Just one year after the World Health Organization declared the novel coronavirus a global pandemic, three COVID-19 vaccines are available in the United States, and more than 2 million Americans are receiving shots each day. Americans are eager to get back to business as usual, but experts caution that opening the economy prematurely could allow a potential resurgence of the virus. How foot traffic patterns in restaurants and bars, schools and universities, nail salons and barbershops affect the risk of transmission has been largely unknown.
In an article published in npj Digital Medicine, researcher-physicians from Beth Israel Deaconess Medical Center (BIDMC) used anonymized cell-phone data to build a Business Risk Index, which quantifies the potential risk of COVID-19 transmission in these establishments. The team’s index accounts for both the density of visits and the length of time individuals linger inside, providing a more precise description of the human interactions — and thus risk of viral transmission — going on inside.
“While business traffic pre-pandemic and during statewide shut downs has been studied, business foot traffic and its relationship to COVID-19 transmission in the so-called ‘new normal’ of re-opening has not been well understood.” said corresponding author Ashley O’Donoghue, PhD, Economist, in the Center for Healthcare Delivery Science at BIDMC. “Many forecasting models use anonymized cell-phone mobility data as a broad measure of the movement of residents. But two regions with same levels of mobility will likely see very different levels of COVID-19 transmission if people in one region are diligently practicing social distancing and people in the other are not.”
O’Donoghue and colleagues built their risk index by analyzing trends in foot traffic patterns in more than 1.25 million businesses across eight states from January to June 2020. In the six New England states, New York and California, the team saw a 30 percent drop in high-density foot traffic and long visit lengths to businesses — two factors that can increase the risk of COVID-19 transmission — from the pre-pandemic baseline to April 2020. They saw similar declines when they looked at similar risky foot traffic patterns in restaurants, bars, universities and personal care establishments (which includes hair and nail salons and barbershops). In both analyses, the risk index rose steadily starting in mid-June as states eased restrictions.
Next, using county-level COVID-19 data for the same time period, the team demonstrated that their index could accurately forecast future COVID-19 cases with a one-week lag. The team found that an increase in a county’s average Business Risk Index was associated with an increase in COVID-19 cases per 10,000 people in one week.
“Not all types of mobility contribute equally to increased risk of transmission, so it is important to directly measure human interaction when weighing the costs and benefits of reopening and lifting restrictions on businesses,” said senior author Jennifer P. Stevens, MD, MS, Director of the Center for Healthcare Delivery Science at BIDMC. “Tracking how individuals use different businesses may provide the kind of information policymakers need to re-open different businesses in the safest way possible.”
O’Donoghue, Stevens and team are now building an online decision-support tool that will help policymakers and hospital decision-makers monitor weekly risk in their areas. They have also deployed a prototype of their tool for Massachusetts that is being used by a large tertiary academic medical center in Boston to monitor potential surges in their service area, and their index has been integrated as a feature in a forecasting model for a large health system in Massachusetts.
“Our index can better quantify close human interactions, which are important predictors of transmission and help identify potential disease surges,” said Stevens.
Study co-authors also include Tenzin Dechen, MPH, of BIDMC; Whitney Pavlova, BA, of Pennsylvania State University; Michael Boals, MS, of Requisite Analytics; Manvi Madan, MInfoTech, of Ports of Auckland; Garba Moussa, PhD, of Open-Classroom; Aalok Thakkar, BS, of University of Pennsylvania; and Frank J. DeFalco, BS, of Janssen Research & Development.
Dr. Stevens is supported by grant number K08HS024288 from the Agency for Healthcare Research and Quality. The authors declare no competing interests.

A Nature study authored by scientists at Sanford Burnham Prebys Medical Discovery Institute and the University of Hong Kong shows that the leprosy drug clofazimine, which is FDA approved and on the World Health Organization’s List of Essential Medicines, exhibits potent antiviral activities against SARS-CoV-2 and prevents the exaggerated inflammatory response associated with severe COVID-19. Based on these findings, a Phase 2 study evaluating clofazimine as an at-home treatment for COVID-19 could begin immediately.
“Clofazimine is an ideal candidate for a COVID-19 treatment. It is safe, affordable, easy to make, taken as a pill and can be made globally available,” says co-senior author Sumit Chanda, Ph.D., professor and director of the Immunity and Pathogenesis Program at Sanford Burnham Prebys. “We hope to test clofazimine in a Phase 2 clinical trial as soon as possible for people who test positive for COVID-19 but are not hospitalized. Since there is currently no outpatient treatment available for these individuals, clofazimine may help reduce the impact of the disease, which is particularly important now as we see new variants of the virus emerge and against which the current vaccines appear less efficacious.”
Promising candidate revealed by screening drug library
Clofazimine was initially identified by screening one of the world’s largest collections of known drugs for their ability to block the replication of SARS-CoV-2. Chanda’s team previously reported in Nature that clofazimine was one of 21 drugs effective in vitro, or in a lab dish, at concentrations that could most likely be safely achieved in patients.
In this study, the researchers tested clofazimine in hamsters — an animal model for COVID-19 — that were infected with SARS-CoV-2. The scientists found that clofazimine lowered the amount of virus in the lungs, including when given to healthy animals prior to infection (prophylactically). The drug also reduced lung damage and prevented “cytokine storm,” an overwhelming inflammatory response to SARS-CoV-2 that can be deadly.
“The animals that received clofazimine had less lung damage and lower viral load, especially when receiving the drug before infection,” says co-senior author Ren Sun, Ph.D., professor at the University of Hong Kong and distinguished professor emeritus at the University of California, Los Angeles (UCLA). “Besides inhibiting the virus, there are indications that the drug also regulates the host response to the virus, which provides better control of the infection and inflammation.”
Clofazimine also worked synergistically with remdesivir, the current standard-of-care treatment for people who are hospitalized due to COVID-19, when given to hamsters infected with SARS-CoV-2. These findings suggest a potential opportunity to stretch the availability of remdesivir, which is costly and in limited supply.

#masthead-section-label, #masthead-bar-one { display: none }The Coronavirus OutbreakliveLatest UpdatesMaps and CasesRisk Near YouVaccine RolloutGuidelines After VaccinationAdvertisementContinue reading the main storyCovid-19 Live Updates: Worries Over AstraZeneca Doses Upend Europe’s Vaccine DriveModerna begins testing Covid vaccine in babies and young children.March 16, 2021, 7:02 a.m. ETMarch 16, 2021, 7:02 a.m. ETBrittany Siguenza, 5, watching her mother receive a Moderna vaccine dose in Massachusetts on Friday.Credit…Cj Gunther/EPA, via ShutterstockThe drug company Moderna has begun a study that will test its Covid vaccine in children under 12, including babies as young as six months, the company said on Tuesday.The study is expected to enroll 6,750 healthy children in the United States and Canada. “There’s a huge demand to find out about vaccinating kids and what it does,” said Dr. David Wohl, the medical director of the vaccine clinic at the University of North Carolina, who is not involved the study.In a separate study, Moderna is testing its vaccine in 3,000 children ages 12 to 17.Many parents want protection for their children, and vaccinating children should help to produce the herd immunity considered crucial to stopping the pandemic. The American Academy of Pediatrics has called for expansion of vaccine trials to include children.Each child in Moderna’s study will receive two shots, 28 days apart. The study will have two parts. In the first, children aged 2 years to less than 12 may receive two doses of 50 or 100 micrograms each. Those under 2 years may receive two shots of 25, 50 or 100 micrograms.In each group, the first children inoculated will receive the lowest doses and will be monitored for reactions before later participants are given higher doses.Then, researchers will perform an interim analysis to determine which dose is safest and most effective for each age group.Children in part two of the study will receive the doses selected by the analysis — or placebo shots consisting of salt water.The children will be followed for a year, to look for side effects and measure antibody levels that will help researchers determine whether the vaccine is effective. The antibody levels will be the main indicator, but the researchers will also look for coronavirus infections, with or without symptoms.Dr. Wohl said the study appeared well designed and likely to be efficient, but he questioned why the children were to be followed for only one year, when adults in Moderna’s study are followed for two years. He also said he was somewhat surprised to see the vaccine being tested in children so young this soon.“Should we learn first what happens in the older kids before we go to the really young kids?” Dr. Wohl asked. Most young children do not become very ill from Covid, he said, though some develop a severe inflammatory syndrome that can be life threatening.Johnson & Johnson has also said it would test its coronavirus vaccine in babies and young children after testing it first in older children.Pfizer-BioNTech is testing its vaccine in children ages 12 to 15, and has said it plans to move to younger groups; the product is already authorized for use in those 16 and up in the United States.Last month, AstraZeneca began testing its vaccine in Britain in children 6 years and older.AdvertisementContinue reading the main story

#masthead-section-label, #masthead-bar-one { display: none }The Coronavirus OutbreakliveLatest UpdatesMaps and CasesRisk Near YouVaccine RolloutGuidelines After VaccinationAdvertisementContinue reading the main storySupported byContinue reading the main storyThe Ethicist I’m Not Eligible for the Vaccine Yet. Can I Hunt for a Surplus Dose?The magazine’s Ethicist columnist on whether securing a dose for yourself means taking someone else’s spot in line — and more.Credit…Illustration by Tomi UmMarch 16, 2021, 5:00 a.m. ETI’m a college student, and I recently learned that my city is going to be opening up spots on the Health Department website for anyone to be vaccinated if there is a surplus of vaccines. We’re still in the first phase of vaccination, but if I were to look frequently at the vaccination website, I could in theory get an appointment. Since I am a healthy, young person who is not an essential worker or at risk, should I wait to get vaccinated in hopes that someone at greater risk or more essential could take the spot? Or should I keep looking at that website and take the dose as soon as it appears? I’m not taking someone else’s spot, or am I? Ben, MontanaWith anything perishable — whether it’s a head of lettuce or a defrosted carton of Covid-19 vaccines — you can have excess and spoilage amid an overall shortage. The minimum Pfizer vaccine order is a tray with about 1,200 doses; once the vials begin thawing, they have to be used in five days. With all the authorized vaccines, a vial, once opened, must be used within six hours — for Johnson & Johnson’s, it’s two hours at room temperature. Each Pfizer vial has up to six doses. Johnson & Johnson, which has a minimum order of 100 doses, puts five doses in a vial; Moderna will soon put 14 doses in each vial.The point is that vaccines don’t come as “loosies.” Vaccination sites can misjudge the number of sign-ups, and even if everything is properly planned, there are sometimes no-shows. Even when a site has a standby list of qualified recipients, there will be occasional instances in which a vaccine will go to waste unless the eligibility rules are suspended.Perhaps the question isn’t whether you’d be taking someone else’s spot but whose spot you’d be taking. I think of the verse that we apparently owe to the 19th-century English jurist and wit Charles Bowen: The rain, it raineth on the justAnd also on the unjust fella.But chiefly on the just, becauseThe unjust steals the just’s umbrella.In a situation where expiring vaccine doses will be offered to all comers — lest they simply go to waste — you have no reason to think that the dose you eschew will go to someone in greater need; if those concerned with justice demur, the dose may simply go to those not so concerned, assuming it goes to anyone. There’s always going to be a trade-off between getting the country swiftly vaccinated and exquisitely fine-tuning the rollout to reflect each person’s risk profile. If a sporadic all-comers approach is the best way to prevent wasted doses, it isn’t unfair, and you’re not wrong to participate in it.There’s always going to be a trade-off between getting the country swiftly vaccinated and exquisitely fine-tuning the rollout to reflect each person’s risk profile.The Coronavirus Outbreak

Researchers believe they may have discovered a possible cause of a mystery condition that can leave sufferers suddenly unable to walk, talk or see.
It’s hoped the study — led by the University of York and Hull York Medical School and supported by Tees, Esk and Wear Valley NHS Trust — will pave the way for new treatments for Conversion disorder which affects around 800,000 people in the UK alone.
The condition, also known as functional neurological disorder (FND), causes physical symptoms that would appear neurological but doctors can’t find an injury or physical condition to explain them.
Professor Christina van der Feltz-Cornelis from the Department of Health Sciences is leading the Conversion And Neuro-inflammation Disorder Observational (CANDO) study. This pilot study is the first in a program of research to explore how conversion disorder/FND can be caused, and to develop and evaluate new treatments.
The first findings suggest that conversion disorder could be caused by a low grade inflammation process that influences gene expression, which is the process by which the instructions in our DNA are converted into a functional product, such as a protein. Protein does most of the work in cells and is required for the structure, function, and regulation of the body’s tissues and organs.
Professor van der Feltz-Cornelis said: “This is a very difficult condition for people to live with and one which is often overlooked because the medical profession doesn’t have the answers.”
“People living with the condition can become very distressed and isolated, often losing jobs and social networks through being unable to communicate or being unwell. Patients can also suffer from memory and concentration problems.”
“We made the discovery by examining levels of inflammation in blood samples from patients with FND that mimicked stroke-like symptoms. They were found to be higher than normal. Also, microRNA levels in the blood seemed to play a role and this influences the expression of genes in the cell.”
“These preliminary results deserve further exploration and replication in larger samples before we can draw firm conclusions.”
The CANDO researchers hope the new study will help in the development of new treatments, as treatments previously given to people with conversion disorder have often not helped ease the symptoms.
Annie, a patient involved in the CANDO study, says: “It is a relief to suddenly find that there may be a reason for this condition. I can’t wait for treatments that may be developed as a result of this work.”
The paper, “Assessment of Cytokines, microRNA and patient related outcome measures in Conversion Disorder/Functional Neurological Disorder (CD/FND): the CANDO clinical feasibility study” is published in the journal, Brain, Behavior, & Immunity — Health.
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Louisiana State University researchers recently published findings that blight leads to an increased abundance of disease-carrying mosquitoes. The researchers investigated the presence of several mosquito species in two adjacent but socio-economically contrasting neighborhoods in Baton Rouge: the historic Garden District, a high-income neighborhood, and the Old South neighborhood, a low-income area. They found significantly higher adult and larvae abundance of the Asian tiger mosquito (a carrier of Zika and dengue) and higher mosquito habitat availability — particularly discarded tires — in the Old South neighborhood. This indicates that environmental conditions in the low-income neighborhood were most ideal for this mosquito to breed and proliferate.
“These two neighborhoods are very similar in terms of vegetation cover, human population and density of households. One of the main differences is blight. One neighborhood has a lot of blight in the form of abandoned residences, empty lots and mismanaged waste, and the other neighborhood does not. It was the perfect set of conditions for addressing this question,” said Rebeca de Jesús Crespo, lead author and an assistant professor in LSU’s College of the Coast & Environment.
In recent years, the Old South neighborhood has been the focus of revitalization plans by multiple stakeholder groups. The researchers recommended that these blight reduction efforts continue for the benefit of public health.
“This is an area at high risk of these mosquito-borne diseases,” said Madison Harrison, co-author of the publication. “All that it takes for these diseases to spread is for the right vector to be infected with the pathogen and to bite humans at the right point of incubation of said pathogen.”
So far, Zika and dengue are not currently present in the state. However, Louisiana’s climate is ideal for these diseases to spread once introduced.
According to de Jesús Crespo, Harrison was an invaluable addition to the team. Currently, she is a public health master’s student at LSU Health New Orleans.
“In the College of the Coast & Environment, for almost every project that we do, we are integrated and interdisciplinary. We take a broad approach to doing research that is important for solving problems in real time. For this project, it was important to me to include Madison from LSU Health Sciences as well as community stakeholders who could provide their expertise and unique perspectives,” de Jesús Crespo said.
The researchers examined the prevalence of two container-breeding species of mosquitoes that are known to spread disease, the Asian tiger mosquito and the southern house mosquito (a carrier of West Nile virus). They inspected potential larvae habitats (such as discarded tires, discarded Styrofoam cups and snack bags, plant pots and water baths) in publicly accessible locations and calculated the percentage of those that contained larvae. Additionally, they placed adult mosquito traps around the perimeter of some private homes with the permission from the homeowner, in an abandoned house and in an empty lot with trash accumulation in the higher income neighborhood.
They found that the adult population of the southern house mosquito was fairly diffuse, but the lower income neighborhood had significantly higher numbers of Asian tiger mosquito (adults and larvae) and higher numbers of total mosquito larvae. This shows that the presence of discarded container habitats due to neglect provides more breeding grounds for disease-carrying mosquitoes, disproportionately affecting low-income groups.
“I think everybody can agree that urban blight is a problem we need to solve here in Baton Rouge. Mosquito risk is one of those factors that could impact human health and that adds another level of importance with that,” de Jesús Crespo said.

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For the first time, researchers have pinpointed what causes normal proteins to convert to a diseased form, causing conditions like CJD and Kuru.
The research team, from Imperial College London and the University of Zurich, also tested a way to block the process, which could lead to new drugs for combatting these diseases.
The research concerned prion diseases — a group of brain diseases caused by proteins called prions that malfunction and ‘misfold’, turning into a form that can accumulate and kill brain cells. These diseases can take decades to manifest, but are then are aggressive and fatal.
They include Kuru, mad cow disease and its human equivalent Creutzfeldt-Jakob disease (CJD), and a heritable condition called fatal familial insomnia.
While the normal, healthy version of prions and the pathogenic (disease-causing) version have been characterised, the intermediate step, when one transforms to the other, was previously unknown.
Now, in a paper published today in Proceedings of the National Academy of Sciences, the research team have isolated this intermediate step, determining the mechanism that turns normal prions into their pathogenic form. The research was supported by Alzheimer’s Research UK.

#masthead-section-label, #masthead-bar-one { display: none }The Coronavirus OutbreakliveLatest UpdatesMaps and CasesRisk Near YouVaccine RolloutGuidelines After VaccinationAdvertisementContinue reading the main storyCovid-19 Live Updates: Germany, France and Italy Join Others in Pausing Use of AstraZeneca’s VaccineVaccinated Americans have been getting their second doses on time, the C.D.C. says.March 15, 2021, 4:39 p.m. ETMarch 15, 2021, 4:39 p.m. ETAnallely Falcon receiving her second dose on in Central Falls, R.I., last month.Credit…David Degner for The New York TimesNearly nine in 10 Americans who received the first dose of a two-dose Covid-19 vaccine went on to complete the regimen, and most people who received two doses got them within the recommended time frames, federal health officials reported on Monday.The analyses, by investigators with the Centers for Disease Control and Prevention, included data on tens of millions of Americans who received the Moderna or Pfizer-BioNTech vaccines between mid-December and mid-February.The percentage of people completing the regimens varied markedly by jurisdiction and between demographic groups, however. Federal health officials urged local vaccinators to take steps to ensure that everyone comes back, including scheduling a return appointment when giving the first shot, sending reminders, and rescheduling missed or canceled appointments.While the data were “reassuring” over all, C.D.C. researchers said, the first groups receiving the vaccine in the United States — health care workers and long-term care facility residents — had easy access to the second dose, since they were likely to have been vaccinated at their workplace or place of residence.As vaccines are offered to broader groups of people, the scientists warned, the percentage getting fully vaccinated may drop.People are not considered fully vaccinated against the coronavirus until two weeks after they receive the second shot of the two-dose regimen (or two weeks after receiving the single-dose vaccine made by Johnson & Johnson).C.D.C. researchers looked at some 40.5 million Americans who were vaccinated between Dec. 14, 2020 and Feb. 14, 2021.In one analysis, they reviewed the records of 12.4 million people who had received the first dose of a two-dose vaccine regimen and had enough time to get the second dose. Some 88 percent had completed the series, while 8.6 percent were still within the allowable interval — 42 days — to receive the second dose. But 3.4 percent had missed that window. (The recommended interval between doses is 21 days for the Pfizer-BioNTech vaccine and 28 days for Moderna).Americans most likely to have missed the second dose varied by locality. Among vaccine recipients for whom information on race and ethnicity were known, the lowest completion rates were among Native American or Alaska Native individuals.A second analysis of 14.2 million people who completed the full regimen found that 95.6 percent received the second dose within the recommended period, though again the figures varied by community.The authors of the study urged providers and public health workers to encourage Americans to come back for second doses and to emphasize the importance of full vaccination. C.D.C. officials also asked that vaccinators work to understand what keeps people from completing the series, and whether access or lack of confidence in the vaccines are playing a role.See How the Vaccine Rollout Is Going in Your StateSee where doses have gone, and who is eligible for a shot in each state.AdvertisementContinue reading the main story

AdvertisementContinue reading the main storySupported byContinue reading the main storyRosalind Cartwright, Psychologist and ‘Queen of Dreams,’ Dies at 98An early researcher of sleep disorders and the role of dreams in emotional health, she studied her subjects’ nights to help them turn their days around.March 15, 2021, 4:10 p.m. ETThe sleep researcher Rosalind D. Cartwright at her dream research laboratory in Chicago in 1991.Credit…Chicago Sun TimesIn 1999, Rosalind D. Cartwright, a sleep expert, testified for the defense in the murder trial of a man who had arisen from his bed early one night, gathered up tools to fix his pool’s filter pump, stabbed his beloved wife to death, rolled her into the pool and gone back to bed. When he was awakened by the police, he said he had no memory of his actions.His lawyers argued that the man, who had no motive to kill his wife, had been sleepwalking, and therefore was in an unconscious state and not responsible for his behavior. Dr. Cartwright, a renowned sleep researcher who a decade earlier had successfully served as a witness for the defense in a similar case (she worked pro bono in both trials), agreed.The jury did not, and the man was sentenced to life in prison. As Dr. Cartwright was leaving the courtroom, however, a bailiff asked for her business card. Abashedly, he told her, “I beat people up in my sleep.”Nicknamed the Queen of Dreams by her peers, Dr. Cartwright studied the role of dreaming in divorce-induced depression, worked with sleep apnea patients and their frustrated spouses, and helped open one of the first sleep disorder clinics.She died on Jan. 15 at her home in Chicago. She was 98. Her daughter, Carolyn Cartwright, said the cause was a heart attack.The earlier sleepwalking murder case that hinged on Dr. Cartwright’s testimony was a notorious one, even inspiring a television movie, “The Sleepwalker Killing”: In 1987 a young Canadian man had murdered his mother-in-law and brutally attacked his father-in-law — after driving from his home to theirs in his pajamas — though he, like the pool man, had no motive to do so.The man was acquitted, and the attacks were ruled “non-insane automatism.” From Dr. Cartwright’s years of research on sleep disorders, she knew the triggers that can propel someone with a history of sleepwalking out of bed. He had gambling debts and marital worries, and was seriously sleep deprived. EEG readings of his brain waves showed him to have an abnormality in moving from one stage of sleep to another.But murder was not Dr. Cartwright’s specialty. Dreaming was.She knew that dreams played a role in regulating a person’s emotions and sense of self. When sleep was disrupted, dreams could not do their work, stitching the messy narratives of life into an emotionally coherent tapestry.Dr. Cartwright in 1985. She joined the Department of Behavioral Sciences at Rush University Medical Center in Chicago in 1977 and later founded the sleep disorder research and treatment center there.Credit…Chicago Sun TimesRosalind Falk was born on Dec. 30, 1922, in New York City, the second-youngest of four children. Her mother, Stella (Hein) Falk, was a poet; her father, Henry, had trained as a lawyer but later became a successful real estate developer in Toronto.Stella Falk was a believer in the healing power of sleep. Her children jokingly called their home “the house of sacred sleep.” She was also fascinated by dreams, and loved to tell hers at the family dinner table. Her husband would shake his head and say, “Stella, you have such an interesting night life.”Years later, in 1977, when Dr. Cartwright published her first book, she titled it “Night Life: Explorations in Dreaming.”Dr. Cartwright grew up believing that sleep was worthy of study — why was it healing, she wondered, and what role did dreams play in that healing? Unable to find a sleep program at college, she studied psychology instead, earning her undergraduate and master’s degrees at the University of Toronto and her Ph.D. from Cornell University.At Cornell, she was an early researcher of empathy, conducting the first tests to measure it and challenging the prevailing wisdom that it was an imaginative projection; instead, she said in a paper, it was the ability to “accurately transpose oneself” into the experiences of another. After teaching for two years at Mount Holyoke College in Massachusetts, she was hired as a researcher at the University of Chicago by Carl Rogers, a founder of what is known as humanistic psychotherapy, who was interested in the work she had done on empathy.It would be a decade before Dr. Cartwright found her way into sleep research, and it happened almost by accident. She was a professor of psychology at the University of Illinois College of Medicine. Her husband, Desmond Cartwright, a British psychologist whom she married in the early 1950s, had walked out on her and their two young daughters, and as she recalled in “Crisis Dreaming: Using Your Dreams to Solve Your Problems” (1992, written with Lynne Lamberg), she was devastated and deeply depressed, her sleep roiled by anxiety-ridden dreams.Since she couldn’t sleep, Dr. Cartwright figured she might as well use her nights for something productive. She hired night babysitters and opened her first sleep lab, using her training in psychotherapy to understand the narratives in the dreams her research subjects reported.That first sleep lab was in the men’s room of an unused psychiatric unit at the University of Illinois Medical College, with a tub room attached. She replaced the tubs with beds; to block off the space from the urinals, she used acoustical paneling. This made the area soundproof, which turned out to be a deterrent to sleep for her urban subjects, so she piped in street noise.At first, her subjects were all men; at the time, she said, it was not considered “nice” for women to sleep somewhere for pay.Early on, Dr. Cartwright studied the relationship between REM sleep and dreaming. She wondered if taking hallucinogens would do the work of dreams (it didn’t) and if watching pornographic films would affect dreams (it did).Dr. Cartwright would go on to study the dreams of those going through a divorce, and from the substance of their dreams she was able to predict who might recover more easily. (Those who had horrible nightmares, early in the night, tended to get better more quickly.) She also taught her subjects how to take control of their dream narratives, and better their emotional outcomes, in a kind of autosuggestion.“Dreams are designed to help us maintain our self-identity, our sense of who we are, as our life circumstances change,” Dr. Cartwright wrote in “The Twenty-Four Hour Mind: The Role of Sleep and Dreaming in Our Emotional Lives” (2010). “A bad dream, like an elevated temperature, is a sign that something is wrong.”“A bad dream, like an elevated temperature, is a sign that something is wrong,” Dr. Cartwright wrote in a 2010 book.Credit…Oxford University PressThe title of Dr. Cartwright’s first book, published in 1977, was inspired by her father’s observation that her mother, who liked to talk about her dreams, had “such an interesting night life.”Credit…Prentice HallFollowing the years her mother was working nights, Carolyn Cartwright said, she suffered from brutal nightmares. “It was a traumatic time, and I was pretty mad at one point,” she said. In her dreams, monstrous giants were chasing her. She had wings to fly, but they wouldn’t work.Her mother took matters in hand. At bedtime, she would sit on the end of her daughter’s bed and say, “Maybe next time you could get the monsters to run slower, and you could make your wings bigger.”She has not had a bad dream since. It was a gift, Ms. Cartwright said — “the gift of sleep.”In 1977, Dr. Cartwright became the chairwoman of the Department of Behavioral Sciences at Rush University Medical Center in Chicago and founded its sleep disorder research and treatment center the next year. She stepped down in 2008 and became professor emeritus.“In the night collecting dreams,” Dr. Cartwright told an interviewer in 2011, “I felt at home.”She studied and treated disorders like sleepwalking, sleep sex, sleep eating and the troubles of those she called the sleep explorers, who would stray from their homes while sleepwalking. She also studied sleep apnea, which she correctly diagnosed as a malady affecting two people: the snorer and his or her long-suffering partner.Dr. Cartwright was married four times, twice to the same man, Richard P. Dennis, president of the Great Books Foundation. He died in 1996. Dr. Cartwright’s daughter Christine Cartwright, a folklore expert, died in 1983, struck by a car while walking in rural New Jersey. In addition to her daughter Carolyn, Dr. Cartwright is survived by a stepdaughter, Amy Russell; three grandchildren; and three great-grandchildren.After his trial, Kenneth Parks, the young Canadian man who was acquitted of murder thanks to Dr. Cartwright’s testimony, asked her if she could help him retrieve his memories of the dreadful night. As she recalled in “The Twenty-Four Hour Mind,” she asked him gently, “Would you want that?” He hung his head before he answered, “Only if you could take it away again.”AdvertisementContinue reading the main story

Trillions of commensal microbes live on the mucosal and epidermal surfaces of the body and it is firmly established that this microbiome affects its host’s tolerance and sensitivity of the host to a variety of pathogens. However, host tolerance to infection with pathogens is not equally developed in all organisms. For example, it is known that the gut microbiome of mice protects more effectively against infection with certain pathogens, such as the bacterium Salmonella typhimurium, than the human gut microbiome.
This raises the interesting possibility that analyzing differences between host-microbiome interactions in humans and other species, such as mice, and pinpointing individual types of bacterial that either protect or sensitize against certain pathogens, could lead to entirely new types of therapeutic approaches. However, while the intestinal microbiome composition and its effect on host immune responses have been well investigated in mice, it is not possible to study how the microbiome interacts directly with the epithelial cells lining the intestine under highly defined conditions, and thereby uncover specific bacterial strains that can induce host-tolerance to infectious pathogens.
Now, a collaborative team led by Wyss Founding Director Donald Ingber, M.D., Ph.D. at Harvard’s Wyss Institute for Biologically Inspired Engineering and Dennis Kasper, M.D. at Harvard Medical School (HMS) has harnessed the Wyss’s microfluidic Organs-on-Chip (Organ Chip) technology to model the different anatomical sections of the mouse intestine and their symbiosis with a complex living microbiome in vitro. The researchers recapitulated the destructive effects of S. typhimurium on the intestinal epithelial surface in an engineered mouse Colon Chip, and in a comparative analysis of mouse and human microbiomes were able to confirm the commensal bacterium Enterococcus faecium contributes to host tolerance to S. typhimurium infection. The study is published in Frontiers in Cellular and Infection Microbiology.
The project was started under a DARPA-supported “Technologies for Host Resilience” (THoR) Project at the Wyss Institute, whose goal it was to uncover key contributions to tolerance to infection by studying differences observed in certain animal species and humans. Using a human Colon Chip, Ingber’s group had shown in a previous study how metabolites produced by microbes derived from mouse and human feces have different potential to impact susceptibility to infection with an enterohemorrhagic E. coli pathogen.
“Biomedical research strongly depends on animal models such as mice, which undoubtedly have tremendous benefits, but do not provide an opportunity to study normal and pathological processes within a particular organ, such as the intestine, close-up and in real-time. This important proof-of-concept study with Dennis Kasper’s group highlights that our engineered mouse Intestine Chip platform offers exactly this capability and provides the possibility to study host-microbiome interactions with microbiomes from different species under highly controllable conditions in vitro,” said Ingber. “Given the deep level of characterization of mouse immunology, this capability could greatly help advance the work of researchers who currently use these animals to do research on microbiome and host responses. It enables them to compare their results they obtain directly with human Intestine Chips in the future so that the focus can be on identifying features of host response that are most relevant for humans.” Ingber also is the Judah Folkman Professor of Vascular Biology at HMS and Boston Children’s Hospital, and Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.
Engineering a mouse Intestine-on-Chip platform
In their new study, the team focused on the mouse intestinal tract. “It has traditionally been extremely difficult to model host-microbiome interactions outside any organism as many bacteria are strictly anaerobic and die in normal atmospheric oxygen conditions. Organ Chip technology can recreate these conditions, and it is much easier to obtain primary intestinal and immune cells from mice than having to rely on human biopsies,” said first-author Francesca Gazzaniga, Ph.D., a Postdoctoral Fellow who works between Ingber’s and Kasper’s groups and spear-headed the project.

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Gazzaniga and her colleagues isolated intestinal crypts from different regions of the mouse intestinal tract, including the duodenum, jejunum, ileum, and colon, took their cells through an intermediate “organoid” step in culture in which small tissue fragments form and grow, which they then seeded into one of two parallel microfluidically perfused channels of the Wyss’ Organ Chips to create region-specific Intestine Chips. The second independently perfused channel mimics the blood vasculature, and is separated from the first by a porous membrane that allows the exchange of nutrients, metabolites, and secreted molecules that intestinal epithelial cells use to communicate with vascular and immune cells.
Homing in on the pathogen
The team then honed in on S. typhimurium as a pathogen. First, they introduced the pathogen into the epithelial lumen of the engineered mouse Colon Chip and recapitulated the key features associated with the break-down of intestinal tissue integrity known from mouse studies, including the disruption of normally tight adhesions between neighboring epithelial cells, decreased production of mucus, a spike in secretion of a key inflammatory chemokine (the mouse homolog of human IL-8), and changes in epithelial gene expression. In parallel, they showed that the mouse Colon Chip supported the growth and viability of complex bacterial consortia normally present in mouse and human gut microbiomes.
Putting these capabilities together, the researchers compared the effects of specific mouse and human microbial consortia that had previously been maintained stably in the intestines of ‘gnotobiotic’ mice that were housed in germ-free conditions by the Kasper team. By collecting complex microbiomes from the stool of those mice, and then inoculating them into the Colon Chips, the researchers observed chip-to-chip variability in consortium composition, which enabled them to relate microbe composition to functional effects on the host epithelium. “Using 16s sequencing gave us a good sense of the microbial compositions of the two consortia, and high numbers of one individual species, Enterococcus faecium, generated by only one of them in the Colon Chip, allowed the intestinal tissue to better tolerate the infection,” said Gazzaniga. “This nicely confirmed past findings and validated our approach as a new discovery platform that we can now use to investigate the mechanisms that underlie these effects as well as the contribution of vital immune cell contributions to host-tolerance, as well as infectious processes involving other pathogens.”
“The mouse intestine on a chip technology provides a unique approach to understand the relationship between the gut microbiota, host immunity, and a microbial pathogen. This important interrelationship is challenging to study in the living animal because there are so many uncontrollable factors. The beauty of this system is that essentially all parameters you wish to study are controllable and can easily be monitored. This system is a very useful step forward,” said Kasper, who is the William Ellery Channing Professor of Medicine and Professor of Immunology at HMS.
The researchers believe that their comparative in vitro approach could uncover specific cross-talk between pathogens and commensal bacteria with intestinal epithelial and immune cells, and that identified tolerance-enhancing bacteria could be used in future therapies, which may circumvent the problem increasing antimicrobial resistance of pathogenic bacterial strains.