Culture

Maths - it's the subject some kids love to hate, yet despite its lack of popularity, mathematics is critical for a STEM-capable workforce and vital for Australia's current and future productivity.

In a new study by the University of South Australia in collaboration with the Australian Council for Educational Research, researchers have been exploring the impact of anxiety on learning maths, finding that boosting student confidence, is pivotal to greater engagement with the subject.

Maths anxiety, or 'mathemaphobia', is the sense of fear, worry and nervousness that students may experience when participating in mathematical tasks.

In Australia a quarter to a third of Australian secondary students report feeling tense, nervous or helpless when doing maths, and it's this reaction that's influencing their decisions to study maths.

Lead researcher, Dr Florence Gabriel says maths anxiety is one of the biggest barriers to students choosing to study it, especially at senior school and tertiary levels.

"Many of us would have felt some sort of maths anxiety in the past - a sense of panic or worry, feelings of failure, or even a faster heart rate - all of which are associated with stress," Dr Gabriel says.

"Maths anxiety is essentially an emotional reaction, but it's just like stress in other situations.

"When students experience maths anxiety, they'll tend to hurry through maths questions, lose focus, or simply give up when it all seems too hard. Not surprisingly, these reactions compound and lead to poor maths achievement - and later a reluctance to engage with the subject at all.

"To break this cycle, our research shows that we need to build and grow student confidence in maths, especially before starting a new maths concept.

"This draws on the notion of self-regulated learning ¬- where students have the ability to understand, track and control their own learning.

"By drawing a student's attention to instances where they've previously overcome a difficult maths challenge, or to a significant maths success, we're essentially building their confidence and belief in their own abilities, and it's this that will start to counteract negative emotions."

The study assessed the responses of 4295 Australian 15-year-old students that participated in the 2012 cycle of the OECD's Program for International Student Assessment (PISA).

It focussed on the psychological factors of maths learning: motivation (the belief that maths is important and useful for their future); maths self-concept (the belief in their ability to do maths); maths anxiety (self-feelings when doing maths); perseverance (their willingness to continue to work on difficult problems); maths self-efficacy (their self-belief that they can successfully solve maths problems); and maths literacy (the ability to apply maths to the real world).

"Importantly, our research shows the domino effect that these variables have on one another," Dr Gabriel says.

"Through structural equation modelling, our data shows that low motivation and self-concept will lead to maths anxiety, which in turn affects perseverance, self-efficacy and, ultimately, maths achievement.

"By developing a student's ability to reflect on past successes - before maths anxiety sets in - we can break through some of the negative and emotional beliefs about maths and, hopefully, pave the way for students to accept and engage with maths in the future."

A test to diagnose two very serious diseases such as ALS and FTD when the pathologies have not yet appeared, thereby providing doctors and patients with essential information tools to tackle them early and develop new treatments. A team of researchers at SISSA in association with different clinical and Italian research institutes have made a first promising step in this direction. The protagonist of the study, published in the journal Brain Communication, is the protein TDP-43 which accumulates in brain cells in 97% of cases of ALS and in approximately 45% of those with frontotemporal dementia. This protein is therefore a possible biomarker for the diseases. In their work, the scientists developed a technique able to detect TDP-43 even when it is present in the body in minute quantities and in the earlier stages of disease, potentially in individuals who are still asymptomatic. The researchers explain that since there are currently no treatments that can interfere with the course of the two diseases, very early detection made thanks to the presence of this protein could be of great help to develop useful drugs to stop their progression and understand their dynamics.

What is the secret behind the technique? Produce many copies of the same protein

"Many neurodegenerative diseases, such as Alzheimer's or Parkinson, and the diseases caused by prions are characterised by the uncontrolled accumulation of specific proteins in the nerve cells" explain Carlo Scialò and Giuseppe Legname of SISSA, respectively first and last author of the publication. "A test called RT-QuIC (Real Time Quaking Induced Conversion Reaction) had already been developed for early identification of the proteins involved in several of these diseases. We thought of using it for the first time for two other diseases, ALS and frontotemporal dementia, where the protein that accumulates is the same: TDP-43". However, identifying it in the early stages of the disease means that the pathological forms of this protein may be present in minute quantities. How to detect them? "The sense of this technology is precisely this: minimum quantities of the pathological protein or fragments of the same are captured and multiplied in many identical copies, until sufficient quantities are obtained to be detected by the instrumentation. The presence of these pathological forms of the protein are an indicator of its accumulation in the central nervous system".

Research that involves more than 10 institutes in Italy

Besides SISSA, the research has involved the San Martino of Genoa, the University of Turin, the Carlo Besta of Milan, the Italian Auxological Institute, the University of Milan, the University of Brescia and the Institute Centro San Giovanni di Dio Fatebenefratelli of Brescia and three other institutes of Trieste: the University of Trieste, Elettra Sincrotrone and the ICGEB. "We have collaborated with all these institutes at various levels," explain Scialò and Legname. "Many of them were essential in the recruitment of patients who took part in the research". A sample of cerebrospinal fluid, the substance that surrounds the central nervous system, was taken from all of them and in which, the researchers deduced, it is likely to find the protein TDP-43, albeit in small quantities. The samples were then tested to identify the protein. "The patients involved were all carriers of a particular genetic mutation which we know leads to the accumulation of TDP-43 in the brain. With our system, we identified it in 94% of them, which is an excellent result".

The next steps to take

The researchers conclude: "In this phase we have developed the test and verified that it works well to identify TDP-43. Now further steps will be needed to fine-tune the methodology and the protocol, for example increasing the number of patients to be analysed. "Only" 36 were involved in this first test, but we are still at an early stage. It will also be necessary to understand in how many cases the detection of the protein at an early stage actually leads to the development of the disease. Therefore further investigations will be necessary before this test can be used safely and reliably for experimental diagnostic purposes, for example for enrolling subjects in clinical trials". But, they assure, the initial results are truly encouraging.

One of the most important and puzzling events in the evolution of life has been the origin of the first complex eukaryotic cells. Almost all lifeforms that we can perceive with the naked eye, such as algae, plants, animals and fungi, are made up of complex cells known as 'eukaryotes'. A collaborative study between the groups of Toni Gabaldón, ICREA researcher at the Institute for Research in Biomedicine (IRB Barcelona) and the Barcelona Supercomputing Center (BSC-CNS), and Berend Snel at the University of Utrecht, has concluded that the first cell to incorporate a mitochondrion (considered the key step to the increased complexity of eukaryotic cells) already presented eukaryote-like complexity in structure and functions. This scenario serves as a bridge between the signs of complexity observed in some archaeal genomes and the proposed role of mitochondria in triggering eukaryogenesis.

"The acquisition of mitochondria was considered either to be the crucial first step or the last step in the development of eukaryotic cell complexity," explains Gabaldón, "our findings show that it was indeed a crucial event, but that it happened in a scenario where cell complexity had already increased."

Complexity as a prelude to the diversity of life

For roughly the first half of the history of life on Earth, the only forms of life were the relatively simple cells of bacteria. "Eukaryotic cells are larger, contain more DNA and are made up of compartments, each with their own task," explains first author Julian Vosseberg. "In that sense, you could compare bacterial cells with a tent, while eukaryotic cells are more like houses with several rooms."

How and when organisms traded the tent for a house is still a mystery, as there are no intermediate forms. One important moment in evolution was the origin of mitochondria, a component of eukaryotic cells that function as their 'power plants'. Mitochondria were once free-living bacteria, but during evolution, they were absorbed by the ancestors of today's eukaryotic cells. As gene duplication probably drove the increase in cell complexity, the researchers attempted to reconstruct the evolutionary events based on these genetic changes.

Bioinformatics for evolutionary path reconstruction

"We can use the DNA of contemporary species to reconstruct evolutionary events. Our genes were formed over aeons of evolution. They have changed dramatically over that time, but they still hold echoes of a distant past." Vosseberg adds, "We have a vast quantity of genetic material available, from a variety of organisms, and we can use computers to reconstruct the evolution of thousands of genes, including ancient gene duplications. These reconstructions have enabled us to uncover the timing of important intermediate steps."

The co-corresponding author, Berend Snel, from the University of Utrecht, says, "Scientists did not have a timeline of these events. But now we've managed to reconstruct a rough timeline." To achieve this, the researchers adapted an existing method developed at Gabaldon's lab to create a new protocol, which has resulted in novel insights. These indicate that a lot of complex cellular machinery had evolved even before the symbiosis with mitochondria, including the development of transport within the cell and the cytoskeleton. "The symbiosis wasn't an event that served as the catalyst for everything else. We observed a peak in gene duplications much earlier in time, indicating that cell complexity had already increased before that moment," says Snel.

"Our study suggests that the ancestral host that acquired the mitochondrial endosymbiont had already developed some complexity in terms of a dynamic cytoskeleton and membrane trafficking" says Gabaldón "this might have favoured the establishment of symbiotic associations with other microorganisms, including the mitochondrial ancestor, which eventually became integrated".

(Jena, Germany) It still sounds unlikely today, but declines in insect numbers could well make it a frequent occurrence in the future: fields full of flowers, but not a bee in sight.

A research group of the University of Jena (Germany) and the German Centre for Integrative Biodiversity Research Halle-Jena-Leipzig (iDiv) has discovered that insects have a decisive influence on the biodiversity and flowering phases of plants. If there is a lack of insects where the plants are growing, their flowering behaviour changes. This can result in the lifecycles of the insects and the flowering periods of the plants no longer coinciding. If the insects seek nectar at the wrong time, some plants will no longer be pollinated.

Innovative research method in iDiv Ecotron

Ecosystems are changing around the world, in particular due to global warming and altered land use. Insect species are dying out and the insect biomass is decreasing. Researchers have therefore studied how the biodiversity of plants is changing in the context of climate change. For this purpose, various climate scenarios have been simulated, using different temperatures and precipitation.

In a new study reported in the specialist journal Frontiers in Plant Science, the Working Group Biodiversity of Plants of the University of Jena, led by Prof. Christine Römermann, presents a different research approach. In cooperation with scientists from iDiv, led by Prof. Nico Eisenhauer, the researchers are focusing on the influence of invertebrates, such as insects, on the biodiversity and flowering behaviour of plants.

"We know that the insect biomass is decreasing," says Josephine Ulrich, a doctoral candidate from Römermann's team, referring to a study from 2017 which detected that insects had declined by 75 per cent over the previous 30 years.

The Jena research group has now studied in detail for the first time the extent to which decreasing insect density influences plant development. Whereas previous studies had only carried out field experiments, the research team used the "Ecotron", an iDiv research facility where identical climatic situations can be simulated in artificial ecosystems and observed with cameras.

In their experiment, the researchers studied how plant composition and plant development change if the number of insects falls by three-quarters.

Mismatch between plant and animal worlds

Ulrich and her colleagues discovered that the reduced insect biomass brings about a change in plant species. It is especially the dominant plant species, such as red clover, which become more prevalent. The development of the flowering period also changes as insect density declines. Some of the plants studied flowered earlier and others later.

"These changes can lead to mismatches between plant and animal species, which lead to adverse consequences for the ecosystem," says Ulrich, the lead author of the study. Examples are the food supply of insects and pollination success. This deterioration in the ecosystem function could entail further losses of insect and plant species. An additional consequence could be that plants become increasingly infested with pests. Due to the falling numbers of insects that feed on aphids, for example, these pests could spread unchecked.

This study proposes a systematic method, which first integrates both the evenness and the overall status of all goals, to distinguish the ideal development pathways from the uneven ones. The results suggest that, despite the remarkable progress, a bottleneck has been reached in China since 2013 due to the stagnant developments in some SDGs. However, many far-reaching policies in China have been targeting these deficiencies since then, providing a perspective on how a country approaches sustainable development by promoting evenness among all SDGs.

At the regional level, all provinces had increased evenness score and sustainable development score from 2000 to 2015 (Fig. 1). Notably, regions with the slowest progress are those developed provinces, owing to the persistent uneven status of all goals. The effective development scores were further used to quantify the progress of 31 provinces towards SDGs from 2000 to 2015 through assessing the developing pathway (Fig. 2). Four of the top five economically developed regions had nearly no improvement from 2000 to 2015 (namely, Shanghai, Beijing, Tianjin, and Jiangsu). The bottleneck for economically developed regions in approaching SDGs is mainly ascribed to the resource and environmental constraints derived from their high population density along with urbanization.

Moreover, the 31 provinces were divided into four categories in terms of their relative status towards sustainable development in 2015 (Fig. 3). According to their current status, the relatively underdeveloped and uneven regions may collaborate in a complementary way towards SDGs, particularly beneficial for economically developed regions (mostly uneven). For instance, the stagnant progress in SDG 15 (life on land) in Beijing may be improved by collaborating with its surrounding regions (e.g., Hebei, which has much lower GDP per capita than Beijing) on ecological conservation. A feasible ecological compensation for Hebei province and the industrial relocation from Beijing to Hebei should help with the conservation and restoration of natural habitats in Beijing and its surrounding areas, and also help Hebei achieve economic development. Regional integration and cooperation might be effective in holistically achieving SDGs across regions.

By integrating all these findings, evenness expands the implications of sustainable development assessment and helps the government to match adaptive strategies to places. Moreover, the methods proposed in the present study can be applied to the rest of the world since they generally follow the widely adopted methods in data selection, normalization, and calculation of SDG scores. Overall, the study provides a new perspective on how a country approaches sustainable development by promoting evenness among all SDGs.

PHILADELPHIA -- Administering radiation therapy to multiple myeloma patients waiting for CAR T cells to be manufactured was found to be safe and undisruptive to CAR T therapy, according to a new study from researchers in the Abramson Cancer Center at the University of Pennsylvania to be presented Tuesday, October 27, at the virtual American Society for Radiation Oncology Annual Meeting (Abstract #35562) .

The study found patients who received radiation 34 days or fewer before their infusion with CART-BCMA (B cell maturation antigen) cells did not have worse rates of severe cytokine release syndrome (CRS) or neurotoxicity, two common side effects of the cellular therapy, and hematologic toxicities than patients who did not have so-called bridging care.

Radiation for relapsed/refractory multiple myeloma is often used to palliate bone pain associated with the disease; however, what effect it may have on patients and CAR T cell therapy hasn't been fully understood. The new findings suggest it appears to be a safe option for patients before they receive their CAR T cell infusions, lending more support for future studies that combine radiation with cellular therapy.

"The most important takeaway here is that bridging radiation doesn't appear to increase the risk of CRS or neurotoxicity," said lead author Shwetha Manjunath, MD, a resident in Radiation Oncology in Penn's Perelman School of Medicine. "These patients safely received bridge radiation without it affecting the efficacy of CAR T cells or the rates of toxicity."

Chimeric antigen receptor T cell therapy, known as CAR T, is an investigational treatment pioneered by researchers at Penn that modifies patients' own immune T cells, which are collected and reprogrammed to seek and destroy the patients' cancer cells. After being infused back into patients' bodies, these newly built "hunter" cells both multiply and attack. The Penn-developed CART-BCMA targets cells that express BCMA, which is highly expressed in myeloma.

This study, which is a retrospective analysis of a collaboration project with Novartis, evaluated the medical records of 25 patients who received CART-BCMA and categorized them into three groups. One group received radiation after their cells were collected for CAR T manufacturing but before their infusion, a period of 34 days or less. A second group of patients had received radiation within one year prior to CAR T infusion. A third group received either no radiation at all or no radiation within the year preceding CAR T infusion.

None of the four patients who received radiation while awaiting manufacturing experienced CRS, gastrointestinal, infectious, liver-related, or neurologic toxicities higher than a grade 3. CRS is a toxicity that includes varying degrees of flu-like symptoms, with high fevers, nausea, and muscle pain, and can require ICU-level care. Those patients also had lower rates of grade 4 hematologic toxicities. Of the eight patients who had a prior history of radiation, three experienced grade 3 or higher CRS. Among the 13 patients who did not receive any radiotherapy, five experienced Grade 3 or higher CRS. Radiation status was not associated with a decrease in overall survival or progression free survival.

In 2019, Penn researchers presented findings at ASTRO that found radiation did not interfere with the efficacy of CAR T cell therapy in non-Hodgkin lymphoma and had the potential to lower side effects in these patients.

"Our work is hypothesis generating, hinting at a potential synergism between radiation and CART-BCMA therapy, which has been reported by others in the literature," Manjunath said. "Future prospective trials that combine radiation with CART-BCMA may further optimize safety and long-term efficacy of this novel cell therapy."

Upper limb forequarter amputations which involve the removal of the entire arm and scapula require highly customized prosthetic devices that are expensive but yet, usually underutilized due to their high maintenance and low comfort levels. At the same time, while cosmetic prostheses - artificial limbs which provide patients the appearance of a pre-amputated body part - have a higher rate of continuous use, they have limitations in functional use.

Combining both technical and clinical expertise, the Singapore University of Technology and Design's (SUTD) Medical Engineering and Design Laboratory collaborated with Tan Tock Seng Hospital's (TTSH) Foot Care and Limb Design Centre, the largest provider of prosthetic services in Singapore, on a patient-specific upper limb prosthesis. This cosmetic prosthesis with a self-locking function was found to be more comfortable and around 20 percent cheaper compared to similar prostheses available in the industry.

To reduce the underutilization and delivery time, while taking improved fit, function and comfort into consideration, the research team turned to 3D printing due to its versatility and ability to cater to the device's geometrical and functional complexity.

The team also adopted a user-centered design approach, involving the patient throughout the customized design and development process. They then meticulously captured and documented the design process so that it can serve as a blueprint for other device applications or be replicated for other patients with limb amputations, thus reducing the over reliance on a prosthetist's judgement, skills and experience for an optimal fit.

Based on regular consultations with the patient and prosthetist at TTSH, including the shadowing of the patient to better understand his daily activities and functional needs, it was concluded that the new prosthesis needed to be lightweight, capable of dissipating heat, locking at 90° of flexion, comfortable to wear and void of metal components that would be detectable by airport scanners.

The research team used a digital scanner to capture residuum and contralateral arm geometries to replicate the patient's arm with high precision. They then designed different parts of the prosthesis from the captured geometries, 3D printed and verified these for fit, comfort, and function (refer to image). Their research paper was published in the Prosthetics and Orthotics International Journal.

The patient's satisfaction for the 3D printed prosthesis over his conventionally made prosthesis rated higher for its overall effectiveness, accurate size, symmetrical appearance and ease of use. Even though the new prosthesis weighed 100 grams more than the current prosthesis, the patient preferred it due to its improved suspension contributing to the feel of a lighter arm during use. However, the prosthesis was perceived to be less durable due to the patient's unfamiliarity with the quality of 3D printing, his concerns of the elbow locking mechanism breaking, and the appearance of the mesh structure compared to his current prosthesis.

"Digitalization and 3D printing have been transforming the design and manufacture of complex medical devices, surgery planning, medical education, and care delivery. Even though 3D printing technology has been around for more than three decades since the early 90's, it wasn't until recently that people really began to appreciate and trust it for end-use fabrication. In this work, 3D printing freed us from the manufacturing constraints and enabled us to optimize the design to suit the patient's needs. More importantly, this work sets the groundwork for future patient-specific end-use 3D printed parts for prosthetic needs," said principal investigator, Assistant Professor Subburaj Karupppasamy from SUTD's Engineering Product Development pillar.

Trevor Binedell, Principal Prosthetist at the Foot Care and Limb Design Centre, TTSH, and PhD student from SUTD, added, "The collaboration between TTSH and SUTD has led to a great outcome for this patient. User-design and the digitalization techniques have elevated the levels of patient-specific care to create individual designs that truly meet the needs of the user. This process has the potential to improve unique designs for many of our patients and enhance their quality of lives."

Shortly after the lockdown began, a huge number of volunteers signed up to help people in coronavirus risk groups - primarily via online platforms. A study by the University of Basel has found that websites such as these can have a positive impact with regard to the mobilization, willingness and satisfaction of volunteers, including in the longer term.

Right at the start of the COVID-19 pandemic, the importance of volunteer work became abundantly clear: thousands and thousands of people signed up spontaneously - and generally outside of formal structures - to buy groceries for others or to help in another way, such as by supporting the public health system. Unlike in previous crises, everyone involved faced the same risk of becoming infected. Their efforts were therefore generally organized through various online platforms that matched up volunteers with people in need.

Offers of help significantly exceeded demand

On all of the platforms, the offers of help far exceeded demand. Now, researchers from the Center for Philanthropy Studies CEPS at the University of Basel have worked with colleagues from the University of Freiburg and the ZHAW in Winterthur to study the importance of online platforms when it comes to the motivation and willingness of volunteers. They have reported their findings in the journal Nonprofit and Voluntary Sector Quarterly.

The researchers' survey of a sample of 565 volunteers from a major platform reveals that online placement can help channel the oversupply of volunteers and thus reduce unrealistic expectations. By providing information on safety and health matters during participation in voluntary work, the coronavirus platforms also had a positive impact on volunteer satisfaction.

Moreover, the satisfaction of active volunteers was higher the more afraid they were of catching the virus. According to the researchers, one possible explanation for this is that volunteer work boosted the volunteers' self-confidence -even more so when they believed themselves to be at greater risk.

Willingness to commit in the long term

"Greater satisfaction gained from spontaneous volunteering means people are more willing to commit to long-term volunteering opportunities at a later stage," says Professor Georg von Schnurbein, associate professor of foundation management at the University of Basel and co-author of the study. "Volunteer work is immensely important for our society - not only in times of crisis."

He highlights the importance of long-term commitment in many areas of society, such as in health and social services, as well as in cultural activities and youth work. According to the most recent survey, 665 million hours of volunteer work were completed in Switzerland in 2013, while paid work in the entire health and social services sector amounted to 853 million hours.

Scientists have used genome sequencing to reveal the extent to which a drug-resistant gastrointestinal bacterium can spread within a hospital, highlighting the challenge hospitals face in controlling infections.

Enterococcus faecium is a bacterium commonly found in the gastrointestinal tract, where it usually resides without causing the host problems. However, in immunocompromised patients, it can lead to potentially life-threatening infection.

Over the last three decades, strains have emerged that are resistant to frontline antibiotics including ampicillin and vancomycin, limiting treatment options - and particularly worrying, these strains are often those found in hospital-acquired E. faecium infections.

A team of scientists at the University of Cambridge and the London School of Hygiene and Tropical Medicine has pioneered an approach combining epidemiological and genomic information to chart the spread of bacteria within healthcare settings. This has helped hospitals identify sources of infection and inform infection control measures.

In a study published today in Nature Microbiology, the team has applied this technique to the spread of drug-resistant E. faecium in a hospital setting.

Dr Theodore Gouliouris from the Department of Medicine at the University of Cambridge, and joint first author on the study, said: "We've known for over two decades that patients in hospital can catch and spread drug-resistant E. faecium. Preventing its spread requires us to understand where the bacteria lives - its 'reservoirs' - and how it is transmitted.

"Most studies to date have relied on culturing the bacteria from samples. But as we've shown, whole genome sequencing - looking at the DNA of the bacteria - combined with detailed patient and environmental sampling can be a powerful tool to help us chart its spread and inform ways to prevent further outbreaks."

The team followed 149 haematology patients admitted to Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, over a six-month period. They took stool samples from the patients and swabs from the hospital environment and cultured them for E. faecium.

Genomic analysis of the bacteria was much more effective at identifying hospital-acquired E. faecium: out of 101 patients who could be followed up, genomic analysis identified that two thirds of patients acquired E. faecium, compared to less than half using culture methods alone.

Just under half (48%) of the swabs taken from the hospital environment were positive for vancomycin-resistant E. faecium. This included 36% of medical devices, 76% of non-touch areas such as air vents, 41% of bed spaces and 68% of communal bathrooms tested.

The researchers showed that even deep cleaning could not eradicate the bacteria. The hospital undertook deep cleaning on one ward over a three-day period during the study, when patients were moved elsewhere; however, when the team sampled locations prior to patients returning to the ward, they found that 9% of samples still tested positive for the bacteria. Within three days of patients returning to the ward, around half of the sampled sites tested positive.

Three-quarters (74%) of the patients (111/149) were carriers of the A1 clade - a multi-drug resistant strain of E. faecium commonly seen in hospitals that is resistant to the antibiotic ampicillin and which frequently acquires resistance to vancomycin. Of these 111 patients, 67 had strong epidemiological and genomic links with at least one other patient and/or their direct environment.

"The fact that these cases were all linked to another patient or their environment suggests strongly that they had picked up the multi-drug resistant bacteria while in the hospital," said Dr Francesc Coll from the London School of Hygiene and Tropical Medicine, joint first author.

Further genomic analysis showed that within this multi-drug resistant strain were several subtypes (defined by how genetically-similar they were). However, it was not uncommon for a patient to be carrying more than one subtype, which - without detailed genomic analysis - could confound attempts to identify the route of transmission of an infection. Notably, despite the circulation of as many as 115 subtypes, 28% of E. faecium acquisitions were caused by just two superspreading subtypes. The authors found no evidence of resistance or tolerance to common disinfectants to explain the success of these subtypes.

Six study patients contracted an 'invasive infection', meaning that they had been carrying E. faecium asymptomatically in their gut, but subsequently developed a symptomatic infection. Comparing the genomes of the infecting and gut strains the authors determined that invasive E. faecium infections originated from the patients' own gut.

"Our study builds on previous observations that drug-resistant strains of E. faecium can persist in the hospital environment despite standard cleaning - we were still surprised to find how short-lasting was the effect of deep cleaning," added Dr Gouliouris.

"We found high levels of hospital-adapted E. faecium despite the use of cleaning products and procedures that have proven effective against the bug. It highlights how challenging it can be to tackle outbreaks in hospitals."

Senior author Professor Sharon Peacock from the Department of Medicine at the University of Cambridge added: "The high rates of infection with drug-resistant E. faecium in specific vulnerable patient groups and its ability to evade cleaning measures pose an important challenge to infection control. Patient screening, adequate provision of isolation and ensuite toilet facilities, improved and more frequent cleaning procedures, and stricter health-care worker hygiene practices will all be needed to curtail this global epidemic.

"But this is also a sign of how urgently we need to tackle inappropriate use of antibiotics worldwide, which is widely recognised as posing a catastrophic threat to our health and our ability to control infections."

T-cells taken from the blood of people who recovered from a COVID-19 infection can be successfully multiplied in the lab and maintain the ability to effectively target proteins that are key to the virus's function, according to a new study published Oct. 26 in Blood.

"We found that many people who recover from COVID-19 have T-cells that recognize and target viral proteins of SARS-CoV-2, giving them immunity from the virus because those T-cells are primed to fight it," says Michael Keller, M.D., a pediatric immunology specialist at Children's National Hospital, who led the study. "This suggests that adoptive immunotherapy using convalescent T-cells to target these regions of the virus may be an effective way to protect vulnerable people, especially those with compromised immune systems due to cancer therapy or transplantation."

Based on evidence from previous phase 1 clinical trials using virus-targeting T-cells "trained" to target viruses such as Epstein-Barr virus, the researchers in the Cellular Therapy Program at Children's National hypothesized that the expanded group of COVID-19 virus-targeting T-cells could be infused into immunocompromised patients, helping them build an immune response before exposure to the virus and therefore protecting the patient from a serious or life-threatening infection.

"We know that patients who have immune deficiencies as a result of pre-existing conditions or following bone marrow or solid organ transplant are extremely vulnerable to viruses like SARS-CoV-2," says Catherine Bollard, M.D., M.B.Ch.B., senior author of the study and director of the novel cell therapies program and the Center for Cancer and Immunology Research at Children's National. "We've seen that these patients are unable to easily clear the virus on their own, and that can prevent or delay needed treatments to fight cancer or other diseases. This approach could serve as a viable option to protect or treat them, especially since their underlying conditions may make vaccines for SARS-CoV-2 unsafe or ineffective."

The T-cells were predominantly grown from the peripheral blood of donors who were seropositive for SARS-CoV-2. The study also identified that SARS-CoV-2 directed T-cells have adapted to predominantly target specific parts of the viral proteins found on the cell membrane, revealing new ways that the immune system responds to COVID-19 infection.

Current vaccine research focuses on specific proteins found mainly on the "spikes" of the coronavirus SARS-CoV-2. The finding that T-cells are successfully targeting a membrane protein instead may add another avenue for vaccine developers to explore when creating new therapeutics to protect against the virus.

"This work provides a powerful example of how both scientific advances and collaborative relationships developed in response to a particular challenge can have broad and unexpected impacts on other areas of human health," says Brad Jones, Ph.D., an associate professor of immunology in medicine in the Division of Infectious Diseases at Weill Cornell Medicine and co-author on the study, whose lab focuses on HIV cure research. "I began working with Dr. Bollard's team several years ago out of our shared interest in translating her T-cell therapy approaches to HIV. This put us in a position to quickly team up to help develop the approach for COVID-19."

Scientists have created synthetic soft surfaces with tongue-like textures for the first time using 3D printing, opening new possibilities for testing oral processing properties of food, nutritional technologies, pharmaceutics and dry mouth therapies.

UK scientists led by the University of Leeds in collaboration with the University of Edinburgh have replicated the highly sophisticated surface design of a human tongue and demonstrated that their printed synthetic silicone structure mimics the topology, elasticity and wettability of the tongue's surface.

These factors are instrumental to how food or saliva interacts with the tongue, which in turn can affect mouthfeel, swallowing, speech, nutritional intake and quality of life.

A biomimetic tongue will help developers to perform screening of newly designed products and accelerate the new development processes without the necessity of human trials at early stages that are often very expensive and time consuming.

Particularly, since the onset of the COVID-19 pandemic, social distancing has posed significant challenges to carry out such sensory trials and consumer tests. A biomimetic tongue will be immensely helpful to increase development productivity and reducing manufacturers' reliance on human trials in the early stages.

A biomimetic tongue could further offer myriad applications to fight against adulteration in food and other orally administered pharmaceutics whether textural attributes are governing features and can save huge economic loss.

The complex nature of the tongue's biological surface has posed challenges in artificial replication, adding major obstacles to the development and screening of effective long-lasting treatments or therapies for dry mouth syndrome -- roughly 10% of the general population and 30% of older people suffer from dry mouth.

Study lead author, Dr Efren Andablo-Reyes conducted this research while a postdoctoral fellow in the School of Food Science and Nutrition at Leeds. He said: "Recreating the surface of an average human tongue comes with unique architectural challenges. Hundreds of small bud-like structures called papilla give the tongue its characteristic rough texture that in combination to the soft nature of the tissue create a complicated landscape from a mechanical perspective.

"We focused our attention on the anterior dorsal section of the tongue where some of these papillae contain taste receptors, while many of them lack such receptors. Both kinds of papillae play a critical role in providing the right mechanical friction to aid food processing in the mouth with the adequate amount saliva, providing pleasurable mouthfeel perception and proper lubrication for swallowing.

"We aimed to replicate these mechanically relevant characteristics of the human tongue in a surface that is easy to use in the lab to replicate oral processing conditions."

The study that brought together unique expertise in food colloid science, soft matter physics, dentistry, mechanical engineering and computer science is published today in the journal ACS Applied Materials & Interfaces.

The team took silicone impressions of tongue surfaces from fifteen adults. The impressions were 3D optically scanned to map papillae dimensions, density and the average roughness of the tongues. The texture of a human tongue was found to resemble a random layout.

The team used computer simulations and mathematical modelling to create a 3D-printed artificial surface to function as a mould containing wells with the shape and dimensions of the different papillae randomly distributed across the surface with right density. This was replica-moulded against elastomers of optimised softness and wettability.

University of Edinburgh co-author, Rik Sarkar of the School of Informatics said: "The randomness in distribution of papillae appears to play an important sensory role for the tongue.

"We defined a new concept called collision probability to measure mechanosensing that will have large impact in this area. In the future, we will use a combination of machine learning and computational topology to create tongue models of diverse healthy and diseased individuals to address various oral conditions."

The artificial surface was then 3D printed using digital light processing technology based in the School of Mechanical Engineering at Leeds.

The team ran a series of experiments using different complex fluids to ensure that the printed surface's wettability - how a liquid keeps contact and spreads across a surface - and the lubrication performance was the same as the human tongue impressions.

Co-author Dr Michael Bryant from the School of Mechanical Engineering at Leeds said: "The application of bio-tribological principles, the study of friction and lubrication, in the creation of this tongue-like surface is a significant step forward in this field.

"The ability to produce accurate replicas of tongue surfaces with similar structure and mechanical properties will help streamline research and development for oral care, food products and therapeutic technologies."

Principal Investigator Anwesha Sarkar, Professor of Colloids and Surfaces at Leeds, said: "Accurately mapping and replicating the tongues surface and combining that with a material that approximates the elasticity of human tongue was no small task. Harnessing expertise from multiple STEM disciplines, we've demonstrated the unprecedented capability of a 3D printed silicone surface to mimic the mechanical performance of the human tongue.

"We believe that fabricating a synthetic surface with relevant properties that mimics the intricate architectural features, and more importantly the lubricating performance of the human tongue is paramount to gaining quantitative understanding of how fluids interact within the oral cavity.

"This biomimetic tongue surface could also serve as a unique mechanical tool to help detect counterfeit in food and high-valued beverages based on textural attributes, which is a global concern and can help to ensure food safety.

"Ultimately, our hope is that the surface we have designed can be important in understanding how the biomechanics of the tongue underpin the fundamentals of human feeding and speech.

NEW YORK, NY (October 26, 2020) - To identify new potential therapeutic targets for SARS-CoV-2, a team of scientists at the New York Genome Center, New York University, and the Icahn School of Medicine at Mount Sinai, performed a genome-scale, loss-of-function CRISPR screen to systematically knockout all genes in the human genome. The team examined which genetic modifications made human lung cells more resistant to SARS-CoV-2 infection. Their findings revealed individual genes and gene regulatory networks in the human genome that are required by SARS-CoV-2 and that confer resistance to viral infection when suppressed. The collaborative study described a wide array of genes that have not previously been considered as therapeutic targets for SARS-CoV-2. Their study was published online by Cell on October 24.

In order to better understand the complex relationships between host and virus genetic dependencies, the team used a broad range of analytical and experimental methods to validate their results. This integrative approach included genome editing, single-cell sequencing, confocal imaging, and computational analyses of gene expression and proteomic datasets. The researchers found that these new gene targets, when inhibited using small molecules (drugs), significantly reduced viral load, and with some drugs, up to 1,000-fold. Their findings offer insight into novel therapies that may be effective in treating COVID-19 and reveal the underlying molecular targets of those therapies.

"Seeing the tragic impact of COVID-19 here in New York and across the world, we felt that we could use the high-throughput CRISPR gene editing tools that we have applied to other diseases to understand what are the key human genes required by the SARS-CoV-2 virus," said the study's co-senior author, Dr. Neville Sanjana, Core Faculty Member at the New York Genome Center, Assistant Professor of Biology, New York University, and Assistant Professor of Neuroscience and Physiology at NYU Grossman School of Medicine. Previously, Dr. Sanjana has applied genome-wide CRISPR screens to identify the genetic drivers of diverse diseases, including drug resistance in melanoma, immunotherapy failure, lung cancer metastasis, innate immunity, inborn metabolic disorders, and muscular dystrophy.

For this project, genome editing was only one-half of the equation. "We previously developed a series of human cell models for coronavirus infection in our work to understand immune responses to the virus. It was great to team up with Neville's group to understand and comprehensively profile host genes from a new angle," said co-senior author Dr. Benjamin tenOever, Fishberg Professor of Medicine, Icahn Scholar and Professor of Microbiology, Icahn School of Medicine at Mount Sinai.

Gene clusters lead the way

The team discovered that the top-ranked genes -- those whose loss reduces viral infection substantially -- clustered into a handful of protein complexes, including vacuolar ATPases, Retromer, Commander, Arp2/3, and PI3K. Many of these protein complexes are involved in trafficking proteins to and from the cell membrane.

"We were very pleased to see multiple genes within the same family as top-ranked hits in our genome-wide screen. This gave us a high degree of confidence that these protein families were crucial to the virus lifecycle, either for getting into human cells or successful viral replication," said Dr. Zharko Daniloski, a postdoctoral fellow in the Sanjana Lab and co-first author of the study.

While researchers performed the CRISPR screen using human lung cells, the team also explored whether the expression of required host genes was lung-specific or more broadly expressed. Among the top-ranked genes, only ACE2, the receptor known to be responsible for binding the SARS-CoV-2 viral protein Spike, showed tissue-specific expression, with the rest of the top gene hits broadly expressed across many tissues, suggesting that these mechanisms may function independent of cell or tissue type. Using proteomic data, they found that several of the top-ranked host genes directly interact with the virus's own proteins, highlighting their central role in the viral lifecycle. The team also analyzed common host genes required for other viral pathogens, such as Zika or H1N1 pandemic influenza.

Mechanistic insights: Cholesterol and viral receptors

After completing the primary screen, the group of researchers used several different techniques to validate the role of many of the top-ranked genes in viral infection. Using human cell lines derived from the lung and other organs susceptible to SARS-CoV-2 infection, they measured viral infection after gene knockout by CRISPR, gene suppression using RNA interference, or drug inhibition. After validating that these manipulations reduced viral infection, they next sought to understand the mechanisms by which loss of these genes block coronavirus infection.

Using a recently-developed technology that couples large-scale CRISPR editing with single-cell RNA-sequencing (ECCITE-seq), the team identified that loss of several top-ranked genes results in upregulation of cholesterol biosynthesis pathways and an increase in cellular cholesterol. Using this insight, they studied the effects of amlodipine, a drug that alters cholesterol levels.

"We found that amlodipine, a calcium-channel antagonist, upregulates cellular cholesterol levels and blocks SARS-CoV-2 infection. Since recent clinical studies have also suggested that patients taking calcium-channel blockers have a reduced COVID-19 case fatality rate, an important future research direction will be to further illuminate the relationship between cholesterol synthesis pathways and SARS-CoV-2," said Dr. Tristan Jordan, a postdoctoral fellow in the tenOever Lab and co-first author of the study.

Building on previous work on mutations in the Spike protein and viral entry through the ACE2 receptor, the research team also asked whether loss of some genes might confer resistance to the coronavirus by lowering ACE2 levels. They identified one gene in particular, RAB7A, that has a large impact on ACE2 trafficking to the cell membrane. Using a combination of flow cytometry and confocal microscopy, the team showed that RAB7A loss prevents viral entry by sequestering ACE2 receptors inside cells.

"Current treatments for SARS-CoV-2 infection currently go after the virus itself, but this study offers a better understanding of how host genes influence viral entry and will enable new avenues for therapeutic discovery and hopefully accelerate recovery for susceptible populations," said Dr. Sanjana.

Monday 26 October 2020 - A world-first double-blind clinical trial, will investigate if a powerful drug used to treat nausea in chemotherapy patients, could alleviate hallucinations in people with Parkinson's.

Parkinson's UK, the largest charitable funder of Parkinson's research in Europe, is partnering with UCL, and investing £1 million in a pioneering phase II clinical trial to explore if the drug ondansetron is safe and effective against hallucinations. There are currently 145,000 people living with Parkinson's in the UK and 75 per cent of them will experience visual hallucinations at some point.

The trial comes at a crucial time as a survey carried out by the charity worryingly found that 1 in 10 people with Parkinson's reported an increase in hallucinations during lockdown, which led to an increase in calls to their helpline.¹

The funding for this four-year project comes via the charity's drug development arm, the Parkinson's Virtual Biotech. Launched in 2017, the innovative programme is plugging the funding gap to fast-track the projects with the greatest scientific potential to transform the lives of people with Parkinson's. This is the second clinical trial to be added to the Virtual Biotech's pipeline of projects in a drive to develop better drug treatments for people with Parkinson's.

Dr Arthur Roach, Director of Research at Parkinson's UK said:

"It's vital we find better treatments for people with Parkinson's who have seen their hallucinations worsen at home and ondansetron offers much hope for them and their families. If successful, positive results from the trial could see this drug, which is already used in the NHS, quickly repurposed to become an available treatment in Parkinson's.

"With the support of Parkinson's UK, UCL has been rapidly adapting the research during the pandemic, to enable us to drive forward and launch this promising trial, which marks another milestone in our thriving Parkinson's Virtual Biotech programme."

Treating hallucinations is one of the most challenging aspects in people with Parkinson's and it can have a big effect on their quality of life. It can be extremely distressing for carers as well as people with Parkinson's, putting stress on relationships. The only medications available to treat it today are anti-psychotic drugs which can worsen Parkinson's symptoms and potentially cause serious side effects. This urgent need for new treatments is why hallucinations are a top priority for the Parkinson's Virtual Biotech.

The 12-week, double-blind, placebo-controlled trial is set to recruit 216 people over 2 years in 20-25 NHS clinics across the UK. Patients will be randomised to receive either drug or placebo tablets, to take at home for 12 weeks. To accommodate social distancing, researchers will conduct the majority of the study via video or telephone consultations, with face-to-face assessments limited to only three for essential blood tests or ECGs. Visual and other types of hallucinations, as well as delusions (false beliefs), will be assessed after 6 and 12 weeks of treatment, along with Parkinson's related motor and non-motor symptoms.

Lead Researcher, Suzanne Reeves, Professor of Old Age Psychiatry and Psychopharmacology at UCL said:

"Visual hallucinations pose a particular challenge in Parkinson's as the very treatments for motor symptoms in Parkinson's can also trigger and worsen this distressing symptom. Finding treatments for hallucinations that are both effective and safe is an area of great unmet need.

"Ondansetron influences visual processing in the brain and its potential for treating visual hallucinations in Parkinson's was first identified in small studies in the early 1990s.

"This trial will enable us to find out if ondansetron is effective and safe as a treatment and if it is, we could see clinicians prescribing an inexpensive drug with fewer side effects to people with Parkinson's throughout the UK."

Parkinson's UK has their own in-house experts, and partners with clinical and academic institutions, pharmaceutical companies and biotechs worldwide. To partner with Parkinson's UK to drive forward potential new treatments, visit http://www.parkinsonsvirtualbiotech.co.uk

"Much of the discussion so far related to the future trajectory of COVID-19 has rightly been focused on the effects of seasonality and non-pharmaceutical interventions [NPIs], such as mask-wearing and physical distancing," said co-first author Chadi Saad-Roy, a Ph.D. candidate in Princeton's Lewis-Sigler Institute for Integrative Genomics. "In the short term, and during the pandemic phase, NPIs are the key determinant of case burdens. However, the role of immunity will become increasingly important as we look into the future."

"Ultimately, we don't know what the strength or duration of natural immunity to SARS-CoV-2 -- or a potential vaccine -- will look like," explained co-first author Caroline Wagner, an Assistant Professor of Bioengineering at McGill University who worked on the study as a postdoctoral research associate in the Princeton Environmental Institute (PEI).

"For instance, if reinfection is possible, what does a person's immune response to their previous infection do?" Wagner asked. "Is that immune response capable of stopping you from transmitting the infection to others? These will all impact the dynamics of future outbreaks."

The current study builds on previous research by the same team, published in Science on May 18 that reported that local variations in climate are not likely to dominate the first wave of the COVID-19 pandemic.

In the most recent paper, the researchers used a simple model to project the future incidence of COVID-19 cases -- and the degree of immunity in the human population -- under a range of assumptions related to how likely individuals are to transmit the virus in different contexts. For example, the model allows for different durations of immunity after infection, as well as different extents of protection from reinfection. The researchers posted online an interactive version of model's predictions under these different sets of assumptions.

As expected, the model found that the initial pandemic peak is largely independent of immunity because most people are susceptible. However, a substantial range of epidemic patterns are possible as SARS-CoV-2 infection -- and thus immunity -- increases in the population.

"If immune responses are only weak, or transiently protective against reinfection, for example, then larger and more frequent outbreaks can be expected in the medium term," said co-author Andrea Graham, professor of ecology and evolutionary biology at Princeton.

The nature of the immune responses also can affect clinical outcomes and the burden of severe cases requiring hospitalization, the researchers found. The key question is the severity of subsequent infections in comparison to primary ones.

Importantly, the study found that in all scenarios a vaccine capable of eliciting a strong immune response could substantially reduce future caseloads. Even a vaccine that only offers partial protection against secondary transmission could generate major benefits if widely deployed, the researchers reported.

Factors such as age and superspreading events are known to influence the spread of SARS-CoV-2 by causing individuals within a population to experience different immune responses or transmit the virus at different rates. The study found that these factors do not affect the qualitative projections about future epidemic dynamics. However, the researchers note that as vaccine candidates emerge and more detailed predictions of future caseloads with vaccination are needed, these additional details will need to be incorporated into more complex models.

The study authors also explored the effect of "vaccine hesitancy" on future infection dynamics. Their model found that people who decline to partake in pharmaceutical and non-pharmaceutical measures to contain the coronavirus could nonetheless slow containment of the virus even if a vaccine is available.

"Our model indicates that if vaccine refusal is high and correlated with increased transmission and riskier behavior such as refusing to wear a mask, then the necessary vaccination rate needed to reach herd immunity could be much higher," said co-author Simon Levin, the James S. McDonnell Distinguished University Professor in Ecology and Evolutionary Biology and an associated faculty member in PEI. "In this case, the nature of the immune response after infection or vaccination would be very important factors in determining how effective a vaccine would be."

One of the main takeaways of the study is that monitoring population-level immunity to SARS-CoV-2, in addition to active infections, will be critical for accurately predicting future incidence.

"This is not an easy thing to do accurately, particularly when the nature of this immune response is not well understood," said co-author Michael Mina, an assistant professor at the Harvard School of Public Health and Harvard Medical School. "Even if we can measure a clinical quantity like an antibody titer against this virus, we don't necessarily know what that means in terms of protection."

Studying the effects of T-cell immunity and cross-protection from other coronaviruses are important avenues for future work.

Leopards are fascinating animals. In addition to being sublime hunters that will eat nearly anything and can survive in varied habitats from forests to deserts, they are able to withstand temperatures ranging from minus 40 degrees Celsius during winter to plus 40 degrees in summer.

Despite their resilience, the majority of leopard species are endangered. Poaching and the clearing of forest habitat for human activities are among the reasons for their global decline.

But in northern China -- and specifically upon the Loess Plateu -- something fantastic is occurring.

Numbers of a leopard subspecies called the North Chinese leopard have increased according to a new study conducted by researchers from the University of Copenhagen and their colleagues in Beijing.

"We were quite surprised that the number of leopards has increased, because their populations are declining in many other places. We knew that there were leopards in this area, but we had no idea how many," says Bing Xie, a PhD student at UCPH's Department of Biology and one of the researchers behind the study.

Together with researchers at Beijing Normal University, she covered 800 square kilometers of the Loess Plateu between 2016 and 2017.

The just-completed count reports that the number of leopards increased from 88 in 2016 to 110 in 2017 -- a 25 percent increase. The researchers suspect that their numbers have continued to increase in the years since.

This is the first time that an estimate has been made for the status of local population in North Chinese leopards.

Five-year reforestation plan has worked

The reason for this spotted golden giant's rebound likely reflects the 13'th five-year plan that the Chinese government, in consultation with a range of scientific researchers, implemented in 2015 to restore biodiversity in the area.

"About 20 years ago, much of the Loess Plateau's forest habitat was transformed into agricultural land. Human activity scared away wild boars, toads, frogs and deer -- making it impossible for leopards to find food. Now that much of the forest has been restored, prey have returned, along with the leopards," explains Bing Xie, adding:

"Many locals had no idea there were leopards in the area, so they were wildly enthused and surprised. And, it was a success for the government, which had hoped for greater biodiversity in the area. Suddenly, they could 'house' these big cats on a far greater scale than they had dreamed of."

Leopards are nearly invisible in nature

The research team deployed camera equipment to map how many leopards were in this area of northern China. But even though the footage captured more cats than expected on film, none of the researchers saw any of the big stealthy felines with their own eyes:

"Leopards are extremely shy of humans and sneak about silently. That's why it's not at all uncommon to study them for 10 years without physically observing one," she explains.

Even though Bing Xie has never seen leopards in the wild, she will continue to fight for their survival.

"That 98 percent of leopard habitat has been lost over the years makes me so sad. I have a great love for these gorgeous cats and I will continue to research on how best to protect them," she concludes.