Culture

CHICAGO: New applications of artificial intelligence (AI) in health care settings have shown early success in improving survival and outcomes in traffic accident victims transported by ambulance and in predicting survival after liver transplantation, according to two research studies presented at the virtual American College of Surgeons Clinical Congress 2020.

Both studies evaluated how AI can crunch massive amounts of data to support decision-making by surgeons and other care providers at the point of care.

In one study, researchers at the University of Minnesota applied a previously published AI approach known as natural language processing (NLP)1 to categorize treatment needs and medical interventions for 22,529 motor vehicle crash patients that emergency medical service (EMS) personnel transported to ACS-verified Level I trauma centers in Minnesota. According to a 2016 study by the National Academies of Sciences, Engineering, and Medicine, 20 percent of medical injury deaths are potentially preventable2 representing a quality gap the researchers sought to address.

Reviewing the performance of EMS teams to profile potentially preventable deaths can enable quality improvement efforts to reduce these deaths. "Currently this process for performance review is manual, time-consuming, and expensive," said senior author Christopher James Tignanelli, MD, FACS. "AI allows possible automation of this process." NLP is an AI protocol that extracts key data from spoken or written text that providers--EMS personnel in this study--enter into the electronic record as a key component of their report. Dr. Tignanelli is an assistant professor of surgery, division of acute care surgery, at the University of Minnesota Medical School, and affiliate faculty at the Institute for Health Informatics at the University of Minnesota.

In this study, two trauma surgeons independently and manually reviewed a random selection of 1 percent of patient records and determined treatment needs and medical interventions. To evaluate the accuracy of the AI system, the manual determinations were compared with the NLP determinations. "Overall the algorithm performed with very high accuracy," Dr. Tignanelli said.

Typically after EMS personnel enter their notes into the electronic health record, oversight personnel cull through them and determine whether the patient received appropriate care, usually a week or so afterward. "That's quite a labor-intensive process," said presenting author Jacob Swann, MD, a burn and trauma fellow at Regions Hospital in St. Paul, Minn. "The goal of this project and what it validated was to automate a lot of those notes."

The NLP approach ran those notes through an algorithm to separate the notes of consequential medical interventions from less consequential ones. "That can streamline the manual review process," Dr. Swann said. "It's not performed at the accuracy level that would allow you to take the physician out of it and say that AI can determine with complete accuracy if the standard of care was given or not, but it does perform well."

The AI pipeline Dr. Swann and colleagues studied determined that only about one quarter (242 of 936) patients who needed an airway intervention actually got one before they arrived at the hospital, and that about two-thirds (110 of 170) of those who did not have adequate intravenous access and needed access into the bone, known as intraosseous (IO) access, during advance cardiac life support did receive IO access.

"Being able to identify systemic errors allows you to improve the entire health system," Dr. Swann said. "Having the ability to look at large aggregate data and go through 330,000 charts over several minutes with an AI-reading algorithm, to identify specific areas for potential improvement--whether it's getting intravenous access in our patients or having problems with splinting long bone fractures--allows you separate the signal from the noise and then figure out where the problem lies."

The "holy grail," noted Dr. Swann, is to have an AI system that can listen and observe EMS personnel during en route care and assist with complex decision making by recommending care options in real time.

For the second AI study, researchers at Baylor College of Medicine, Houston, tested four different machine-learning models for predicting survival after liver transplantation. The two models that showed high accuracy for predicting survival are known as the Random Forest and AdaBoost models. Lead author Rowland Pettit, MD-PhD candidate at Baylor, explained that Random Forest (RF) is an ensemble learning method that combines the outputs of multiple decision trees and predicts an outcome by a "majority wins" approach.

The models took into account a total of 324 disease characteristics to determine survivability. The strongest factors were acuity of illness and the recipient's disease course, Mr. Pettit said.

The study selected all 109,742 adult patients who had one liver transplant from the United Network of Organ Sharing database since its inception in 1984. The RF model showed an accuracy, reported as area under the curve, of 80 percent for predicting survival at one month, 79 percent at three months, 75 percent at one year, and 73 percent at three and five years. None of the other models showed predictability exceeding 70 percent.

"The most readily accessible application of these models would be for regulation, providing immediate feedback to clinicians about their outcomes for the past year and how they and their centers performed compared to others," Mr. Pettit said. "Being able to accurately predict whether a patient should have survived or not is crucial to then accurately providing feedback."

This type of AI model also has the potential to integrate with electronic medical record systems and physician workflows to provide benchmarks, he added. "It would be very easy with an integrated model to run predictions for every patient on a liver transplant waiting list in real time and determine the probability of each patient living at one, three or five years," he said. "This step is not to make the decision for the clinician, but to add a further clinician-assistance decision-making tool to give them quantitative data for use in organ allocation decisions."

CHICAGO: Surgical patients who participate in virtual follow-up visits after their operations spend a similar amount of time with surgical team members as those who meet face-to-face. Moreover, these patients benefit by spending less time waiting at and traveling to the clinic for in-person appointments, according to research findings presented at the virtual American College of Surgeons Clinical Congress 2020.

"I think it's really valuable for patients to understand that, in the virtual space scenario, they are still going to get quality time with their surgical team," said lead study author Caroline Reinke, MD, FACS, associate professor of surgery at Atrium Health in Charlotte, N.C. "A virtual appointment does not shorten that time, and there is still an ability to answer questions, connect, and address ongoing medical care."

Due to the Coronavirus Disease 2019 (COVID-19) pandemic and the widespread adoption of technology, many surgical patients are being offered virtual appointments in place of traditional in-person visits. The researchers say this is one of the first studies to look at how patients spend their time in post-operative virtual visits compared with face-to-face consultations.

The study design was a non-inferiority, randomized controlled trial that involved more than 400 patients who underwent laparoscopic appendectomy or cholecystectomy at two hospitals in Charlotte, N.C. and were randomized 2:1 to a post-discharge virtual visit or to an in-person visit. The study began in August 2017 but was put on hold in March 2020 due to COVID-19.

"Other studies have looked at the total visit time, but they haven't been able to break down the specific amount of time the patient spends with the provider. And we wanted to know if that was the same or different between a virtual visit and an in-person visit," Dr. Reinke said. "We wanted to get down to the nitty gritty of how much face time was actually being spent between the surgical team member and the patient."

Researchers tracked total time the patients spent checking in, waiting in the waiting room and exam room, meeting with the surgical team member, and being discharged after the exam. For in-person visits, on-site waiting time and an estimated drive time was factored into the overall time commitment.

Just 64 percent of patients completed the follow-up visit. "Sometimes, patients are doing so well after minimally invasive surgery that about 30 percent of these patients don't show up for a post-operative visit," Dr. Reinke said.

Overall, results showed that the total clinic time was longer for in-person visits than virtual visits (58 minutes vs. 19 minutes). However, patients in both groups spent the same amount of face time with a member of their surgical team (8.3 minutes vs. 8.2 minutes) discussing their post-operative recovery.

"I was pleasantly surprised that the amount of time patients spent with the surgical team member was the same, because one of the main concerns with virtual visits is that patients feel disconnected and that there isn't as much value in it," Dr. Reinke said.

Importantly, patients placed a high value on convenience and flexibility. "We received overwhelmingly positive responses to this patient-centered care option." Dr. Reinke said. "Patients were able to do the post-operative visit at work or at home while caring for children, without having to disrupt their day in such a significant way."

The researchers also found that patients embraced the virtual scenario. The satisfaction rate between both groups of patients was similar (94 percent vs. 98 percent).

In addition, wait time was much less for patients who got virtual care. "Even for virtual visits, the amount of time the patients spent checking in and waiting was about 55 percent of total time. Because virtual visits have the same regulations as in-person visits, even if you take out the components of waiting room and patient flow within the clinic, patients are still spending about half of their time on the logistics of check in," Dr. Reinke. "Yet, with virtual visits, there is still much less time spent waiting, about 80 percent less time."

Still, some patients are not comfortable with the technology. The number of patients who couldn't or didn't want to do a virtual visit was higher than expected, according to the authors.

"I think there are some patients that would really just rather come in and shake someone's hand," Dr. Reinke said. "I think for surgery it's a little bit different, because with surgical care there are incisions to check on. However, we were able to check on incisions pretty easily, having patients show us their incisions virtually on the video screen."

CHICAGO: The STOP THE BLEED® course teaches a skill with lifesaving potential that is easy to learn and globally relevant. Two studies presented at the American College of Surgeons (ACS) Clinical Congress 2020 provide evidence that STOP THE BLEED® training is effective and has made a lifesaving difference around the world.

In one study, an hour-long STOP THE BLEED® course was taught to 121 nursing students at the Kabala Nursing School in rural Sierra Leone. After one year, a survey was administered to the participants to learn whether they encountered bleeding emergencies and whether they were able to administer bleeding control techniques. Seventy-six people responded to the survey, reporting a total of 190 encounters with life-threatening bleeding situations.

The most common injuries requiring a bleeding control intervention were motorcycle collisions (34 percent), knife wounds (19 percent), and car accidents (13 percent). Participants reported they most commonly used wound packing (41 percent), direct pressure (26 percent), and tourniquet application (20 percent). Because they were able to intervene, nearly all of the patients (94 percent) survived, with a majority (82 percent) reporting to the hospital for further medical care.

"People are getting basic medical knowledge, which is essential. With or without a medical background, they can apply this knowledge to save a life," said Samba Jalloh, MB, ChB, of the College of Medicine and Allied Health Sciences, Freetown, Sierra Leone.

In low-to-middle income countries (LMICs), access to health care can be sporadic and the burden of injury can be significant. The findings from this study provide evidence that STOP THE BLEED® training can be implemented in LMICs with sustained success in treating bleeding emergencies before a patient is able to be transported to a hospital.

"Here, there are a lot of risks. Transportation is not very safe, and hospitals can be far away from villages. Knowing how to stop the bleed is very important. People are using the skill to save lives," Dr. Jalloh said.

The researchers stressed that these findings demonstrate enormous lifesaving applicability of STOP THE BLEED® training in Sierra Leone. They noted that future studies should focus on the specifics of adapting bleeding control for use in other LMICs.

"With the efforts of Dr. Jalloh, the course became a mandatory component of house staff training in Freetown. Successful technique usage and course dissemination have encouraged us to think of ways to improve bleeding control training in the United States and abroad. These findings support further emphasis on lifesaving prehospital interventions and represent a great example of sustainable, bidirectional global surgical teamwork," said lead study author Vennila Padmanaban, MD, a surgical resident at Rutgers New Jersey Medical School, Newark.

In another study from researchers in Connecticut, STOP THE BLEED® course attendees demonstrated a strong proficiency of bleeding control knowledge after one year, and course participants, including previously untrained attendees, reported successfully applying hemorrhage control techniques to save lives.

"In our study, we had people as young as 14 and as old as 64 report that they used bleeding control skills. Eight of these people had not undergone any previous training in bleeding control and seven of the people who used the skills did not work as a first responder or in a health care setting," said lead study author Jeremy Fridling, a fourth-year medical student at the Frank H. Netter MD School of Medicine at Quinnipiac University, North Haven, Conn.

The researchers tracked 1,030 STOP THE BLEED® course attendees, administering surveys before and after the course, as well as six and twelve months later. Of the respondents, 31 participants (8.4 percent) applied bleeding control skills to live victims, with 29 (93.5 percent) reporting a successful outcome.

In the post-course surveys, the average response was between "agree" and "strongly agree" for confidence in knowledge and skills. Notably, the average response (on a 1-5 scale) significantly increased from pre (4.1) to post (4.6), six-month (4.4), and twelve-month (4.5) for willingness to treat a victim with serious bleeding.

"This study is a validation that regular, ordinary people--if you train them and give them a chance and empower them to do a public good and stop bleeding--can stop bleeding with a successful outcome," said study coauthor Lenworth Jacobs, MD, MPH, FACS, professor of surgery, University of Connecticut, and Medical Director, ACS STOP THE BLEED® program.

CHICAGO: People age 65 years and older account for 40 percent of inpatient operations and one-third of outpatient procedures,1,2 and these older patients are more vulnerable to longer hospital stays and other complications after surgery than younger patients. A beta test of a program for older adults who undergo major surgery has resulted in shorter hospital stays and lower rates of post-surgery delirium, among other improved outcomes, according to research presented at the virtual American College of Surgeons (ACS) Clinical Congress 2020.

The Aging Veterans Surgical Wellness (AVSW) program at the Rocky Mountain Regional Veterans Affairs Medical Center in Aurora, Colorado, served as a beta testing site for the American College of Surgeons Geriatric Surgery Verification program (ACS GSV). The study involved 186 patients, 158 of whom were matched according to age and type of operation to a comparative control group of 308 patients from the national Veterans Affairs Surgical Quality Improvement Program (VASQIP) database.

"When we looked at the matched cohort from the VASQIP data base, we found a decreased hospital length of stay of four days compared to five days, which is very significant," said Alexandra Kovar, MD, a general surgery resident at the University of Colorado School of Medicine and chief resident for quality and safety at the Rocky Mountain Regional VA Medical Center.

"When we compared our outcomes to those reported in previously published research, two important postoperative outcomes in our patient population showed significant improvement: development of postoperative delirium and functional health postoperatively."

The rate of post-surgery delirium in the AVSW population was 9.3 percent compared with 12.1 percent reported in the ACS National Surgical Quality Improvement Program Geriatric Surgery Pilot study.3 Likewise, only 19.1 percent of the AVSW patients reported functional cognitive decline after their operations compared with 42.9 percent in the pilot study. "These variables are specifically important to older adults because the development of postoperative delirium can affect their cognition long term," Dr. Kovar said. "Functional health is related to independence, mobility, and overall quality of life."

The ACS GSV program was introduced July 2019. It sets forth 32 different surgical standards that hospitals can use for a multidisciplinary team approach to optimize surgical care for older adults facing surgery. The standards address the preoperative work-up, postoperative management, care transition, data collection, quality improvement, professional and community outreach, and research.

Senior study author Thomas Nichols Robinson, MD, FACS, chief of surgery at Rocky Mountain Regional VA Medical Center and a member of the ACS GSV program panel, noted that the standards can be implemented at any hospital. "The majority of these standards are aimed at the clinical processes necessary to optimize the surgical care of older adults, but the standards also address the administrative support needed to improve the surgical care of older adults, and measurement outcomes necessary to improve the care of older adults in your hospital," he said.

Dr. Kovar noted two interventions were important to the success of the AVSW program. "The implementation of the preoperative multidisciplinary conference where we talk about the patients prior to having surgery," she said. "We discuss their needs in the three phases of care, for example, whether they're going to need physical therapy, occupational therapy, or a nutritional consult. We get them teed up for surgery so when they arrive they're ready to go. The second intervention is the daily inpatient rounding team, who assesses the patient on a daily basis."

In the next step for their research, Dr. Kovar and colleagues aim to enroll more patients and include more specific internal and external cohorts to evaluate more postoperative outcomes, including 30-day post-surgery death and complications. Future variables would include patient-reported outcomes and outcomes using telehealth, she said.

Added Dr. Robinson, "Surgeons intuitively recognize that the group at highest risk of poor outcomes are older adults; the frail older adult is at highest risk for longer hospital stays, complications, and needing to go to institutions after discharge. This program directly addresses those needs unique to frail older adults to try to prevent poor outcomes after surgery."

"The results of this beta pilot show how well the Geriatric Surgery Verification program works in a hospital that puts forth the institutional commitment to improve the care of older adults facing surgery. Identifying and addressing potential vulnerabilities specific to the geriatric surgical patient such as delirium, result in better patient outcomes. And a reduced hospital stay is not only a good outcome for patients, it also indicates a more efficient use of resources," said Clifford Y. Ko, MD, MSHS, FACS, principal investigator for the ACS Geriatric Surgery Verification program, who was not involved with the study.

CHICAGO: Pregnant women who underwent immediate surgery to treat a ruptured or abscessed appendix and their fetuses had significantly better outcomes than those whose condition was managed without an operation. Results from a nationwide study presented at the virtual American College of Surgeons Clinical Congress 2020 form the basis for the potential development of a consensus on optimal management of complicated appendicitis in pregnancy.

Currently, the management of appendicitis in the general population is somewhat controversial and is especially true for complicated appendicitis. Increasing numbers of surgeons prefer a trial of nonsurgical management; others recommend an immediate operation," explained Kazuhide Matsushima, MD, FACS, an assistant professor of clinical surgery, Keck School of Medicine, University of Southern California (USC), Los Angeles. "This study is a great first step toward a consensus regarding the optimal management of complicated appendicitis in pregnant patients. Randomized clinical trials are necessary to provide that consensus," he added.

"Based on the current evidence we have, which includes this study, our recommendation would be for surgeons to pursue immediate operation for pregnant patients with complicated appendicitis. Every day of delay to surgery means worse clinical outcomes for the patients as well as the fetus," said Vincent Cheng, MD, a general surgery resident and lead author of the study at USC.

Since the 19th Century, surgery has been the most widely accepted treatment for appendicitis; more than 300,000 appendectomies are performed annually in the US.1 Laparoscopic appendectomy is the most common surgical treatment.2,3 Despite this history, the management of acute appendicitis is still open to debate in terms of such questions as the timing of appendectomy, the safety of in-hospital delay, and the indications for performing appendectomy following a course of antibiotics.4, 5, 6, 7

Moreover, increasing numbers of patients in the U.S. are being treated for appendicitis non-operatively. The number has doubled in the last 20 years, according to results of a study presented at the American College of Surgeons Clinical Congress 2017.8

Appendicitis during pregnancy is relatively uncommon. While the raw number and incidence of appendicitis during pregnancy is low, it is actually the most common non-obstetric emergency during pregnancy. It is also the most common non-obstetric reason for surgery during pregnancy, Dr. Cheng said. About 0.1 percent of pregnant women have appendicitis; in one study, 25 percent of 713 pregnant patients with appendicitis had a perforated appendix.9,10,11 Nonetheless, the condition carries a high risk of serious complications, including loss of the fetus.9 Perforation of the appendix increases the risk of death of the mother.11

Because of the low incidence of complicated appendicitis in pregnancy, there are no specific recommendations or guidelines on management. A team of surgeons from USC therefore set out to evaluate current treatment of complicated appendicitis in pregnancy by comparing maternal and fetal complications after operative and non-operative management.

The researchers reviewed the National Inpatient Sample dataset from 2003-2015 to identify 8,087 cases of complicated appendicitis in pregnancy. Most (55 percent) had immediate non-invasive surgery. Forty-five percent began a course of non-operative management, which involved a course of antibiotics with or without percutaneous drainage of the inflamed organ. Of the 45 percent of patients who began non-operative management, 74 percent failed and later required an operation (either a laparoscopic procedure or an open appendectomy).

Preterm labor, delivery, and pregnancy termination were more common in the group of women who had non-operative management or delayed surgery than in those who had immediate surgery; the odds of developing these complications were one to three times higher for the non-operative group. Sepsis also was two to four times more common in these groups of patients. The rate of any complication was lowest among patients who had immediate surgery (30 percent) and overall length of stay was two days shorter for these patients.

While further study is needed to eventually arrive at a consensus for treating complicated appendicitis in pregnancy, findings from the study may help guide surgeons and patients. Dr. Matsushima stressed the importance of telling patients that the management of this condition is controversial and explaining the treatment options and risks.

Dr. Cheng pointed out that "every situation is different and every patient is different so the discussion about how to manage this disease process should be a joint process between the patient and the surgeon that presents the pros and cons of the treatment options."

CHICAGO: Transportation barriers, such as personal access to a vehicle or public transportation, disproportionally affect minority communities, according to results of a new study presented at the virtual American College of Surgeons (ACS) Clinical Congress 2020.

The study was performed by researchers at the University of Colorado at Aurora who used geographic information systems (GIS) to better understand traffic paths to hospitals offering elective and emergency surgical care throughout Denver. They tracked public transportation routes across census tracts and found areas with higher minority populations have nearly double the travel time burden to health care facilities when using public transportation.

Facilities with acute surgical capacity (emergency department, intensive care unit, and acute care surgery services) were identified within a 20-mile radius of the city center. Travel times were then estimated from the center of each census tract to the nearest facility by the shortest route. Using this method, the researchers determined travel times for individuals traveling by both car and public bus for a Monday morning appointment, weighted by percentage of the population in each census tract without vehicle access according to the American Community Survey.

For the 144 census tracts within Denver, the researchers found patients traveling by car were likely to spend approximately 12 minutes time driving to a health care facility as opposed to 33 minutes each way when traveling by public transportation. The overall drive times weighted by lack of vehicle access across the city are estimated to be 11 minutes by car and 28 minutes by bus. Additionally, census tracts with higher minority populations and higher populations without access to a personal vehicle saw approximately 3 minutes in increased travel time by bus for every 10 percent increase in the minority population.

Impact of Transportation Access on Medical Care

Barriers to health care access like race, income, and having insurance are well-documented, but structural barriers, like geography, can act in similar ways. In Denver specifically, freeway routes dividing the city and communities have shut residents off from resources to which they were previously able to walk. Prior work by the same group found that lack of health care coverage was not a significant barrier to surgical care where the majority of patients who presented emergently had some health care coverage, and many of the patients had sufficient coverage such that they had already been scheduled for elective surgical consultation, or even surgery itself.1

Regardless of type of health care coverage, patients who presented emergently tended to live in areas of higher social vulnerability and were overwhelmingly non-white.2 Qualitative data derived from narrative data in the charts revealed that a common factor leading to emergent presentation included difficulties arranging transportation. In fact, approximately 3.6 million people in the United States forgo medical care due to transportation issues, such as lack of vehicle access, inadequate infrastructure, long distances, and lengthy travel times to reach services.3 As a result, procedures that could be treated in an outpatient appointment can frequently run the risk of becoming emergency situations.

Transportation patterns in areas where people don't have access to a vehicle can add 30 or more minutes to travel to an appointment. "When you factor in that people have to take additional time off from their jobs to go to an appointment to get elective care, and add in the fact that a lot of people have jobs where they don't have a lot of paid time off or the ability to take off that much time in a day, you may be looking at them having to take an entire day off to be able to make it to an elective surgical appointment. So, you're adding barrier after barrier, and these things tend to compound themselves," said study coinvestigator Catherine Velopulos, MD, MHS, FACS, a health services researcher and associate professor of surgery at the University of Colorado School of Medicine.

The findings also suggest a double effect of transportation barriers. Not only are some patients facing a greater barrier in terms of the percent of the population that has access to a private vehicle, but those same populations also have longer public transportation times per mile to acute care surgical facilities.

Using GIS to improve health care access

Census data can be used with GIS mapping to collect information about the environment, allowing local governments to identify communities with disproportionate transportation burden to acute care surgical services. By identifying where increased burden exists, cities can make structural changes to accommodate these needs.

"Place truly matters. Where you're located and where you live affects your health care outcomes," said coinvestigator Heather Carmichael, MD, a surgical resident at the University of Colorado School of Medicine. "If you can identify where patients are coming from, that gives you a lot of information about the environment that they're in that can affect their health care outcomes. And location of residence may be easier to determine in a research setting than in individually collecting each of those sociodemographic variables for an individual patient."

Understanding this combined data helps communities focus on where best to place resources like outreach programs and other forms of health care navigation, like Colorado's Non-Emergent Medical Transportation services, as well as to reevaluate traditional bus routes and pick up locations to better suit the needs of the community.

"A lot of people's access to the health care system is through surgical disease," added Dr. Velopulos, "And it's important for us as surgeons to recognize that we have a duty to improve access to care all around because it makes our patients healthier and our surgical outcomes better, and it allows us to reach our patients at an earlier point in their disease."

A study conducted at 19 universities by IU researchers and their colleagues in the U.S. and Canada, found that a brief social belonging exercise, administered online before students arrive on campus, boosts the performance and persistence of students in STEM disciplines - science, technology, engineering and math - who speak English as a second language.

Published this week in the journal Science Advances, the study demonstrates that the exercise increases ESL students' perception that a sense of belonging on campus will grow over time. It also increases the number of STEM credits ESL students successfully completed, as well as their STEM GPAs.

As Jennifer LaCosse, an IU post-doctoral researcher and lead author on the study, explained, ESL students are greatly underrepresented in U.S. colleges, particularly within STEM fields, and their absence is a disadvantage both to the students themselves and the economy more broadly. Having a college degree, particularly in STEM fields, gives ESL students the opportunity to have higher paying jobs and more successful careers overall. It also creates a diverse and multilingual workforce that is needed to meet the needs of an increasingly globalized economy.

Results of the study suggest that one way to increase the representation and academic success of ESL students in STEM is to target their sense of belonging. "Students often ask themselves, 'Do I belong here?' and we know that this concern can undermine academic performance and persistence," said LaCosse.

Students who speak English as a second language often report concerns about not fitting in with native English-speaking students and a lack of social connections. In addition, many are required to pass language proficiency tests or enroll in special ESL courses during their first few years of college.

"These policies can metaphorically and literally separate ESL students from non-ESL students during the pivotal transition to college when feelings of belonging are critical," said LaCosse. "Finding ways of buttressing ESL students' feelings of belonging may be essential to their academic success--which is what we wanted to examine in our research."

The study utilized data collected at 19 universities from more than 12,000 STEM students by the College Transition Collaborative, a partnership co-founded by IU social psychologist and study co-author Mary Murphy. Students in the study who were randomly assigned to receive the social belonging treatment, read short stories attributed to juniors and seniors describing the challenges they faced in their transition to college. The students in the stories initially questioned the degree to which they belonged in college; and yet, with time they ultimately developed a greater sense of belonging. Study participants followed the readings with a writing exercise about their own experiences.

Results of the study revealed that both ESL and non-ESL students who received the social belonging exercise anticipated greater growth in their sense of belonging than students who received the control treatment. However, these psychological gains in belonging only bolstered the academic persistence and performance of ESL students. Specifically, STEM-interested ESL students who received the social-belonging exercise (vs. the control group, which did not) completed more of the STEM courses that they began in their first term in college--and this effect persisted through the first year. ESL students who completed the social belonging exercise also earned higher STEM GPAs in Term 1 than did their ESL peers who did not.

"People do not often think about ESL students as a disadvantaged group in the same way they do about other disadvantaged students, such as Black or women students," observed LaCosse. "The results of this study, however, provide rigorous empirical evidence that ESL students have similar psychological experiences to these other disadvantaged students."

As co-author Mary Murphy, IU professor of psychological and brain sciences noted, "Because of the large sample size across so many universities this is one of the first studies to quantitatively examine and mitigate this important psychological barrier for ESL students in STEM fields as they begin college."

"The findings are really exciting," said LaCosse, "because ESL students' psychological experiences in higher education have received far less attention than they deserve. Our research suggests that we need to rethink the policies and practices that are in place that create and maintain the underrepresentation of ESL students in higher education."

ATLANTA--A combination of two substances secreted by the immune system can cure and prevent rotavirus infection, as well as potentially treat other viral infections that target epithelial cells, which cover body surfaces such as skin, blood vessels, organs and the urinary tract, according to researchers in the Institute for Biomedical Sciences at Georgia State University.

Rotavirus, which causes severe, life-threatening diarrhea in young children and moderate gastrointestinal distress in adults, leads to thousands of deaths in children annually, particularly in developing countries where rotavirus vaccines are only moderately effective. Rotavirus is an RNA virus that primarily infects intestinal epithelial cells.

The substances identified in the study, officially known as cytokines, are interleukin 18 (IL-18) and interleukin 22 (IL-22). IL-18 and IL-22 are produced when the body detects a protein in the whip-like appendage of bacteria.

The study, which investigated how these cytokines inhibit rotavirus infection, found when mice were treated with both IL-18 and IL-22, the cytokines promoted each other's expression, but also impeded rotavirus by independent, distinct mechanisms that involved activating receptors in intestinal epithelial cells. These actions resulted in rapid and complete expulsion of rotavirus, even in hosts with severely compromised immune systems. The therapy was also found to be effective for norovirus, a contagious virus that causes vomiting and diarrhea. The findings are published in the journal Science Immunology.

"Our study reports a novel means of eradicating a viral infection, particularly viruses that infect epithelial cells," said Dr. Andrew Gewirtz, senior author of the study and a professor in the Institute for Biomedical Sciences at Georgia State. "The results suggest that a cocktail that combines IL-18 and IL-22 could be a means of treating viral infections that target short-lived epithelial cells with high turnover rates."

Breast cancers that are detected in the interval between national screening programme mammograms have a worse prognosis than those detected at the time of a screening, even if they have the same biology, according to research presented at the 12th European Breast Cancer Conference on Saturday.

Analysis of results from over eight years' follow-up of the international MINDACT randomised phase III clinical trial shows that although tumours may have the same genetic make-up, the way they are detected makes a significant difference to the period of time before the disease starts spreading to other parts of the body or results in death, whichever comes first. This is known as the distant metastasis-free interval (DMFI).

Dr Josephine Lopes Cardozo (MD), a PhD candidate at the Netherlands Cancer Institute (NKI) in Amsterdam, The Netherlands, and medical fellow at the European Organisation for Research and Treatment of Cancer (EORTC) in Brussels, Belgium, told the conference that the method of detection gave additional prognostic information and should be taken into account when deciding on what treatments in addition to surgery might be needed.

Dr Lopes Cardozo and her colleagues had found previously that tumours that occurred in the interval between screening mammographies, known as interval cancers, were more likely to have a high-risk genetic profile, as shown by a test that looks at the activity of 70 genes in the tumour tissue (the 70-gene signature, commercially known as MammaPrint), and were therefore at higher risk of distant metastases.

"However, there are also screen-detected cancers with a high-risk 70-gene signature," she said. "In our current analysis, we found a significant difference in survival between high-risk cancers detected during screening or in the interval between screenings. The eight-year DMFI rate was higher among women with screen-detected cancers than for women with interval cancers: 93.8% versus 85.2%.

"Although these tumours have the same biology - all 70-gene, high-risk and with similar tumour characteristics - they have different prognoses based on their method of detection. This suggests that the method of detection is an additional prognostic factor in this group of patients. The method of detection combined with the 70-gene signature can further optimise treatment for patients at high risk of recurrence. For patients with a very low risk of recurrence, longer follow-up may also help to identify those who are currently at risk of being over-treated."

A total of 1102 Dutch breast cancer patients enrolled in the MINDACT trial between 2007 and 2011, who participated in the national screening programme and who were aged 50-75, were included in the analysis. The Dutch national screening programme invites women aged 50-75 years for screening every two years. The researchers evaluated differences in DMFI for high, low and ultra-low risk tumours, as classified by the 70-gene signature. A total of 754 cases were detected during screening, and 348 during the interval between screenings.

With 50% of patients having reached at least 8.6 years of follow-up, there were 83 occurrences of distant metastases or death due to breast cancer. Among patients with screen-detected cancers, 36% received no adjuvant systemic treatment (such as chemotherapy and hormone therapy, in addition to surgery and radiotherapy), 33% received hormone therapy only and 30% received chemotherapy with or without hormone therapy. Among patients with interval cancers, 17% received no adjuvant systemic treatment, 35% had hormone therapy only and 47% had chemotherapy with or without hormone therapy.

"Most patients who received no adjuvant systemic therapy had grade I tumours, smaller than 2cms, had no signs of cancer in their lymph nodes and were classified as ultra-low or low risk by the 70-gene signature," said Dr Lopes Cardozo.

When the researchers looked at survival rates at eight years, they found that patients with screen-detected cancers had an eight-year DMFI rate of 98.2% in 118 women with ultra-low-risk tumours, 94.6% in the 398 women with low-risk tumours, and 93.8% in the 238 women with high-risk tumours.

Patients with interval cancers had an eight-year DMFI rate of 97.4% in the 39 women with ultra-low-risk tumours, 92.2% in the 143 women with low-risk tumours, and 85.2% in the 166 women with high-risk tumours.

Among patients with high-risk tumours, those that were detected in the interval between screenings had a 2.4-fold increased chance of developing distant metastases compared to those whose cancer was detected during screening.

Dr Lopes Cardozo concluded: "Both screen-detected and interval breast cancers have very good eight-year distant metastasis-free interval rates. However, among patients with high-risk tumours as classified by the 70-gene signature, there is a significant difference in these rates between screen-detected and interval cancers. Combining the prognostic information provided by the 70-gene signature and the method of detection can help to choose the best treatment for these patients."

Professor David Cameron, from the University of Edinburgh Cancer Centre, UK, who represents the European Breast Cancer Council at EBCC12, was not involved with the research. He commented: "This study highlights an interesting difference between breast cancers that are detected at the time a woman attends a scheduled appointment as part of a national screening programme (screen detected) and those that are diagnosed in the interval between screenings (interval cancers). It has been previously noted that interval cancers are more likely to be high grade and that would be associated with a poorer outcome, but the novel finding here is that for those cancers identified biologically as being high risk by the 70-gene signature test, the screen detected ones do better than those presenting as interval cancers.

"If these results are confirmed in another series, it would suggest that earlier diagnosis via screening of more biologically aggressive cancers is worthwhile: screen-detecting such cancers may improve patients' survival. The findings also suggest that clinicians should take into account the method of detection as an additional prognostic factor when considering adjuvant therapy, enabling further personalisation of therapy to the individual woman and her cancer. This is as important for low-risk cancers as for high-risk ones. Longer follow-up for low-risk cancers could give us more information as to whether more aggressive treatments could be avoided, as these tumours can recur 15 to 20 years later."

Patients receiving care for advanced cancer at Moores Cancer Center at UC San Diego Health were more likely to survive or experience a longer period without their disease progressing if they received personalized cancer therapy, report University of California San Diego School of Medicine researchers.

Led by Razelle Kurzrock, MD, director of the Center for Personalized Cancer Therapy at Moores Cancer Center and senior author of the study, a multidisciplinary molecular tumor board was established to advise treating physicians on course of care using an individual patient's molecular tumor makeup to design precision medicine strategies.

"Patients who underwent a molecular tumor board-recommended therapy were better matched to genomic alterations in their cancer and had improved outcomes," said Kurzrock. "The three-year survival for patients with the highest degree of matching and who received a personalized cancer therapy was approximately 55 percent compared to 25 percent in patients who received therapy that was unmatched or had low degrees of matching."

Of 429 patients evaluated by the molecular tumor board, 62 percent were matched to at least one drug, report the researchers in the October 2, 2020 online issue of Nature Communications. Twenty percent of patients matched to all recommended drugs, including combination therapies.

The tumor board acted in an advisory role and treating physicians chose not to use the board's recommended strategy in 38 percent of cases, opting instead for a standard therapy approach that might have been unmatched to the patient's genetic alterations or had a low degree of matching. These patients experienced a lower progression-free survival and overall survival rates.

The use of next-generation sequencing allows for the identification of novel potential targets for patients with cancer to improve outcomes, but there are challenges to using this approach widely, said Shumei Kato, MD, associate professor of medicine at UC San Diego School of Medicine and first author.

"One of the hurdles is that every cancer patient appears to be carrying different molecular and genomic patterns despite having the same cancer type," said Kato, a Moores Cancer Center medical oncologist specializing in rare and gastrointestinal cancers. "This can be challenging since we are customizing therapy based on the unique genomic pattern patients have, and thus it is difficult to predict the response. In addition, this approach requires multidisciplinary expertise as well as access to drugs or clinical trials not always available in smaller practices."

At Moores Cancer Center, the molecular tumor board is composed of experts in basic, transitional and clinical research as well as bioinformatics, genetics, radiology, pathology and physicians in multiple specialties such as medical, surgical and radiation oncology.

Further clinical investigations with a larger sample size are necessary to identify the matching score thresholds that determine the usefulness of a precision medicine approach, said the researchers.

Allowing farmers to harvest vegetation from their riparian buffers will not significantly impede the ability of those streamside tracts to protect water quality by capturing nutrients and sediment -- and it will boost farmers' willingness to establish buffers.

That is the conclusion of Penn State College of Agricultural Sciences researchers, who compared the impacts of six riparian buffer design scenarios over two, four-year crop rotations in two small central and southeastern Pennsylvania watersheds. Two of the buffer scenarios included the harvesting of switchgrass and swamp willow trees.

Allowing farmers to harvest vegetation from their riparian buffers and sell it for biofuels -- not permitted under current Conservation Reserve Enhancement Program, or CREP, federal regulations -- would go a long way toward persuading farmers to establish riparian buffers, researchers contend. And farmers' buy-in is badly needed in Pennsylvania, where hundreds of miles of new buffers are needed along streams emptying into the Chesapeake Bay to help the state meet water-quality standards.

"This is the first long-term study in the Chesapeake Bay watershed to model how harvesting vegetation affects riparian buffer performance over the full length of a buffer contract," said researcher Heather Preisendanz, associate professor of agricultural and biological engineering. "Allowing harvesting of the buffer vegetation -- either trees or grasses -- minimally impacted water quality, with only slight annual average reductions in the capture of nitrogen, phosphorus and sediment."

In addition, she noted, under the highest input loading conditions -- heavy runoff after storms -- buffers with lower removal efficiencies removed more total mass of pollutants than did buffers with high-removal efficiencies, if they were between streams and fields with row crops such as corn and soybeans. The location of the buffer was most important.

The researchers, who modeled runoff and resulting pollution from agricultural fields reaching the streams, studied riparian buffer performance on Spring Creek in Centre County and Conewago Creek in Lancaster County. Buffer design scenarios studied included 35-feet-wide grass; 50-feet-wide grass; 50-feet-wide deciduous trees; 100-feet-wide grass and trees; 100-feet-wide grass and trees, with trees harvested every three years; and 100-feet-wide grass and trees, with grass harvested every year.

The research team developed these scenarios after considering feedback from focus group meetings with farmers in the two watersheds. Farmers indicated they wanted to be able to install buffers tailored to their properties with the prospect of generating limited revenue.

In the Spring Creek watershed -- which has been studied closely by Penn State agricultural scientists for decades -- 16 years of daily-scale nutrient and sediment loads from three crop rotations and two soils were simulated in a soil and water assessment tool. That data was used as an input to a riparian ecosystem management model used nationally to better understand how a buffer's effectiveness changes as a function of input load, buffer design and buffer management.

The simulation results, recently published in the Journal of Environmental Quality, suggest that for buffers of the same width, the farmer-preferred grass vegetation outperformed policy-preferred vegetation of trees for sediment, nitrogen and phosphorus removal.

The findings of the research have important implications for informing flexible buffer design policies and enhanced placement of buffers in watersheds impaired by nutrient and sediment, Preisendanz explained. She pointed out, however, that more research may be needed to examine tradeoffs between water-quality impacts and other ecosystem services, such as streambank stabilization, habitat and stream shading.

"If incorporated into policy, these findings could remove one barrier to farmer adoption of riparian buffers," she said. "Based on our conversations with famers in focus groups, we think this approach -- government being more flexible with buffer designs and allowing harvesting -- would go a long way toward farmers agreeing to create more riparian buffers."

The state Department of Conservation and Natural Resources currently is promoting "multifunctional" buffers, Preisendanz added. "Our hope is that this work will help to inform tradeoffs of flexible buffer designs and management options in this new program."

A major roadblock to large scale testing for coronavirus infection in the developing world is a shortage of key chemicals, or reagents, needed for the test, specifically the ones used to extract the virus's genetic material, or RNA.

A team of scientists at the University of Vermont, working in partnership with a group at the University of Washington, has developed a method of testing for the COVID-19 virus that doesn't make use of these chemicals but still delivers an accurate result, paving the way for inexpensive, widely available testing in both developing countries and industrialized nations like the United States, where reagent supplies are again in short supply.

The method for the test, published Oct. 2 in PLOS Biology, omits the step in the widely used reverse transcription polymerase chain reaction (RT-PCR) test where the scarce reagents are needed.

92% accuracy, missing only lowest viral loads

The accuracy of the new test was evaluated by a team of researchers at the University of Washington led by Keith Jerome, director of the university's Molecular Virology Lab, using 215 COVID-19 samples that RT-PCR tests had shown were positive, with a range of viral loads, and 30 that were negative.

It correctly identified 92% of the positive samples and 100% of the negatives.

The positive samples the new test failed to catch had very low levels of the virus. Public health experts increasingly believe that ultra-sensitive tests that identify individuals with even the smallest viral loads are not needed to slow spread of the disease.

"It was a very positive result," said Jason Botten, an expert on pathogenic RNA viruses at the University of Vermont's Larner College of Medicine and senior author on the PLOS Biology paper. Botten's colleague Emily A. Bruce is the paper's first author.

"You can go for the perfect test, or you can use the one that's going to pick up the great majority of people and stop transmission," Botten said. "If the game now is focused on trying to find people who are infectious, there's no reason why this test shouldn't be front and center, especially in developing countries where there are often limited testing programs because of reagent and other supply shortages."

Skipping a step

The standard PCR test has three steps, while this simpler version of the standard test has only two, Botten said.

"In step 1 of the RT-PCR test, you take the swab with the nasal sample, clip the end and place it in a vial of liquid, or medium. Any virus on the swab will transfer from the swab into the medium," he said. "In step 2, you take a small sample of the virus-containing medium and use chemical reagents, the ones that are often in short supply, to extract the viral RNA. In step 3, you use other chemicals to greatly amplify any viral genetic material that might be there. If virus was present, you'll get a positive signal."

The new test skips the second step.

"It takes a sample of the medium that held the nasal swab and goes directly to the third, amplification step," Botten said, removing the need for scarce RNA extraction reagents as well as significantly reducing the time, labor and costs required to extract viral RNA from the medium in step 2.

Botten said the test is ideally suited to screening programs, in both developed and developing countries, since it is inexpensive, takes much less processing time and reliably identifies those who are likely to spread the disease.

Its low cost and efficiency could extend testing capacity to groups not currently being tested, Botten said, including the asymptomatic, nursing home residents, essential workers and school children. The standard RT-PCR test could be reserved for groups, like health care workers, where close to 100% accuracy is essential.

An influential pre-print points way to widespread adoption of test

The two-step test developed by the University of Vermont team first caught the attention of the scientific community in March, when preliminary results that accurately identified six positive and three negative Vermont samples were published as a preprint in bioRxiv, an open access repository for the biological sciences. The preprint was downloaded 18,000 times -- in its first week, it ranked 17th among 15 million papers the site had published -- and the abstract was viewed 40,000 times.

Botten heard from labs around the world who had seen the preprint and wanted to learn more about the new test.

"They said, 'I'm from Nigeria or the West Indies. We can't test, and people's lives are at stake. Can you help us?'"

Botten also heard from Syril Pettit, the director of HESI, the Health and Environmental Sciences Institute, a non-profit that marshals scientific expertise and methods to address a range of global health challenges, who had also seen the preprint.

Pettit asked Botten to join a think tank of likeminded scientists she was organizing whose goal was to increase global testing capacity for COVID-19. The test developed by the University of Vermont and University of Washington teams would serve as a centerpiece.
To catalyze a global response, the group published a call to action in EMBO Molecular Medicine.

And it took action, reaching out to 10 laboratories in seven countries, including Brazil, Chile, Malawi, Nigeria and Trinidad/Tobago, as well as the U.S. and France, to see if they would be interested in giving the two-step test a trial run.
"Universally, the response was yes," Pettit said.

The outreach led to a new HESI program called PROPAGATE. Each of the labs in the PROPAGATE Network will use the two-step test on a series of positive and negative samples sent to them by the University of Washington to see if they can replicate the results the university achieved.

The study has already shown promising results. One of the labs in Chile has also used the test on its own samples from the community and got accurate results.

Assuming all goes well, Pettit and her colleagues at the University of Vermont and the University of Washington as well as scientists from the 10 partner sites plan to publish the results.

"The goal is the make the two-step test accessible to any lab in the world facing these hurdles and see a broad uptake," she said.

ITHACA, N.Y. - For one low-income woman, not having a car meant long commutes on public transit with her children in tow, sometimes slogging through cold or inclement weather. But after buying a subsidized car through a Maryland-based nonprofit, she was able to move to a home located farther from bus stops, send her children to better schools and reach less expensive medical services.

"So many different things open up to a person that is mobile," the woman told Nicholas Klein, assistant professor of city and regional planning at Cornell University.

In "Subsidizing Car Ownership for Low-Income Individuals and Households," published in the Journal of Planning Education and Research, Klein reports insights from interviews with 30 people who gained access to inexpensive, reliable cars through the nonprofit Vehicles for Change (VFC).

He found that the cars conferred wide-ranging benefits, not only shortening commutes and opening opportunities for higher-paying jobs, but also dramatically improving quality of life. The recipients of subsidized cars spent more time with family, visited doctors they preferred, shopped for groceries more efficiently, attended more school events and enrolled kids in previously inaccessible after-school enrichment programs.

"For a lot of families, it's a really transformative moment that allows them to move up the economic ladder, to access all sorts of sort of social benefits and to just make their lives easier," Klein said of the access to subsidized cars. "It permeated everyone's lives in all sorts of different ways."

Transportation planners and scholars have debated subsidizing car ownership for decades, and VFC, which has provided more than 6,000 cars in Maryland and Virginia since 1999, is one of only a handful of such programs across the country. Critics say subsidizing cars on a large scale would exacerbate environmental pollution, traffic congestion and sprawl, and impose new cost burdens on car owners.

Klein said his research took a longer, more nuanced view that suggested such answers are "not so clear-cut." Beyond interviewees' experiences with a subsidized car, he also learned about their personal and car-ownership histories.

Most had owned cars before and planned to purchase cars again, typically through used car dealers that Klein called "pernicious." The interviewees had typically paid significantly more for used cars that were less reliable than those provided by VFC, which cost less than $1,000 and passed thorough inspections (through a job training program for formerly incarcerated individuals).

Considering that context, Klein said, scholars and policymakers should be asking not only about the benefits and consequences of having a car, but about the consequences of not making subsidized car ownership available to low-income families.

"What I see is that a lot of low-income households are going out and spending quite a bit more on unreliable used cars, and those cars may be polluting much more," he said.

Klein concluded that subsidized car ownership should be implemented more broadly, along with complementary programs providing subsidized repairs or replacement of older, more polluting and less efficient cars.

Such programs shouldn't come at the expense of longer-term investments in public transit and infrastructure expanding alternatives to cars, Klein said. But that infrastructure takes time to build and can't support everyone living in suburban or rural areas.

"In the meantime, these families are struggling, and we can think about ways to help them while also investing in high-quality public transit, and biking and walking infrastructure," Klein said.

Klein said his research relying on interviews proved valuable in a transportation field that emphasizes quantitative methods - for example, to measure economic outcomes such as how car ownership affects income or employment.

"When we only do that, we miss a lot of important nuance and details and we miss people's voices and stories," he said. "Qualitative research lets us understand the broader scope of effects that we might miss if we only rely on what's in the data, allowing us to see a broader range of possibilities."

CAMBRIDGE, MA - September 30, 2020--The MIT Press Journal Rapid Reviews: COVID-19 (RRC:19) has openly published the first official scholarly peer reviews of pre-print research from Li-Meng Yan, Shu Kang, Jie Guan, and Shanchang Hu that claims to show that unusual features of the SARS-CoV-2 genome suggest sophisticated laboratory modification rather than natural evolution. Reviewers Robert Gallo, Takahiko Koyama, and Adam Lauring rate the study as misleading and write that the "manuscript does not demonstrate sufficient scientific evidence to support its claims."

Find peer reviews and information about this study at Rapid Reviews website.

While this research has been widely debunked in popular media, scholarly peer review represents a different type of rebuke from the scientific community. The original study was posted on a public pre-print server without the benefit of peer review--a necessary part of the scientific publishing process in which scientists review one another's work, vetting research for accuracy and evaluating methods and evidence. Pre-prints enable researchers to share information quicker, but they have created a need for rapid and transparent peer review to correct misinformation about COVID-19 and to minimize the influence of unverified research.

"While pre-print servers offer a mechanism to disseminate world-changing scientific research at unprecedented speed, they are also a forum through which misleading information can instantaneously undermine the international scientific community's credibility, destabilize diplomatic relationships, and compromise global safety," explains the RR:C19 Editorial Office.

RR:C19 was launched in June 2020 to provide rapid and transparent peer review of COVID-19 pre-prints. When the 'Yan Report' was published in September, RR:C19 quickly sought out peer reviews from world-renowned experts in virology, molecular biology, structural biology, computational biology, vaccine development, and medicine.

These reviews are now openly published, along with a response from the RR:C19 Editorial Office, that states, "Collectively, reviewers have debunked the authors' claims that: (1) bat coronaviruses ZC45 or ZXC21 were used as a background strain to engineer SARS-CoV-2, (2) the presence of restriction sites flanking the RBD suggest prior screening for a virus targeting the human ACE2 receptor, and (3) the furin-like cleavage site is unnatural and provides evidence of engineering. In all three cases, the reviewers provide counter-arguments based on peer-reviewed literature and long-established foundational knowledge that directly refute the claims put forth by Yan et al. There was a general consensus that the study's claims were better explained by potential political motivations rather than scientific integrity."

Reviewer Dr. Robert Gallo, biomedical researcher and co-founder of The Institute of Human Virology
Evidence Scale Rating: Misleading

"Widely questionable, spurious, and fraudulent claims are made throughout the paper about the thought-to-be precursor of SARS-2, RaTG13, found in bat caves. The author's attacks include quotes which have not been referenced, including how this 'has been disputed and its truthfulness widely questioned. Soon a paper proving that will be submitted.' She then goes on to attack several genome sequences as fraudulent, ranging from pangolin coronaviruses to bat coronaviruses, again without evidence. The reference she cites for that, in fact, does not make that claim."

Reviewer Dr. Takahiko Koyama, IBM Research, Computational Biology Center
Evidence Scale Rating: Misleading

"[The] authors' speculation of furin cleavage insert PRRA in spike protein seemed quite interesting at first. Nevertheless, recently reported RmYN02 (EPI_ISL_412977), from a bat sample in Yunnan Province in 2019, has PAA insert at the same site[2]. While the authors state that RmYN02 is likely fraudulent, there are no concrete evidences to support the claim in the manuscript. In addition, argument of codon usage of arginine in PRRA is not convincing since these are likely derived from some kind of mobile elements in hosts or other pathogens. Further investigations are necessary to unravel the mystery of the PRRA insert. For these reasons, we conclude that the manuscript does not demonstrate sufficient scientific evidences to support genetic manipulation origin of SARS-CoV-2."

Reviewer Dr. Adam Lauring, University of Michigan, Internal Medicine
Evidence Scale Rating: Misleading

"A key aspect of research ethics and the responsible conduct of research is to include information on who supported the work - financially or otherwise. The authors' affiliation is the "Rule of Law Society & Rule of Law Foundation." It is not clear who supports this Foundation or what its purpose is. It is important for there to be transparency regarding research support, especially for a manuscript that is based on conjecture as opposed to data or empiricism. It is also unethical to promote what are essentially conspiracy theories that are not founded in fact."

What The Study Did: Extended follow-up of randomized clinical trial participants was used to investigate whether the risk of asthma or recurrent wheeze among young children was changed by avoiding supplementing breastfeeding with cow's milk formula after birth.

Authors: Mitsuyoshi Urashima, M.D., Ph.D., M.P.H., of the Jikei University School of Medicine in Tokyo, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2020.18534)

Editor's Note: The article includes conflicts of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.