The origins of unpredictability in life outcome prediction tasks.

Why are some life outcomes difficult to predict? We investigated this question through in-depth qualitative interviews with 40 families sampled from a multidecade longitudinal study. Our sampling and interviewing process was informed by the earlier efforts of hundreds of researchers to predict life outcomes for participants in this study. The qualitative evidence we uncovered in these interviews combined with a mathematical decomposition of prediction error led us to create a conceptual framework. Our specific evidence and our more general framework suggest that unpredictability should be expected in many life outcome prediction tasks, even in the presence of complex algorithms and large datasets. Our work provides a foundation for future empirical and theoretical work on unpredictability in human lives.

The relationship between unpredictability in childhood and depression among college students: the mediating roles of coping style and resilience.

BACKGROUND: According to previous studies, unpredictability in childhood could significantly increase the risk of depression in adulthood. Only a few studies have explored the relationship between these two variables in China. This paper aims to explore the relationship between unpredictability in childhood and depression and examine the mediating roles of coping styles and resilience. METHODS: We investigated 601 college students, who had an average age of 19.09 (SD = 2.78) years. Participants completed questionnaires regarding unpredictability in childhood, coping style, resilience, and depression. We analyzed survey data using the bias-corrected bootstrap method. RESULTS: The findings revealed a significant positive association between unpredictability in childhood and depression among college students. Mature coping style, immature coping style, and resilience were found to mediate this relationship independently. Furthermore, the study unveiled a serial mediation process, wherein both mature and immature coping styles, followed by resilience, sequentially mediate the relationship between unpredictability in childhood and depression, underscoring the complex interplay between these variables. CONCLUSIONS: The results indicated that the risk of depression among college students who have experienced unpredictable childhood should be valued. Attention to coping styles and resilience should be paid to decrease depression among college students who have experienced unpredictable childhood.

Intolerance of uncertainty and negative emotions among high school art students during COVID-19 pandemic: a moderated mediation analysis.

Objectives: A number of high school art students experience negative emotions during their preparation for the art college entrance examination, characterized by worries and fear of uncertainty. Therefore, how individual difference factors, such as intolerance of uncertainty, affect the negative emotions of students needs to be examined. Inspired by the integrative model of uncertainty tolerance, the current study seeks to explain the association between intolerance of uncertainty and negative emotions by testing the potential mediating role of psychological capital and the moderating role of family functioning. Patients and methods: A total of 919 Chinese high school art students (Mage = 18.50 years, range = 16-22) participated from November 2022 to December 2022. Convenience sampling strategies were used. The participants were asked to complete the measures of intolerance of uncertainty scale, psychological capital questionnaire, depression anxiety stress scale, and family adaptability and cohesion evaluation scale. The data were analyzed using Pearson's r correlations and moderated mediation analysis. Results: Results showed that intolerance of uncertainty was positively associated with negative emotions but negatively associated with psychological capital, which in turn, was negatively associated with negative emotions. Psychological capital mediated the indirect link of intolerance of uncertainty with negative emotions. Family functioning buffered the impact of psychological capital on negative emotions. Conclusion: This study can enhance our understanding of the intolerance of uncertainty on negative emotions and provide insights on interventions for high school art students' negative emotions for educators. The interventions targeting intolerance of uncertainty, psychological capital and family functioning may be beneficial in reducing the effect of intolerance of uncertainty on negative emotions faced by high school art students.

How and why do doctors communicate diagnostic uncertainty: An experimental vignette study.

BACKGROUND: Diagnostic uncertainty is common, but its communication to patients is under-explored. This study aimed to (1) characterise variation in doctors' communication of diagnostic uncertainty and (2) explore why variation occurred. METHODS: Four written vignettes of clinical scenarios involving diagnostic uncertainty were developed. Doctors were recruited from five hospitals until theoretical saturation was reached (n = 36). Participants read vignettes in a randomised order, and were asked to discuss the diagnosis/plan with an online interviewer, as they would with a 'typical patient'. Semi-structured interviews explored reasons for communication choices. Interview transcripts were coded; quantitative and qualitative (thematic) analyses were undertaken. RESULTS: There was marked variation in doctors' communication: in their discussion about differential diagnoses, their reference to the level of uncertainty in diagnoses/investigations and their acknowledgement of diagnostic uncertainty when safety-netting. Implicit expressions of uncertainty were more common than explicit. Participants expressed both different communication goals (including reducing patient anxiety, building trust, empowering patients and protecting against diagnostic errors) and different perspectives on how to achieve these goals. Training in diagnostic uncertainty communication is rare, but many felt it would be useful. CONCLUSIONS: Significant variation in diagnostic uncertainty communication exists, even in a controlled setting. Differing communication goals-often grounded in conflicting ethical principles, for example, respect for autonomy versus nonmaleficence-and differing ideas on how to prioritise and achieve them may underlie this. The variation in communication behaviours observed has important implications for patient safety and health inequalities. Patient-focused research is required to guide practice. PATIENT OR PUBLIC CONTRIBUTION: In the design stage of the study, two patient and public involvement groups (consisting of members of the public of a range of ages and backgrounds) were consulted to gain an understanding of patient perspectives on the concept of communicating diagnostic uncertainty. Their feedback informed the formulations of the research questions and the choice of vignettes used.

Correlation between uncertainty stress and depression among healthcare professionals in China: a nationwide cross-sectional survey.

OBJECTIVE: This study investigated the correlation between uncertainty stress (US) and depression among healthcare professionals (HCPs) in China. DESIGN, SETTINGS AND PARTICIPANTS: A cross-sectional online survey was conducted by recruiting HCPs from three provinces in China (central, eastern and western) through purposive sampling between 29 September 2022 and 18 January 2023. US was measured using the Life Stress Questionnaire and depression was measured using the Patient Health Questionnaire-9. In total, 2976 questionnaires were deemed valid. PRIMARY AND SECONDARY OUTCOME: This study examined the prevalence of US and depression among HCPs in China; the correlating sociodemographic traits; and the correlation between US and depression. RESULTS: The prevalence of US and depression among HCPs in China was 26.54% (790 out of 2976) and 71.63% (2132 out of 2976). Binary logistic analysis revealed that individuals with graduate degrees (OR: 1.83; 95% CI 1.07 to 3.11; p<0.05), central China (OR: 1.75; 95% CI 1.36 to 2.24; p<0.01), primary medical institutes (OR: 1.33; 95% CI 1.03 to 1.72; p<0.05), secondary medical institutes (OR: 1.30; 95% CI 1.01 to 1.68; p<0.05), an annual income of less than ¥50 000 (OR: 1.85; 95% CI 1.26 to 2.73; p<0.01) and an income range of ¥50 000-¥99 999 (OR: 1.49; 95% CI 1.10 to 2.03; p<0.05) were associated with a higher likelihood of US. The adjusted logistic regression model demonstrated that HCPs with higher US had a greater likelihood of depression (adjusted OR: 5.02; 95% CI 3.88 to 6.50; p<0.01). The increase in the US score was paralleled by an increased depression score (beta (B): 1.32; 95% CI 1.25 to 1.39; p<0.01). CONCLUSION: These findings reveal a significant correlation between US and depression among HCPs and suggest that improving the management of US may help reduce the prevalence of depression among HCPs.

Large environmental changes reduce valence-dependent belief updating.

When updating beliefs, humans tend to integrate more desirable information than undesirable information. In stable environments (low uncertainty and high predictability), this asymmetry favors motivation towards action and perceived self-efficacy. However, in changing environments (high uncertainty and low predictability), this process can lead to risk underestimation and increase unwanted costs. Here, we examine how people (n = 388) integrate threatening information during an abrupt environmental change (mandatory quarantine during the COVID-19 pandemic). Given that anxiety levels are associated with the magnitude of the updating belief asymmetry; we explore its relationship during this particular context. We report a significant reduction in asymmetrical belief updating during a large environmental change as individuals integrated desirable and undesirable information to the same extent. Moreover, this result was supported by computational modeling of the belief update task. However, we found that the reduction in asymmetrical belief updating was not homogeneous among people with different levels of Trait-anxiety. Individuals with higher levels of Trait-anxiety maintained a valence-dependent updating, as it occurs in stable environments. On the other hand, updating behavior was not associated with acute anxiety (State-Anxiety), health concerns (Health-Anxiety), or having positive expectations (Trait-Optimism). These results suggest that highly uncertain environments can generate adaptive changes in information integration. At the same time, it reveals the vulnerabilities of individuals with higher levels of anxiety to adapt the way they learn.

Decision-making under conditions of explicit risk and uncertainty in autistic and typically developing adolescents and young adults.

Adolescence has been characterized as a period of risky and possibly suboptimal decision-making, yet the development of decision-making in autistic adolescents is not well understood. To investigate decision-making in autism, we evaluated performance on 2 computerized tasks capturing decision-making under explicit risk and uncertainty in autistic and non-autistic adolescents/young adults ages 12-22 years. Participants completed the Game of Dice Task (32 IQ-matched participant pairs) to assess decision-making under explicit risk and the modified Iowa Gambling Task (35 IQ-matched pairs) to assess decision-making under uncertainty. Autistic participants overall made riskier decisions than non-autistic participants on the Game of Dice Task, and the odds of making riskier decisions varied by age and IQ. In contrast, the autistic group showed comparable levels of learning over trial blocks to the non-autistic group on the modified Iowa Gambling Task. For both tasks, younger autistic participants performed poorer than their non-autistic counterparts, while group differences diminished in older ages. This age-related pattern suggests positive development during adolescence on risk assessment and decision-making in autism but also implies differential developmental trajectories between groups. These findings also suggest differential performance by the risk type, with additional complex influences of IQ and fluid cognition, which warrants further investigations.

Verbal Probability Terms for Communicating Clinical Risk - a Systematic Review.

Verbal probability expressions such as 'likely' and 'possible' are commonly used to communicate uncertainty in diagnosis, treatment effectiveness as well as the risk of adverse events. Probability terms that are interpreted consistently can be used to standardize risk communication. A systematic review was conducted. Research studies that evaluated numeric meanings of probability terms were reviewed. Terms with consistent numeric interpretation across studies were selected and were used to construct a Visual Risk Scale. Five probability terms showed reliable interpretation by laypersons and healthcare professionals in empirical studies. 'Very Likely' was interpreted as 90% chance (range 80 to 95%); 'Likely/Probable,' 70% (60 to 80%); 'Possible,' 40% (30 to 60%); 'Unlikely,' 20% (10 to 30%); and 'Very Unlikely' with 10% chance (5% to 15%). The corresponding frequency terms were: Very Frequently, Frequently, Often, Infrequently, and Rarely, respectively. Probability terms should be presented with their corresponding numeric ranges during discussions with patients. Numeric values should be presented as X-in-100 natural frequency statements, even for low values; and not as percentages, X-in-1000, X-in-Y, odds, fractions, 1-in-X, or as number needed to treat (NNT). A Visual Risk Scale was developed for use in clinical shared decision making.

Distinct neural markers of evidence accumulation index metacognitive processing before and after simple visual decisions.

Perceptual decision-making is affected by uncertainty arising from the reliability of incoming sensory evidence (perceptual uncertainty) and the categorization of that evidence relative to a choice boundary (categorical uncertainty). Here, we investigated how these factors impact the temporal dynamics of evidence processing during decision-making and subsequent metacognitive judgments. Participants performed a motion discrimination task while electroencephalography was recorded. We manipulated perceptual uncertainty by varying motion coherence, and categorical uncertainty by varying the angular offset of motion signals relative to a criterion. After each trial, participants rated their desire to change their mind. High uncertainty impaired perceptual and metacognitive judgments and reduced the amplitude of the centro-parietal positivity, a neural marker of evidence accumulation. Coherence and offset affected the centro-parietal positivity at different time points, suggesting that perceptual and categorical uncertainty affect decision-making in sequential stages. Moreover, the centro-parietal positivity predicted participants' metacognitive judgments: larger predecisional centro-parietal positivity amplitude was associated with less desire to change one's mind, whereas larger postdecisional centro-parietal positivity amplitude was associated with greater desire to change one's mind, but only following errors. These findings reveal a dissociation between predecisional and postdecisional evidence processing, suggesting that the CPP tracks potentially distinct cognitive processes before and after a decision.

Another nursing is possible: Ethics, political economies, and possibility in an uncertain world.

Overtaxed by the realities laid bare in the pandemic, nursing has imminent decisions to make. The exigencies of pandemic times overextend a health care infrastructure already groaning under the weight of inequitable distribution of resources and care commodified for profit. We can choose to prioritise different values. Invoking philosopher of science Isbelle Stengers's manifesto for slow science, this is not the only nursing that is possible. With this paper, I pick up threads of nursing's historical ontology, drawing previous scholarship on the historical narratives nurses use to understand themselves. Peeling back nursing's myth to alternate points of origin allows me to consider alternate lines of flight, a speculative adventure in paths not taken but paths that exist nonetheless. I go on to examine what a collective ethic of nursing could be, when we make space for these alternate histories, considering the confluences and conflicts that enable nurses to care and those that inhibit them from doing so. The imperative for this lies in the central importance of the reproductive labour of nursing health care, which leads me to a critique of nursing's capitulation to the pressures of late stage capitalism. This is a problem with ethical and ontological implications both for nursing, and also for those who require nursing care, an imperative to think about the kinds of present/futures for health, care, and health care we might cocreate in collaboration and solidarity with the communities in which nurses are imbricated, shedding the trappings of neoliberalism. There is significant power in the vision and praxis of 28 million nurses and midwives worldwide. Our ethics can guide our imagination which can in turn create possibility. This kind of endeavour-that of dreams and imagination-leads us to what could be, if only we leap.

The perpetual need of randomized clinical trials: challenges and uncertainties in emulating the REDUCE-AMI trial.

Trial emulations in observational data analyses can complement findings from randomized clinical trials, inform future trial designs, or generate evidence when randomized studies are not feasible due to resource constraints and ethical or practical limitations. Importantly, trial emulation designs facilitate causal inference in observational data analyses by enhancing counterfactual thinking and comparisons of real-world observations (e.g. Mendelian Randomization) to hypothetical interventions. In order to enhance credibility, trial emulations would benefit from prospective registration, publication of statistical analysis plans, and subsequent prospective benchmarking to randomized clinical trials prior to their publication. Confounding by indication, however, is the key challenge to interpreting observed intended effects of an intervention as causal in observational data analyses. We discuss the target trial emulation of the REDUCE-AMI randomized clinical trial (ClinicalTrials.gov ID NCT03278509; beta-blocker use in patients with preserved left ventricular ejection fraction after myocardial infarction) to illustrate the challenges and uncertainties of studying intended effects of interventions without randomization to account for confounding. We furthermore directly compare the findings, statistical power, and clinical interpretation of the results of the REDUCE-AMI target trial emulation to those from the simultaneously published randomized clinical trial. The complexity and subtlety of confounding by indication when studying intended effects of interventions can generally only be addressed by randomization.

How Chronic Pain Patients' and Physicians' Communication Influences Patients' Uncertainty: A Pre- and Post-Consultation Study.

Chronic pain is a health problem that is difficult to diagnose, treat, and manage, partly owing to uncertainty surrounding ambiguous causes, few treatment options, and frequent misunderstandings in clinical encounters. Pairing uncertainty management theory with medical communication competence, we predicted that both physicians and patients are influential to patients' uncertainty appraisals and uncertainty management. We collected pre- and post-consultation data from 200 patients with chronic neck and spine/back pain and their physicians. Patients' reports of their physician's communication were a consistent predictor of their post-consultation uncertainty outcomes. Physicians' reports of both their own and patients' communication competence were associated with patients' positive uncertainty appraisals. Physicians' reports of patients' communication competence were also associated with reductions in patients' uncertainty. Findings illustrate how both interactants' perceptions of communication competence-how they view their own (for physicians) and the other's-are associated with patients' post-consultation outcomes.

Understanding the Impact of Communicating Uncertainty About COVID-19 in the News: Randomized Between-Subjects Factorial Experiment.

BACKGROUND: Whether and how the uncertainty about a public health crisis should be communicated to the general public have been important and yet unanswered questions arising over the past few years. As the most threatening contemporary public health crisis, the COVID-19 pandemic has renewed interest in these unresolved issues by both academic scholars and public health practitioners. OBJECTIVE: The aim of this study was to investigate the impact of communicating uncertainty about COVID-19-related threats and solutions on individuals' risk perceptions and misinformation vulnerability, as well as the sequential impact of these effects on health information processing and preventative behavioral intentions. METHODS: A 2×2 (threat uncertainty [presence vs absence]×solution uncertainty [presence vs absence]) full-fractional between-subjects online experiment was conducted with 371 Chinese adults. Focusing on the discussion of whether the asymptomatic cases detected during the COVID-19 pandemic would further lead to an uncontrolled pandemic, news articles were manipulated in terms of whether the infectiousness of asymptomatic cases and the means to control the transmission are presented in terms of their certainty or uncertainty. Participants were randomly assigned to one of the four experimental conditions, being instructed to read one news article. After reading the news article assigned, participants were asked to respond to a series of questions to assess their cognitive and behavioral responses. RESULTS: Individuals were more susceptible to believing false COVID-19-related information when a certain threat and uncertain solution were framed in the news article. Moreover, individuals' perceptions of crisis severity increased when exposed to news information containing uncertain solutions. Both misinformation vulnerability and perceived severity were positively associated with information processing. Information seeking was positively associated with protective behavioral intention, whereas information avoidance was negatively associated with protective behavioral intention. CONCLUSIONS: Our findings imply that uncertainty, depending on its aspect, can be effectively communicated to the public during an emerging public health crisis. These results have theoretical and practical implications for health communicators and journalists. Given its limited influence on individuals' cognitive and behavioral responses, uncertainty related to a health threat should be disseminated to meet the public's expectation of information transparency. However, caution is advised when communicating uncertainty related to potential solutions, as this factor exhibited a mixed impact on individual responses during a crisis.

Residents' willingness towards first-contact with primary health care under uncertainty in healthcare: a cross-sectional study in rural China.

OBJECTIVE: To estimate Chinese rural residents' willingness degree of initially contacting primary healthcare (PHC) under uncertainty in healthcare and to explore its influencing factors. SETTING: This study collected primary data from rural residents in Dangyang, Hubei Province in China. PARTICIPANTS: The study investigated 782 residents and 701 finished the survey. The response rate was 89.64%. A further 27 residents failed the internal consistency test, so the effective sample size was 674. DESIGN: In this cross-sectional study, residents' willingness was reflected by the threshold of disease severity for PHC (TDSP), the individual maximal disease scope for considering PHC based on residents' decision-making framework. TDSP was measured through scenario tests. Univariate analysis and unordered multiple logistic regression were used to explore the influencing factors of three-level TDSP: low, general, and high. RESULTS: Only 28.2% of respondents had high TDSP and high willingness towards PHC. Compared with general TDSP, respondents who were younger than 40 (OR 7.344, 95% CI 2.463 to 21.894), rich (OR 1.913, 95% CI 1.083 to 3.379), highly risk-averse (OR 1.958, 95% CI 1.016 to 3.774), had substitute medical decision-maker (OR value of parent/child was 2.738, 95% CI 1.386 to 5.411) and had no visits to PHC in the last 6 months (OR 2.098, 95% CI 1.316 to 3.346) tended to have low TDSP and low willingness towards PHC. Compared with general TDSP, no factors were found to significantly influence respondents' high TDSP. CONCLUSIONS: TDSP can be a good indicator of residents' willingness. TDSP results demonstrate rural residents' generally low willingness towards first-contact with PHC that some residents refuse to consider PHC even for mild diseases. This study provides practical significance for elaborating the underutilisation of PHC from resident decision-making and offers advice to policymakers and researchers for future modifications.

Alexithymia, intolerance to uncertainty and mental health difficulties in adolescents with Type 1 diabetes mellitus.

BACKGROUND: Type 1 Diabetes Mellitus (T1DM) represents a serious chronic condition affecting a wide number of people. Discussion of the physical issues associated with T1DM pervades the literature, however, there is less discussion of the psychological consequences. Mental health difficulties, alexithymia and uncertainty are present in this population, and known to be harmful for the onset, maintenance and worsening of T1DM. This study aimed to evaluate the presence of these phenomena in people with T1DM. METHODS: 105 participants aged between 11 and 17 years old (M: 13.88; SD: 2.16) affected by T1DM were included in the sample. To assess the presence of mental health difficulties, SAFA scales (Depression, Anxiety and Somatic symptoms) were included in the protocol together with TAS-20 and IUS-12, which evaluate the presence and role of alexithymia and intolerance to uncertainty in the sample, respectively. RESULTS: A concerning presence of anxiety, depression and somatic symptoms was found in the sample. Mental health difficulties appeared to be consistently present in the sample, often overcoming pathological thesholds. Alexithymia and uncertainty were also common, highlighting their role in T1DM. CONCLUSIONS: Active mental health difficulties together with high rates of alexithymia and intolerance to uncertainty were prevalent in the sample of adolescents with diabetes.

Uncertainty reduction for precipitation prediction in North America.

Large differences in projected future annual precipitation increases in North America exists across 27 CMIP6 models under four emission scenarios. These differences partly arise from weak representations of land-atmosphere interactions. Here we demonstrate an emergent constraint relationship between annual growth rates of future precipitation and growth rates of historical temperature. The original CMIP6 projections show 0.49% (SSP126), 0.98% (SSP245), 1.45% (SSP370) and 1.92% (SSP585) increases in precipitation per decade. Combining observed warming trends, the constrained results show that the best estimates of future precipitation increases are more likely to reach 0.40-0.48%, 0.83-0.93%, 1.29-1.45% and 1.70-1.87% respectively, implying an overestimated future precipitation increases across North America. The constrained results also are narrow the corresponding uncertainties (standard deviations) by 13.8-31.1%. The overestimated precipitation growth rates also reveal an overvalued annual growth rates in temperature (6.0-13.2% or 0.12-0.37°C) and in total evaporation (4.8-14.5%) by the original models' predictions. These findings highlight the important role of temperature for accurate climate predictions, which is important as temperature from current climate models' simulations often still have systematic errors.

Graded decisions in the human brain.

Decision-makers objectively commit to a definitive choice, yet at the subjective level, human decisions appear to be associated with a degree of uncertainty. Whether decisions are definitive (i.e., concluding in all-or-none choices), or whether the underlying representations are graded, remains unclear. To answer this question, we recorded intracranial neural signals directly from the brain while human subjects made perceptual decisions. The recordings revealed that broadband gamma activity reflecting each individual's decision-making process, ramped up gradually while being graded by the accumulated decision evidence. Crucially, this grading effect persisted throughout the decision process without ever reaching a definite bound at the time of choice. This effect was most prominent in the parietal cortex, a brain region traditionally implicated in decision-making. These results provide neural evidence for a graded decision process in humans and an analog framework for flexible choice behavior.

A time-varying analysis between economic uncertainty and tourism development in Singapore.

Tourism development (TO) is seen as a viable solution to address economic policy uncertainty (EPU) risks. However, previous studies have largely ignored the relationship between short, medium, and long term by decomposing TO and EPU index at different time-frequency scales, especially in Singapore. In this study, the Wavelet tools analysis and a rolling window algorithm are employed to re-visit the causal relationship between EPU, industrial production index (IPI), government revenue (GR), and tourism development (TO) in Singapore from January 2003 to February 2022. The findings revealed the heterogeneous effects of EPU on TO at different time horizons in terms of importance and magnitude over time. A rise in EPU results in a decline in TO at the low frequencies, indicating that EPU has a detrimental effect on TO over the short term. Conversely, in the long term, an increase in TO results in a decrease in EPU. Furthermore, the outcome also indicated that there is a uni-directional causality running from TO to EPU, GR and IPI. Expressly, we confirm that the negative co-movement is more pronounced in the aftermath of the COVID-19 crisis, particularly for EPU, and GR at low-medium frequencies throughout the research period. The findings provide tourism policymakers with insight to develop strategic plans for tourism development that consider the effects of economic policy uncertainty. By understanding how uncertainty impacts tourism, governments can tailor development strategies to mitigate risks and capitalize on opportunities.

Evolving Improved Sampling Protocols for Dose-Response Modelling Using Genetic Algorithms with a Profile-Likelihood Metric.

Practical limitations of quality and quantity of data can limit the precision of parameter identification in mathematical models. Model-based experimental design approaches have been developed to minimise parameter uncertainty, but the majority of these approaches have relied on first-order approximations of model sensitivity at a local point in parameter space. Practical identifiability approaches such as profile-likelihood have shown potential for quantifying parameter uncertainty beyond linear approximations. This research presents a genetic algorithm approach to optimise sample timing across various parameterisations of a demonstrative PK-PD model with the goal of aiding experimental design. The optimisation relies on a chosen metric of parameter uncertainty that is based on the profile-likelihood method. Additionally, the approach considers cases where multiple parameter scenarios may require simultaneous optimisation. The genetic algorithm approach was able to locate near-optimal sampling protocols for a wide range of sample number (n = 3-20), and it reduced the parameter variance metric by 33-37% on average. The profile-likelihood metric also correlated well with an existing Monte Carlo-based metric (with a worst-case r > 0.89), while reducing computational cost by an order of magnitude. The combination of the new profile-likelihood metric and the genetic algorithm demonstrate the feasibility of considering the nonlinear nature of models in optimal experimental design at a reasonable computational cost. The outputs of such a process could allow for experimenters to either improve parameter certainty given a fixed number of samples, or reduce sample quantity while retaining the same level of parameter certainty.