You have full access to this article via your institution. Download PDF Recent publications present an opportunity to reflect on the importance of sharing negative results and the

opportunity this presents for growth as a scientist and as a scientific mentor. We share these perspectives, acknowledging that they may not be generalizable to other research teams. From

the mentor’s point of view: Every time I arrive at the end of an experiment or a clinical trial, I hold my breath as I await the analysis of results that may have taken years to acquire—the

stakes are so high, that I often ask for three independent analyses. Sometimes, I experience a surreal moment of relief and elation because my hypothesis turned out to be correct—and I made

re-assessment, however, I start worrying about how I will convince a journal to publish my study results, so that another person asking the same question might learn from my study and

answers. Most often, the publication system is skewed towards positive results or successful studies. But there are still journals publishing negative results, and I am grateful to their

editors, who not only help science progress but also help me model what being a scientist is for my mentees. When we publish negative results, we demonstrate the following: * 1. Integrity to

the scientific method—we are trying to support OR refute our hypothesis, but not prove that we are always right. I am grateful to the editors who allowed me to publish an early negative

study showing that cry amplitude did not predict the intensity of nociception in typical newborns. When my initial hypothesis predicting a positive association was wrong, I could have sliced

and diced my data and focused solely on the fact that newborns could differentiate cold from pain—a finding that was exciting, but secondary. While other cry characteristics might prove

useful in evaluating pain (e.g., fundamental frequency), and other scientists have gone on to investigate these factors, our initial study showed that term newborns could experience painful

somatosensory stimuli without crying or even grimacing.1 * 2. Responsible use of resources—we work in a field where there are neither enough funds nor time to investigate the million

questions we generate every day. By letting funders know the results, we keep them from allocating their limited resources to performing the same experiments over. We help other

investigators not waste their time and resources in performing the same experiments, and sometimes we may even prevent potentially harmful side effects. I will always greatly admire Dr. Juul

and Dr. Wu for publishing the results of the HEAL trial in their unvarnished accuracy.2 Because of their courage, and their well-designed and executed science, they showed erythropoietin

combined with hypothermia does not improve developmental outcomes in the way many had hoped. They also helped point out potential safety risks that should be considered in neonatal trials of

erythropoietin with other purposes. As a result of their work, limited research resources can now be re-allocated to future new treatments for hypoxic–ischemic encephalopathy. * 3. Failure

to prove a hypothesis as a true opportunity—as senior researchers, we are all used to failure and have learned to leverage it as an opportunity. We teach the importance of failed experiments

to those we mentor when we acknowledge it publicly, and then move on from there to rigorously extract what we can from our science. We pick ourselves up off the floor and rise in search of

new ideas, demonstrating resilience. One of the most remarkable articles I read illustrating this concept was directed by Dr. Yoder, whose team carefully examined the results of a randomized

control trial of an early intervention for Autism Spectrum Disorders (ASD) that produced negative results for its primary hypothesis, as intervention group assignment did not improve

outcomes. However, leveraging the study data, the team was able to examine causation in a pathway from early social motivation to receptive language outcomes at 2 years. Using modern

mediation analyses, the team demonstrated intermediate steps of intentional communication, which in turn elicited parental linguistic input resulting in the spectrum of observed outcomes.3

The manuscript that stemmed from the initial one with negative results shed light on mechanistic pathways for the disorder, critically confirming one of the three current ASD theoretical

models as more valid than the others. From the mentee’s point of view: As a junior investigator, I sometimes feel pressure to not only “prove” my research hypothesis but also to prove myself

as a scientist. After all, the countless hours spent reading, planning, designing, revising, collecting, and analyzing have all been leading to this point—the results—and with so much at

stake, it becomes easy to conflate the success of an experiment with personal success as an investigator. But sometimes, experimental results do not support our hypothesis. And while being

wrong might lead us to think the experiment was a failure or lead us to question what _we_ did wrong or how we personally failed, it is important to recognize that even when our experiments

“fail,” we ourselves are not “failures.” As Bearer and Molloy emphasize, “the criteria for what constitutes failure is actually a personal choice. Each individual decides when they have met

their criteria for failure.”4 So, after some initial discouragement and wondering how to possibly salvage what feels like wasted time and effort, I rely on the mentorship and guidance I have

received throughout my training and reframe my perception of “negative” results as the following: * 1. An opportunity to ask new questions—negative results provide an opportunity to think

critically about where we may have been wrong, where we might make a modification in the future, and perhaps even drive new questions we had not considered previously. Negative results have

value, and we ourselves have value as scientists-in-training. * 2. The understanding that reward comes with risk—negative results teach us to have a healthy respect for the unknown at the

same time as we tackle it. Developing hypotheses based on the current evidence involves a degree of uncertainty; risk in research is what makes it inherently exciting. My mentor often quotes

her mentor, Dr. Judy Aschner, who told her that there are those who _RE_-search and those who re-_SEARCH_—the second group pushes their curiosity to the edge of what seems possible, into

innovation. However, anyone who seeks out the thrill of discovery must also be prepared to contend with the consequences. By preparing for our results at the outset of an experiment,

including the possible implications of negative results, we can enjoy conducting re-_SEARCH_ even more. (As trainees, it also prevents us from anxiously wondering if we will need to add

unplanned years to our training. Yes, it is possible to earn that degree even if your results did not support your hypothesis.). * 3. The importance of being earnest—negative results can be

proof of the quality of our work. Throughout our training, the ultimate goal is to establish ourselves as honest researchers whose science is sound. If we don’t report negative results, we

risk the scientific community losing faith in our integrity as researchers. While these sentiments may seem like the naive musings of an early career researcher, I know from observing more

senior researchers that they firmly believe this as well. In fact, some of the most critical and frequent discussions in our laboratory concern data quality and verification, with no

compromise allowed. We hold ourselves and each other accountable and develop systematic safeguards to ensure our processes maintain the highest degree of rigor. Because of this, we know that

when our data are negative, they are unequivocally so. And if the science is sound, the science should be disseminated. From both: When we publish our negative results, even when it is

challenging, we make a difference, not in the way we intended, but still a difference—to Science, to our colleagues, to our institutions, and to those who will come after us and make their

own difference. We are privileged to be explorers and to follow our passion and curiosity, even when they lead us to unexpected paths, full of negative results. REFERENCES * Maitre, N. L. et

al. Cry presence and amplitude do not reflect cortical processing of painful stimuli in newborns with distinct responses to touch or cold. _Arch. Dis. Child. Fetal Neonatal Ed._ 102,

F428–F433 (2017). Article  PubMed  Google Scholar  * Wu et al. Trial of erythropoietin for hypoxic-ischemis encephalopathy in newborns. _N. Engl. J. Med._ 387, 148–159 (2022). Article  CAS 

PubMed  PubMed Central  Google Scholar  * Su, P. L., Rogers, S. J., Estes, A. & Yoder, P. The role of early social motivation in explaining variability in functional language in toddlers

with autism spectrum disorder. _Autism_ 25, 244–257 (2020). Article  PubMed  PubMed Central  Google Scholar  * Bearer, C. F. & Molloy, E. J. The willingness to risk failure: advice to

Early Career Investigators. _Pediatr. Res._ 92, 1490–1491 (2022). Article  PubMed  Google Scholar  Download references FUNDING Funding N.L.M.’s time and efforts are funded by NIH

5R01HD081120-07 and 5R01HC093706-05 and a Cerebral Palsy Foundation Network Award. C.P.K.’s time and efforts are partially funded by NIH 5R01HC093706-05. AUTHOR INFORMATION AUTHORS AND

AFFILIATIONS * Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA Nathalie L. Maitre & Caitlin P. Kjeldsen * Children’s Healthcare of Atlanta, Atlanta, GA,

USA Nathalie L. Maitre * Department of Speech and Hearing Science, The Ohio State University, Columbus, OH, USA Caitlin P. Kjeldsen Authors * Nathalie L. Maitre View author publications You

can also search for this author inPubMed Google Scholar * Caitlin P. Kjeldsen View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS N.L.M. and

C.P.K. contributed equally to the drafting and revisions of this manuscript. CORRESPONDING AUTHOR Correspondence to Nathalie L. Maitre. ETHICS DECLARATIONS COMPETING INTERESTS N.L.M. is a

co-founder and has equity in SmallTalk and a patent licensed to Enlighten Mobility. C.P.K. previously consulted for Thrive Neuromedical. ADDITIONAL INFORMATION PUBLISHER’S NOTE Springer

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ARTICLE Maitre, N.L., Kjeldsen, C.P. On being earnest: a mentor and her mentee’s perspective. _Pediatr Res_ 94, 1596–1597 (2023). https://doi.org/10.1038/s41390-023-02702-2 Download citation

* Received: 31 May 2023 * Accepted: 05 June 2023 * Published: 22 June 2023 * Issue Date: November 2023 * DOI: https://doi.org/10.1038/s41390-023-02702-2 SHARE THIS ARTICLE Anyone you share

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