyperintensities" (WMH). These show up on MRI brain scans as brighter regions and they indicate damage to the small blood vessels in the brain that increases with age and blood pressure. WMH are associated with an increased risk of stroke, dementia, physical disabilities, depression and a decline in thinking abilities.

Dr Wartolowska said: "Not all people develop these changes as they age, but they are present in more than 50% of patients over the age of 65 and most people over the age of 80 even without high blood pressure, but it is more likely to develop with higher blood pressure and more likely to become severe."

Information on the participants was collected when they enrolled in UK Biobank between March 2006 and October 2010, and follow-up data, including MRI scans, were acquired between August 2014 and October 2019. The researchers adjusted the information to take account of factors such as age, sex, risk factors such as smoking and diabetes, and diastolic as well as systolic blood pressure. Systolic blood pressure is the maximum blood pressure reached each time the heart beats and is the top number in blood pressure measurements.

"To compare the volume of white matter hyperintensities between people and to adjust the analysis for the fact that people's brains vary slightly in size, we divided the volume of WMH by the total volume of white matter in the brain. In that way, we could analyse the WMH load, which is the proportion of the WMH volume to the total volume of white matter," said Dr Wartolowska.

The researchers found that a higher load of WMH was strongly associated with current systolic blood pressure, but the strongest association was for past diastolic blood pressure, particularly when under the age of 50. Any increase in blood pressure, even below the usual treatment threshold of 140 mmHg for systolic and below 90 mmHg for diastolic, was linked to increased WMH, especially when people were taking medication to treat high blood pressure. [2]

For every 10mmHg increase in systolic blood pressure above the normal range, the proportion of WMH load increased by an average (median) of 1.126-fold and by 1.106-fold for every 5mmHg increase in diastolic blood pressure. Among the top 10% of people with the greatest WMH load, 24% of the load could be attributed to having a systolic blood pressure above 120mmHg, and 7% could be attributed to having diastolic blood pressure above 70mmHg, which reflects the fact that there is a greater incidence of elevated systolic rather than diastolic blood pressure in older patients.

Dr Wartolowska said: "We made two important findings. Firstly, the study showed that diastolic blood pressure in people in their 40s and 50s is associated with more extensive brain damage years later. This means that it is not just the systolic blood pressure, the first, higher number, but the diastolic blood pressure, the second, lower number, that is important to prevent brain tissue damage. Many people may think of hypertension and stroke as diseases of older people, but our results suggest that if we would like to keep a healthy brain well into our 60s and 70s, we may have to make sure our blood pressure, including the diastolic blood pressure, stays within a healthy range when we are in our 40s and 50s.

"The second important finding is that any increase in blood pressure beyond the normal range is associated with a higher amount of white matter hyperintensities. This suggests that even slightly elevated blood pressure before it meets the criteria for treating hypertension has a damaging effect on brain tissue.

"Our results suggest that to ensure the best prevention of white matter hyperintensities in later life, control of diastolic blood pressure, in particular, may be required in early midlife, even for diastolic blood pressure below 90mmHg, whilst control of systolic blood pressure may be more important in late life. The long time interval between the effects of blood pressure in midlife and the harms in late life emphasises how important it is to control blood pressure long-term, and that research has to adapt to consider the very long-term effects of often asymptomatic problems in midlife."

Potential mechanisms for the development of WMH include damage to the delicate blood vessels in the brain through sustained elevated pressures over time that directly cause damage to the blood vessels; this leads to the lining of the vessels becoming leaky and results in WMH. Alternatively, diastolic pressure might cause large blood vessels to become stiffer with time, which increases pulsations of blood pressure to the brain; this causes high blood pressure with each heart beat, rapid changes in blood pressure, and blood flow that is too low between heart beats, resulting in damage to white matter.

As MRI scans were only available at one time point, the researchers could not quantify the progression of WMH directly. Other limitations include that further analysis is needed to identify differences in different regions of white matter, and that although the researchers showed associations with smoking and diabetes, the potential complex interaction between risk factors, which also include high cholesterol levels, obesity and kidney problems, require further investigation.

Fiji's national vaccine program against pneumonia, a serious lung condition, and rotavirus, a common disease which causes severe diarrhoea and vomiting, has reduced illness and death, new research shows.

The University of Melbourne-led research team, which worked with the Fiji Ministry of Health and Medical Services, says the results underline the importance of vaccines and how they can potentially reduce the impact of viruses such as COVID-19.

Published in The Lancet Regional Health - Western Pacific, the first study looked at Fiji's national rotavirus vaccine program five years after it became the first independent Pacific island country to introduce the vaccine in 2012, and one of few in the Asia-Pacific region.

Morbidity (disease or symptom) and mortality (death) due to rotavirus and all-cause diarrhoea in Fiji fell in those aged two months to 55 years. Rotavirus diarrhoea admissions at the largest hospital among children aged under five fell by 87 per cent.

Lead researcher Professor Fiona Russell, of Murdoch Children's Research Institute and the University of Melbourne, said the findings underlined a wider effort to introduce the vaccine across the Pacific.

"The high uptake means the vaccine was acceptable to the children and their carers," Professor Russell said.

"It showed sustained effectiveness, working in vaccinated children and helping to prevent other members of their household falling ill."

Rotavirus is severely contagious and the most common cause of diarrhoeal disease among infants and young children. It can cause death in extreme cases.

In October 2012, the Fiji Government introduced a rotavirus vaccine into the national immunisation schedule at six and 14 weeks with the Australian Department of Trade and Foreign Affairs' support. National coverage estimates were 85, 91, 94, 93 and 98 per cent in 2013, 2014, 2015, 2016 and 2017, respectively.

"Fiji is the first Pacific island country to show a decline in the burden of rotavirus diarrhoea, and all-cause diarrhoea admissions in people of all ages and mortality in children after rotavirus vaccine introduction," Professor Russell said.

"These reductions were most likely due to the vaccine as rotavirus diarrhoeal outbreaks remained blunted for the five years after vaccine introduction. While improved outpatient management practices may have contributed to the decline in diarrhoea, the temporal relationship to vaccine introduction is compelling."

At the same time in 2012, the Fiji Government introduced a routine infant immunisation schedule for ten-valent pneumococcal conjugate (PCV10) vaccine using three primary doses and no booster dose.

Published in The Lancet Global Health, this study looked at hospital admission rates for children presenting with pneumonia from January 2007 - December 2017 at three Fiji public tertiary hospitals.

Five years after the vaccine was introduced, hospital admissions for all-case pneumonia had fallen for children aged 24-59 months.

Mortality was down by 39 per cent among children aged two-24 months who were admitted to hospital with all-case pneumonia, bronchiolitis, and asthma.

Professor Russell said the second study was the first in a middle-income Asia-Pacific region country to show the effect of PCV10 vaccine and supported its introduction for children in other low and middle-income countries in that region.

"These results provide supportive evidence of the probable benefits of PCV10 in reducing pneumonia in children in Fiji," Professor Russell said.

"Our findings are likely to be helpful for decision making regarding PCV introduction in other low and middle-income countries. Most importantly, for the past four years, these vaccines have been fully funded by the Fiji government."

Over 1 billion people globally are affected by iron-deficiency anaemia. In sub-Saharan Africa, anaemia is a major public health concern with roughly 60% of the population suffering from anaemia. Around half of those cases are due to iron deficiency. Anaemia has a negative impact on an individual's quality of life, and the economic development of a country. Women are at particularly high risk, and their risk increases during pregnancy, childbirth and postpartum.

In a new study published yesterday by Swiss TPH and the Ifakara Health Institute in The Lancet Global Health, researchers compared the safety and efficacy of iron infusion versus oral iron tablets to treat iron-deficiency anaemia in Bagamoyo and Dar es Salaam, Tanzania. Results showed that iron infusion is highly effective in low-income settings compared to oral iron tablets.

"This is the first study to provide evidence of the benefits and safety of iron infusion compared with oral iron tablets for the treatment of iron-deficiency anaemia following childbirth in a resource-limited setting," said Sandrine Meyer-Monard, independent haematologist and senior author of the study. "We have demonstrated that iron infusions can be safely used in a rural African setting - just as it is in high-income settings."

Iron infusion proves successful

In this phase III clinical trial, postpartum women in Bagamoyo and Dar es Salaam received either an iron infusion or oral iron tablets to treat their iron-deficiency anaemia. The study found that 80% of the women who received an iron infusion had normalised levels of haemoglobin after just six weeks, compared to 51% of women who were given the oral iron tablets. Importantly, the women who received the iron infusion continued to have better haemoglobin and ferritin levels after one year, indicating that the iron storage in their bodies had been regenerated.

"This is an important finding, particularly for women who have subsequent pregnancies but do not seek medical care between births," said Claudia Daubenberger, Head of the Clinical Immunology unit at Swiss TPH. "Providing an iron infusion during their time at the hospital is a powerful strategy to deliver a straightforward, effective and longer-lasting iron supplementation before discharge."

Treating iron-deficiency anaemia

The currently recommended therapy for iron-deficiency anaemia in low-resource settings is daily oral iron tablets. These tablets are affordable but they require strict compliance over a long period of time, and may cause side effects. Iron infusion, while more expensive than oral iron tablets, requires just one or two doses, and treatment can be delivered at time points coinciding with routine medical visits.

Treatment with iron infusions is routinely done in high-income settings and is increasingly replacing oral iron tablets. This study shows that infusions can be delivered safely in district hospitals in a resource-limited setting. Further, the infusions can be stored at room temperature, and have a shelf life of three years making the supply chain of this product manageable.

"The results of this study show the possibilities of iron infusion with ferric carboxymaltose in helping to reduce iron-deficiency anaemia where there is the greatest burden, and pave the way for approval of this drug in such settings," said Fiona Vanobberghen, first author of the publication and Senior Scientific Collaborator at the Department of Medicine, Swiss TPH.

People with Rheumatoid Arthritis (RA) could soon benefit from a new drug treatment that not only suppresses inflammation but also significantly reduces patient reported pain scores. Otilimab is a monoclonal antibody, biologic drug, which targets and suppresses the inflammatory cytokine GM-CSF.

In a multicentre, dose-ranging trial, led by Professor Chris Buckley at the Universities of Oxford and Birmingham, and sponsored by the Pharmaceutical company GSK, researchers explored the clinical effects of otilimab to prevent inflammation, tissue damage and pain in people with RA.

The study evaluated the effects of five doses of otilimab (22·5 mg, 45 mg, 90 mg, 135 mg, or 180 mg) versus a placebo. 222 patients with active RA received weekly subcutaneous injections for 5 weeks, which was reduced to every other week for one year. A range of patient reported outcomes for function and pain were measured. Otilimab treatment led to a rapid reduction in tender and swollen joints but patients also reported very significant improvements in pain scores.

Professor Buckley, Kennedy Professor of Translational Rheumatology at the Universities of Oxford and Birmingham said: "The assumption has always been that if drugs suppress inflammation, they will also help suppress pain, but this hasn't always been the case. Now, for the first time we are seeing a biologic therapy, the first in the rheumatoid space, that offers two for the price of one. It's suppressing inflammation, but it's also helping pain, and that's very important to the patient."

The trial was novel in that it offered an escape arm for patients receiving the placebo or in whom the drug dose to which they were randomised did not achieve a reduction in their disease activity. "One of the problems with placebo arms is it's hard to get people to go into the study if they know they might get a dummy drug ," said Prof. Buckley. "In this trial, if a patient wasn't seeing improvements after 12 weeks they were automatically transferred to the highest dose of otilimab at 180 mg and we were able to then see the improvements."

This study helped lay the infrastructure groundwork for the CATALYST Trial, also a collaboration between Oxford and Birmingham, which is measuring the effectiveness of GM- CSF and another anti-inflammatory drug (anti TNF) in the treatment of COVID-19.

Pre-eclampsia, usually diagnosed by increased blood pressure and protein in urine, affects up to 5% of pregnant women. It contributes worldwide to the death of estimated 50 000 women and up to one million babies annually. The condition is also associated with an increased risk of cardiovascular diseases among mothers and their children later in life. There is an inherited risk, with women with a family history of pre-eclampsia at greater risk of developing the condition themselves.

In the InterPregGen study, researchers from the UK, Iceland, Finland, Norway, Denmark, Kazakhstan and Uzbekistan studied how maternal genetic variation influences the risk of pre-eclampsia. The team studied the genetic make-up of 9,515 pre-eclamptic women and 157,719 control individuals.

The results, reported today in Nature Communications, pinpointed DNA variants in the ZNF831 and FTO genes as risk factors for pre-eclampsia. These genes have previously been associated with blood pressure, and the FTO variant also with body mass index. Further analysis revealed other blood pressure related variants in the MECOM, FGF5 and SH2B3 genes also associating with pre-eclampsia. These variants increase the risk of pre-eclampsia by 10-15%.

The study also shows that overall genetic predisposition to hypertension is a major risk factor for preeclampsia and thus a large number of variants each with a small effect may also contribute to the risk. These current results complement the earlier findings of the same researchers, who showed that a variant near FLT1 gene in the fetal genome affects mothers' risk of developing pre-eclampsia.

The genes identified so far fit hand-in-glove with other current knowledge of pre-eclampsia as hypertension and obesity are known maternal risk factors. This study shows that these associations are partly explained by inherited predispositions. However, they only explain a part of the pre-eclampsia risk. Whether the remaining unidentified factors act through the maternal or fetal genome, or both, remains to be seen.

The new insights from this study could form the basis for more effective prevention and treatment of pre-eclampsia in the future, and improve the outcome of pregnancy for mother and child.

The five-year study was coordinated by Dr Linda Morgan from the University of Nottingham's School of Life Sciences; Nottingham Professors Emeritus Noor Kalsheker (Clinical Chemistry) and Fiona Broughton Pipkin (Obstetrics and Gynaecology) were among the collaborators.

Professor Fiona Broughton Pipkin said: "The new insights from this study could form the basis for more effective prevention and treatment of pre-eclampsia in the future, and improve the outcome of pregnancy for mother and child."

"They could also encourage GPs to follow-up more closely women who have had pre-eclampsia".

Lung tissue of patients who suffered severely from COVID-19 shows good recovery in most cases. This was revealed by a study carried out by the Radboud university medical center that has now been published in Clinical Infectious Diseases. A striking conclusion is that the group who was referred by a GP did not recover as well as patients who were admitted to the hospital's Intensive Care Unit (ICU).

The study, led by pulmonologist Bram van den Borst, included 124 patients who had recovered from acute COVID-19 infections. They visited the Radboud university medical center corona aftercare clinic. The patients were examined by CT scan, a lung functional test and more. After three months, the researchers took stock, which revealed that the patients' lung tissue is recovering well. Residual damage in the lung tissue was generally limited and is most often seen in patients who were treated in the ICU.

The most common complaints after three months are fatigue, shortness of breath and chest pains. Many people also still experience limitations in their daily life as well as a decreased quality of life. Main researcher and pulmonologist Bram van den Borst explains: "The patterns we see in these patients show similarities with recovery after acute pneumonia or acute respiratory distress syndrome (ARDS), in which fluid accumulates in the lungs. Recovery from these conditions also generally takes a long time. It is encouraging to see that lungs after COVID-19 infections exhibit this level of recovery."

Referred patients do not recover as well as admitted patients

Patients were divided into three categories for the study: a group with patients who were admitted to the ICU, a group of patients who were admitted to a nursing ward in the hospital, and finally a group with patients who could stay home but experienced persisting symptoms that eventually warranted a referral from their GP.

The study assessed how patients fared after three months and revealed that the patients who were referred to the aftercare clinic by their GP showed the worst recovery in the following period. Of course, this latter group of patients was referred because of their persisting symptoms. "However, it does seem that there is a clear subgroup of patients who initially experienced mild COVID-19 symptoms and later kept experiencing persistent long-term complaints and limitations", Bram van den Borst elaborates. "What is striking is that we barely found any anomalies in the lungs of these patients. Considering the variety and seriousness of the complaints and the plausible size of this subgroup, there is an urgent need for further research into explanations and treatment options."

Aftercare clinic for patients with persisting symptoms

Radboud university medical center established the corona aftercare clinic at the Dekkerswald location as a reaction to an observed increase in the signals that a substantial number of COVID-19 patients was experiencing long-term complaints, ranging from coughing, fatigue and shortness of breath to anxiety and physical limitations. At the aftercare clinic, an extensive analysis is performed involving multiple disciplines. Based on this analysis, the care requirements of the patients and the subsequent steps are determined. Patients who were admitted at Radboud university medical center with COVID-19 will receive an invitation from the corona aftercare clinic. People who went through COVID-19 from home and are still experiencing symptoms can get a referral from their GP to visit the aftercare clinic as well.

Researchers at the Estonian Genome Center at the University of Tartu studied how people at high risk for breast, ovarian or prostate cancer responses to the feedback of genetic findings. Gene donors who chose to receive results appreciated being contacted and considered the information provided to be valuable. Authors find that knowing more about people's genetic traits will significantly expand the chances of early detection of breast-, ovarian- and prostate cancer in the future.

The national breast cancer screening program in Estonia and in many other countries targets women in a limited age group (50-69 years). However, it's been known for quite some time that smaller proportion breast, ovarian or prostate cancer can be caused by high-risk genetic variants genes and then cancer often occurs at a younger age. Therefore, the medical system consistently misses people with a hereditary predisposition. If scientists succeed in translating large-scale genomic research into clinical practice, healthcare could improve markedly and enable healthcare providers to personalise prevention plans and treatments.

"In this case, we applied genotype-first method. In other words, we contacted biobank participants with specific findings in their BRCA1 and 2 genes, therefore being at higher risk for breast, ovarian or prostate cancer. In contrast to the approach current personal or family history based clinical approach, we selected participants according to their genetic variants. We started from biobank participants, and then included their family members" explained Marili Palover, one of the authors of the paper and a biomedical specialist.

According to the authors' results, all study participants considered the information provided to be understandable, interesting and valuable. Researchers recommend the return of results in population-based biobanks. Although receiving genetic information may in theory cause difficult emotions, this study proved otherwise - even 6 months later people reported that they were coping with the information received and had no regret regarding their decision to receive it.

Authors believe that this method could be viewed as a model for population-wide genetic testing. It helps to identify people at risk who would otherwise be unnoticed by the medical system based on personal and family histories only. Palover added that identifying people at risk before symptoms means individual surveillance and risk-reducing plan therefore better survival rate and preparedness, when symptoms arrive.

"Unfortunately, only 55% of the invites received responses and we do not know the reasons for not responding to our invite letter," said Palover. Authors discussed that it could be that some were fearful of receiving results, but it could also be that some did not understand that they could get valuable information as part of this study, and additionally non-responders could have had more practical reasons such as not receiving the letter, or being unable to attend the face-to-face counselling sessions held in Tartu. "Therefore, we are really grateful to those of the biobank participants and their relatives who joined the study," added Palover.

Researchers at the Estonian Genome Center at the University of Tartu described hitherto undiscovered associations between miscarriage and maternal genes, reveals a recent article published in the Nature Communications.

Miscarriage is the most common complication of pregnancy, affecting about 15% of clinically confirmed pregnancies. Although, the risk of miscarriage increases with maternal age, and has been associated with number of different reasons, up to two-thirds of miscarriages are unrecognized or undiagnosed and causal underlying factors remain largely unknown.

It has been found that miscarriage has a genetic component, with most previous studies focusing on associations of single maternal genetic variants with recurrent miscarriage. Furthermore, the majority of these studies have had small sample sizes and as a consequence identified largely inconsistent results. "Our study involved a large number of women whose gene variants were examined throughout the genome to find risk factors for sporadic or consecutive miscarriages," explained Triin Laisk, the first author of the paper and a Senior Research Fellow at the Estonian Genome Center.

Results show that miscarriage etiopathogenesis is partly driven by genetic variation potentially related to placental biology. Additionally, analysis of health outcomes associated with miscarriage confirms previous observations and identifies several novel ones, such as associations with asthma, depression and irritable bowel syndrome. Authors also noted links between smoking, mental health and general well-being and miscarriage. "Although previous studies have shown that miscarriage increases the risk of depression and cardiovascular diseases, the underlying reasons are unknown. However, genetic research will help us better understand what could be behind such associations," said Laisk.

The study only assessed the effect of maternal genetics on the risk of miscarriage. According to Laisk, further investigation into paternal and fetal genomes should be carried out to better understand the causes of miscarriage. "Although this study of maternal genetic variation shed some light on the causes of miscarriage , further research is definitely needed. In the future, we could know more about the biology behind a successful pregnancy and also about the long-term impact of miscarriage on overall health," added Laisk.

The study formed the basis of an international consortium that will continue to study the genetic causes of miscarriage. Authors analysed genetic information of 420 000 women and data were collected from biobanks around the world, including from the Estonian population-based biobank. "The results of this study illustrate the utility of large-scale biobank data for understanding this pregnancy complication," concluded Laisk.