Goldilocks Principle Research Articles

Trainee growth vs. fixed mindset in clinical learning environments: enhancing, hindering and goldilocks factors

BackgroundDoctors in training (trainees) have higher rates of burnout, anxiety and depression than other professionals. An important psychological tool to combat this crisis is promotion of a growth mindset, which increases resilience and improves mental health outcomes. How growth mindset might be promoted within the clinical learning environment is underexplored. This study aimed to explore the factors promoting a growth mindset versus fixed mindset in trainees from the perspective of the trainees.MethodsThis constructivist study employed a novel method of encouraging trainees’ reflections on mindset adoption in the clinical learning environment. Trainees played Mindset, a tabletop simulation board game that included challenges encountered within training. This was followed by a facilitated debriefing, focusing on factors that promoted growth or fixed mindset adoption in the clinical learning environment. Debriefing transcripts were analysed using template analysis.ResultsThree groups of oncology trainees and one group of medical education fellows participated (16 participants in total). Factors promoting growth mindset adoption included passion, collaboration, diverse career and role modelling. Factors promoting fixed mindset adoption included burnout and competition. Some factors, such as grit, previous success experience and singular training location promoted a fixed mindset when too much or too little were present, and promoted a growth mindset when they were in balance (the Goldilocks principle).ConclusionsThe importance of balance versus excess of certain factors, and the ubiquitous competitive culture in medicine promoting a fixed mindset, were compelling reflections. This study may aid invested parties to reflect on what factors they can upregulate and down regulate to optimise trainees’ adoption of a growth mindset.

Soilscapes of mortality risk suggest a Goldilocks effect for overwintering ectotherms

Soilscapes of mortality risk suggest a Goldilocks effect for overwintering ectotherms

Goldilocks Effect: Finding the ‘Just Right’ Style in Corporate Responsibility

Goldilocks Effect: Finding the ‘Just Right’ Style in Corporate Responsibility

Striking a balance: the Goldilocks effect of CD8α expression on NK cells.

NK cells are cytotoxic innate immune cells involved in antitumor immunity, and they provide a treatment option for patients with acute myeloid leukemia (AML). In this issue of the JCI, Cubitt et al. investigated the role of CD8α, a coreceptor present on approximately 40% of human NK cells. IL-15 stimulation of CD8α- NK cells induced CD8α expression via the RUNX3 transcription factor, driving formation of a unique induced CD8α (iCD8α+) population. iCD8α+ NK cells displayed higher proliferation, metabolic activity, and antitumor cytotoxic function compared with preexisting CD8α+ and CD8α- subsets. Therefore, CD8α expression can be used to define a potential dynamic spectrum of NK cell expansion and function. Because these cells exhibit enhanced tumor control, they may be used to improve in NK cell therapies for patients with AML.

Slc25a3-dependent copper transport controls flickering-induced Opa1 processing for mitochondrial safeguard

Following the Goldilocks principle, mitochondria size must be "just right." Mitochondria balance division and fusion to avoid becoming too big or too small. Defects in this balance produce dysfunctional mitochondria in human diseases. Mitochondrial safeguard (MitoSafe) is a defense mechanism that protects mitochondria against extreme enlarging by suppressing fusion in mammalian cells. In MitoSafe, hyperfused mitochondria elicit flickering-short pulses of mitochondrial depolarization. Flickering activates an inner membrane protease, Oma1, which in turn proteolytically inactivates a mitochondrial fusion protein, Opa1. The mechanisms underlying flickering are unknown. Using a live-imaging screen, we identified Slc25a3 (a mitochondrial carrier transporting phosphate and copper) as necessary for flickering and Opa1 cleavage. Remarkably, copper, but not phosphate, is critical for flickering. Furthermore, we found that two copper-containing mitochondrial enzymes, superoxide dismutase 1 and cytochrome c oxidase, regulate flickering. Our data identify an unforeseen mechanism linking copper, redox homeostasis, and membrane flickering in mitochondrial defense against deleterious fusion.

The Goldilocks principle of learning unitaries by interlacing fixed operators with programmable phase shifters on a photonic chip

Programmable photonic integrated circuits represent an emerging technology that amalgamates photonics and electronics, paving the way for light-based information processing at high speeds and low power consumption. Programmable photonics provides a flexible platform that can be reconfigured to perform multiple tasks, thereby holding great promise for revolutionizing future optical networks and quantum computing systems. Over the past decade, there has been constant progress in developing several different architectures for realizing programmable photonic circuits that allow for realizing arbitrary discrete unitary operations with light. Here, we systematically investigate a general family of photonic circuits for realizing arbitrary unitaries based on a simple architecture that interlaces a fixed intervening layer with programmable phase shifter layers. We introduce a criterion for the intervening operator that guarantees the universality of this architecture for representing arbitrary N×N\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$N \ imes N$$\\end{document} unitary operators with N+1\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$N+1$$\\end{document} phase layers. We explore this criterion for different photonic components, including photonic waveguide lattices and meshes of directional couplers, which allows the identification of several families of photonic components that can serve as the intervening layers in the interlacing architecture. Our findings pave the way for efficiently designing and realizing novel families of programmable photonic integrated circuits for multipurpose analog information processing.

Abstract A017: Computational and mouse models of adaptive therapy with multiple drugs in breast cancer

Abstract Adaptive therapy is an evolutionary approach to cancer therapy designed to maintain control of therapeutically resistant cells and thereby extend both time to progression and patient survival. Most of the previous work in adaptive therapy has used a single cytotoxic drug, and yet there are still many variations of adaptive therapy protocols. Although multidrug therapy is standard for most cancers, there is a combinatorial explosion of possible protocols with an increase in the number of drugs used. We set out to explore which protocols are likely to work best, under which conditions, using computational models. We explored 2 drug therapies but allowed the drugs to be cytotoxic or cytostatic. We tested the effects of varying the fitness cost of resistance, the amount of turnover in the tumors, and the ability of cells to replace their neighbors under crowded conditions. Adaptive therapy tends to work best when there is more competition between cells in the cancers. We also explored different dosing schedules with both fixed doses and with varying the doses as a function of tumor burden dynamics. We also selected ER+ breast cancer (MCF7) cells to be resistant to both fulvestrant (an anti-estrogen therapy) and palbociclib (a CDK4/6 targeted therapy). These endocrine-resistant ER+ breast cancer cells represent the target population for a clinical trial in endocrine-resistant ER+ metastatic breast cancer that we are seeking to open at the Mayo Clinic. We tested a few of the adaptive therapy protocols with those cells in immune-compromised mice, using either gemcitabine, capecitabine or both drugs. In general, our computational models suggest that the less drug that a protocol uses, the longer we are able to keep control over the cancers. This was corroborated in our mouse experiments. However, if too little drug is used it can’t even control the sensitive cells in the tumors, leading to a sort of Goldilocks effect for the dosing. Capping the maximum dose at a relatively low level, and modulating the dose below that level, led to long-term control for many of the protocols. Many of the tumors in the mice remained dormant for many weeks after we stopped adaptive therapy, for unknown reasons. Our results support adaptive therapy as a promising approach for both extending time to progression and improving quality of life by reducing toxicity. We are using these results to design our clinical trial. Citation Format: Carlo C. Maley, Sareh Seyedi, Daniel Saha, Alexander Anderson. Computational and mouse models of adaptive therapy with multiple drugs in breast cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr A017.

Extracellular Signal-Regulated Kinases: One Pathway, Multiple Fates.

This comprehensive review delves into the multifaceted aspects of ERK signaling and the intricate mechanisms underlying distinct cellular fates. ERK1 and ERK2 (ERK) govern proliferation, transformation, epithelial-mesenchymal transition, differentiation, senescence, or cell death, contingent upon activation strength, duration, and context. The biochemical mechanisms underlying these outcomes are inadequately understood, shaped by signaling feedback and the spatial localization of ERK activation. Generally, ERK activation aligns with the Goldilocks principle in cell fate determination. Inadequate or excessive ERK activity hinders cell proliferation, while balanced activation promotes both cell proliferation and survival. Unraveling the intricacies of how the degree of ERK activation dictates cell fate requires deciphering mechanisms encompassing protein stability, transcription factors downstream of ERK, and the chromatin landscape.

Taking a Break: The Effects of Partaking in a Two-Week Social Media Digital Detox on Problematic Smartphone and Social Media Use, and Other Health-Related Outcomes among Young Adults.

Despite their increasing popularity, especially among young adults, there is a dearth of research examining the effectiveness of digital detoxes focused on restricting or limiting social media use. As such, the purpose of this exploratory study was to create and carry out a social media digital detox among young adults and evaluate its effectiveness with regards to smartphone and social media addiction, as well as several health-related outcomes. Additionally, the study also sought to obtain an understanding of participants' experiences and perceptions regarding the digital detox via semi-structured exit interviews in order to improve and maximize the effectiveness of future social media digital detox interventions. Thirty-one young adults completed a two-week social media digital detox (preceded by a two-week baseline period and followed up by a two-week follow-up period), whereby their social media use was limited to 30 min per day. A series of one-way repeated measures analyses of variance revealed that a two-week social media detox improved smartphone and social media addiction, as well as sleep, satisfaction with life, stress, perceived wellness, and supportive relationships. Thematic analysis of exit interviews also revealed eight themes: feelings, effort to detox, adjustment period, the Goldilocks effect, screen to screen, post-detox binge, progress not perfection, and words of wisdom, all of which provide contextualization of the quantitative findings and valuable insights for future detoxes. In conclusion, the findings of this exploratory study provide initial support for the use of social media digital detoxes, suggesting that limiting usage can have beneficial effects with regards to smartphone and social media addiction, as well as many other health-related outcomes.

The Goldilocks Principle: Balancing Familiarity and Novelty in the Selection of Play Partners in Groups of Juvenile Male Rats

Like many mammals, rats frequently engage in play fighting as juveniles, an activity that influences the development of socio-cognitive skills. Most studies that assess play are based on staged dyadic encounters, implying that some average quantity and quality of play are sufficient to produce these developmental effects. However, there are individual differences, with some rats not only preferring to play more, but also to have more physical contact than others. Given that rats have individual differences in play, it raises the possibility that rats might express these preferences when playing in groups. To determine whether rats form partner preferences, trials were conducted in which a focal rat was given the opportunity to play with three partners of varying familiarity. One partner was a cage mate, another was housed on the other side of a transparent and perforated divider and so familiar, but not a prior play partner, and the third was a stranger from another cage. A total of 36 focal rats, between 30-36 days of age, were tested and video recorded in 20-minute trials following 2.5 h of social isolation. Focal rats expressed a preference for neighbors over both strangers and cage mates, indicating that balancing between familiarity and novelty influences social play partner preferences. Mechanisms by which this preference might have been established, such as dominance relationships, weight differences, and congruency of play style, were investigated, but none were correlated with the preferences expressed. This group dynamics perspective provides a novel approach to studying play, and more generally, provides insights into social exploration and decision-making.

Automation Bias and the “Goldilocks Effect” in Auditing Blockchain

ABSTRACT Blockchain technology appears to have unique characteristics such as inherent trust, immutability, transparency, and tighter security that might facilitate the audit process. Using a survey of AICPA members, we examine responses to the evaluation of audit evidence related to management assertions in a blockchain-enabled environment. We posit three possible effects pertaining to reliance on audit evidence in blockchain-enabled environments: (1) Goldilocks Effect (no automation bias) or the ideal scenario where auditors exhibit “just right” levels of professional skepticism and due care resulting in an optimal level of auditing; (2) Halo Effect or positive automation bias, which potentially results in over-reliance on evidence and, in turn, underauditing and; (3) Hype Effect or negative automation bias, which potentially results in under-reliance on evidence and, in turn, overauditing. Our results suggest that respondents to our survey are predominantly influenced by the Halo Effect, indicating a propensity for positive automation bias across management assertions.

Goldilocks principle and recessive disease.

Goldilocks principle and recessive disease.

Goldilocks principle of minimally invasive surgery for gastric subepithelial tumors.

Minimally invasive surgery had been tailored to individual cases of gastric subepithelial tumors (SETs) after comparing the clinical outcomes of endoscopic resection (ER), laparoscopic resection (LR), and hybrid methods. To study the use of Goldilocks principle to determine the best form of minimally invasive surgery for gastric SETs. In this retrospective study, 194 patients of gastric SETs with high probability of surgical intervention were included. All patients underwent tumor resection in the operating theater between January 2013 and December 2021. The patients were divided into two groups, ER or LR, according to the tumor characteristics and the initial intent of intervention. Few patients in the ER group required further backup laparoscopic surgery after an incomplete ER. The patients who had converted open surgery were excluded. A logistic regression model was used to assess the associations between patient characteristics and the likelihood of a treatment strategy. The area under the curve was used to assess the discriminative ability of tumor size and Youden's index to determine the optimal cut-off tumor size. One-hundred ninety-four patients (100 in the ER group and 94 in the LR group) underwent tumor resection in the operating theater. In the ER group, 27 patients required backup laparoscopic surgery after an incomplete ER. The patients in the ER group had small tumor sizes and shorter procedure durations while the patients in the LR group had large tumor sizes, exophytic growth, malignancy, and tumors that were more often located in the middle or lower third of the stomach. Both groups had similar durations of hospital stays and a similar rate of major postoperative complications. The patients in the ER group who underwent backup surgery required longer procedures (56.4 min) and prolonged stays (2 d) compared to the patients in the LR group without the increased rate of major postoperative complications. The optimal cut-off point for the tumor size for laparoscopic surgery was 2.15 cm. Multidisciplinary teamwork leads to the adoption of different strategies to yield efficient clinical outcomes according to the tumor characteristics.

Is it the Goldilocks principle? The impact of environmental decentralization on total factor carbon productivity in China

The current severe carbon emissions situation in China increases the demand for a sound environmental governance system. Using provincial panel data from 2003 to 2017, this study investigates the spatial impact of different types of environmental decentralization (ED) on total factor carbon productivity (TFCP) and its internal mechanisms and explores the threshold effect of horizontal environmental decentralization (HED) and fiscal decentralization (FD) on this impact. The results indicate that the effect of ED on TFCP exists after considering the spatial dependence. An inverted “U-shaped” relationship exists between vertical environmental decentralization (VED) and TFCP, and a “U-shaped” relationship between horizontal environmental decentralization (HED) and TFCP; that is, excessive VED and insufficient HED will inhibit TFCP. Green technology innovation acts as a mediator in the impact of ED on TFCP, including VED and HED. The dynamic threshold panel model finds that both the increase of HED and FD improved the promotion effect of VED on TFCP, but the change in HED gradually reduced the promotion effect. China should adhere to the Goldilocks principle, strengthen vertical environmental centralization and promote horizontal environmental decentralization to create a superior institutional environment for stimulating green technological innovation to further weaken the “free rider” effect of environmental governance caused by externalities.

Invited Commentary: Goldilocks Principle in Opioid Prescribing.

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Inborn errors of immunity: the Goldilocks effect-susceptibility to disease due to a little too much or a little too little.

Journal Article Accepted manuscript Inborn errors of Immunity: The Goldilocks effect – susceptibility to disease due to a little too much or a little too little Cindy S Ma, Cindy S Ma Garvan Institute of Medical Research, Sydney, NSW, AustraliaSchool of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Sydney, NSW Australia Corresponding author: c.ma@garvan.org.au Search for other works by this author on: Oxford Academic Google Scholar Stuart G Tangye Stuart G Tangye Garvan Institute of Medical Research, Sydney, NSW, AustraliaSchool of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Sydney, NSW Australia Search for other works by this author on: Oxford Academic Google Scholar Clinical and Experimental Immunology, uxad039, https://doi.org/10.1093/cei/uxad039 Published: 12 April 2023 Article history Received: 03 April 2023 Published: 12 April 2023

Mistuned NF-κB signaling in lymphocytes: lessons from relevant inborn errors of immunity.

Inborn errors of immunity (IEIs) continuously remind us that multiple checks and balances are built into the adaptive immune system to maintain homeostasis, ensuring effective pathogen defense without causing inadvertent immunopathology, autoimmunity, or lymphomagenesis. The nuclear factor of κB (NF-κB) family of transcription factors serve a vital role in the immune system, inducing scores of genes responsible for lymphocyte survival, proliferation, differentiation and effector function. In recent years, the discovery and characterization of IEIs that impact NF-κB activity have illuminated the importance of carefully tuning this pathway to ensure effective immune defense without hyperinflammation and immune dysregulation. Here we examine several illustrative cases of IEIs that arise from pathogenic mutations encoding NF-κB inducers, regulators, and NF-κB family components themselves, illuminating how these genes ensure normal adaptive immune system function by maintaining a "Goldilocks effect" state in NF-κB pathway activity.

Goldilocks calcium concentrations and the regulation of oxidative phosphorylation: Too much, too little, or just right

Calcium (Ca2+) is a key regulator in diverse intracellular signaling pathways and has long been implicated in metabolic control and mitochondrial function. Mitochondria can actively take up large amounts of Ca2+, thereby acting as important intracellular Ca2+ buffers and affecting cytosolic Ca2+ transients. Excessive mitochondrial matrix Ca2+ is known to be deleterious due to opening of the mitochondrial permeability transition pore (mPTP) and consequent membrane potential dissipation, leading to mitochondrial swelling, rupture, and cell death. Moderate Ca2+ within the organelle, on the other hand, can directly or indirectly activate mitochondrial matrix enzymes, possibly impacting on ATP production. Here, we aimed to determine in a quantitative manner if extra- or intramitochondrial Ca2+ modulates oxidative phosphorylation in mouse liver mitochondria and intact hepatocyte cell lines. To do so, we monitored the effects of more modest versus supraphysiological increases in cytosolic and mitochondrial Ca2+ on oxygen consumption rates. Isolated mitochondria present increased respiratory control ratios (a measure of oxidative phosphorylation efficiency) when incubated with low (2.4± 0.6μM) and medium (22.0± 2.4μM) Ca2+ concentrations in the presence of complex I-linked substrates pyruvate plus malate and α-ketoglutarate, respectively, but not complex II-linked succinate. In intact cells, both low and high cytosolic Ca2+ led to decreased respiratory rates, while ideal rates were present under physiological conditions. High Ca2+ decreased mitochondrial respiration in a substrate-dependent manner, mediated by mPTP. Overall, our results uncover a Goldilocks effect of Ca2+ on liver mitochondria, with specific "just right" concentrations that activate oxidative phosphorylation.

Beautiful on the inside: Aesthetic preferences and the skeletal complexity of shapes.

A plain, blank canvas does not look very beautiful; to make it aesthetically appealing requires adding structure and complexity. But how much structure is best? In other words, what is the relationship between beauty and complexity? It has long been hypothesized that complexity and beauty meet at a "sweet spot," such that the most beautiful images are neither too simple nor too complex. Here, we take a novel experimental approach to this question, using an information-theoretic approach to object representation based on an internal "skeletal" structure. We algorithmically generated a library of two-dimensional polygons and manipulated their complexity by gradually smoothing out their features-essentially decreasing the amount of information in the objects. We then stylized these shapes as "paintings" by rendering them with artistic strokes, and "mounted" them on framed canvases hung in a virtual room. Participants were shown pairs of these mounted shapes (which possessed similar structures but varied in skeletal complexity) and chose which shape looked best by previewing each painting on the canvas. Experiment 1 revealed a "Goldilocks" effect: participants preferred paintings that were neither too simple nor too complex, such that moderately complex shapes were chosen as the most attractive paintings. Experiment 2 isolated the role of complexity per se: when the same shapes were scrambled (such that their structural complexity was undermined, while other visual features were preserved), the Goldilocks effect was dramatically diminished. These findings suggest a quadratic relationship between aesthetics and complexity in ways that go beyond previous measures of each and demonstrate the utility of information-theoretic approaches for exploring high-level aspects of visual experience.

The Goldilocks principle: Finding the balance between water volume and nutrients for ovipositing Culex mosquitoes (Diptera: Culicidae).

Females of container-breeding mosquito species use visual and chemical cues to determine suitable habitats to oviposit their eggs. Female Culex mosquitoes oviposit single egg rafts containing hundreds of eggs on the surface of water in container habitats. In this project, the effects of water volume and nutrient concentration were studied using three semi-controlled field assays to determine the role these parameters play on female Culex mosquito oviposition preference. The results of this study suggest female Culex prefer to oviposit in larger volumes of water and higher concentrations of nutrients separately, but chose intermediate conditions when presented with a combination of these two variables, which follows the Goldilocks principle. This choice may provide their offspring with optimal conditions for development by reducing intraspecific competition, thereby maximizing the biological fitness of the ovipositing Culex females.