Human Behavior

Second Ithaca Drought in Five Years Threatens Water Supply and Local Ecosystem – Cornell University The Cornell Daily Sun

Climate change is driving the development of drought patterns in New York, threatening the agricultural sector and drying up local water sources including Ithaca.

Last month, the water supply in Six Mile Creek was at a third of its average flow rate: an alarming five cubic feet per second as opposed to its standard rate of 15 cubic feet per second. The low flow rate prompted Cornell and the City of Ithaca to issue a Level 1: Limited Water Use Advisory to encourage more water conservation on Sept. 22. The advisory was only lifted on Oct. 21.

This is the second time in less than five years that Ithaca has experienced a drought. According to the Cornell Institute for Climate Smart Solutions, the 2016 drought caused a majority of unirrigated rain-fed crops in New York to experience crop failures.

Drought is how far we are from our normal amount of rainfall relative to what the ecosystem has evolved to need, said Prof. M. Todd Walter, biological and environmental engineering.

This shift in water supply can be severely detrimental it would take only a year of continuous drought conditions in Ithaca for many species in the current ecosystem to either adapt or die off and be replaced with more drought-tolerant species.

We are very sensitive to short-term drought because our soil is shallow, and our plants have a small reservoir of water to draw from, Walter said.

Fall Creek is at half its average water level, further exacerbated by the Universitys lack of a water reservoir or other water storage methods.

Cameron Pollack / Sun File Photo

Cayuga Lake, as seen from Stewart Park, in 2017.

Another challenge we face here is this cyclical movement of people, said Harman Singh Dhodi, grad, who studies urban water systems. [Students] move in during the semester and [then leave].

The oscillating demand for water, which mirrors student residential periods, shapes the Universitys water management systems. Last semester when students were suddenly asked to leave campus there was an excess of water, but the University took no proactive measures to use the water, Dhodi said.

The University could not direct its water toward the citys needs because of the distinct systems that are employed by Ithaca and Cornell. This caused Ithacas water system to deplete while the Universitys supply sat idle, according to Dhodi.

On the other hand, Dhodi said that water recycling and reuse are not employed enough, and advocates for tackling the stigma against using chemically and biologically treated wastewater that is otherwise ejected into Cayuga Lake.

Because of water supply reducing naturally due to global warming and climate change, [time has come] to use our water more judiciously and efficiently, Dhodi said. Why is this not a common practice? Its because everyone thinks we have plenty of water, we have the Great Lakes and Finger Lakes, its a psychological thing.

The droughts in Ithaca represent a larger pattern across New York State as it increasingly experiences arid conditions due to climate change.

The biggest issue is communication and human behavior. People are struggling with the timescale of climate change, said Prof. Edwin Cowen, civil and environmental engineering, and director of the DeFrees Hydraulics lab. COVID-19 demonstrates the challenges we face with climate change. How can people worry about long-term consequences when they cant get food on the table for their kids?

Increased climate variance has major consequences on New Yorks ecosystems and the likelihood of future droughts in Ithaca.

I wouldnt be shocked before I die to hear that the Adirondacks and Catskills [are burning], Cowen said.

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Second Ithaca Drought in Five Years Threatens Water Supply and Local Ecosystem - Cornell University The Cornell Daily Sun

Human Behavior

Bryant establishes Center for Health and Behavioral Sciences with $200000 Roddy Foundation Grant – Bryant University

Bryant Provost and Chief Academic OfficerGlenn Sulmasy, JD, LL.M,and College of Arts and Sciences InterimDean Wendy Samter, Ph.D., announce the establishment of the Center for Health and Behavioral Sciences (CHBS), which is supported by a $200,000 grant from the Fred M. Roddy Foundation, a non-profit organization that supports the fields of medicine, health care, and education. Kirsten Hokeness, Ph.D., Professor and Chair of the Science department, was appointed by Sulmasy as Director of the Center.Joseph Trunzo, Ph.D., Professor and Chair of the Psychology department, will serve as Deputy Director.

Building on our historic strengths, we are developing strategies for innovation and future growth to position our faculty and students to make significant contributions in the areas of the healthand behavioral sciences.

A multi-disciplinary approach to improving health and well-being

The mission of the CHBS is to educate and train the next generation of leaders who are dedicated to improving the health and well-being of others.The challenges of the ongoing global pandemic have highlighted the critical need for multi-disciplinary approaches to identifying and solving problems in this sector.The Center will leverage the strength of Bryants business core to become a premiere choice for students pursuing a career in health sciences, health care, or behavioral sciences.

The truly innovative and holistic approach to research and health care is what attracted us to this initiative at Bryant University."

We are grateful for the generosity of the Fred M. Roddy Foundation in providing critical funding for this important initiative that will support research and education in these interconnected disciplines, says Bryant Provost and Chief Executive Officer Glenn Sulmasy, JD, LL.M. Building on our historic strengths, we are developing strategies for innovation and future growth to position our faculty and students to make significant contributions in the areas of the health and behavioral sciences.

The truly innovative and holistic approach to research and health care is what attracted us to this initiative at Bryant University. We are also pleased to support a generation of students who will be able to work across disciplines to address complex global challenges, said Elizabeth McIntyre, President of the Fred M. Roddy Foundation. The Foundations essential mission is to support organizations carrying on research, educational or operational efforts for the cure or alleviation of afflictions of body or mind, or for general educational or charitable purposes.

"Bryant is removing traditional intellectual, physical, and geographic boundaries to enable innovation and collaboration that will prepare leaders and practitioners to solve some of the most difficult problems we face today and in the future.

We recognize that the world is not divided by academic disciplines, adds Samter. Through initiatives such as the Center for Health and Behavioral Sciences, Bryant is removing traditional intellectual, physical, and geographic boundaries to enable innovation and collaboration that will prepare leaders and practitioners to solve some of the most difficult problems we face today and in the future.

Enhancing high-quality scientific research

In addition to providing needed funding to help establish the CHBS, the Fred M. Roddy Foundation grant is funding lab equipment that will enable high-quality research. This includes a Mass Spectrometer used for the study of small molecules as part of the antimicrobial discovery program; a Behavioral Assay set-up (an environment to test stimulus response) to support neuroscience and addiction research; Dissecting Microscopes; a Superspeed Centrifuge to process different types of biological materials; and a Psychophysiology iMotion Computer package that measures physiological responses to stimuli.

With this equipment, faculty, including the two newly hired tenure track faculty in the science and psychology departments and students will be better equipped to produce high-quality research and secure additional funding through various granting agencies. Undergraduate students will have the unique opportunity to work one-on-one with faculty on projects linked to health and healthcare, preparing them to be competitive when seeking employment or to succeed in gaining acceptance to prestigious graduate programs in the health and behavioral sciences.

A holistic view

Our goal is to ensure that students understand the scientific foundations of human health and disease along with the core concepts in their chosen field of study, while gaining a holistic view of the healthcare industry, human behavior, and mental processes, says Hokeness describing her vision for the Center. Student researchers and graduates will emerge with a skillset required of practitioners, employees, and scholars who will ultimately become leaders and change agents who value collaboration, enriching the lives of their community.

Whether its a practitioner on the front lines treating patients, a researcher hunting for vaccine candidates, a psychologist addressing the impact of the virus on the wellness of the population, a communication expert working to deliver messaging to the public, an economist examining the effects of the pandemic on the global economy, or a manager in a healthcare facility understanding patient needs, The education and training that happens at the CHBS will enable students, scholars, leaders, and practitioners to successfully navigate the interconnected nature of human health and wellness, adds Trunzo.

Building on Bryants unique integration of the arts and sciences with business, academic program development in the area of health and behavioral sciences will develop highly skilled employees for a sector that positioned for future growth.

For 158 years, Bryant University has been at the forefront of delivering an exceptional education that anticipates the future and prepares students to be innovative leaders of character in a changing world. Located on a contemporary campus in Smithfield, R.I., Bryant enrolls approximately 3,800 undergraduate students from 38 states and 49 countries. Bryantis recognized as a leader in international education and regularly receives top rankings fromU.S. News and World Report, Money, Bloomberg Businessweek, Wall Street Journal, College Factual,andBarron's.Visithttps://www.bryant.edu/.

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Bryant establishes Center for Health and Behavioral Sciences with $200000 Roddy Foundation Grant - Bryant University

Human Behavior

Seasonality of the SARS 2 Coronavirus – Harvard Magazine

Many viruses are known to be seasonal, but as COVID-19 cases in late October reached a record high in the United States, even epidemiologists who have been warning for months that the pandemic will worsen with the approach of Northern hemisphere winter were surprised by the sudden upturn in casesand the accelerating pace of deaths.

The seasonality of the disease may have lulled many people into believing that their efforts at masking and social distancing were responsible for decreased cases during the summer, according to assistantprofessor of epidemiology Michael Mina, who is a leadingadvocate of the use of rapid testingas a public-health measure to suppress outbreaks and allow re-opening of schools and the economy. A better way to think about it, he said during an October 23 call with reporters, is thatWe had an opportunity to use and leverage the decreased transmission of the virus during the summer months to prepare for the fall. Now that the opportunity to deploy vast numbers of cheap tests before a fall reopening has been squandered, We are really left with impossible decisions, he said: either remaining locked down and dealing with the political and economic fallout; or staying open and reckoning with the health consequencesmeaning some people wont live as a result.

On October 25, Mina tweeted thatthe 14-day average rate of growth in COVID-19 deaths had leapt from 7 percent to 15 percent in just 3 days, meaning thatU.S. deaths were accelerating at a rapid pace.

As the reopening of society collided with seasonal factors, Mina and other epidemiologists had expected an increase in coronavirus infections and deaths. He had tweeted in early October that If we do not get this virus under control now, we are in for a perfect and terrible storm. But even experts have difficulty predicting the extent of seasonalitys impact in the months ahead,because We dont know either the magnitude or the mechanisms, says professor of epidemiology Marc Lipsitch, director of Harvards Center for Communicable Disease Dynamics.

Last spring, he and other epidemiologists estimated about a 20 percent difference in transmissibility between the seasonal trough in summer and the peak in winter, based on studies of other coronaviruses. That modest-seeming effect could nevertheless have a significant impact if the use of masks and social distancing in summer, plus a drop in viral activity, ensured thatinfected individuals transmitted the virus to just one other person on average. Conversely, an increase of 20 percent from that rate would drive anexpandingnumber of infections.

There are plenty of theories, and enough circumstantial evidence, to suggest that seasonality is driven by multiple factors, including environmental impacts on the virus and the host immune system, as well as human behavior. When temperatures drop below 65 degrees, for example, many people begin to spend more time indoors, where distancing is more difficult, and the lack of ventilation allows airborne viral particles to accumulate.

Edward Nardell, professor of environmental health and immunology and of medicine, illustrated the latter point during a June 26 talk. Much of the transmission of SARS-CoV-2 is thought be via large respiratory droplets, he said:Normally we think of them as settling down within a meter or so of the source and for good measure, weve insisted on a six-foot distance between people. While facemasks capture large respiratory droplets, and even small ones to some degree, evaporation from very small exhaled particles can allow droplet nuclei to become suspended and move with air patterns. Nardell documented the concentration of carbon dioxide (CO2) in an office with five occupants during a three-hour timespan. (Because people exhale CO2, the gas is a good surrogate for the fraction of rebreathed air in a room, and thus the risk of infection from airborne viral particles.) During the first two hours, with the window open, the level of CO2remained fairly constant. But within just 60 minutes of closing the window, the rebreathed fraction of air, and thus the risk of infection,doubled.

Several other factors could play a role in seasonal transmission:

On the other hand, Lipsitch said to reporters last week, scientists may already know the most important, actionable factors relevant to transmission of SARS-CoV-2: airflow, crowding, mask-wearing, and distance. It may not matter whether someone is in a grocery store, a fabric store, or a bar, he said. What may matter most is the number of people, the space between them, the ventilation, and the amount of vocalization.

As the holidays approach, students travel home, and temperatures drive people indoors, Lipsitch is often asked what he would recommend with respect to annual family gatherings. One neighbor asked him in particular what to do about Thanksgiving. His own gathering of 16 family members, he told her, would not be taking place this year. But people have a very real need to see their families and will have to figure out how to do that safely. One suggestion he made was to celebrate early, outdoors, with a couple of people at a time: a backyard Thanksgiving in October, or later in the yearfarther south.

The guiding principles are all the same, he continued: ventilation [by being] outdoors; small groups; staying at a distance; and masking. I dont think that big holiday gatherings make a lot of sense. So, I would recommend doing as much socializing as you can outdoors while the weather permits.

Asked why it was important to keep gatherings small, Lipsitch explained that the risk to each person in a group goes up in proportion to the size of the gathering. If theres a half percent chance that each person is infectious, then in a group of five, theres approximately a two-and-a-half percent chance that at least one person is infectious. The probability rises as the numbers increase, and at the same time, the chance that the number of people exposed goes up. Roughly speaking,doubling the size of a group increases the risk of transmission by a factor of fourandtripling(from two people to six, for example)raises risk ninefold, because you have three times as many potentially infectious people and three times as many recipients. Furthermore, Lipsitch added, Risk always rises with the prevalence of infection in the places people are coming from.

Knowing all this can help individuals, families, and local communities mitigate their risk, but What we dont have right now is a comprehensive answer for how to get from high levels of community transmission back down to very low levels without lockdown or intense social-distancing interventions, Lipsitch continued. That is the task that lies ahead for [epidemiologists] and I think testing would be at the center of that, but on a much, much larger scale than we have. Already, he pointed out, places that have the resources (including some universities, companies, and the NBA) have successfully controlled transmission with very extensive testing together with isolation of infected individuals. The question, he said, is whether the amount of testing that the United States can realistically create overlaps with the amount that would be effective at scale.

Mina, at the forefront of efforts to develop faster, cheaper testing, has met with officials at U.S. regulatory agencies, and says that several significant bureaucratic obstacles to rapid testing have been removed. Still missing, however, is a coordinated federal response, including a commitment to spend the $20 billion that he estimates would be needed to deploy a national testing strategy by Januarysmall change compared to the$16 trillion in estimated economic damagesattributable to the pandemic, includingthe loss of 2.5 million years of potential lifeso far in the United States alone. Were all hoping that a vaccine will create herd immunity, he continued, but there wont be enough vaccine for everyone until late spring or early summer.

At this point for Mina, it is dj vu, as once-avoidable increases in hospitalizations threaten to overwhelm the capacity of health-care systems, just as they did in April. I dont want to see everything close down again, he tweeted recently. I dont want to see people spending their last days alone.

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Seasonality of the SARS 2 Coronavirus - Harvard Magazine

Human Behavior

What’s behind Virginia’s increasing pedestrian death toll and how to reverse the trend – Virginia Mercury

On Thursday evening, friends and family were at the intersection of Jahnke and German School roads on Richmonds Southside to mourn the loss of 16-year-old Aajah Rosemond, who was killed by a driver while walking to the store.

According to police, a collision with a GMC Yukon sent a roughly 6,000 pound Nissan Titan spiraling up and onto the sidewalk, fatally striking the teenager. The evening news tells such tales with disturbing regularity, a product of Virginias rapidly rising pedestrian death rate. However, whats behind the spike and how to fix it are questions without simple answers.

Over the past half century, Virginia and the rest of the country have generally enjoyed a steady decline in traffic deaths. While fatalities have reached record lows for drivers, starting 10 years ago, however, that trend began to reverse for people outside of a vehicle. During the 10-year period from 2009 to 2018, the number of pedestrian fatalities increased by 53 percent (from 4,109 deaths in 2009 to 6,283 deaths in 2018), stated a recent report from the Governors Highway Safety Association. By comparison, the combined number of all other traffic deaths increased by 2 percent.

According to Mark Cole, a highway safety engineer with the Virginia Department of Transportation, pedestrian deaths truly began to shoot up in the state four years ago. Prior to 2016 Virginia was seeing about 80-100 pedestrian deaths per year. Then in 2016 we saw a big jump to over 120, he said. In 2018, there were 123 pedestrian fatalities, an increase of nearly 8 percent from the year before, according to the DMV.

Last year, 126 pedestrians and 13 bicyclists were killed on Virginias roads, the nonprofit Drive Smart Virginia reported. Nationwide, the number of people killed while walking hit a 30-year high and roads have only gotten more dangerous as some driving during the pandemic took empty streets as a chance to speed. Although some initially blamed the proliferation of smartphones, the past decade of data has shown the roots of the rising fatalities run far deeper.

One of the most obvious answers behind the jump in pedestrian deaths are the types of vehicles hitting people. It is hard to overemphasize just how suddenly and completely [SUV] crossovers have come to dominate the auto market in recent years, wrote Angie Schmitt, a planning consultant with 3MPH, in her recent book: Right of Way: Race, Class, and the Silent Epidemic of Pedestrian Deaths in America. When the economy was still recovering from a recession, in 2012, 83 percent of vehicles sold in the United States were sedans.

As wages rose and gas prices dropped, however, Americans increasingly began purchasing SUVs and heavy-duty trucks. Now almost no sedans are being sold, and the whole market is trucks and SUVs, she said in an interview. That means cars are getting bigger, taller and deadlier.

From his work mapping and analyzing crash data with VDOT, Cole agrees with the diagnosis: The vehicle fleet has been changing over time with SUVs and trucks becoming the greater proportion of the fleet thats on the road. Weve seen an increased number of those types of vehicles involved in crashes too. SUVs and pickups which have a higher center of gravity and higher weight result in more serious crashes.

When drivers in a sedan run into someone, that person is more likely to fly up onto the hood, an occurrence with a far higher survival rate than when someone is run over. With many SUV and truck grills now reaching as high as five feet, its nearly impossible for pedestrians not to be pushed under the vehicle. The data bear this out: One hundred percent of pedestrians in SUV collisions at speeds of 40 mph or greater died, versus 54 percent who were struck by cars.

Melicent Miller, a project manager with the state Department of Healths Virginia Walkability Action Institute, acknowledges the increased danger posed by this bigger fleet: There are some really monstrous vehicles on the streets. The odds of someone surviving contact with an SUV or a truck is much lower than when someone gets hit by a sedan.

Who pedestrians are and where theyre walking are also driving pedestrian fatalities to record highs. According to the Department of Motor Vehicles the number of individuals 65 and older killed while walking is up 95 percent over 2018 alone. Seniors have always made up one of the highest risk groups to be run over by drivers, and as the Baby Boomer generation ages, the number of those most vulnerable has multiplied.

The other factor influencing the rising pedestrian death rate is the displacement of the urban poor to the suburbs. As wealthier Whites return to city centers, Black and brown communities with lower rates of vehicle ownership are being pushed into suburban sprawl often characterized by 45 mile-per-hour speed limits, lack of sidewalks and eight-lane arterial roads.

Between 2010 and 2015, about half the growth in poverty took place in U.S. suburbs, according to the Institute for Research on Poverty at the University of WisconsinMadison, wrote Schmitt. In the United States today, more than three million more people are living in poverty in suburbs than in cities. These places and their streets, almost without exception, were not designed to accommodate people walking or relying on transit.

Americas changing vehicle fleet and shifting demographics arent responsible for the entirety of the tragic trend. Its not always easy to put your finger on what causes a crash because they reflect a lot of structural issues like land use and how a road is designed but they also bring in human behavior, Cole said. The majority of crashes weve seen involve human error.

DOTs and traffic safety campaigns often note that 94 percent of all crashes are due to human error; however, a growing coterie of city planners and urbanists are increasingly pushing back on that claim as an out for engineers to place the blame on victims of traffic collisions rather than fixing the infrastructure and design failures that cause crashes to be so deadly.

In a recent interview, Leah Shahum director of the Vision Zero Network, which is pushing to eliminate traffic fatalities said, We need to debunk the 94 percent myth because it detracts focus from the actual risk factors that are most deadly, such as poorly designed roads and dangerously high speed limits. This myth keeps communities from implementing effective policy and design solutions, which is literally killing people, especially our most vulnerable road users, including children, seniors, people with vision impairments and those walking and biking.

When explaining the growing disparities in death rates, Schmitt points to the different attention paid to making roads safe for drivers versus ensuring that people on foot can safely get where they need to go. If youre on a highway you can count on everything you need to be safe like guardrails and good lighting to be there. On our local and arterial roads a lot of the things needed to keep pedestrians safe like guard rails and curb ramps are missing.

The engagement of public health officials has helped to strengthen this approach to the problem. One of the central tenets of Vision Zero is that humans are fallible and are going to make mistakes, but we can use that information to plan for human error, said Sarah Shaughnessy, the built environment & health specialist for the Richmond City Health District. We are smart enough that we should be able to put policies and infrastructure in place to account for that.

The skyrocketing pedestrian death rate over the last four years doesnt mean Virginia officials have been sitting on their hands. There are certain ways VDOT impacts this trend like our construction and maintenance programs, and there are certain ways we dont, said John Bolecek, VDOTs bicycle and pedestrian program manager. Every way in which we interact with this issue something has changed to improve it.

A new LED lighting policy has made it cheaper to keep streets well-lit a critical enhancement since 75 percent of all pedestrian deaths occur at night. A crash-mapping project begun several years ago has also borne fruit: We learned that the majority of deaths almost always occur when a pedestrian is crossing the road, but we dont do a good job as a state, as VDOT, and as a society in providing safe crossing infrastructure for pedestrians, Cole said.

Although Virginia hasnt fully embraced Vision Zero and its goal of zero traffic fatalities as the guiding principle of its transportation planning, VDOTs most recent Strategic Highway Safety Plan Arrive Alive comes close. The two year old Pedestrian Safety Action Plan is another VDOT tool meant to guide the commonwealths cities and counties to invest more in pedestrian safety.

When localities take pedestrian deaths seriously and apply for VDOT funding to fix bad infrastructure, Bolecek has seen dramatic results: In Northern Virginia alone over the past five years theyve built out over 200 miles of bike lanes, often via road diets which have also turned center lanes into pedestrian refuges. Thats added a lot of crosswalks and moved bus stops to better locations.

Recent pushes to lower speed limits and implement handsfree bans may help, but lacking infrastructure is such a localized problem that Schmitt advises communities to conduct pedestrian safety audits to identify and address unsafe streets. Shaughnessys office often helps Richmond residents invite key stakeholders like city council members, police officers and public works officials to walk with residents and then packages that information for grants to fix the problems found.

With so much of the problem beyond the power of local and even state governments, Schmitt hopes that a new presidential administration next year could begin to tackle the epidemic of pedestrian deaths at the federal level too by dedicating more dollars to pedestrian safety and by introducing stricter vehicle safety guidelines.

Pedestrian detection and automatic braking have reduced insurance claims for pedestrian crashes by 35 percent, but the National Highway Traffic Safety Administration currently doesnt require car companies to install those technologies, which limits how effective and widespread those are, Schmitt said. The U.S. government regulates vehicles for all kinds of safety issues like air bags and auto-lock brakes, but none of those things protect folks outside of the vehicle; they only protect drivers.

CORRECTION: Mark Cole works for the Virginia Department of Transportation. This story has been update to reflect that correction.

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What's behind Virginia's increasing pedestrian death toll and how to reverse the trend - Virginia Mercury

Human Behavior

Research finds a problem with concept of herd immunity in COVID-19 – News-Medical.Net

A recent study published on the preprint server medRxiv* in October 2020 suggests that arguments in favor of herd immunity are weakened by the fact that the steep increase in the number of COVID-19 deaths as a result of being exposed to the virus many times instead of once or a few times is not taken.

While most have mild COVID-19, a severe disease associated with diffuse pneumonia may require hospitalization. Many in this group will eventually require intensive care, with oxygen supplementation and mechanical ventilation.

In a sizable minority of cases, death supervenes due to multi-organ failure. The survivors in this group may experience permanent disabling symptoms.

Lockdown strategies were meant to buy time for productive and preparatory measures by slowing the pace of viral transmission. Vaccines are meant to elicit neutralizing immunity to the virus and prevent endemicity. Since this is an RNA virus, it is bound to undergo numerous mutations, which will make it more difficult to eradicate it in endemic form.

Another school of thought holds that herd immunity is the best way to handle the pandemic. Without any interventions, the population will develop immunity naturally, while the economy will remain stable, so goes the argument. However, the World Health Organization (WHO) chief has termed this an unethical idea.

The researchers in the current study say that herd immunity appears appealing only because it is backed by simplistic simulations that ignore real-time health care challenges. Moreover, durable immunity to SARS-CoV-2 has not yet been proved.

Again, this model does not consider the higher death rates bound to occur with an overburdened healthcare system as infections surge. And finally, it ignores the long-term disabling effects of this illness, the medical and the social costs of caring for such individuals.

The uncontrolled viral spread will cause endemic COVID-19. Novel variants may emerge that are more destructive to lung tissue. Even worse, multiple exposures may lead to a higher viral load, and therefore a more significant proportion of severe disease.

Repeated exposures could also trigger antibody-dependent enhancement (ADE) of disease severity. This is one area where wearing face masks in public all the time could make a big difference in the load placed on hospitals and HCWs, by preventing severe infections.

There are many distinct variants of the virus in circulation at the current time. These variants do show different degrees of infectivity and pathogenicity. It is unclear whether these can exist simultaneously in one patient and how they interact, if so.

Since current estimates of mortality depend on information from the early part of the pandemic, they are likely to be inaccurate since, at this time, individuals were unlikely to have repeated contacts with infected persons. One exception was HCWs, since their daily and repeated contacts with many potentially infected people rendered them capable of super-infections.

The present study aims to understand how mortality is related to the presence of multiple variants of SARS-CoV-2 acquired through multiple exposures. This model also examines how measures intended to reduce contact with infected people affect super-infections and mortality. It uses a model adapted from the free tool CovidSIM.

The researchers assumed disease stages of latent (3.7 days), prodromal (1 day), fully contagious (7 days), and late infectious (7 days), and also assumed a doubling of infectivity in the fully contagious stage compared to the first two. They found that multiple infections had a ~64% risk of causing severe symptoms and 4% mortality compared to 58% and 3%, respectively, for single infections.

Multiple infections caused more symptomatic infections, therefore more isolation, resulting in less spread and a smaller peak. But while the total number of multiple infections is somewhat reduced, especially during the epidemic's peak, the number of deaths increases.

However, seasonal infections affect this relationship, with a higher narrower peak resulting if it overlaps with the beginning of the flu season. In this case, more multi infections, and significantly more deaths, will occur than expected.

Symptom severity is measured by the number of infected individuals who come to medical attention and enter isolation, with a direct relationship between the two parameters. Higher isolation of symptomatic multi infections reduces total infection numbers somewhat, reducing the epidemic's peak and of multi infections.

The total mortality rises, however, due to the increased number of deaths caused by multi infections.

Again, multi infections reduce the overall case number but push up the number of deaths in proportion to the case fatality rate of multi infections. Again, this is aggravated by seasonality, with a higher epidemic peak, more multi infections, and more deaths if the peak comes at the beginning of the flu season.

Multi infections may be caught by one or consecutive exposures. If the latter, the effects will be delayed, and in this period, the spread is limited, while recovery may occur rather than death. Thus, this subset of infected individuals does not significantly increase the total number of multi infections.

However, the higher the risk of multi infection spread, the higher is the epidemic peak, and the greater the case fatality.

Prior infection with one strain of SARS-CoV-2 may confer partial immunity to multi infections, depending on the contagious person's stage of infection. Susceptibility is significantly less, and therefore the risk of multi infections if the susceptible person is in the late infectious phase.

While variations in susceptibility do not affect the epidemic peak, they do affect the multi infection case number. Around the peak, multi infection by exposure to two or more single infections is more likely than that due to exposure to one multi infection.

The researchers also found that reducing inter-individual contacts over a range of scenarios ranging from a second lockdown to no intervention would result in a delayed but not smaller epidemic peak in a non-seasonal scenario. Case isolation reduces the peak. In both cases, multi infections and deaths are unaffected.

With seasonal changes, fewer contacts can delay the epidemic peak to coincide with that of the flu season, increasing the peak height. The narrow, sharp peak limits the multi infection case number slightly, and the number of deaths is also somewhat lower.

A second lockdown, properly timed, can reduce the number of infections occurring after the relaxation of the first, if the epidemic peaks while the reproduction number is declining. The earlier such a lockdown is put into force, the more it overlaps the pandemic's early peak, and the greater is the delay in the eventual peak. This will also result in a broader but flatter peak.

The number of cases and deaths can be still further reduced by extending an early lockdown. If too late, however, the lockdown will be ineffective as cases are already declining.

The researchers point out, "Multiple infectious contacts and longer (average) exposure to the virus is initially restricted to certain risk groups, but will become common during the pandemic peak."

Different variants of SARS-CoV-2 may be acquired at different points by exposure to different infectious individuals. Viral diversity will also only increase during a pandemic.

Herd immunity becomes a less attractive concept given the higher viral load and multi infection risk as the pandemic progresses, coupled with more significant morbidity and mortality. Herd immunity becomes a less attractive concept versus a properly timed second lockdown. The results may vary with the duration of immunity and human behavior. For instance, some individuals may choose to avoid most forms of contact with others. The model parameters can be tweaked for several such differences.

The researchers also point out, "Notably, multi infections are not the only danger when aiming for herd immunity. An uncontrolled (or hardly controlled) pandemic inevitably renders the virus endemic."

If so, not only will it become difficult to get rid of the virus, but it could find reservoir hosts in pet animals, escaping control measures. As viral diversity increases, so might its virulence, requiring the vaccines to be adapted each year. Multiple vaccination rounds will then be required to eradicate the virus, resulting in ADE in some individuals.

The study concludes, "Increased morbidity and mortality due to multi infections is an important but overseen risk, particularly in the context of herd immunity. Evidence-based research on multi infections is necessary."

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

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Research finds a problem with concept of herd immunity in COVID-19 - News-Medical.Net

Immunology

Video: COVID-19 Why it Matters: Part 12, Why huge COVID-19 spikes in Wisconsin? – UWGB

This video series features UW-Green Bays Immunologist Brian Merkel on COVID-19 and Why it Matters. This series empowers viewers with knowledge to help them navigate through the pandemic. Merkel has a Ph.D. in Microbiology & Immunology from the Medical College of Virginia. He is an associate professor in UW-Green Bays Human Biology & Biology programs and has an appointment at the Medical College of Wisconsin Department of Microbiology and Immunology. He will be responding to a number of questions related to COVID-19 and try to get behind the why its important to be educated in your decision-making as we navigate the pandemic together.

Video Transcript COVID-19 Why it Matters, Part 12: Why HUGE COVID-19 spikes in Wisconsin?

Hello, Brian Merkel, Microbiology and Immunology UW-Green Bay and we are here today to talk about why COVID-19 matters to you.

Specifically, we want to address the current spike that were having in COVID-19 in Wisconsin. I think one of the best examples of why we should be so concerned about the spikes that were currently dealing with in Wisconsin, has to do with the reality that we just opened up a field hospital in Milwaukee.

Now thats something as an educator at UW-Green Bay, that I used to talk about just in history books with the pandemic problem of 1918. Never in my life would I ever thought for a minute that we would be doing something like that now.

So, here we are. We have this terrible spike in Wisconsin now. In terms of explanations, it has to do with large gatherings and people not following the prescribed safeguards. The challenge is compliance and so we strongly encourage people to realize and theres empowerment to this because the more each of us does our part to comply with the prescribed safeguards, the better off were going to be, and themore likely were going to get a good handle on this virus.

We strongly encourage you to wear masks, wash your hands, and keep your distance, and avoid large gatherings and please stay at home when youre sick.

COVID-19 Why it Matters Video Series:

Introduction with Brian Merkel https://youtu.be/M-yYPSPk30Q

Part 1: What are viruses and where did this one come from https://youtu.be/DYbiIv8ICgs

Part 2: Two main types of viruses https://youtu.be/O-OVk3rx96s Part 3: Why is this virus serious? https://youtu.be/EDFyNN8i5G4

Part 4: Why wash hands/wear mask? https://youtu.be/FlcAvlt876Y

Part 5: Im young! Why should I care? https://youtu.be/TDrEV_beY1U

Part 6: Can pandemics be stopped before they start? https://youtu.be/lgWnJZNYbFI

Part 7: Pandemic is not local, why wear a mask? https://youtu.be/IG3Sl3q-xH8

Part 8: Why does everyone need a flu shot this year? https://youtu.be/DGpBFj0fJkA

Part 9: What is the science behind a vaccine? https://youtu.be/eQ3FclkYaQo

Part 10: Where can I find accurate information? https://youtu.be/pLMlU5Xnkgo

Part 11: What type of mask should I wear? https://youtu.be/gCFHxQvkVYE

Part 12: Why HUGE COVID-19 spikes in Wisconsin? https://youtu.be/OuqmXvrDApY

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Video: COVID-19 Why it Matters: Part 12, Why huge COVID-19 spikes in Wisconsin? - UWGB

Immunology

GentiBio Expands Leadership Team and Partnership with MIGAL to Help Advance Development of Engineered Regulatory T Cell Therapies – BioSpace

BOSTON, Oct. 28, 2020 /PRNewswire/ --GentiBio, Inc., an emerging biotherapeutics company developing engineered regulatory T cells (EngTregs) programmed to treat autoimmune, alloimmune, autoinflammatory, and allergic diseases, announced today the appointments of Catherine Thut as Chief Business Officer and Thomas Wickham as Chief Scientific Officer. In these roles, Thut will be responsible for leading the company's corporate development, strategy and financing, and Wickham will drive the company's research and development activities to advance the company's scientific platform and shape research strategy. Additionally, GentiBio expanded its existing partnership with MIGAL Galilee Research Institute to further leverage the institute's expertise in synthetic immunology.

"We are excited to welcome Cathy and Tom to our team as both come at a pivotal time for the company as we advance the development of our Regulatory T cell-based therapies," said Adel Nada, Co-founder, President and CEO of GentiBio. "Catherine brings to GentiBio extensive experience and a proven track record in business development and fundraising in the biopharmaceutical space, while Tom's deep expertise in immunology and a diverse spectrum of drug and engineered cell therapy platforms will be invaluable to the company as we further the progress of our research programs and pursue moving our therapies into the clinic. Adding their leadership to GentiBio will be critical in helping us achieve our business and scientific goals."

Catherine Thut, Ph.D., MBAThut brings vast biopharmaceutical industry experience to the GentiBio team. Cathy most recently served as CEO of Makana Therapeutics, a preclinical stage company focused in alleviating organ shortage crisis through xenotransplantation, where she led the merger of Makana with Recombinetics. Prior to Makana, Cathy was Executive Director in the Business Development and Licensing group at Novartis Institutes for BioMedical Research (NIBR), where she worked across multiple therapeutic areas and was responsible for negotiating a number of immuno-oncology partnerships. Cathy also worked at Merck Research Laboratories as Therapeutics Area group leader for Ophthalmology Research. She pursued her graduate and postdoctoral training at U.C. Berkeley and Stanford University Medical School, respectively, and received her MBA from MIT's Sloan School of Management.

"I'm excited to work with the GentiBio team to bring my corporate development and business strategy experience to the company as we work to determine how our unique therapeutic modality can directly address the underlying cause of autoimmune, alloimmune, auto inflammatory and allergic diseases," said Thut. "GentiBio's platform has the potential to realize the promise of EngTregs cell therapy products in the treatment of serious diseases, and I'm eager to help make this a reality for patients."

Tom Wickham, Ph.D.Tom brings over 25 years of experience in advancing drug platforms in a variety of therapeutic areas from discovery through clinical trials. Most recently, Tom served as Senior Vice President of Research and Development at Rubius Therapeutics, where he pioneered synthetic biology approaches using genetically engineered red cells for autoimmunity, immuno-oncology, and rare disease applications, building a full discovery and preclinical organization leading to multiple product programs and two regulatory filings. Prior to Rubius, he held senior roles at numerous leading biopharmaceutical companies, including as Vice President of R&D at Merrimack Pharmaceuticals, Senior Director of Preclinical Pharmacology at EMD Lexigen (now Merck-Serono), and at GenVec, Inc. Tom holds a B.S. in chemical/biomedical engineering from Carnegie Mellon University, a Ph.D. in biochemical engineering from Cornell University, and pursued his postdoctoral training at the Scripps Research Institute in the Department of Immunology.

"Understanding the limitations in existing regulatory T cell-based therapeutics, I'm motivated by the innovative approach GentiBio is taking to successfully restore immune tolerance in the body," said Wickham. "I look forward to bringing my expertise with advancing drug platforms to GentiBio as I truly believe Regulatory T cell biology coupled with smart and fit-for-purpose receptor engineering has the potential to treat and cure many patients living with serious autoimmune and inflammatory diseases."

Expanded MIGAL Galilee Research Institute PartnershipIn addition to the new executive hires, GentiBio has expanded its partnership with MIGAL-Galilee Research Institute through the exclusive licensing of its unique immune evasive technology that can potentially enable durable engraftment of allogeneic cells, including EngTregs. This proprietary technology has been conceptualized and achieved building on the long standing and pioneering insights of Prof. Gidi Gross, Head, and Dr. Hadas Weinstein-Marom, Senior Scientist, Immunology Laboratory, MIGAL and Scientific Co-Founders and Scientific Advisory Board members of GentiBio.

"Enabling durable cell therapy engraftment in immune competent patients will advance the reach of EngTregs and cell therapy platforms, positioning GentiBio to become a leader in allogeneic cell therapy," said Nada. "We are thrilled to continue partnering with a premier research organization like MIGAL to advance novel and potent engineered cell therapies with the potential to treat and cure serious autoimmune and inflammatory diseases."

"The immune evasive technology is a product of many years of synthetic immunology tinkering and engineering. We are delighted to see this technology further developed and advanced by GentiBio to make it available for the many patients who can benefit from it," said Prof. Gross.

About GentiBio, Inc.GentiBio, Inc., is an early stage biotherapeutics company co-founded by pioneers in Treg biology and synthetic immunology to develop engineered regulatory T cells (EngTregs) programmed to treat autoimmune, alloimmune, autoinflammatory and allergic diseases. GentiBio's proprietary autologous and allogeneic EngTregs platform integrates key complimentary technologies needed to successfully restore immune tolerance and overcome major limitations in existing regulatory T cell therapeutics. GentiBio is at the forefront of leveraging a unique therapeutic modality that can be used to address the fundamental cause of many diseases that result from overshooting and/or malfunctioning of the immune system. To learn more visit https://www.gentibio.com/

About MIGAL Galilee Research InstituteMIGAL Galilee Research Institute Ltd is a regional R&D center of the Israeli Science and Technology Ministry owned by the Galilee Development Company ltd. An internationally-recognized multi-disciplinary applied research institute, MIGAL specializes in biotechnology and computer sciences, plant science, precision agriculture and environmental sciences, and food, nutrition and health. Recognized as a powerhouse of applied research, for forty years MIGAL has cooperated closely with industry leaders, innovative startups, and technological accelerators. MIGALs' employees include 90 PhDs and 190 researchers distributed across 44 research groups, operating as an innovative research ecosystem that encourages collaboration across scientific, industrial, agricultural, academic and technological specialties.

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Immunology

La Jolla Institute for Immunology professor receives $500 000 for COVID-19 research – COVID-19 patients around the world are experiencing lasting…

La Jolla Institute for Immunology professor receives $500,000 for COVID-19 research

San Diego Community News Group

Colorized scanning electron micropgraph of an apoptotic cell heavily infected with SARS-CoV-2. Photo Credit: NIAID.

COVID-19 patients around the world are experiencing lasting cardiovascular issues, even after they've recovered from other symptoms. In fact, one in four COVID-19 patients suffers from damage to the heart muscles, and problems with blood clotting and inflammation have been reported even in elite athletes.

"We're concerned that there could be permanent or long-term changes in these patients," says Catherine "Lynn" Hedrick, Ph.D., professor at La Jolla Institute for Immunology (LJI).

Hedrick recently received $523,914 in funding from the National Institutes of Health's National Heart, Lung, and Blood Institute (NHLBI) to study how immune cells may contribute to cardiovascular problems in COVID-19 patients. Hedrick's work will focus on how the SARS-CoV-2 virus may affect monocytes, a type of immune cell in the bloodstream.

"We know that even people with mild COVID-19 cases have changes in their monocytes," says Hedrick. "We want to know why."

Monocytes are part of the body's first line of defense against viral invaders. As COVID-19 has spread, more and more studies suggest SARS-CoV-2 affects monocytes in an unexpected way. In fact, COVID-19 symptoms like abnormal blood clotting, heart damage, and even lung inflammation can be tied to problems with monocytes.

For the new study, Hedrick's lab will measure a protein that monocytes makecalled tissue factorin blood plasma from COVID-19 patients. This work will depend on LJI's new IDEA Facility, a biosafety-level 3 laboratory designed for safe studies of highly infectious pathogens such as SARS-CoV-2.

Hedrick is also collaborating with Pandurangan Vijayanand, M.D., Ph.D., associate professor at LJI, and Christian H. Ottensmeier, M.D., Ph.D., FRCP, professor at the University of Liverpool and adjunct professor at LJI, to study gene expression in monocytes from COVID-19 patients. The team will track gene expression over several months to see how the virus may affect different subtypes of monocytes.

Hedrick also plans to work with a new mouse model, developed by the lab of LJI Professor Sujan Shresta, Ph.D., to better understand how changes in monocytes may affect cells in the cardiovascular system and lungs.

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La Jolla Institute for Immunology professor receives $500 000 for COVID-19 research - COVID-19 patients around the world are experiencing lasting...

Immunology

The lymphatic system 2: structure and function of the lymphoid organs – Nursing Times

The lymphoid organs purpose is to provide immunity for the body. This second article in a six-part series explains the primary and secondary lymphoid organs and their clinical significance and structure. It comes with a self-assessment enabling you to test your knowledge after reading it

This article is the second in a six-part series about the lymphatic system. It discusses the role of the lymphoid organs, which is to develop and provide immunity for the body. The primary lymphoid organs are the red bone marrow, in which blood and immune cells are produced, and the thymus, where T-lymphocytes mature. The lymph nodes and spleen are the major secondary lymphoid organs; they filter out pathogens and maintain the population of mature lymphocytes.

Citation: Nigam Y, Knight J (2020) The lymphatic system 2: structure and function of the lymphoid organs. Nursing Times [online]; 116: 11, 44-48.

Authors: Yamni Nigam is professor in biomedical science; John Knight is associate professor in biomedical science; both at the College of Human and Health Sciences, Swansea University.

This article discusses the major lymphoid organs and their role in developing and providing immunity for the body. The lymphoid organs include the red bone marrow, thymus, spleen and clusters of lymph nodes (Fig 1). They have many functional roles in the body, most notably:

The red bone marrow and thymus are considered to be primary lymphoid organs, because the majority of immune cells originate in them.

Bone marrow is a soft, gelatinous tissue present in the central cavity of long bones such as the femur and humerus. Blood cells and immune cells arise from the bone marrow; they develop from immature stem cells (haemocytoblasts), which follow distinct developmental pathways to become either erythrocytes, leucocytes or platelets. Stem cells rapidly multiply to make billions of blood cells each day; this process is known as haematopoiesis and is outlined in Fig 2.

To ensure there is a continuous production and differentiation of blood cells to replace those lost to function or age, haematopoietic stem cells are present through adulthood. In the embryo, blood cells are initially made in the yolk sac but, as development of the embryo proceeds, this function is taken over by the spleen, lymph nodes and liver. Later in gestation, the bone marrow takes over most haematopoietic functions so that, at birth, the whole skeleton is filled with red bone marrow.

Red bone marrow produces all erythrocytes, leucocytes and platelets. Haematopoietic stem cells in the bone marrow follow either the myeloid or lymphoid lineages to create distinct blood cells (Fig2); these include myeloid progenitor cells (monocytes, macrophages, neutrophils, basophils, eosinophils, erythrocytes, dendritic cells and platelets), and lymphoid progenitor cells (T-lymphocytes, B-lymphocytes and natural killer cells).

Some lymphoid cells (lymphocytes) begin life in the red bone marrow and become fully formed in the lymphatic organs, including the thymus, spleen and lymph nodes. As puberty is reached and growth slows down, physiological conversion occurs, changing red bone marrow to yellow bone marrow. This entire process is completed by the age of 25years, when red bone marrow distribution shows its adult pattern in the bones.

The pattern is characterised by:

However, under particular conditions, such as severe blood loss or fever, the yellow marrow may revert back to red marrow (Malkiewicz and Dziedzic 2012).

Any disease or disorder that poses a threat to the bone marrow can affect many body systems, especially if it prevents stem cells from turning into essential cells. Those known to damage the marrows productive ability and destroy stem cells include:

A growing number of diseases can be treated with a bone marrow transplant or haematopoietic stem cell transfer; this is often achieved by harvesting suitable donor stem cells from the posterior iliac crests of the hip bone, where the concentration of red bone marrow is highest.

The thymus gland is a bi-lobed, pinkish-grey organ located just above the heart in the mediastinum, where it rests below the sternum (breastbone). Structurally, the thymus resembles a small bow tie, which gradually atrophies (shrinks) with age. In pre-pubescents, the thymus is a relatively large and very active organ that, typically, weighs around 40g, but in a middle-aged adult it may have shrunk sufficiently to be difficult to locate. By 20 years of age, the thymus is 50% smaller than it was at birth, and by 60years of age it has shrunk to a sixth of its original size (Bilder, 2016); this is called thymic involution

Each of the two lobes of the thymus is surrounded by a capsule, within which are numerous small lobules typically measuring 2-3mm in width which are held together by loose connective tissue. Each lobule consists of follicles that are composed of a framework of thyomsin-secreting epithelial cells and a population of T-lymphocytes; these cells are commonly referred to as T-cells (the T denotes their origin as mature cells from the thymus). Lobules have two distinct areas:

In addition to being a major lymphoid organ, the thymus is also recognised as part of the endocrine system because it secretes a family of hormones collectively referred to as thymosin; this is a group of several structurally related hormones secreted by the thymic epithelial cells. These hormones are essential for normal immune function and many members of the thymosin family are used therapeutically to treat cancers, infections and diseases such as multiple sclerosis (Severa et al, 2019).

T-cells originate as haematopoietic stem cells from the red bone marrow (Fig2). A population of these haematopoietic stem cells infiltrate the thymus, dividing further within the cortical regions of the lobules then migrating into the medullary regions to mature into active T-cells; this process of T-cell maturation is controlled by the hormone thymosin. A proportion of these mature T-cells continually migrate from the thymus into the blood and other lymphoid organs (spleen and lymph nodes), where they play a major role in the bodys specific immune responses (which will be discussed in detail in part 3 of this series). The importance of these cells is apparent in patients who have depleted T-cell populations, such as those infected with HIV.

One of the most important functions of the thymus is programming T-cells to recognise self antigens through a process called thymic education. This process allows mature T-cells to distinguish foreign, and therefore potentially pathogenic, material from antigens that belong to the body. It has been demonstrated that removal of the thymus may lead to an increase in autoimmune diseases, as this ability to recognise self is diminished (Sherer et al, 1999).

Diseases of the thymus include thymic cancer and myasthenia gravis (MG). MG occurs when the thymus produces antibodies that block or destroy the muscle-receptor sites, causing the muscles to become weak and easily tired. It most commonly affects muscles that control the eyes and eyelids, resulting in droopy eyelids and difficulty making facial expressions; chewing, swallowing and speaking also become difficult. MG can affect people of any age, but typically starts in women aged <40years and men aged >60years.

In most cases of either MG or thymic cancer, thymectomy is recommended. Patients who have had a thymectomy may develop an immunodeficiency known as Good syndrome, which increases their susceptibility to bacterial, fungal and viral opportunistic pathogens; this condition is, however, relatively rare.

The spleen and lymph nodes are two major secondary lymphoid organs that play key roles in:

When foreign antigens reach these organs, they initiate lymphocyte activation and subsequent clonal expansion and maturation of these important white blood cells. Mature lymphocytes can then leave the secondary organs to enter the circulation, or travel to other areas, and target foreign antigens.

The spleen is the largest lymphoid organ. Situated in the upper left hypochondriac region of the abdominal cavity, between the diaphragm and the fundus of the stomach, it primarily functions as a filter for the blood, bringing it into close contact with scavenging phagocytes (white blood cells in the spleen that will seek out and eat any pathogens in the blood) and lymphocytes.

Due to its extensive vascularisation, the spleen is a dark-purplish oval-shaped organ; in adults it is approximately 12cm long, 7cm wide and weighs around 150g. However, the size of the spleen can vary with circumstance: it diminishes in starvation, after heavy exercise and following severe haemorrhage (Gujar et al, 2017), and recent investigations indicate an increase in size in well-fed individuals and during the ingestion of food (Garnitschnig et al, 2020).

The spleen (Fig3) is enclosed in a dense, fibro-elastic capsule that protrudes into the organ as trabeculae; these trabeculae constitute the organs framework. Blood enters the spleen from the splenic artery and leaves via the splenic vein, both of which are at the hilum; the splenic vein eventually becomes a tributary of the hepatic portal vein.

The spleen is made up of two regions:

White pulp is a mass of germinal centres of dividing B-lymphocytes (B-cells), surrounded by T-cells and accessory cells, including macrophages and dendritic cells; these cells are arranged as lymphatic nodules around branches of the splenic artery. As blood flows into the spleen via the splenic artery, it enters smaller, central arteries of the white pulp, eventually reaching the red pulp. The red pulp is a spongy tissue, accounting for 75% of the splenic volume (Pivkin et al, 2016); it consists of blood-filled venous sinuses and splenic cords.

Splenic cords are made up of red and white blood cells and plasma cells (antibody-producing B-cells); therefore, the red pulp primarily functions as a filtration system for the blood, whereas the white pulp is where adaptive T- and B-cell responses are mounted. The colour of the white pulp is derived from the closely packed lymphocytes and the red pulps colour is due to high numbers of erythrocytes (Stewart and McKenzie, 2002).

The spleen has three major functions:

The spleens main immunological function is to remove micro-organisms from circulation. The lymphatic nodules are arranged as sleeves around the blood vessels, bringing blood into the spleen. Within the white pulp are splenic nodules called Malpighian corpuscles, which are rich in B-cells, so this portion of lymphoid tissue is quick to respond to foreign antigenic stimulation by producing antibodies. The walls of the meshwork of sinuses in the red pulp also contain phagocytes that engulf foreign particles and cell debris, effectively filtering and removing them from circulation.

In the spleens destruction of old and senescent red blood cells, they are digested by phagocytic macrophages in the red pulp. The haemoglobin is then split apart into haem and globin. The globin is broken down into its constituent amino acids, which can be utilised in the synthesis of a new protein. Haem consists of an iron atom surrounded four non-iron (pyrrole) rings.

The iron is removed and transported to be stored as ferritin, then reused to make new haemoglobin in the red bone marrow; macrophages convert the pyrrole rings into the green pigment biliverdin and then into the yellow pigment bilirubin. Both are transported to the liver bound to plasma albumin. Bilirubin, the more toxic pigment, is conjugated in the liver to form a less toxic compound, which is excreted in bile.

The red pulp partly serves to store a large reserve of the bodys platelets up to a third of the total platelet supply. In some animals particularly athletic mammals such as horses, greyhounds and foxes the spleen is also an important reservoir of blood, which is released into circulation during times of stress to improve aerobic performance. In humans, however, the spleen contributes only a small percentage of blood cells into active circulation under physiological stress; the total stored blood volume is believed to be only 200-250ml (Bakovic et al, 2005). The capsule of the spleen may contract following haemorrhage, releasing this reserve into circulation in the body.

The spleen also plays a minor role in haematopoiesis: usually occuring in foetuses of up to five months gestation, erythrocytes, along with the bone marrow, are produced by the spleen.

As the spleen is the largest collection of lymphoid tissue in the body, infections that cause white blood cell proliferation and antigenic stimulation may cause germinal centres in the organ to expand, resulting in its enlargement (splenomegaly). This happens in many diseases for example, malaria, cirrhosis and leukaemia. The spleen is not usually palpable, but an enlarged spleen is palpable during deep inspiration. Enlargement may also be caused by any obstruction in blood flow, for example in the hepatic portal vein.

The anatomical position of the spleen coincides with the left tenth rib. Given its proximity to the abdominal wall, it is one of the most commonly injured organs in blunt abdominal trauma. The spleen is a fragile organ and, due to its highly vascularised nature, any injury causing rupture will rapidly lead to severe intraperitoneal haemorrhage; death may result due to massive blood loss and shock.

A moderate splenic injury may be managed conservatively, but an extensively burst or ruptured spleen may be treated by complete and prompt removal (splenectomy). However, current data supports successful non-operative management of many traumatic splenic injuries, with the intention of reducing the need for complete removal (Armstrong et al, 2019).

Patients being treated for certain malignant diseases may also require a partial or total splenectomy and, although other structures such as the bone marrow and liver can take over some of the functions that are usually carried out by the spleen, such patients may be at increased risk of infection. With an overwhelming post-splenectomy infection, there is also an increased risk of sepsis, which is associated with significant morbidity and mortality. Infection is usually with encapsulated pathogens, including Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis. Clinical guidelines to help reduce the risk of infection advocate education about infection prevention, vaccination and antibiotic prophylaxis (Arnott et al, 2018).

Swollen lymph nodes and a fever are sure signs that the body is mounting an effective immune response against an offending pathogen

Lymph nodes vary in size and shape, but are typically bean-shaped structures found clustered at specific locations throughout the body. Although their size varies, each node has a characteristic internal structure (Fig4).

The central portions of the lymph node are essential to its function; here, there are large numbers of fixed macrophages, which phagocytose foreign material such as bacteria on contact, and populations of B- and T-cells. Lymph nodes are crucial to most antibody-mediated immune responses: when the phagocytic macrophages trap pathogenic material, that material is presented to the lymphocytes so antibodies can be generated.

Each lymph node is supplied by one or more afferent lymphatic vessels, which deliver crude, unmodified lymph directly from neighbouring tissues. A healthy, fully functioning node removes the majority of pathogens from the lymph before the fluid leaves via one or more efferent lymphatic vessels. In addition to its lymphatic supply, each lymph node is supplied with blood via a small artery; the artery delivers a variety of leucocytes, which populate the inner regions of the node.

When infection is present, the lymph nodes become increasingly metabolically active and their oxygen requirements increase. A small vein carries deoxygenated blood away from each node and returns it to the major veins. In times of infection, this venous blood may carry a variety of chemical messengers (cytokines) that are produced by the resident leucocytes in the nodes. These cytokines act as general warning signals, alerting the body to the potential threat and activating a variety of specific immune reactions.

The structure of a lymph node is not unlike that of the spleen. Each lymph node is divided into several regions:

During infection, antibody-producing B-cells begin to proliferate in the germinal centres, causing the affected lymph nodes to enlarge and become palpable and tender. Some of the cytokines released are pyrogenic (meaning they cause fever) and act directly on the thermoregulatory centre in the hypothalamus to increase body temperature. As the majority of human pathogens divide optimally at around 37C, this increase in body temperature serves to slow down bacterial replication, allowing the infection to be dealt with more efficiently by the immune system. Swollen lymph nodes and a fever are both sure signs that the body is mounting an effective immune response against the offending pathogen; this will be discussed in more detail in part 3 of this series.

Other types of lymphatic tissue also exist. Mucosa-associated lymphoid tissue (MALT) is positioned to protect the respiratory and gastrointestinal tracts from invasion by microbes. The following are made up of MALT:

The tonsils are aggregates of lymphatic tissue strategically located to prevent foreign material and pathogens from entering the body. The palatine tonsils are in the pharynx, the lingual tonsils in the oral cavity and the pharyngeal tonsils (adenoids) are at the back of the nasal cavity; as a result of this, the tonsils themselves are at high risk of infection and inflammation (tonsillitis). This will also be discussed further in part 3.

Armstrong RA et al (2019) Successful non-operative management of haemodynamically unstable traumatic splenic injuries: 4-year case series in a UK major trauma centre. European Journal of Trauma and Emergency Surgery; 45: 5, 933-938.

Arnott A et al (2018) A registry for patients with asplenia/hyposplenism reduces the risk of infections with encapsulated organisms. Clinical Infectious Diseases; 67: 4, 557-561.

Bakovi D et al (2005) Effect of human splenic contraction on variation in circulating blood cell counts. Clinical and Experimental Pharmacology and Physiology; 32: 11, 944-951.

Bilder G (2016) Human Biological Aggin: From Macromolecules to Organ Systems. Wiley.

Garnitschnig L et al (2020) Postprandial dynamics of splenic volume in healthy volunteers. Physiological Reports; 8: 2, e14319.

Gujar S et al (2017) A cadaveric study of human spleen and its clinical significance. National Journal of Clinical Anatomy; 6: 1, 35-41.

Makiewicz A, Dziedzic M (2012) Bone marrow reconversion: imaging of physiological changes in bone marrow. Polish Journal of Radiology; 77: 4, 45-50.

Pivkin IV et al (2016) Biomechanics of red blood cells in human spleen and consequences for physiology and disease. Proceedings of the National Academy of Sciences of the United States of America; 113: 28, 7804-7809.

Severa M et al (2019) Thymosins in multiple sclerosis and its experimental models: moving from basic to clinical application. Multiple Sclerosis and Related Disorders; 27: 52-60.

Sherer Y et al (1999) The dual relationship between thymectomy and autoimmunity: the kaleidoscope of autoimmune disease. In: Paul S (ed) Autoimmune Reactions. Contemporary Immunology. Totowa, NJ: Humana Press.

Stewart IB, McKenzie DC (2002) The human spleen during physiological stress. Sports Medicine; 32: 6, 361-369.

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Immunology

Harnessing the Microbiome to Understand Rheumatic Diseases – Rheumatology Advisor

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There is growing evidence both in animal models and humans to suggest the significant role of the microbiome in the etiology of rheumatic diseases. Over the years, multiple microbial agents and changes in the composition of the microbiota have been associated with specific autoimmune diseases, only emphasizing the importance of the microbiome in rheumatology research today.

To give us further insight, we are joined in this episode by Maximilian Konig, MD, Division of Rheumatology at the Johns Hopkins Hospital in Baltimore, Maryland, and Veena Taneja, PhD, associate professor of immunology in the Department of Immunology and Rheumatology at the Mayo Clinic in Rochester, Minnesota.

Maximilian Konig, MD, is a rheumatologist at the Johns Hopkins University School of Medicine in Baltimore, Maryland, and a postdoctoral fellow at the Ludwig Center for Cancer Genetics and Therapeutics & Howard Hughes Medical Institute at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center. He received his medical degree from Charit Universittsmedizin Berlin and completed his residency training in internal medicine at the Massachusetts General Hospital, Harvard Medical School in Boston, before pursuing a fellowship in rheumatology at Johns Hopkins.

Dr Konig has a long-standing interest in mechanisms underlying the initiation of autoimmunity in rheumatic diseases. As a postdoctoral fellow working with Felipe Andrade, MD, PhD, he studied mechanisms by which microbial species associated with periodontitis induce protein citrullination. His work proposed a role for the periodontal pathogen Aggregatibacter actinomycetemcomitans in the immunopathogenesis of rheumatoid arthritis (RA).

Dr Konigs current research is focused on adoptive cell therapy and chimeric antigen receptor (CAR) T-cell immunotherapy in autoimmune rheumatic disease and cancer.

Veena Taneja, PhD, is an associate professor in the Department of Immunology with a joint appointment in the Division of Rheumatology at Mayo Clinic. She is a member of the Mayo Clinic Cancer Center Immunology and Immunotherapy Program, and a member of the Clinical Immunology Committee of the American Association of Immunologists. Dr Taneja serves on various study sections for the National Institute of Health and Canadian Institute of Health Research and is also an academic editor for PLOS One and Autoimmune Diseases.

The focus of research in her laboratory is on investigating the immunopathology of aging-related chronic conditions, including RA and associated diseases, with her laboratory making seminal discoveries in these areas of research. To simulate human autoimmune diseases and sex bias, her laboratory has generated a mouse model that mimics human RA in sex bias and autoantibody profile. Her laboratory has been at the forefront of developing microbial markers for pathogenicity as well as therapy.

Dr Taneja and her colleagues have isolated the bacterium Prevotella histicola from a human gut biopsy and are directing their efforts toward investigating the basis for therapeutic potential of the gut microbiome. P histicola was found to be successful in phase 1 trials. In addition, her laboratory is exploring ways to use this research and technology for comorbidities like lung fibrosis and emphysema that are associated with rheumatic diseases to ensure healthy aging for patients.

Dr Taneja has received numerous awards and honors for her work. She recently received the Excellence in Research award from the Military Health Research for her work in delineating the use of gut microbiome for treating arthritis. Her research has been funded by the National Institute of Allergy and Infectious Disease, the Department of Defense, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Regenerative Medicine Minnesota, and the Arthritis Foundation.

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Harnessing the Microbiome to Understand Rheumatic Diseases - Rheumatology Advisor