Caroline Kumsta Archives - Sanford Burnham Prebys

Tag: Caroline Kumsta

Institute News

Women in Science event at Sanford Burnham Prebys examines how female faculty members navigate research careers

AuthorGreg Calhoun
Date

August 19, 2024

left to right Alessandra Sacco, Caroilne Kumsta, Sherine Sun and Linday Bradley sit on panel
The Women in Science event at Sanford Burnham Prebys on Monday, August 12, 2024, focused on how female faculty members at different career stages have navigated their professional journeys in academia and the life sciences.

Four panelists at different career stages shared insights and answered audience questions

Sanford Burnham Prebys held a Women in Science event on Monday, August 12, 2024. The session was in Fishman Auditorium on the Institute’s campus and focused on how female faculty members at different career stages have navigated their professional journeys in academia and the life sciences. 

Eric Wang,  PhD, an assistant professor in the Cancer Molecular Therapeutics Program at Sanford Burnham Prebys and co-chair of the Education and Training Diversity, Equity and Inclusion (DEI) Committee, opened the event and introduced the moderator, Shanshan Yin, PhD, a postdoctoral associate working in the lab of Peter D. Adams, PhD, and four panelists from Sanford Burnham Prebys: 

  • Caroline Kumsta, PhD, an assistant professor in the Development, Aging and Regeneration Program and associate dean of Student Affairs of the Graduate School of Biomedical Sciences 
  • Alessandra Sacco, PhD, the director of the Development, Aging and Regeneration Program and dean of the Graduate School of Biomedical Sciences 

Shanshan Yin, PhD, is a postdoctoral associate working in the lab of Peter D. Adams, PhD. She was the panel discussion moderator.

Work and life balance 

Yin asked the panelists to discuss how they balance their work and personal lives, and what strategies they use to restore their energy levels and maintain a positive mindset. 

“I had to learn to manage my schedule, rather than letting it manage me,” said Kumsta. “I’ve gained a greater appreciation for stepping away from problems, and I often find that I come up with new solutions during or after hiking or working out, instead of by just working more and more.” 

“Because I am setting up a new lab, it feels like I am working even more than I did as a postdoctoral fellow,” said Sun. “My persistence, curiosity and interest in the scientific process are the key drivers that are helping me as the lab gets up to speed.” 

Caregiving 

Yin followed this conversation by requesting that the panelists comment on the factors of childcare and family obligations throughout the careers of female faculty members. 

“The childcare system for working parents in the U.S. leaves a lot of room for improvement,” said Bradley. “This has not improved through the course of my career, and it is something we think about a lot within the Postdoctoral Training Advisory Group as we discuss ways to improve the experience of postdoctoral fellows at the institute.” 

Panelist Xueqin (Sherine) Sun, PhD, is an assistant professor in the Cancer Genome and Epigenetics Program.

“It can be hard to feel less productive as a scientist after having kids,” said Sun. “This is something we each have to navigate and there are no easy answers.” 

Audience questions 

Yin welcomed audience members to ask the panelists additional questions. 

Sacco fielded a question about the balancing act of working long hours for short-term gain versus the increased risk of burnout. She said, “For me, this has really happened in phases. Some parts of certain experiments or application cycles require extra effort, and you have to learn when you can pull back and have a more balanced schedule.” 

Kumsta answered a question about unrealistic expectations for postdoctoral fellows. She said, “I encourage every postdoc and principal investigator to have open and honest conversations about expectations for working hours, vacation time and weekend emails, among other topics. That won’t fix everything, but it will prevent a lot of uncertainty and build a foundation for addressing issues.” 

The panelists had noted the strong representation of male scientists and staff members in the audience. Sacco responded to a question about what male scientists could do better to improve the environment for women in the field. She said, “We should all recognize our own biases, minimize their impact when making decisions, and be good listeners to other scientists’ needs.”      

Gender and academic rank 

The event closed with a conversation about gender disparities in academic ranks at research and higher education institutions. The panelists focused on the attrition than can occur after the end of postdoctoral fellowships as a major challenge for retaining women in academic science.  

Kumsta explored some potential solutions that funders and institutions could consider. She said, “An extra year of funding for early-career female scientists and an extra year on the tenure clock may help us retain women and support their promotion from junior faculty positions. We also need to find ways to reward the extra administrative service that many female faculty members are asked to give on faculty committees.” 

Caroline Kumsta, PhD

Panelist Caroline Kumsta, PhD, is an assistant professor in the Development, Aging and Regeneration Program and associate dean of Student Affairs of the Graduate School of Biomedical Sciences.

“I think certain things are getting better, but we need to do even more to retain women in the field,” said Sun. “The National Institutes of Health allowing time and budget for childcare costs in training grants was an important step.” 

“Today’s event reminds us of the importance of speaking up,” said Sacco. “We can articulate and share our vision for a better tomorrow and work together to achieve it.” 

The Women in Science event was hosted by the Education and Training DEI Committee at Sanford Burnham Prebys and supported by the Institute’s Diversity, Equity, Inclusion and Belonging (DEIB) Council and DEIB program manager, Lauren Mitchell.  

Institute News

Caroline Kumsta awarded $2.9M to study how short-term stress improves health and life expectancy

AuthorSusan Gammon
Date

July 11, 2024

Caroline Kumsta headshot outdoors

By learning how small amounts of stress activate autophagy, researchers may create new approaches to combat age-related disease

Assistant Professor Caroline Kumsta, Ph.D., has been awarded a five-year, $2.9 million grant from the National Institute on Aging (NIA), part of the National Institutes of Health (NIH). The funding will advance research to better understand how the body’s cellular recycling system (autophagy) needs to be activated to produce long-term health benefits.

“This award will enable us to take a deeper dive into the fascinating concept of hormesis, where mild, sublethal stress leads to improved health and a longer lifespan,” says Kumsta. “Our goal with this grant is to learn more about how this is regulated, which may lead to healthier aging and improved treatments for age-related conditions.”

Like many researchers, Kumsta uses C. elegans—a tiny roundworm—as a model organism to reveal important lessons about aging and autophagy. C. elegans is a powerful tool for biological research because it shares many of the same anatomic and cell functions as humans, and their short lifespan (average 17 days) enables researchers to study how genes are activated and measure the effects in just two to three weeks.

Kumsta’s lab has previously shown how brief exposure to heat shock (stress) early in life triggers autophagy, which is crucial for maintaining cellular health and function. They identified two key transcription factors, HLH-30/TFEB and HSF-1, proteins that help turn specific genes on or off, which play a significant role in regulating autophagy and are required for these long-term benefits.

“Next, we aim to pinpoint the exact timing and specific tissues where autophagy must be activated to achieve these long-term health benefits,” says Kumsta. “We will investigate how heat shock affects autophagy-related genes over time and uncover new regulators of HLH-30/TFEB.

“Our preliminary data suggest that certain autophagy genes maintain elevated transcript levels for several days post-heat shock, indicating a sustained beneficial effect. We will use cutting-edge techniques like single-cell RNA sequencing to identify these long-term transcriptional changes and determine their roles in promoting longevity and improved proteostasis,” adds Kumsta.

By understanding the precise spatiotemporal requirements for autophagy activation, Kumsta hopes to develop innovative strategies, such as heat therapy, to enhance cellular health during aging and treat age-related diseases.

The grant, awarded by the National Institute on Aging, is titled, “Hormetic regulation of Autophagy in Aging” R01 AG083373).

Institute News

Time to talk about aging research

AuthorGreg Calhoun
Date

February 29, 2024

abstract illustration of DNA and clocks

Hundreds of scientists gather in San Diego and virtually to share knowledge on the science of aging

For scientists in San Diego and across the United States, March 6-7, 2024, is an important time to talk about developments in aging research. To kick off two scientific meetings on the subject, the NIH-funded San Diego Nathan Shock Center, a collaboration among the Salk Institute for Biological Studies, Sanford Burnham Prebys and the University of California San Diego, will host its 2024 symposium focused on the center’s primary research area, “The Heterogeneity of Aging,” on Wednesday, March 6 at the Salk Institute for Biological Studies in the Conrad T. Prebys Auditorium in La Jolla.

Just as people and organisms age at different rates, scientists have demonstrated that tissues also age at their own speeds – even some cells within tissues age at a unique pace. This phenomenon, known as heterogeneity of aging, is of great interest to researchers as it may hold clues for how to develop interventions that enable people to lead healthier lives as they age. to discuss this topic.

Caroline Kumsta, PhD, assistant professor in the Development, Aging and Regeneration Program at Sanford Burnham Prebys and associate dean of student affairs of the Institute’s Graduate School of Biomedical Sciences, will speak at the 2024 symposium about heterogeneity of aging within the process cells use to recycle or dispose of damaged DNA and other waste products. Kumsta recently coauthored a manuscript in Nature Aging that found new functions for genes involved in this waste management process, known as autophagy. Gaining a better understanding of autophagy is important as scientists have demonstrated that autophagy genes are responsible for prolonged life span in a variety of long-lived organisms. Kumsta received a pilot award from the San Diego Nathan Shock Center in 2022 to support her research on the subject.

“We’re excited to once again offer the La Jolla Aging Meeting on the next day, as we have found that many people like to attend both, and that both meetings help each other,” says Alessandra Sacco, PhD, cohost of both events, director of and professor in the Development, Aging and Regeneration Program at Sanford Burnham Prebys, and dean of the Institute’s Graduate School of Biomedical Sciences.

The 7th annual La Jolla Aging Meeting will be held on Thursday, March 7, also in Salk’s Conrad T. Prebys Auditorium. The meeting was organized by Sacco and Peter Adams, PhD, director of and professor in the Cancer Genome and Epigenetics Program at Sanford Burnham Prebys, and by Jan Karlseder, PhD, Donald and Darlene Shiley Chair, senior vice president and chief science officer at the Salk Institute. The event features mostly short talks from San Diego-based postdoctoral fellows and students researching the biology of aging. The meeting’s goal is to enable participants to meet other researchers and start new collaborations.

“The La Jolla Aging Meeting has more of a focus on early career development, so the events complement each other very well,” adds Sacco.

Three members of Sanford Burnham Prebys will be presenting at the La Jolla Aging Meeting, including Xiao Tian, PhD, who recently joined the Institute as an assistant professor in the Degenerative Diseases Program. Tian focuses on epigenomic changes and deterioration that influence age-related diseases by studying the remarkable traits of naked mole rats: They rarely get cancer. They are resistant to some types of pain. They can survive up to 18 minutes without oxygen. And compared to their rodent peers, naked mole rats age very slowly. Tian’s goal is to unravel the molecular basis of aging and develop strategies to promote a healthier, more vital lifespan.

Last year, more than 400 academics, students and trainees at every career stage gathered in person and virtually from 20 states and several countries to participate in the San Diego Nathan Shock Center “The Heterogeneity of Aging” Symposium and the La Jolla Aging Meeting.

About the San Diego Nathan Shock Center
The San Diego Nathan Shock Center (SD-NSC), led by Gerald Shadel, PhD, Audrey Geisel Chair in Biomedical Science and professor in the Molecular and Cell Biology Laboratory at the Salk Institute, was established in the fall of 2020 with the overall goal of understanding the heterogeneity of aging in order to allow development of personalized interventions to increase the number of years of healthy life. To this end, the center provides three novel scientific Research Resource Cores to develop new human cell models of aging and enable the integrated analysis of molecular, cellular and tissue heterogeneity. The SD-NSC also supports and advocates basic biology of aging research in general through the development, training and mentoring activities of a Research Development Core and robust outreach efforts. All of these activities are accomplished via a consortium of three premier research institutions on the La Jolla Research Mesa: the Salk Institute for Biological Studies, Sanford Burnham Prebys and the University of California San Diego.

Alessandra Sacco serves as director of the SD-NSC Research Development Core and Peter Adams serves as codirector of the SD-NSC Heterogeneity of Aging Core.

Institute News

The heterogeneity of aging, a symposium

AuthorScott LaFee
Date

February 9, 2024

many clock faces with different colors

Aging research is always timely, and here’s a date: On March 6, the San Diego Nathan Shock Center, a consortium of Sanford Burnham Prebys, Salk and UC San Diego, will hold its second annual Symposium on the Heterogeneity of Aging at the Salk Institute.

The day-long, hybrid program will include scientific presentations from a diverse group of researchers focused on the biology and secrets of aging, including Caroline Kumsta, PhD, co-author of a recently published paper that revealed possible novel functions for various autophagy genes, which may control different forms of disposal including misfolded proteins — and ultimately affect aging.

For more information about the symposium and to register, click here.

Institute News

Speaking of International Day of Women and Girls in Science

AuthorScott LaFee
Date

February 7, 2024

illustration of women in STEM

Designated by the United Nations, the 9th International Day of Women and Girls in Science is Sunday, February 11, preceded by two days of meetings, presentations and outreach among global leaders, with a focus on women scientific leadership in sustainable development.

The real work, of course, is what happens afterward. Women continue to be underrepresented in the science, technology, engineering and mathematics (STEM) workforce. In 2021, according to the National Center for Science and Engineering Statistics, 65% of STEM jobs in the United States were held by men, 35% by women. Less than 30% of researchers worldwide are women.

These numbers have long held sway, both in academia and industry. There has been progress, to be sure, but it has been slow and uneven, hindered by stereotypes and biases, a dearth of role models, educational differences and opportunities and sheer inertia. The hurdles to equity and equality are deep and ingrained.

Every female scientist has stories about their own efforts and struggles. We asked scientists at Sanford Burnham Prebys to recount some of theirs, the lessons learned and the challenges yet to be overcome.

A fighting chance

My personal experience can testify to the importance of appreciation of diversity.

As an international scholar, it was not always easy to navigate an entirely new culture. I remember my first few months in America when going to a restaurant felt like a small adventure. Now I look back to those days with fondness and gratitude because my mentor and colleagues showed me what an inclusive community means to a newcomer.

They encouraged my expression, valued my input and always waited with great patience when I needed a second or two to fetch a perfect word for the moment. It was their kindness that helped me through the initial adjustment period.

And then one day, I found the sense of belonging in a roaring ballpark with my lab mates around me, rooting for Giants. I am grateful that I was shown how “diversity” is done because that is exactly how I aspire to build a team in my future lab, a team where uniqueness is not only accepted but even celebrated so everyone can be at ease as themselves and feels free to explore and express no matter where they are from and what they believe.

While it is important to level the playing field for everyone, sometimes it will not suffice for a disadvantaged group until we vigorously advocate for their rights. As a woman scientist, it pains me that I have witnessed over the years so many brilliant young women who had to stop chasing their dreams at one point or another. They let go of their passion and settled for less ambitious career paths for various reasons: lack of mentorship, family responsibilities and even the pressure of conforming to social norms.

I know how hard it is to achieve success in the highly competitive realm of scientific pursuit while managing a functional family because I am too a mother of two young children. Our society asks women to juggle too many balls. It is no wonder that far fewer
women reach the promised land of professorship when roughly equal numbers of students of
both genders started out on this journey.

Shengjie Feng, PhD

Shengjie Feng, PhD
Assistant Professor
Degenerative Diseases Program

I consider it rare fortune that I have been blessed with constant guidance from mentors and unwavering support from family. It will be my mission to pass on this blessing to all the women I have the honor to work with in the future. A fighting chance is all they ask, and I will strive to be the helping hand that delivers that chance.

Mentors make a difference

Even though gender inequities in STEM are slowly improving, we still have a lot of work to do. Several studies have shown that among early career investigators, women experience a one-to-two delay in getting their first grants funded, publish fewer high-impact papers and get credited and cited less frequently for their work, as compared to men. I believe that creating awareness and building a supportive network of mentors and peers is extremely important to navigate and overcome the challenges we face in science.

I have always been fascinated by the complex mechanisms underlying disease, and specifically cancer. I was the first woman in my family to attend university and to pursue a PhD degree in the biomedical sciences.

With few women in leading academic positions that could serve as a role model, I found it difficult to believe that I could someday be successful as a scientist. Fortunately, over the past years I have had the opportunity to work with some incredible female scientists who helped me along the way.

During my master’s program at Utrecht University, I secured an internship in the laboratory of the late-Professor Zena Werb at University of California San Francisco. She had an incredible track record of mentoring early career researchers and was a big advocate for (young) women in science.

For my graduate training, I joined the lab of Professor Karin de Visser at the Netherlands Cancer Institute in Amsterdam. Karin is an incredibly smart and determined principal investigator who taught me to be resilient and persistent, and the importance of always following the data. The mentorship and support of these remarkable women has been instrumental in the decisions I have made to date in my career, and I am grateful for the opportunity to have trained under them.

Kelly Kersten, PhD

Kelly Kersten, PhD
Assistant Professor
Cancer Metabolism and Microenvironment Program

We all need some support and encouragement to excel in our scientific journey. It’s never too early to start building your network of mentors, peers and sponsors to support you along the way.

We’re still a minority

During my PhD and postdoctoral training, I have been lucky to have two amazing female scientists as mentors, who made it seem easy to be successful in science. The reality however is that female scientists get less lab space, have a longer path to their first independent research grant and have a more extended review process for their publications than their male peers.

To achieve equitable treatment and full inclusion of women in science, we have to constantly examine and dismantle the barriers that create these disparities. At Sanford Burnham Prebys, we have started to work toward a more welcoming environment for everyone, including women.

The truth is, however, that we’re still a minority here, and we, as women in science, still have to push for fairer policies and to make sure our voices are heard and valued. Personally, I am involved in outreach programs to get young girls excited about science. Seeing their excitement when they learn something new in the lab reminds me why this is so important, and I get excited when I see the next generation of girls who can see themselves as scientists without a second thought.

Caroline Kumsta, PhD

Caroline Kumsta, PhD
Assistant Professor
Development, Aging and Regeneration Program

Note: On February 14, there will be a roundtable discussion on the topic of women and girls in science from 9:30 a.m. to 10:30 a.m. in Fishman Auditorium. Coffee, pastries and fruit will be served. Click here to RSVP.

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New roles for autophagy genes in cellular waste management and aging

AuthorCommunications
Date

January 3, 2024

3D illustration Mechanism of cellular authophagy, illustration for Nobel Prize Award in Medicine 2016

Autophagy genes help extrude protein aggregates from neurons in the nematode C. elegans.

Autophagy, which declines with age, may hold more mysteries than researchers previously suspected. In the January 4 issue of Nature Aging, it was noted that scientists from the Buck Institute, Sanford Burnham Prebys and Rutgers University have uncovered possible novel functions for various autophagy genes, which may control different forms of disposal including misfolded proteins—and ultimately affect aging.

“While this is very basic research, this work is a reminder that it is critical for us to understand whether we have the whole story about the different genes that have been related to aging or age-related diseases,” said Professor Malene Hansen, PhD, Buck’s chief scientific officer, who is also the study’s co-senior author. “If the mechanism we found is conserved in other organisms, we speculate that it may play a broader role in aging than has been previously appreciated and may provide a method to improve life span.”

These new observations provide another perspective to what was traditionally thought to be occurring during autophagy.

Autophagy is a cellular “housekeeping” process that promotes health by recycling or disposing of damaged DNA and RNA and other cellular components in a multi-step degradative process. It has been shown to be a key player in preventing aging and diseases of aging, including cancer, cardiovascular disease, diabetes and neurodegeneration. Notably, research has shown that autophagy genes are responsible for prolonged life span in a variety of long-lived organisms.

The classical explanation of how autophagy works is that the cellular “garbage” to be dealt with is sequestered in a membrane-surrounded vesicle, and ultimately delivered to lysosomes for degradation. However, Hansen, who has studied the role of autophagy in aging for most of her career, was intrigued by an accumulation of evidence that indicated that this was not the only process in which autophagy genes can function.

“There had been this growing notion over the last few years that genes in the early steps of autophagy were ‘moonlighting’ in processes outside of this classical lysosomal degradation,” she said. “Additionally, while it is known that multiple autophagy genes are required for increased life span, the tissue-specific roles of specific autophagy genes are not well defined.”

To comprehensively investigate the role that autophagy genes play in neurons—a key cell type for neurodegenerative diseases—the team analyzed Caenorhabditis elegans, a tiny worm that is frequently used to model the genetics of aging and which has a very well-studied nervous system. The researchers specifically inhibited autophagy genes functioning at each step of the process in the neurons of the animals, and found that neuronal inhibition of early-acting, but not late-acting, autophagy genes, extended life span.

An unexpected aspect was that this life span extension was accompanied by a reduction in aggregated protein in the neurons (an increase is associated with Huntington’s disease, for example), and an increase in the formation of so-called exophers. These giant vesicles extruded from neurons were identified in 2017 by Monica Driscoll, PhD, a collaborator and professor at Rutgers University.

“Exophers are thought to be essentially another cellular garbage disposal method, a mega-bag of trash,” said Caroline Kumsta, PhD, co-senior author and assistant professor at Sanford Burnham Prebys “When there is either too much trash accumulating in neurons, or when the normal ‘in-house’ garbage disposal system is broken, the cellular waste is then being thrown out in these exophers.

“Interestingly, worms that formed exophers had reduced protein aggregation and lived significantly longer. This finding suggests a link between this process of this massive disposal event to overall health,” said Kumsta. The team found that this process was dependent on a protein called ATG-16.2.

The study identified several new functions for the autophagy protein ATG-16.2, including in exopher formation and life span determination, which led the team to speculate that this protein plays a nontraditional and unexpected role in the aging process. If this same mechanism is operating in other organisms, it may provide a method of manipulating autophagy genes to improve neuronal health and increase life span.

“But first we have to learn more—especially how ATG-16.2 is regulated and whether it is relevant in a broader sense, in other tissues and other species,” Hansen said. The Hansen and Kumsta teams are planning on following up with a number of longevity models, including nematodes, mammalian cell cultures, human blood and mice.

“Learning if there are multiple functions around autophagy genes like ATG-16.2 is going to be super important in developing potential therapies,” Kumsta said. “It is currently very basic biology, but that is where we are in terms of knowing what those genes do.”

The traditional explanation that aging and autophagy are linked because of lysosomal degradation may need to expand to include additional pathways, which would have to be targeted differently to address the diseases and the problems that are associated with that. “It will be important to know either way,” Hansen said. “The implications of such additional functions may hold a potential paradigm shift.” 
 
DOI: 10.1038/s43587-023-00548-1

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Do worms get stressed? We asked an expert

AuthorMiles Martin
Date

April 19, 2023

Nematodes under a microscope

The National Institutes of Health recognizes April as National Stress Awareness Month, with the goal of bringing awareness to the health impact of stress.

Stress comes in many forms—from the psychological stress we experience during difficult moments to the biological stress in our smallest cells. At Sanford Burnham Prebys, Assistant Professor Caroline Kumsta, PhD, uses small worms (nematodes) to study the negative relationship between cellular stress and aging (yes, aging can be stressful!). On the flip side, she’s also exploring how we can use small amounts of stress to improve health and potentially treat neurodegenerative diseases. 

We spoke to Kumsta about her research to learn more about how nematodes, stress and neurodegenerative diseases are all related.

Why do you work with nematodes?
Nematodes are very good for aging research because they have a short life span—only a few weeks—so we can measure the effects of aging within a reasonable amount of time. Another reason why we like these worms is because we can measure stress responses in more than individual cells. We can use nematodes to study broader, more systemic responses, as well as how stress responses are communicated from tissue to tissue. We can only see these effects if we look at how stress responses are orchestrated across the entire organism. Even though worms don’t look like us, a lot of the basic biological machinery we study is the same as in humans because stress responses evolved a long, long time ago.

How do worms help you study aging and cellular stress responses?
“What doesn’t kill you makes you stronger” is true in biology—in other words, small amounts of stress can actually be beneficial for organisms, including humans. We’re studying this idea in nematodes by giving them a small heat shock early in their lives, almost like giving them a few minutes in a sauna. The heat triggers stress responses in the worms at the cellular level, and one of these responses is that the worms’ cells induce a cellular recycling process, called autophagy. Autophagy recycles cellular components and helps keep cells healthy and free from debris. This is a beneficial process that helps increase the life span of the worms. My team is exploring how this process works and figuring out how we can use it to fight diseases.

How can your work in nematodes help us study human diseases?
Our main target is neurodegenerative diseases. One of the drivers of diseases like Alzheimer’s, Parkinson’s or Huntington’s disease is that proteins accumulate in the brain in aggregates or clumps. We’ve seen that nematodes that have had a heat shock early in their lives have reduced clumping of disease-relevant proteins. This is because when autophagy kicks in as a stress response, it helps slow the accumulation of these clumpy proteins. We’re ultimately looking for ways to boost the cellular recycling process in humans as a way to treat degenerative diseases. We can imagine heat therapy as a treatment intervention, and we are currently developing methods of measuring autophagy status in humans so that we will be able to test potential interventions.