Culture

Coronavirus Pneumonia and Pulmonary Thromboembolism
https://doi.org/10.15212/bioi-2020-0030

Announcing a new publication for BIO Integration journal. In this article the authors Mingkang Yao; Phei Er Saw and Shanping Jiang from Sun Yat-Sen University, Guangzhou, China review Coronavirus Pneumonia and Pulmonary Thromboembolism.

In this review, the authors summarize the harmful effects of that coronavirus pneumonia and highlight the clinical relationship between PTE and coronavirus infection. Potential mechanisms and prophylaxis and therapeutic measures are also discussed.

The COVID-19 global pandemic has severely threatened public respiratory health and medical services. Coagulation disorders, especially pulmonary thromboembolism (PTE), has proved to be a complication in severe COVID-19 patients, with the incidence of PTE causing poor clinical outcome and increased fatality.

It is important that healthcare providers recognize that patients with COVID-19 are at increased risk of PTE, and ensure that appropriate prophylaxis is administered to the appropriate patients, and that they effectively manage PTE when it does occur.

The mechanism of PTE in patients with coronavirus pneumonia consists of endothelial injury, activated platelet, cytokine storm, and a suppressed fibrinolytic system. Early prophylaxis, antiviral therapy, anticoagulation, and supportive treatment are beneficial to COVID-19 patients.

In this review, the authors summarize the harmful effects of that coronavirus pneumonia and highlight the clinical relationship between PTE and coronavirus infection. Potential mechanisms and prophylaxis and therapeutic measures are also discussed.

A laser-based sensor developed at KAUST could improve monitoring of benzene emissions and limit exposure to this pollutant. In collaboration with Saudi Aramco, KAUST researchers have developed a device that accurately senses extremely low concentrations of benzene in real time.

Benzene can cause serious health conditions, including cancer and the blood-related disease aplastic anemia. This harmful volatile compound, which originates from natural sources and human activities, mainly exists in industrial settings ranging from crude oil and petrochemical processing facilities to service stations, putting the health of workers at risk. It is also present in vehicle exhaust, biomass-based heating fuels and some consumer products, which can lead to dangerous exposure.

Typical approaches designed to control benzene emissions rely on gas chromatography and mass spectrometry but demand stringent maintenance schedules, complex sampling protocols and time-consuming measurements. Commercially available sensors present interference problems from other ambient air components and detection limits exceeding 100 parts per billion, failing to meet the recommended thresholds.

Now, a team led by Aamir Farooq--in a project funded by Saudi Aramco's Environmental Protection Department--has developed a compact laser-based sensor that exhibits high selectivity and sensitivity to benzene with a detection limit of 2 parts per billion, outperforming existing devices. Robust enough for field applications, the sensor performs measurements in seconds without preliminary calibration.

To achieve this unprecedented sensitivity, the researchers designed a sensor with walls that comprise two parallel concave mirrors that face each other to form a cavity around the sample. The cavity traps the laser beam, which keeps reflecting back and forth between the mirrors. "In this way, it travels a dramatically larger distance through the sample than the inter-mirror separation," explains Ph.D. student Mhanna Mhanna, who performed the experiments. "It enables us to detect concentrations that are three orders of magnitude lower than in a conventional sensor," he adds.

Farooq's team optimized the light absorption of benzene by selecting the laser wavelength and mathematically eliminating any interference from methane, ethylene and water vapor. This provided accurate benzene concentrations in the presence of interfering components.

The sensor detected trace benzene in real samples collected from various locations. For example, the sensor detected higher benzene concentrations in parking garage on weekdays than on weekends, consistent with traffic conditions. Service stations showed the highest levels, but these amounts were well below recommended thresholds.

"The sensor could be attached to a drone or carried by hand to scan target areas daily for benzene emissions," Mhanna says. The team is also looking into ways to make the sensor more portable.

Since its appearance in early 2020, COVID-19 has been unpredictable for both physicians and affected individuals given the variety and duration of its symptoms. Notably, it appears to have the potential to cause an unusually long-lasting illness, and the term "long COVID" describes the disease in people who continue to report symptoms several weeks following the infection. To better understand this phenomenon, a team of physicians and epidemiologists from the University of Geneva (UNIGE) the University Hospitals of Geneva (HUG) and the General Health Directorate of the State of Geneva followed nearly 700 people who tested positive for SARS-COV2 but did not require hospitalisation. Six weeks after diagnosis, 33% of them still reported suffering from fatigue, loss of smell or taste, shortness of breath or cough. These results, which can be seen in the Annals of Internal Medicine, call for better communication, particularly with patients and with the physicians who follow them, and for ongoing messages to the general public, reminding them that SARS-CoV-2 infection is not trivial.

Even if in just a few months medical and scientific knowledge about SARS-COV2 has considerably improved, several aspects of this disease remain unknown. In particular, many people are wondering about the evolution and long-term consequences of this novel virus. "As soon as the pandemic arrived in our country, we were confronted with these questions," reports Professor Idris Guessous, physician epidemiologist at the Department of Community Health and Medicine of the UNIGE Faculty of Medicine and Chief Physician of the Division of Primary Care at HUG, who directed this work. "In March, the COVICARE program was set up to offer remote monitoring to patients who can be followed on an outpatient basis, when this follow-up could not be carried out by the primary care physician. This has enabled us to better understand the evolution of the disease in people who generally suffer neither from specific risk factors nor from a serious form of the disease."

Some Very Tired Patients

A total of 669 people were followed (mean age 43 years, 60% female, 25% of healthcare professionals and 69% without underlying risk factors that could be related to complications from COVID-19). At 6 weeks from diagnosis, nearly a third of participants still had one or more symptoms related to COVID-19, mainly fatigue (14%), shortness of breath (9%) and loss of taste or smell (12%). In addition, 6% reported a persistent cough and 3% reported headaches. Dr. Mayssam Nehme, Senior Resident in Professor Guessous's team and first author of this work, also explains how these patients felt: "In addition to the physical distress of their symptoms, many were very worried: how much longer would it last? Were some after-effects irrecoverable? Even without a clear medical answer, in the current state of knowledge, it is important to accompany concerned patients and to listen to them," she adds. With this in mind, the HUG has set up a specific consultation for long COVID patients in order to improve their care and guide them through the health system.

Better Understanding for Better Information

The persistence of symptoms must be recognised in order to legitimise the concerns of patients faced with a new and unknown disease, and to optimise their management. "This requires an information campaign towards the general public and healthcare workers, but also, more broadly, among employers, insurance companies and society in general. Everyone should realise that previously healthy people can also be affected by COVID-19, weeks or even months following the infection. Prevention is therefore of the utmost importance," add the authors, who are continuing their studies to understand the long-term evolution of these patients. Indeed, a follow-up of the same cohort 3 months, 7 months and 12 months following the infection is in progress.

UTERINE FIBROIDS CAN TAKE A HEAVY EMOTIONAL TOLL ON WOMEN, STUDY SHOWS

Media Contact: Marisol Martinez, mmart150@jhmi.edu

In a comprehensive review of 57 research studies looking at the quality of life of women with uterine fibroids compared with that of people with other chronic diseases, Johns Hopkins Medicine researchers found that the psychological and social burden of the condition is comparable with those for heart disease, diabetes or breast cancer.

The findings, published in the Nov. 1, 2020, issue of the American Journal of Obstetrics & Gynecology, suggest that fibroids affect a woman's quality of life both physically and emotionally. Furthermore, the condition may become a disability in terms of bodily pain, mental health, social functioning and satisfaction with sex life.

Uterine fibroids are the most prevalent benign gynecologic tumors, affecting up to 80% of women of reproductive age. They are made of smooth muscle cells and fibrous connective tissue, and their cause is unknown. One in four women with fibroids may experience heavy menstrual bleeding, anemia, abdominal pain or pressure, increased urinary frequency, and infertility or recurrent miscarriages.

"Over half of the women in the United States will have fibroids, so their overall impact is substantial and yet, this fact does not receive enough attention," says James Segars Jr., M.D., director of the Division of Reproductive Science and Women's Health Research, and professor of gynecology and obstetrics at the Johns Hopkins University School of Medicine.

Women with fibroids, the study states, may experience debilitating feelings of worry, fear, anxiety, insecurity and helplessness, as well as issues with self-image and depression. Moreover, the findings show that lack of control over the condition is a leading cause of distress.

"For some women, the unpredictability and intensity of the heavy bleeding and related symptoms associated with the condition go beyond an inconvenience," says Segars. "Many women suffer in silence, and feel they can't go out or be social because they may start bleeding at any time."

Treatment for uterine fibroids depends on the condition's severity. Medication may be used to help shrink the size of the fibroids or they may be surgically removed. With fibroids resulting in approximately 600,000 hysterectomies per year, the tumors are the second most common reason for surgery among pre-menopausal women.

Segars is available for interviews.

FOR BLACKS WITH RESPIRATORY ILLS, INDIVIDUAL AND NEIGHBORHOOD POVERTY YIELD WORSE OUTCOMES

Media Contact: Helen Jones, hjones49@jhmi.edu

Research has shown that African Americans have worse health outcomes than non-Hispanic whites regarding respiratory illnesses such as chronic obstructive pulmonary disease (COPD). Now, a new study by Johns Hopkins Medicine researchers reveals that much of this racial disparity can be explained by differences in the socioeconomic status of individuals and neighborhoods.

The findings were published Oct. 2, 2020, in the American Journal of Respiratory and Critical Care Medicine.

In their study, the researchers looked at 2,649 current and former smokers, with or without COPD. They assessed racial differences for different COPD characteristics, including symptoms; results of functional and imaging tests, including scores on a COPD Assessment Test (the questionnaire that measures COPD's impact on a person's life); the ability to perform a six-minute walk test; and the risk for severe worsening of symptoms.

Then, they compared the Black participants with the white participants regarding the socioeconomic status reported by each person and federal data on neighborhood poverty levels. The researchers adjusted for several known risk factors influencing respiratory health outcomes, including smoking status and pack-years (calculated by multiplying the number of packs of cigarettes smoked per day by the number of years a person has smoked).

"We found that Black study participants fared worse than their non-Hispanic white counterparts in a number of areas, including respiratory symptoms, quality of life measures, functional status and imaging findings, as well as having higher rates of severe exacerbations," says study lead author Chinedu Ejike, M.D., M.P.H., a postdoctoral research and clinical fellow at the Johns Hopkins University School of Medicine. "However, several but not all of these racial differences could be explained by lower socioeconomic status and living in poor neighborhoods."

The researchers say that low individual socioeconomic status has previously been associated with higher odds of having COPD, and according to their recent study's findings, residing in lower-income neighborhoods also has detrimental associations with respiratory morbidity. Several factors, they explain, associated with living in disadvantaged neighborhoods -- such as higher stress, poor access to health care, lower quality of care, lack of access to healthy food, exposure to environmental contamination, poor neighborhood walkability and diminished physical activity -- may affect COPD outcomes.

"Thus, to fully understand racial disparities with COPD, one must take into consideration where people live," says Ejike.

"Our work adds to the understanding of the complex relationship among race, socioeconomic status -- both at the individual and neighborhood levels -- and respiratory health outcomes," says study co-author Han Woo, Ph.D., a biostatistician at the Johns Hopkins University School of Medicine.

Ejike and Woo hope their study will encourage health care providers to develop strategies that can break the current link between socioeconomic disadvantage and poor health outcomes.

In further research, they plan to (1) identify more risk factors leading to increased respiratory morbidity among Blacks with COPD, (2) understand why neighborhood context plays a role in COPD health and (3) examine constructs of a neighborhood, such as residential segregation, that contribute to the racial gap in COPD health.

Ejike and Woo are available for interviews.

LYME DISEASE BACTERIA ALTER IMMUNE SYSTEM AND MAY CAUSE IT TO ATTACK HEALTHY CELLS

Media Contact: Waun'Shae Blount, wblount1@jhmi.edu

With the incidence of Lyme disease rising to over 300,000 new U.S. cases annually, more people are suffering with the debilitating and persistent symptoms associated with what clinicians call post-treatment Lyme disease syndrome. Now, researchers at the Johns Hopkins Lyme Disease Research Center have found that the bacterium behind the disease, Borrelia burgdorferi, causes significant changes in how the human body responds to its presence.

In a recent study, the researchers showed that Borrelia burgdorferi alters dendritic cells, which normally present antigens -- proteins from pathogens such as bacteria and viruses -- to immune system T-cells, signaling an immune response against the foreign invaders. However, Borrelia burgdorferi stops this communication, which may then lead to the immune system mistakenly attacking healthy cells.

A report on the findings were published in the September 2020 issue of Frontiers in Medicine.

"We believe these observations are relevant not only to how Borrelia burgdorferi disrupts the immune system but other infections as well," says senior author Mark Soloski, Ph.D., co-director for basic research at the Johns Hopkins Lyme Disease Clinical Research Center, and professor of medicine at the Johns Hopkins University School of Medicine. "Antibodies that react with a person's own tissues or organs have been reported in patients with infections, including COVID-19."

In an attempt to better understand how a Lyme disease infection contributes to weakening the immune system, the Johns Hopkins Medicine researchers isolated dendritic cells from healthy study participants and exposed them to Borrelia burgdorferi. They found that bacterial infection causes receptor sites on the surface of dendritic cells, known as HLA-DRs, to mature and become active. HLA-DRs normally present antigens to killer T-cells, the immune system agents that remove invaders from the body.

However, the researchers believe that when the HLA-DRs interact with Borrelia burgdorferi, they are structurally changed and keep the dendritic cells from "marking" the bacterial proteins as foreign. As a result, the dendritic cells attract T-cells but in response to healthy cells in the area rather than the Lyme disease microbes.

The researchers further surmise that if a person has a genetic predisposition to autoimmune diseases such as lupus or rheumatoid arthritis, infection by Borrelia burgdorferi may trigger their development.

Future research on HLA-DR and dendritic cell response to Borrelia burgdorferi, the researchers say, could contribute to new treatments for Lyme disease and a better understanding of how autoimmune diseases may arise.

Soloski is available for interviews.

BRAIN IMPLANTS ENABLE MAN TO SIMULTANEOUSLY CONTROL TWO PROSTHETIC LIMBS WITH 'THOUGHTS'

Media Contact: Brian Waters, bwaters3@jhmi.edu

In what is believed to be a medical first, researchers from Johns Hopkins Medicine (JHM) and the Johns Hopkins University Applied Physics Laboratory (APL) have enabled a quadriplegic man to control a pair of prosthetic arms with his mind.

In January 2019, surgeons implanted six electrodes into the brain of Robert "Buz" Chmielewski, during a 10-hour operation. The goal was to improve the sensation in his hands and enable him to mentally operate his prostheses. For more than three decades after a surfing accident while in his teens, Chmielewski has been paralyzed with only minimal movement in his arms and hands.

Now, almost two years into the joint JHM/APL research study following the surgery, Chmielewski has reached an important milestone -- he can now use both of his robotic appendages to perform simple tasks such as feeding himself.

"This type of research, known as brain-computer interface [BCI], has for the most part focused on only one arm, controlled from only one side of the brain," says Pablo Celnik, M.D., professor and director of physical medicine and rehabilitation at the Johns Hopkins University School of Medicine and a member of the research team. "Thus, being able to control two robotic arms performing a basic activity of daily living -- in this case, cutting a pastry and bringing it to the mouth using signals detected from both sides of the brain via implanted electrodes -- is a clear step forward to achieve more complex task control directly fed from the brain."

"Simultaneous brain-machine interface control of two limbs is a particular challenge because it's not a simple 1+1 summation of what the left arm is doing plus what the right arm is doing in the brain, but more like trying to calculate the sum of the two arms as 1 plus 1 equals 3.8," adds Gabriela Cantarero, Ph.D., assistant professor of physical medicine and rehabilitation at the Johns Hopkins University School of Medicine and a member of the research team.

The technology uses a system of devices that automates a portion of the robotic control with artificial intelligence.

"Our goal is to make activities, such as eating, easy to accomplish by having the robot do one part of the work and leaving the user in charge of the details: which food to eat, where to cut, how big the cut piece should be, and so on," says David Handelman, Ph.D., a senior roboticist at APL and a member of the research team. "By combining brain-computer interface signals with robotics and artificial intelligence, we allow the user to focus on the parts of the task that matter most."

"Our next steps for this work include expanding the number and types of activities of daily living that we can demonstrate with this form of human-machine teaming, as well as providing users with additional sensory feedback as tasks are conducted," says Francesco Tenore, Ph.D., an electrical engineer at APL and a member of the research team. "This means that the user won't have to rely entirely on vision to know if he's succeeding, in the same way that uninjured people can 'feel' how they're tying their shoelaces without having to look."

A recent video shows Chmielewski cutting food with his left hand and feeding himself with the right, at times simultaneously controlling both robot arms.

All of the researchers are available for interviews.

Researchers share important information and solutions related to the challenges facing human resources and system managers in a special issue of Human Systems Management

Amsterdam, NL, December 8, 2020 - The COVID-19 pandemic has disrupted all types of organizations, leading human resources managers to reconsider their roles to support the implementation of social distancing practices, safety measures, and new ways of working. A special issue of Human Systems Management looks at the behavioral challenges posed by new ways of working and presents new models and tools to help organizations manage the transition.

"The most significant challenges organizations must overcome during the pandemic relate to human systems change management," explained Guest Editor Prof. Anca Draghici, PhD, Faculty of Management in Production and Transportation, Politehnica University of Timisoara, Romania; and President of the Ergonomics and Workplace Management Society in Romania. "Most organizations do not know how to manage the transition to a 'new normal,' or indeed may not even believe change is necessary."

The papers in this issue take a critical look at the challenges posed directly by the pandemic and explore new working models in new working environments, such as increased organizational responsibility and new paradigms for health and safety; new organizational experiences related to learning, education and knowledge management; and the human side of the enterprise under new conditions using new tools that require specific employees' skilling, re-skilling, and up-skilling.

Contributions explore:

Virtual working and teams dealing with crises and catastrophes. How to convert the COVID-19 and similar crises into opportunities for keeping businesses on track for growth.

A "learning by doing" framework for micro-knowledge management. This framework can ensure that knowledge learned by individuals working on projects is shared and integrated into project management tools and resources.

A digital service approach to foster team autonomy, distant collaboration, and knowledge sharing. A "self-service" kit for distance learning and team coaching.

The impact of employee engagement on organizational performance during COVID-19. Knowledge sharing has a mediating effect and human resource managers must think about how to direct this opportunity in the virtual setting.

How the National Human Capital Index influences productivity in research and development firms. It influences firm productivity in the long run, but larger and more financially stable firms record higher total factor productivity.

An easier and more comprehensive structural framework to identify risks in a 4.0 working environment. Companies that offshored their production and operate in the international business environment are studied to identify risk factors related to the work environment and human resources.

The challenges educators face during emergency remote learning. A comparison of education continuity measures concludes that a hybrid approach, combining face-to-face with online learning is the way forward in the "new normal."

The importance of learning organizations during times of risk and disruption. Cooperation and collaboration inside and outside of school boundaries and continuous learning opportunities for staff support the "school as learning organization" model.

A debate about implementing immersive technology for higher education. Participants in virtual reality training applications rate the experience much higher than common learning methods.

A global study of youth perception about their post-pandemic future. They see hope in the future and provide insights on areas of strength and weakness in programs, schemes, and curriculum in their communities.

A novel approach for improving stakeholders' commitment and responsibility for occupational health and safety (OHS) practices in an organization. An OHS Responsibility Multilevel Model for the implementation of the OHSAS 18001: 2007 standard.

Preventing and controlling back pain in computer workers. Treatment by an interdisciplinary team that includes an occupational physician, an ergonomist, and a physiotherapist can improve the health status of these workers.

"During the last eight months we have all recognized rapid progress in the implementation and use of technology, particularly web and cloud technologies, digitization, and also, intelligent automation. This change of culture makes human resources and work management key issues in this adaptation process," commented Prof. Draghici.

New insight on how bacteria in the lungs protect against invading pathogens has been published today in the open-access eLife journal.

The study in mice shows that a strain of lung bacteria called Lactobacillus provides a barrier against Streptococcus pneumoniae (S. pneumoniae) colonisation in animals previously infected with influenza A virus when applied therapeutically following infection. S. pneumoniae can cause severe pneumonia especially in elderly patients. In light of increasing antibiotic resistance, these findings suggest that probiotics may offer an alternative treatment approach for bacterial lung infections.

In healthy organisms, 'commensal' bacteria, which live inside the host without harming it, provide a competitive barrier against invading bacterial pathogens. "It is already well known how commensal bacteria in the gut fight off pathogens," explains co-first author Soner Yildiz, Postdoctoral Research Fellow at the University of Geneva, Switzerland. "But how lung bacteria such as Lactobacillus carry out this role is less clear."

To address this gap, Yildiz and colleagues studied the role of lung microbiota against Pneumococcus colonisation in mice. The team had previously reported that a significant amount of Lactobacillus bacteria, which are known to act as antimicrobials and immune system modulators, exist in the lung microbiota of healthy mice. In the current study, they identified these commensal bacteria as Lactobacillus murinus (L. murinus), with further gene sequencing and microscopy showing that the bacteria are tightly associated with mouse lung tissue.

The team next exposed cultures of L. murinus to S. pneumoniae. They found that L. murinus inhibited the growth of the pathogen through the release of lactic acid. "This antibacterial activity was not limited to S. pneumoniae," says co-first author João Pereira Bonifacio Lopes, PhD student at the University of Geneva. "It also affected S. aureaus, the pathogen that can cause bloodstream, bone and joint infections, as well as pneumonia."

Finally, they treated mice with L. murinus following influenza A infection and found that the bacteria provided a barrier against pneumococcal colonisation in the animals.

"This suggests that resident commensals in the lung could be applied as probiotics to counteract lung colonisation by pathogenic bacteria," concludes senior author Mirco Schmolke, Group Leader at the University of Geneva. "However, further studies are needed before this can be explored as a potential treatment in humans. If it one day proves to be effective, the approach could improve the clinical outcomes for patients who are susceptible to respiratory tract infections."

First full results from interim analysis confirm that the Oxford COVID-19 vaccine (AZD1222) has an acceptable safety profile and is efficacious against symptomatic COVID-19 disease, with no hospitalisations or severe disease reported in the COVID-19 vaccine group so far

First clinical efficacy results of the vaccine are based on a pre-specified pooled analysis of phase 3 trials in UK and Brazil (11,636 people), alongside safety data from a total of 23,745 participants in 4 trials in the UK, Brazil and South Africa

Interim results of the Oxford COVID-19 vaccine trials find that the vaccine protects against symptomatic disease in 70% of cases - with vaccine efficacy of 62% for those given two full doses, and of 90% in those given a half then a full dose (both trial arms pre-specified in the pooled analysis). The results are the first full peer-reviewed efficacy results to be published for a COVID-19 vaccine, and are published in The Lancet.

The vaccine was found to be safe, with only three out of 23,745 participants over a median of 3.4 months experiencing serious adverse events that were possibly related to a vaccine; one in the vaccine arm, one in the control arm, and one in a participant who remains masked to group allocation. All participants have recovered or are recovering, and remain in the trial.

Study author, Dr Merryn Voysey, University of Oxford, UK, says: "The results presented in this report provide the key findings from our first interim analysis. In future analyses, with more data included as it becomes available, we will investigate differences in key subgroups such as older adults, various ethnicities, doses, timing of booster vaccines, and we will determine which immune responses equate to protection from infection or disease." [1]

Study lead author Professor Andrew Pollard, University of Oxford, UK, says: "Control of the pandemic will only be achieved if the licensing, manufacturing and distribution of these vaccines can be achieved at an unprecedented scale and vaccination is rolled out to those who are vulnerable. Our findings indicate that our vaccine's efficacy exceeds the thresholds set by health authorities and may have a potential public health impact." [1]

The Oxford COVID-19 vaccine uses a chimpanzee adenovirus viral vector that cannot cause disease in humans and expresses the SARS-CoV-2 spike protein. This means the vaccine delivers the spike protein genetic code into vaccinated people's cells, which then produce the protein, and teaching the immune system to recognise and attack the virus. Past trial results have found that the vaccine induces antibody and T cell immune responses, and is safe in adults aged 18 years and over, including older adults [2].

For the new study, the authors analysed data from 23,745 adults in the UK, Brazil and South Africa (11,730, 10,002, and 2,013 in each country, respectively). The interim analysis published today pools the data from these for analysis, providing greater precision for efficacy and safety outcomes than possible in individual trials and giving a broader understanding of the use of the vaccine in different populations [3].

In the trial, half of the participants were given the COVID-19 vaccine and the other half given a control (either a meningococcal conjugate vaccine or saline [4]). The trial was originally designed to assess a single dose of the vaccine, but following review of the immune response data in the UK phase 1/2 study (which found a second dose boosted immune responses) another dose was added to the trial protocol, then, once approved, second doses were given to participants.

Participants in the COVID-19 vaccine group received two doses each containing 5x1010 viral particles (a standard dose). However, a subset (1,367 people) in the UK received a half dose as their first dose, followed by a full second dose. This was because of differences in the results of quantification methods between batches of the vaccine. The low-dose/standard-dose group did not include adults over the age of 55 years as the low-dose was given in an early stage of the trial before recruitment of older adults had commenced.

The authors used the numbers of cases of symptomatic and asymptomatic infection to determine vaccine efficacy.

Overall, most participants were aged 18-55 years (82%,19,588/23,745) as people aged 56 years and older were recruited later and will be studied in future analyses of the trial. In the 11,636 people included in the vaccine efficacy against symptomatic disease analysis, 12% (1,418/11,636 people) were older adults and most were white (83%, 9,625/11,636 people).

Findings from the trial safety data

Safety was monitored for a median of 3.4 months in all 23,745 participants from the UK, Brazil and South Africa. Out of 23,745 participants, 168 experienced a total of 175 severe adverse events over the period, but 172 events were unrelated to the COVID-19 or control vaccines. One event was in the control group (a case of haemolytic anaemia), one event was in the COVID-19 vaccine group (a case of transverse myelitis considered possibly related to the vaccine), and a case of severe fever (> 40oC) was reported in South Africa in a participant who remains masked to group allocation and recovered rapidly without an alternative diagnosis and was not hospitalised. All three participants have recovered or are recovering, and continue to be part of the trial.

Safety monitoring of all participants in the trial continues.

Vaccine efficacy against symptomatic COVID-19 disease

The primary outcome of the study was to determine how many cases of symptomatic COVID-19 disease (confirmed by positive test, and the participant having a fever, cough, shortness of breath, or loss of smell or taste) there were in participants who had received two doses of the vaccine (with the first dose being either low or standard dose, and the second dose being standard dose), compared with controls. Only cases that occurred 14 days after the second vaccination had been given were included (11,636 participants in the UK and Brazil trials).

There were 131 cases of symptomatic COVID-19 disease more than 14 days after the second vaccine dose in these 11,636 people. This included 30/5,807 (0.5%) cases in the vaccine group and 101/5,829 (1.7%) cases in the control group, which equates to a vaccine efficacy of 70%.

When breaking this down based on vaccine dose, those who received two standard doses of the vaccine saw a vaccine efficacy of 62% (based on 27/4,440 (0.6%) cases in the vaccine group, and 71/4,455 (1.6%) cases in the control group), and the low-dose/standard-dose group vaccine efficacy was 90% (based on 3/1,367 (0.2%) cases in the vaccine group, and 30/1,374 (2.2%) cases in the control group).

The authors completed exploratory subgroup analyses at the request of peer-reviewers to study the difference in efficacy against symptomatic disease in the low-dose/standard-dose group and two standard doses group. These were to help understand whether the difference was related to the dose or other factors (participant age and time between vaccine doses [5]). They found that, irrespective of age or time between doses, their analyses suggested higher efficacy in the low-dose/standard-dose group. However, these exploratory analyses provide a suggestion, and will require further research as more data becomes available from the trial.

Five cases of symptomatic COVID-19 disease occurred in people aged over 55 years old, but vaccine efficacy in older age groups could not be assessed as there were too few cases. The authors say that this analysis will be completed in future.

"In order to assess vaccine efficacy, we need to have a sufficient number of COVID-19 cases among participants to indicate that the vaccine is protecting them from disease. Since recruitment of older adults started later than in younger adults there has been less follow up time for these cohorts and less time to accrue COVID-19 cases. This means we have to wait longer to have sufficient data to provide good vaccine efficacy estimates in smaller subgroups." says Dr Voysey. [1]

Asymptomatic transmission

The trial also measured protection against asymptomatic infection by asking 6,638 UK participants to complete weekly COVID tests. However, it is important to note these data are secondary outcomes [6] and findings need to be confirmed when there is more data available from the trial.

There were 69 cases of asymptomatic COVID-19 disease identified in the UK study's weekly COVID-19 testing of 6,638 people. This included 29/3,288 (0.9%) cases in the vaccine group, and 40/3,350 (1.2%) cases in the control group, leading to a vaccine efficacy against asymptomatic transmission of 27%.

In the low-dose/standard-dose group, there were 7/1,120 (0.6%) cases in the vaccine group and 17/1,127 (1.5%) cases in the control group, resulting in a vaccine efficacy against asymptomatic transmission of 59%. In people given two standard doses, there were 22/2,168 (1%) cases in the vaccine group and 23/2,223 (1%) in the control group, which equates to a vaccine efficacy against asymptomatic transmission of 4%.

Protection against severe disease

Cases of severe disease and hospitalisation were monitored for in all 23,745 participants. From 21 days after the first dose there were 10 cases hospitalised for COVID-19, all in the control arm, and two were classified as severe, including one death. These are also secondary outcomes and will require additional confirmation.

Co-author, Professor Sarah Gilbert, University of Oxford, UK, says: "Despite global spread of COVID-19, a large proportion of the population in many countries have not been infected and are not immune. Vaccines may play an important role in increasing immunity, preventing severe disease, and reducing the health crisis, so the possibility that more than one efficacious vaccine may be approved for use in the near future is encouraging. Here we have shown for the first time that an adenoviral vectored vaccine - a type of vaccine technology which has been in use since 2009 - is efficacious and could contribute to disease control in the COVID-19 pandemic." [1]

The authors note that they are not yet able to assess duration of protection, as the first trials were initiated in April 2020 and all disease episodes have accrued within six months of the first dose being administered. Further evidence will be required to determine duration of protection and the need for additional booster doses of vaccine.

Writing in a linked Comment, Dr Maria Deloria Knoll and Dr Chizoba Wonodi, Johns Hopkins Bloomberg School of Public Health, USA (who were not involved in the study), say: "Oxford-AstraZeneca's US$2-3 per dose agreement with the COVAX facility holds good promise for equitable access for LMICs, compared with the high cost of the two mRNA vaccines that have also reported more than 90% efficacy. The ChAdOx1 nCoV-19 vaccine can also use routine refrigerated cold chain, which is important since the ultra-low temperature freezers required to store mRNA vaccines could be unaffordable and impractical in many countries and in settings such as nursing homes. However, other challenges with any two-dose regimen will exist in many LMICs where platforms to easily identify, locate, and reach--twice-- adults targeted for vaccination are lacking. If the two vaccine injections require different doses, this will add complexity for health workers with little formal training, but can be managed with innovative packaging and proper change management to reduce errors... When faced with vaccine choices, National Immunization Technical Advisory Groups will have to consider all factors and decide which vaccine is right for their setting. Efficacy is an important consideration, but so are pragmatics of delivery, community acceptance, longevity of effect, whether a vaccine reduces infection and transmission as well as disease, efficacy in high-risk groups, and, of course, safety. Despite the outstanding questions and challenges in delivering these vaccines, it is hard not to be excited about these findings and now the existence of three safe and efficacious COVID-19 vaccines, with 57 more in clinical trials. With a range of manufacturers, a very large global investment in production and cooperation in procurement and distribution, it seems likely that 2021 will see COVID-19 vaccines made available to all countries in the world. Perhaps by this time next year, we can celebrate the global control of SARS-CoV-2, in person."

The partial re-opening of schools during the summer 2020 half-term in England was associated with a low risk of COVID-19 cases or outbreaks, with 113 single cases, nine co-primary cases, and 55 outbreaks recorded.

Outbreaks in schools correlated strongly with local infection rates, highlighting a need to reduce community transmission in order to protect educational settings.

Confirmed infections and outbreaks were more likely to involve staff members than students, though fewer students were in attendance than normal and their infection rates may be underestimated.

With little research in this area internationally, the authors note that their insights could have global implications, although the specific results are only applicable to England.

COVID-19 cases and outbreaks were low among staff and students in schools and nurseries in England that re-opened during the summer half-term after lockdown, according to research published in The Lancet Infectious Diseases journal.

Nurseries, primary and secondary schools were closed in late March 2020 as part of the first national lockdown to help reduce the spread of COVID-19. Following the rollout of strict infection control measures, including smaller classes separated into distinct social bubbles, most educational settings re-opened during the summer half-term from June 1 to July 17, 2020.

Educational settings re-opened to children in nurseries, primary school reception and years 1 and 6 (ages 4-5, 5-6 and 10-11 years, respectively), secondary school years 10 and 12 (ages 14-15 and 16-17 years, respectively), and children of any age whose parents were key workers, or who were classified as vulnerable. Of the 8.9 million students in England, 1.6 million attended school during the period. The new study included data from all early years settings, primary and secondary schools open in England during this time - spanning around 38,000 nurseries, 15,600 primary schools, and 4,000 secondary schools at any one time.

To date, few studies have assessed COVID-19 cases and outbreaks in educational settings, with most involving a single school with a small number of staff and students affected. The authors suggest that while their findings are specific to England, insights gained into the risks of infection and the impact of community transmission could have implications for infection control measures in schools and nurseries in other parts of the world.

The findings may not be generalisable to all schools and nurseries, since those that re-opened in summer 2020 did so at a time when COVID-19 cases had fallen nationally. Additionally, stringent infection control measures were in place with strict limits on bubble sizes, which might not be achievable in fully opened school settings.

Dr Shamez Ladhani, Public Health England, said: "SARS-CoV2 infections and outbreaks were uncommon in educational settings after they reopened during the summer term. The strong correlation with rates in the wider community also emphasises the importance of controlling transmission outside the school gates to protect educational settings. This is consistent with studies that have been conducted since this paper was completed in August, and forthcoming PHE research into transmission in schools during the autumn term." [1]

The authors used COVID-19 data recorded in Public Health England's online national database for recording events that need public health management, HPZone, to calculate case and event rates for staff and students in schools and nurseries that re-opened during the half-term. Events were classified as single cases, co-primary cases (two or more confirmed cases within 48hrs, typically children who live in the same household), and outbreaks (two or more linked cases diagnosed within 14 days in the same educational setting). All events were followed-up for 28 days after schools and nurseries closed for the summer holidays.

Statistical analyses were used to reveal how COVID-19 cases and events in schools and nurseries were affected by the size and density of the local population, and levels of community transmission on a regional level. Authors determined whether infections were passed from staff to students, students to staff, or within these groups based on the first identified cases, dates when symptoms began, and when testing was done.

Rates of COVID-19 infection and outbreaks were very low across all educational settings, with 113 single cases, nine co-primary cases, and 55 outbreaks between June 1 and July 17. The 113 single cases included 55 (49%) children and 58 (51%) staff, and occurred mainly in primary schools (61%, 69/113 cases). There were nine co-primary cases including 19 children and one staff member. Six co-primary cases were in primary schools, two were in nurseries, and one involved a parent and child at the same school. Of the 55 outbreaks identified in the analysis, 27 were in primary schools, with 16 in nurseries, seven in secondary schools, and five in schools of mixed age groups.

A strong association was identified between outbreaks in schools and levels of community transmission, with the risk of an outbreak rising by 72% for every increase of five cases per 100,000 within the local community. The analysis also revealed that cases brought into educational settings increased the risk of an outbreak by 40% in nurseries, 26% in primary schools, and 39% in secondary schools.

Infection rates were higher in staff than students, with 27 cases per 100,000 per day compared with 18 for children in nurseries, 6 in primary school students, and 6.8 in secondary school students. The virus was most often spread between staff, while student-to-student transmission was rare. Staff members accounted for 73% of cases (154/210 cases) linked to outbreaks compared with 27% (56/210) for students. The probable direction of transmission was staff to staff in 26 outbreaks, staff to student in eight, student to staff in 16, and student to student in five.

Dr Sharif Ismail, from the London School of Hygiene & Tropical Medicine, UK, said:: "While staff did have higher infection rates, it's important to note that the overall number of cases was very small and the vast majority of staff were completely fine and able to protect themselves and their students. Teachers were very cautious with physical distancing and infection control practices when they were in class with their students, but this was more difficult to maintain outside the classroom. Teachers are also more likely to develop symptoms than students and are, therefore, more easily identified, which almost certainly contributed to their higher infection rate."

Limitations in swab testing used to confirm COVID-19 infections, coupled with the fact few schools or nurseries were selected for wider testing, could mean the size of some outbreaks identified in the analysis were underestimated. Very few secondary school years were open during the summer half-term, therefore the results cannot be generalised to all secondary schools, especially since the risk of infection, disease, and transmission is likely to be higher in older than younger children. It is also likely that some populations, such as children of key workers, were over-represented in the analysis.

Writing in a linked Comment, lead authors Stefan Flasche and John Edwards (who were not involved in the study), from the London School of Hygiene & Tropical Medicine, note that the partial re-opening of schools during the UK in summer half-term, when COVID-19 levels were low, was reassuringly associated with very few confirmed outbreaks in schools. However, they say: "The partial opening of schools in June and July with small bubbles and much fewer children attending, particularly in secondary education, may have led to considerably less within-school transmission than the reopening of schools to all children after the summer." They also note that more transmission likely occurred among children than was recorded, saying: "Children rarely display obvious symptoms and are likely missed by the largely passive case finding that was in place at the time. In fact, in most instances where further symptom agnostic testing was initiated in response, a substantial number of additional cases were identified."

URBANA, Ill. - Careers in science, technology, engineering, and mathematics (STEM) are one of the fastest-growing areas of work in the United States, yet racial and gender disparities remain in STEM occupations.

A recent study from University of Illinois researchers examining reasons for such disparities shows the overall racial climate on a college campus--informed by experiences of racial microaggressions--is a contributing factor in the lack of representation of students of color in STEM education programs.

In other words, the study found when students of color in STEM majors felt excluded, invisible, or isolated on their college campus because of their race, sometimes combined with discouraging experiences in academic settings, they were less likely to continue in STEM.

"Racial microaggressions are subtle, as opposed to overt, behaviors or remarks that can serve to demean, degrade, invalidate, or otherwise make a person take a step back to try to figure out, 'was that because of my race?' That's the difficult thing about racial microaggressions, they can catch you off guard to a point where, in the moment, you may not necessarily know how to react," explains Jasmine Collins, assistant professor of organizational and community leadership in the Agricultural Leadership, Education and Communications program at Illinois and co-author of the study.

For the study, Collins and colleagues from disciplines including sociology and African American studies analyzed the experiences of students of color in STEM majors who reported experiencing racial microaggressions across three levels: on campus (characterized by students' general feelings about being a student of color on their university campus); in academic settings (e.g., classrooms or exchanges with instructors or academic advisers); and with peers (e.g.. interpersonal interactions with other students).

Using data collected from more than 4,800 students of color at a large, public university in the United States, the study also found Black students in STEM majors are more likely to experience racial microaggressions than other students of color in STEM, with Black women reporting the highest rates.

Black men and women, Latina women, Asian women, and Indigenous women in the study, in particular, reported experiencing racial microaggressions more frequently at the campus level than in classrooms or between peers.

The researchers hope the findings from the study, published in the International Journal of STEM Education, will encourage STEM-related academic programs to address the larger campus culture in their classrooms and other academic settings. "The aim is not to call attention to a particular campus, but we do make the connection to the broader national context. Colleges and universities play an important role in the STEM pipeline," Collins says.

Survey participants responded to questions asking, for example, if they have had their contributions minimized in classrooms because of their race; experienced negative and insulting comments because of their race; or felt invisible or unwelcome on their campus because of their race.

Some students reported dropping out of STEM majors because of these experiences or having been encouraged by advisers or instructors to change to a non-STEM major.

As one respondent in the study, a Latina woman who changed from a STEM to a non-STEM major, noted, "I changed my desired major from Engineering to Latin American Studies because of my race and sadly encountered others like myself within the humanities who had to change their major because of their race. If you aren't White, and you aren't Asian, and you aren't 'Indian,' you aren't an engineer."

One Black woman who is a STEM student noted, "A lot of people automatically assume that since I'm a Black female that I should be a [non-STEM] major. Every time I walk into a lab, I always get looks. I'm not sure if it's because I don't 'look' like a [STEM] major in general or if it's because I'm Black."

Others described eagerness to meet new people at the beginning of the school year, but experienced rejection when they tried to make friends.

A significant contribution of this study, Collins explains, is the layering of different levels at which students encountered microaggressions. "We introduce this framework of the campus racial climate to show how, for students of color in STEM who experience racial microaggressions, they not only receive messages in their classrooms, but it's part of the institutional fabric. It's the culture of the institution that tends to reinforce these messages."

Collins says universities must find ways to create more welcoming and supportive environments for students of color, for all majors, and employ a level of accountability at the campus and departmental level.

"In order to educate our workforce, students have to come through our doors and if these are the kinds of experiences [students of color] are facing--the campus signals to them they don't belong in STEM, their peers in class don't want to work with them because they think they're incompetent, or their adviser recommends they switch majors because this might be too hard for them--if it's just message after message saying, 'you don't belong here, you're not smart enough, you're not skilled enough to have this kind of job,' then we're losing a lot of talent in the pipeline," Collins says.

"It's one of the reasons why we see such stark racial and gender disparities in the STEM workforce. And it really is a pipeline issue."

Collins hopes to see a shift in research that focuses a little less on confirming that these things happen and focuses more on solutions. "I find it to be quite taxing as a scholar, and even personally as someone who also faces racial microaggressions, reading through the data in the midst of a global pandemic, in the midst of racial protests, and seeing that not a lot has changed," she says. "I think we have enough evidence that these things occur.

"If we can find those ways to reenergize ourselves toward solutions and toward working collaboratively to find solutions, that's where I would love to see future research in this field go."

(Boston)-- Prior research has revealed sexual minority youth (lesbian, gay, bisexual) are more likely to carry weapons both outside of and within school. However, until now, no study has examined the degree to which bullying and harassment is associated with weapon carrying among this group.

A new study has found youth who report carrying a weapon have higher odds of experiencing bullying and bullying-related victimization. Minoritized student populations, especially sexual minority youth disproportionately experience bullying and bullying victimization.

"Pediatricians should recognize that experiencing bullying and feeling unsafe are associated with weapon carrying, particularly among sexual minorities," says corresponding author Carl Streed, Jr., MD, MPH, FACP, assistant professor of medicine at Boston University School of Medicine (BUSM).

Using the Youth Risk Behavior Survey to examine the prevalence and likelihood of carrying weapons by sexual identity, the researchers examined self-report of adverse experiences (being bullied, skipping school due to fear for personal safety) and performed analysis to estimate the odds of carrying a weapon. When surveyed by sexual identity, 14 percent of heterosexual, 21.8 percent of gay/lesbian,18.5 percent of bisexual and 17.4 percent of "not sure" students reported carrying a weapon in the past 30 days.

The odds of carrying a weapon were significantly increased for youth who skipped school due to feeling unsafe at school, had ever been threatened with a weapon in the past year and had ever been in a physical fight. Compared to heterosexual female peers, sexual minority women had increased odds of carrying a weapon. "Pediatricians and professionals who work with youth should recognize that reported experiences of bullying may not be the most salient indicator of risk for weapon carrying among all youth, and that other fears of or experiences with bullying are crucial to screen for among sexual minorities in particular," adds Streed, who also is a primary care physician and research lead in the Center for Transgender Medicine & Surgery at Boston Medical Center.

According to the researchers, this work is critical in the current political climate that is witnessing an erosion of LGBTQ acceptance (GLAAD, 2019) and is leading to a potential increase in minority stress through the bullying of certain youth populations, particularly sexual minority youth. They believe future research should investigate associations between longitudinal trends in bullying and attitudes toward sexual and gender minority persons in U.S. politics.

A considerable number of existing and proposed post-2020 biodiversity targets by international organizations are at risk of being severely compromised due to climate change, even if other barriers such as habitat exploitation are removed argue the authors of a study led by Almut Arneth from Karlsruhe Institute of Technology (KIT). According to their analysis published in PNAS, global warming accelerates the loss of biodiversity. Vice versa, measures to protect biodiversity may also mitigate the impacts of climate change. The authors suggest that flexible approaches to conservation would allow dynamic responses to the effects of climate change on habitats and species. (DOI: 2009584117)

About a million plant and animal species are endangered worldwide. At least 13 of the 17 sustainable development goals of the United Nations, however, depend on biodiversity, including species diversity, the genetic diversity within species and the diversity of ecosystems. Biodiversity regulates fundamental processes, such as soil formation and water-, trace-gas-, and nutrient cycles and thus contributes notably l to regulating the climate. The continued loss of biodiversity makes humankind face ecological, social, and economic problems. "Apart from the over-exploitation of natural resources on land and in water, or environmental pollution, climate change also causes loss of biological diversity. This impact will increase in future," says Almut Arneth, Professor at the Atmospheric Environmental Research Division of the Institute of Meteorology and Climate Research (IMK-IFU), KIT's Campus Alpine in Garmisch-Partenkirchen. She led an international study that is now published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) under the title "Post-2020 biodiversity targets need to embrace climate change."

Targets for Worldwide Biodiversity Conservation Missed

In their study, scientists from Germany, France, Italy, Spain, Russia, South Africa, Mexico, and Japan analyzed the so-called Aichi targets for the worldwide protection of biodiversity that were adopted by the 10th Conference of the Parties of the UN Convention on Biodiversity in Nagoya, prefecture of Aichi, in 2010 for compliance by 2020. Most of these targets will be missed. In addition, the researchers analyzed the set of revised biodiversity protection targets currently negotiated by the parties for the time after 2020, which are to be reached by 2030 or 2050. They found that many existing or proposed targets are at risk due to global warming, even if the mean global temperature increase would remain at the lower limit of projections. "It certainly is a big challenge, but also an important opportunity to better handle on the political level the interactions between climate change and biodiversity loss, and to better coordinate the biodiversity targets with the Paris Agreement on Climate Change and the Sustainable Development Goals," Arneth explains. The biodiversity targets proposed should therefore consider climate change much more explicitly, she thinks.

Species Are Leaving Nature Reserves

Arneth gives an example: A biodiversity target for nature reserves must consider the fact that composition and growth of vegetation will change with climate change and that certain species of plants and animals will either migrate or be threatened, if climatic conditions are changing. For instance, climate change causes mountain glaciers to shrink. In semi-arid regions, however, lower lying valley ecosystems depend on melting water from glaciers in summer. If this melt-water flow will decrease due to retreating glaciers, precipitation alone may not be sufficient to supply the plants in the catchment with water. This will then also affect the animals that are dependent on the plants.

The study underscores the demand to quickly and significantly reduce anthropogenic greenhouse gas emission and to halt climate change. Vice versa, it also shows that measures to protect biodiversity would contribute to climate protection. "Better coordination of political agreements and scientific findings may accelerate urgent decarbonization of economy and ensure slowdown of climate change by biodiversity protection measures," Arneth summarizes.

New research has shown how microbubbles carrying powerful cancer drugs can be guided to the site of a tumour using antibodies.

Microbubbles are small manufactured spheres half the size of a red blood cell - and scientists believe they can be used to transport drugs to highly specific locations within the body.

In a paper published in the journal Theranostics, the lead authors of the study, Drs Nicola Ingram and Laura McVeigh from the University of Leeds, describe how they have targeted microbubbles through the use of a 'navigational aid' - antibodies attracted to the growth hormone found in high levels in the blood vessels supplying a tumour.

The antibodies were attached to the microbubbles - and as a result of being attracted to the growth hormone, the microbubbles became concentrated at the site of the tumour. A pulse from an ultrasound device was used to burst open the microbubbles, and that released the anti-cancer agent.

Dr Ingram, Senior Research Fellow in the School of Medicine at Leeds, said being able to deliver anticancer drugs in a very targeted fashion would be a major advance in cancer therapy.

She added: "One of the big problems with cancer drugs is that they are highly toxic to the rest of the body too. Microbubble technology allows us to use these very powerful drugs with precision and that reduces the risk of the drug damaging healthy cells nearby.

"It is about finely focused drug delivery."

The animal-based study also revealed that by attaching the drug directly to the microbubbles allowed it to circulate in the body for longer, increasing delivery into the tumour - in effect making the drug more potent.

As a result, the scientists were able to slow cancer growth with a much smaller drug dose.

Professor Stephen Evans, head of the Molecular and Nanoscale Physics Group at Leeds and one of the paper's authors, said: "The results of this study are exciting because we not only show the very precise and targeted way microbubbles can be guided to cancer sites but that the efficacy of drug delivery is substantially improved, opening the way to use highly toxic drugs to fight cancer, without the harmful side effects.

"Put simply: you get more bang for your buck."

The next stage of the research is to look at using microbubbles to develop targeted, triggered, delivery systems in patients for the diagnosis and treatment of advanced colorectal cancer, the third most common cancer in the UK.

Professor Peter Simpson, Chief Scientific Officer at Medicines Discovery Catapult said: "Complex medicines have the potential to be the third wave of medicines, addressing patients' problems which conventionally administered small molecules and monoclonal antibodies cannot.

"This project is a very encouraging example of exploring how using an advanced drug delivery technology could improve biodistribution, targeting and efficacy of a potentially toxic therapeutic."

This study involved a research team from the universities of Leeds, Bradford, Manchester, and the Medicines Discovery Catapult in Cheshire. The study and a follow-on study were funded by the Engineering and Physical Sciences Research Council. In addition, several PhD students are also developing microbubbles for treatment of other diseases and have been funded by Alumni.

The University of Leeds has established the Leeds Microbubble Consortium, a group of cancer scientists, engineers, physicists and chemists to develop ways microbubble technology could enhance cancer treatment.

Animal Study/ Peer Review/ Experimental

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We are a top ten university for research and impact power in the UK, according to the 2014 Research Excellence Framework, and are in the top 100 of the QS World University Rankings 2019.

The University was awarded a Gold rating by the Government's Teaching Excellence Framework in 2017, recognising its 'consistently outstanding' teaching and learning provision. Twenty-six of our academics have been awarded National Teaching Fellowships - more than any other institution in England, Northern Ireland and Wales - reflecting the excellence of our teaching. http://www.leeds.ac.uk

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Theranostics

DOI

10.7150/thno.49670

Philadelphia, December 8, 2020--Researchers at Children's Hospital of Philadelphia (CHOP) have found elevated levels of a biomarker related to blood vessel damage in children with SARS-CoV-2 infection, even if the children had minimal or no symptoms of COVID-19. They also found that a high proportion of children with SARS-CoV-2 infection met clinical and diagnostic criteria for thrombotic microangiopathy (TMA). TMA is a syndrome that involves clotting in the small blood vessels and has been identified as a potential cause for severe manifestations of COVID-19 in adults.

The findings were published today in Blood Advances.

"We do not yet know the clinical implications of this elevated biomarker in children with COVID-19 and no symptoms or minimal symptoms," said co-senior author David T. Teachey, MD, an attending physician, Co-Leader of the Immune Dysregulation Frontier Program, and Director of Clinical Research at the Center for Childhood Cancer Research at CHOP. "We should continue testing for and monitoring children with SARS-CoV-2 so that we can better understand how the virus affects them in both the short and long term."

Most children infected with SARS-CoV-2 have mild or minimal symptoms, although a small proportion develop severe disease or Multisystem Inflammatory Syndrome in Children (MIS-C), a post-viral inflammatory response to COVID-19. Researchers have identified TMA mediated by the complement cascade as a potential cause for severe manifestations of COVID-19 in adults. The complement cascade is part of the immune system that enhances the immune response but also promotes inflammation. However, the role of complement-mediated TMA has not been studied in children.

To assess the role of complement activation in children with SARS-CoV-2, the Immune Dysregulation Frontier Program, including co-senior authors Edward Behrens, MD and Hamid Bassiri, MD, PhD and co-first authors Caroline Diorio, MD and Kevin McNerney, MD, analyzed 50 pediatric patients hospitalized at CHOP with acute SARS-CoV-2 infection between April and July 2020. Of those 50 patients, 21 had minimal COVID-19, 11 had severe COVID-19, and 18 were diagnosed with MIS-C. The researchers used soluble C5b9 (sC5b9) as a biomarker for complement activation and TMA. sC5b9 has been implicated as an indicator of severity in TMA after hematopoietic stem cell transplant; transplant patients with markedly elevated sC5b9 have increased mortality.

The researchers found elevations of C5b9 in patients with severe COVID-19 and MIS-C, but to their surprise, they also found that C5b9 was elevated in patients with minimal or asymptomatic disease. Although the study was prospective, meaning patients were enrolled and data collected from the time of hospitalization, the researchers obtained some of the laboratory data retrospectively when it came to evaluating whether they met the clinical criteria for TMA. Of the 22 patients for whom complete data were available, 19 (86%) met the criteria for TMA. Additionally, sC5b9 levels were elevated both in patients who did and did not meet criteria for TMA.

"Although most children with COVID-19 do not have severe disease, our study shows that there may be other effects of SARS-CoV-2 that are worthy of investigation," Dr. Teachey said. "Future studies are needed to determine if hospitalized children with SARS-CoV-2 should be screened for TMA, if TMA-directed management is helpful, and if there are any short- or long-term clinical consequences of complement activation and endothelial damage in children with COVID-19 or MIS-C. The most important takeaway from this study is we have more to learn about SARS-CoV-2. We should not make guesses about the short and long-term impact of infection."

Leipzig/Frankfurt/Main/Düsseldorf. Aerosols and their spread play an essential role in the transmission of COVID-19. However, the risk of transmission could be significantly reduced if more could be done to reduce indoor airborne viruses. The Working committee particulate matter (AAF) has therefore issued an statement with concrete recommendations. These include window ventilation, exhaust ventilation, air purification systems and CO2 measuring devices for indoor areas such as classrooms or transportation, and the increased use of N95 and FFP2 masks. These countermeasures could help in the short term to better contain the corona pandemic, especially in winter, until vaccination is effective on a large scale. They could also help in the long term to better control infections such as seasonal fluor even other pandemics in the future.

The German Working committee particulate matter (AAF) brings together experts from the fields of engineering, chemistry, physics, biology, meteorology and medicine, who are organised in the professional associations ProcessNet (DECHEMA/ VDI-GVC), Gesellschaft Deutscher Chemiker (GDCh) and VDI/DIN Commission Reinhaltung der Luft (KRdL). In its autumn meeting, the AAF discussed the role of aerosol particles in the spread of the SARS-CoV2 viruses and prepared a statement on this topic. On the basis of their expertise, the authors describe in the now published statement different aerosol types with regard to their formation, range, residence time in the air and derive recommendations for protection by various measures. The authors expressly support the current recommendations of the Robert Koch Institute (RKI), but suggest that even more should be done to reduce the number of viruses in indoor air.

The Working committee particulate matter (AAF) advises strict application of the recommendations based on the active aerosol propagation path: masks (especially the use of N95 and FFP2 masks) are helpful and necessary, ventilation is a good immediate measure and suitable air purifiers should be used.

Furthermore, the Panel concludes that more attention should be paid to the type of ventilation in addition to the measures already taken: Especially the smaller aerosol particles rise with the warm air we breathe and then spread below the ceiling. The experts on the working committee therefore recommend that in ventilation systems, care should be taken to ensure that fresh air is not supplied from top to bottom, as this leads to turbulence between the fresh air and the air we breathe and viruses can then float in the room air for longer. Ceiling fans, which are counterproductive in the current COVID 19 pandemic, would also contribute to this. Instead, care should be taken to ensure that air is actually extracted upwards. In the future, a reversal of the air supply and extraction in aircraft or public transport could help.

The panel of experts also advises to install ventilation and especially overhead exhaust suction systems in many areas at short notice, especially in classrooms or in the catering industry. Monitoring the CO2 concentration is a suitable indicator of how well the ventilation works. For cultural facilities, too, monitoring the CO2 content and thus the indoor air could later provide opportunities for normalising operation. In the Länder, funds should be made available so that ventilation, extraction, air purification systems and CO2 measuring devices can be installed in school classes. At the local level, it would be helpful if administrative regulations were relaxed and school managements were given more freedom of action. If these measures were implemented consistently, about 90 percent of all potentially viral aerosols could be removed from classrooms.

"We clearly see the human and technical effort involved in the short and medium term, but we are convinced that the appropriate consideration of the virus spread via the aerosol path can lead to a short-term and also sustainable containment of the current incidence of infection. Such investments would also be beneficial for later, for example for the air quality in classrooms", explains Prof. Hartmut Herrmann of the Leibniz Institute for Tropospheric Research (TROPOS), who is chairman of the Working Committee on Particulate Matter (AAF). Herrmann also contributes torecommendations by an international group of aerosol researchers) and via the VDI/DIN Commission on Air Pollution Control (KRdL), which were incorporated into specific recommendations for German conditions. Even if the World Health Organization (WHO) still pays too little attention to this, experts have long been convinced that aerosols, i.e. tiny suspended particles in the air, contribute strongly to the spread of the SARS-CoV2 viruses. "We are aware that the technical implementation of more efficient ventilation measures is probably one of the most demanding measures in the current situation in Germany. However, protection against infection from virus-contaminated aerosol particles in indoor rooms and means of transport through improved ventilation technology is particularly important in the cold winter months in order to avoid corona superspreader events", emphasises Prof. Peter Wiesen from the Bergische Universität Wuppertal, who is one of the authors of the statement.

Protective measures against the spread of SARS-CoV-2 via indoor aerosols currently pose major challenges for many sectors of society. The risk of infection is particularly high in hospitals and nursing homes because infected and healthy people can stay sometimes in the same room for long periods of time. According to media reports, COVID-19 infections are already reported in almost one tenth of the 12,000 old people's homes and nursing homes in Germany. Homes are now also considered as hotspot for the spread of the virus among new infections in Saxony. An international group of aerosol researchers proposes therefore a variety of measures to prevent the spread of the virus in hospitals and nursing homes. It is particularly important to develop an appropriate strategy to protect healthcare workers from airborne transmission. Their recommendations in the International Journal of Environmental Research and Public Health include regular ventilation, controlling fresh air consumption via CO2 monitor and using humidifiers to keep the relative humidity indoors at 40 to 60 percent. If it is not possible to ventilate sufficiently, the use of portable air purifiers are also advisable.

In addition to the recommendations already made by the Robert Koch Institute and the National Academy of Sciences Leopoldina in Germany, the Working Committee sees an opportunity to take additional protective measures to contain the Covid-19 pandemic, initially in the short term, until a vaccine has reached a really broad section of the population. In addition, these measures could in the future also help to reduce infections such as seasonal influenza, which are spread through the air.

Bartonella bacteria are increasingly recognized as an emerging infectious disease threat. A new study by North Carolina State University researchers has found additional instances of Bartonella infection in humans who exhibited neuropsychiatric symptoms, a subset of whom also had skin lesions. This research adds to the body of evidence that not only can Bartonella infection mimic a spectrum of chronic illnesses - including mental illness - but also that dermatological symptoms may accompany infection.

Bartonella henselae is a bacterium historically associated with cat-scratch disease, which until recently was thought to be a short-lived (or self-limiting) infection. There are at least 30 different known Bartonella species, of which 13 have been found to infect humans. Improved methods for detecting Bartonella infection in animals and humans - it is notorious for "hiding" in the linings of blood vessels and potentially the skin - has led to the diagnosis of bartonelloses in patients with a host of chronic illnesses.

In 2019, Dr. Edward Breitschwerdt, Melanie S. Steele Distinguished Professor of Internal Medicine at NC State, published a case study involving an adolescent boy diagnosed with rapid onset schizophrenia, who had accompanying skin lesions. After Breitschwerdt's research group documented Bartonella henselae infection, the patient received antimicrobial therapy and all neuropsychiatric symptoms resolved.

The new study is a follow-up to the 2019 work and is published in the journal Pathogens. Thirty-three participants suffering from neuropsychiatric symptoms ranging from sleep disorders and migraines to depression and anxiety enrolled in the study. Twenty-nine of 33 participants were found to have Bartonella infections based upon serology and enrichment blood culture polymerase chain reaction (PCR) testing. Twenty-four of the 29 Bartonella-positive participants (83%) reported the appearance of skin lesions during their illness.

Skin lesions ranged from cutaneous eruptions to red, irregular linear lesions randomly located on various parts of the patient's body. Many of these lesions resembled striae distensae (stretch marks); however, typical risk factors for striae distensae, such as body building activities, obesity, pregnancy, prednisone treatment and other known disease associations, were either infrequently or not reported by study participants.

"This research, a follow-up to our initial case report of Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS), was initiated to further investigate a possible association between neuropsychiatric illness, skin lesions and a bacterial infection of emerging biomedical importance," Breitschwerdt says. "We hope that this research will enable physicians to suspect connections between disparate symptoms involving the nervous system and skin that could be associated with an underlying bacterial cause."