Published in the journal GUT, the Northwell-CSHL case series is unique in its adaptation of quantitative tracking of patient-reported outcome measures. The methodology is suitable for testing drugs in patients well enough to be managed at home and allows the recruitment of diverse subjects via community-based health organizations and individual practitioners.

The lead author of the study, CSHL Assistant Professor Tobias Janowitz, is a Medical Oncologist and a Cancer Researcher, who investigates the whole-body causes and effects of diseases. “The experience of a patient at one point in time is very valuable, but learning about the change in their experience over time is even more important,” says Janowitz. “Change indicates if the patients’ condition is getting better or worse. A graded symptom score enables the physician and the patient to track symptoms using numbers.”

Observing that for COVID-19, most symptomatic people do not require hospitalization, Janowitz and colleagues developed a 4-point scale for six common COVID-19 associated symptoms that patients score every day. Janowitz simplifies how the scale can help track the course of a patient’s disease:

“You may call up your doctor and say, I have headaches and shortness of breath, and am only able to do the basics for self-care, which would be grade 3 symptoms. If you still had the symptoms two days later, but are now able to do light work, these symptoms would now be scored at grade 2. This approach makes it very easy for you and your doctor to document that your symptoms are improving. The value of this approach from a research perspective is that experiences from many patients become comparable and can be pooled for analysis.”

If a drug speeds recovery, then most patients will report more rapid improvement of symptoms.

The innovations in this study are the product of scientists and physicians who never expected to work on a pandemic infection. But the collaborative, multidisciplinary approach is a hallmark of the strategic research affiliation between CSHL and the academic physicians at Northwell Health. Chief, General Internal Medicine, Northwell Health and Professor at the Feinstein Institutes, and a co-author on the study, Joseph Conigliaro says:

“There are a lot of things that we were doing that worked well in how we address this pandemic. I’m a health services addiction researcher. I didn’t think I’d ever be the person who would be studying this pandemic and this virus. And Tobias does cancer research. What we did is we used our existing tools and talents that were not specifically geared towards studying a viral pandemic, but we used it and modified it in ways that were very, very helpful.”

CSHL Professor David Tuveson, Director of the CSHL Cancer Center and another co-author, is interested in the broader implications of the patient-oriented research approach as a way to better connect science and healthcare. CSHL’s commitment to bridging the gap between research and the clinic is evident in an initiative championed by Janowitz to study how disease impacts the entire body. Tuveson says:

“You’re trying to scientifically assess a symptom, is what you’re really doing. Tobias and his colleagues can look at the whole body while they study cancer. And so Tobias is someone who thinks about the big picture of health. He’s basically shifting his approach to solving complex problems to COVID-19 and he started by saying ‘how can we describe one patient relative to the next?'”

Janowitz agrees, “It seems reasonable to me to make that extension to this healthcare crisis and to acknowledge that we can learn a lot from the individual who has the disease as long as we find a way to make it quantifiable.”

Once validated, the patient-reported symptom tracking method will be a key component in a clinical trial that is “double-blind,” meaning that neither patient nor doctor know whether the patient is getting the test drug or a placebo until the trial is completed. Without a double-blind clinical trial and a careful scientific examination of the mechanism of action of a drug and its side effects, it is impossible to rule out that the preliminary findings were due to factors other than the drug. The early findings of this case series were communicated to co-author Dr. Timothy Wang at Columbia University Medical Center. Interestingly, Dr. Wang and colleagues were also able to find an association between famotidine usage and the improved outcomes of patients hospitalized for COVID-19. Based on the findings in the case series, a double-blind clinical trial of famotidine is the next step in the joint plan of the Northwell-CSHL team. Other treatments may also be explored.

Conigliaro explains why he is hopeful that the study will work as designed to find drugs that will be effective against COVID-19:

“We had about a thousand patients that we tracked in our practices, just in my couple of academic practices, that never made it to the hospital. And my Doc’s were calling them every day and asking all those questions: ‘Do you have aches and pains? Do you have fever today? How’s your breathing today?’ We didn’t know what their blood levels were. We didn’t know what their oxygen levels, because we didn’t have access to that. So these surrogate measures are very common and the best way to assess what’s going on in the outpatient. I’m actually pretty confident. I think there’ll be another surge but I think we’ll be much better prepared and I think that hopefully lives will be saved.”

The Caribbean was one of the last regions of the Americas to be settled by humans. Now, a new study published in the journal Science sheds new light on how the islands were settled thousands of years ago.

Using ancient DNA, a team of archaeologists and geneticists led by researchers from the University of Copenhagen and the Max Planck Institute for the Science of Human History found evidence of at least three population dispersals that brought people to the region.

“The new data give us a fascinating glimpse of the early migration history of the Caribbean. We find evidence that the islands were settled and resettled several times from different parts of the American mainland,” says Hannes Schroeder, Associate Professor at the Globe Institute, University of Copenhagen, and one of the senior authors of the study.

More data, more details

The researchers analysed the genomes of 93 ancient Caribbean islanders who lived between 400 and 3200 years ago using bone fragments excavated by Caribbean archaeologists from 16 archaeological sites across the region.

Due to the region’s warm climate, the DNA from the samples was not very well preserved. But using so-called targeted enrichment techniques, the researchers managed to extract enough information from the remains.

“These methods allowed us to increase the number of ancient genome sequences from the Caribbean by almost two orders of magnitude and with all that data we are able to paint a very detailed picture of the early migration history of the Caribbean,” says Johannes Krause, Director of the Max Planck Institute for the Science of Human History, and another senior author of the study.

The researchers’ findings indicate that there have been at least three different population dispersals into the region: two earlier dispersals into the western Caribbean, one of which seems to be linked to earlier population dispersals in North America, and a third, more recent “wave,” which originated in South America.

Connections across the Caribbean Sea

Although it is still not entirely clear how the early settlers reached the islands, there is growing archaeological evidence indicating that, far from being a barrier, the Caribbean Sea served as a kind of ‘aquatic highway’ that connected the islands with the mainland and each other.

“Big bodies of water are traditionally considered barriers for humans and ancient fisher hunter gatherer communities are usually not perceived as great seafarers. Our results continue to challenge that view, as they suggest that there was repeated interaction between the islands and the mainland,” says Kathrin Nägele, PhD student at the Max Planck Institute for the Science of Human History and one of the first authors of the study.

Biological and Cultural Diversity in the Ancient Caribbean

“The new data support our previous observations that the early settlers of the Caribbean were biologically and culturally diverse, adding resolution to this ancient period of our history,” says Yadira Chinique de Armas, Assistant Professor in Bioanthropology at the University of Winnipeg who currently co-directs three large scale excavations in Cuba as part of the SSHRC project.

The researchers found genetic differences between the early settlers and the newcomers from South America who, according to archaeological evidence, entered the region around 2800 years ago.

“Although the different groups were present in the Caribbean at the same time, we found surprisingly little evidence of admixture between them,” adds Cosimo Posth, group leader at the Max Planck Institute for the Science of Human History and joint-first author of the study.

“The results of this study provide yet another layer of data that highlights the diverse and complex nature of pre-Columbian Caribbean societies and their connections to the American mainland prior to the colonial invasion,” says Corinne Hofman, Professor of Archaeology at Leiden University and PI of the ERC Synergy project NEXUS1492.

“Genetic data provide a new depth to our findings” agrees Mirjana Roksandic, Professor at the University of Winnipeg and the PI on the SSHRC project.

Mangrove forests store large amounts of carbon, help protect coastlines and provide habitat for fish and other species. Using sediment data from the last 10,000 years, an international team led by Macquarie University in Australia estimated the chances of mangrove survival based on rates of sea-level rise.

When rates exceeded 6 millimeters per year, similar to estimates under high-emissions scenarios for 2050, scientists found that mangroves were very likely to stop keeping pace with the rising water levels. Mangroves are more likely to survive when sea-level rise is less than 5 millimeters (about 0.2 inches) per year, which is projected for low-emissions scenarios this century.

“Under high-emissions scenarios, rates of sea-level rise on many tropical coastlines will exceed 7 millimeters per year, the rate at which we concluded there’s a 6.2 percent probability mangroves can sustain growth,” said co-author Erica Ashe, a post-doctoral scientist in the Department of Earth and Planetary Sciences in the School of Arts and Sciences at Rutgers University-New Brunswick. “The loss of these mangrove ecosystems could result in increased carbon dioxide in the atmosphere and fewer vital buffers against storm surges in the long run.”

There are about 80 species of mangrove trees, which grow in tropical and subtropical areas. Mangrove forests stabilize the coastline, reducing erosion from storm surges, currents, waves and tides, according to the National Oceanic and Atmospheric Administration. Mangroves’ intricate root system makes the forests attractive to fishes and other organisms seeking food and shelter from predators. In the Florida Keys National Marine Sanctuary alone, mangroves line more than 1,800 miles of shoreline.

The study covered 78 locations and explored how mangroves responded as the rate of sea-level rise slowed from more than 10 millimeters yearly 10,000 years ago to nearly stable conditions 4,000 years later. The storage of carbon as mangrove forests expanded during that period contributed to lower greenhouse gas levels.

Mangroves will naturally move inland if they can’t build vertically, but coastal developments along many coastlines already greatly impede such movement. The findings stress the importance of mitigating the magnitude of rapid sea-level rise and ensuring that coastal adaptation measures allow mangroves to expand across coastal lowlands.

Story Source:

Materials provided by Rutgers University. Note: Content may be edited for style and length.