OBJECTIVES/GOALS: We aimed to find the histology-specific markers that were predictive of post-operative long-term chordoma recurrence (≤1 year) using trained multiple tree-based machine learning (ML) algorithms. METHODS/STUDY POPULATION: We reviewed the records of patients who had treatment for clival and spinal chordomas between January 2017 and June 2021 across the Mayo Clinic enterprise (Minnesota, Florida, and Arizona). Patients were excluded if they had no histopathology or recurrence as an outcome. Demographics, type of treatment, clinical and radiological follow-up duration, histopathology, and other relevant clinical factors were abstracted from each patient record. Decision tree and random forest classifiers were trained and tested to predict the long-term recurrence based on unseen data using an 80/20 split. The performance of the model was optimized using tenfold cross-validation. RESULTS/ANTICIPATED RESULTS: One hundred fifty-one patients were identified: 58 chordomas from the clivus, 48 chordomas of the mobile spine, and 45 sacrococcygeal. Subtotal Resection followed by radiation therapy, was the most common treatment modality, followed by Gross Total resection, then radiation therapy. The multivariate analysis defines the molecular predictors of recurrence following resection. S100 and pan-cytokeratin is more likely to increase the risk of post-operative recurrence (OR= 3.67; CI= [1.09,12.42], p=0.03). In the decision tree analysis, a clinical follow-up > 1897 days was found in 37 % of encounters and a 90% chance of being classified for recurrence (Accuracy= 77%). Factors predicting long-term recurrence are the patient’s age, type of surgical treatment, location of the tumor, S100, pan-cytokeratin, and EMA. DISCUSSION/SIGNIFICANCE: Our molecular and clinicopathological variables combined with tree-based ML tools successfully demonstrate a high capacity to individually identify the patient’s recurrence pattern with an accuracy of 77%. S100, pan-cytokeratin, and EMA were the histologic drivers of recurrence.

OBJECTIVES/GOALS: 1. Describe method of Community Based System Dynamics. 2. Describe CBSD as used in addressing structural racism in a previously redlined community. 3. Review example causal loop diagrams and simulation models developed using CBSD focused on structural racism as a social determinant of health. METHODS/STUDY POPULATION: Community Based System Dynamics (group model building and computer simulation development). Cuyahoga County, Ohio, a previously redlined community of more than 1.2 million people. RESULTS/ANTICIPATED RESULTS: Actionable Community identified leverage points for action to mitigate structural racism. Computer simulation models built on causal loop diagrams built by Community members with loved experience. DISCUSSION/SIGNIFICANCE: Structural and social determinants of health, such as racism, have profound impacts on the health of individuals and populations, however they remain challenging to address in pragmatic ways. CBSD is a novel method to engage community members not proximal to the impact of structural racism in generating maps of the complex, dynamic system they live in.

Precision Medicine/Health

The near-field characteristics of highly buoyant plumes, commonly referred to as lazy plumes, remain relatively poorly understood across a range of flow conditions, particularly compared with our understanding of far-field characteristics. Here, we perform fully resolved three-dimensional numerical simulations of round helium plumes to characterize the effects of different inlet Richardson, ${Ri}_0$, and Reynolds, ${Re}_0$, numbers on first- and second-order statistical moments as well as average vertical fluxes in the near field. For sufficiently high ${Re}_0$ at a particular ${Ri}_0$, heavy air can penetrate the core of the plume, reminiscent of spikes in the classical Rayleigh–Taylor instability. In the most turbulent simulation, this penetration becomes so strong that a recirculation zone forms along the centreline of the plume. Vertical fluxes are found to scale linearly with vertical distance from the plume inlet, consistent with experimental and numerical observations (Jiang & Luo, Flow Turbul. Combust., vol. 64, 2000, pp. 43–69; Kaye & Hunt, Intl J. Heat Fluid Flow, vol. 30, 2009, pp. 1099–1105). We analytically derive this linear scaling from the governing equations by making a radial entrainment hypothesis whereby ambient fluid is entrained, on average, only in the radial direction at a finite distance from the inlet. Through this derivation, we identify physical mechanisms that can cause these relationships to remain only approximately valid for the present simulations. Lastly, we identify near-field power-law scaling relations for the flux magnitudes based on ${Ri}_0$, and also examine vertical profiles of the non-dimensional Richardson number flux. Ultimately, insights from the present simulations are used to define near-, intermediate- and far-field regions in buoyant plumes.

Fetal liver tissue collected from a nonhuman primate (NHP) baboon model of maternal nutrient reduction (MNR) at four gestational time points (90, 120, 140, and 165 days gestation [dG], term in the baboon is ∼185 dG) was used to quantify MNR effects on the fetal liver transcriptome. 28 transcripts demonstrated different expression patterns between MNR and control livers during the second half of gestation, a developmental period when the fetus undergoes rapid weight gain and fat accumulation. Differentially expressed transcripts were enriched for fatty acid oxidation and RNA splicing-related pathways. Increased RNA splicing activity in MNR was reflected in greater abundances of transcript splice variant isoforms in the MNR group. It can be hypothesized that the increase in splice variants is deployed in an effort to adapt to the poor in utero environment and ensure near-normal development and energy metabolism. This study is the first to study developmental programming across four critical gestational stages during primate fetal liver development and reveals a potentially novel cellular response mechanism mediating fetal programming in response to MNR.

The spherical encompassing final chamber of the planktonic foraminifera Orbulina universa is a prime example of a complex character whose evolution has been documented by a sequence of intermediate forms. However, the mechanism that induced evolution of the spherical chamber remain unclear. Here we show that shortly after the emergence of Orbulina, documented throughout the oceans, a convergent evolutionary transition occurred in the semi-isolated Paratethys, leading to the emergence of the endemic Velapertina, which occupied a similar niche to Orbulina in the surface waters. Using X-ray computed tomography scanning, we show that the evolution of the encompassing final chamber involved the same sequence of steps in both lineages, combining a progressively spherical shell shape with changes in the position, number, and sizes of apertures. The similarity in the sequence of character acquisitions suggests structural determinism in the way foraminiferal shells are constructed and the presence of natural selection favoring a spherical morphology. Collectively, the emergence of spherical chambers in the two lineages at a similar time suggests that the evolution of this spectacular complex character occurred in response to a singular environmental driver.

Long-chain omega-3 polyunsaturated fatty acid (LC n-3 PUFA) supplements, rich in eicosapentaenoic acid and/or docosahexaenoic acid, are increasingly being recommended within athletic institutions. However, the wide range of doses, durations and study designs implemented across trials makes it difficult to provide clear recommendations. The importance of study design characteristics in LC n-3 PUFA trials has been detailed in cardiovascular disease research, and these considerations may guide LC n-3 PUFA study design in healthy cohorts. This systematic review examined the quality of studies and study design considerations used in evaluating the evidence for LC n-3 PUFA improving performance in physically trained adults. SCOPUS, PubMed and Web of Science electronic databases were searched to identify studies that supplemented LC n-3 PUFA in physically trained participants. Forty-six (n = 46) studies met inclusion. Most studies used a randomised control design. Risk of bias, assessed using the design-appropriate Cochrane Collaboration tool, revealed that studies had a predominant judgment of ‘some concerns’, ‘high risk’ or ‘moderate risk’ in randomised controlled, randomised crossover or non-randomised studies, respectively. A custom five-point quality assessment scale demonstrated that no study satisfied all recommendations for LC n-3 PUFA study design. This review has highlighted that the disparate range of study designs is likely contributing to the inconclusive state of outcomes pertaining to LC n-3 PUFA as a potential ergogenic aid. Further research must adequately account for the specific LC n-3 PUFA study design considerations, underpinned by a clear hypothesis, to achieve evidence-based dose, duration and composition recommendations for physically trained individuals.

This paper describes and analyses aspects of Australian income support and service arrangements for the aged in the context of broader issues relating to privatisation. It is argued that much of the welfare privatisation debate is overly simplistic and does not recognise the important role which the non-government sector already plays in aspects of support for the age. Analysis of income data shows, for example, that transfer income currently accounts for less than half of the income of the aged. The trend towards superannuation is apparent in the data, although some doubts are raised about the impact of superannuation expansion on the finance of population ageing. In the area of community services, the paper describes the development of policy over the last few decades in order to illustrate the complexity of existing arrangements. The switch from institutional to community care is identified as a major trend, particularly during the 1980s, and some of the implications of this development for privatisation are drawn out and analysed.

This article has three objectives. First, we examine what is meant by minimum labour standards, including the array of different standards and their procedural and substantive elements, in differing or even diverging regulatory jurisdictions. Examination of different areas of labour standards provides instruction in the dynamics of these protections and we give illustrative examples, from several countries. The second objective is to highlight the importance of enforcement of standards. We do this through a brief historical overview of the emergence of labour standards as well as of how the recent rise of neo-liberalism has shaped current debates over their development and application. The third element of the analysis is an examination of some contemporary debates, pointing to areas requiring further study as well as to positive examples both in research and in policy/regulation.

This discussion paper by a group of scholars across the fields of health, economics and labour relations argues that COVID-19 is an unprecedented humanitarian crisis from which there can be no return to the ‘old normal’. The pandemic’s disastrous worldwide health impacts have been exacerbated by, and have compounded, the unsustainability of economic globalisation based on the neoliberal dismantling of state capabilities in favour of markets. Flow-on economic impacts have simultaneously created major supply and demand disruptions, and highlighted the growing within-country inequalities and precarity generated by neoliberal regimes of labour market regulation. Taking an Australian and international perspective, we examine these economic and labour market impacts, paying particular attention to differential impacts on First Nations people, developing countries, women, immigrants and young people. Evaluating policy responses in a political climate of national and international leadership very different from those in which major twentieth century crises were addressed, we argue the need for a national and international conversation to develop a new pathway out of crisis.

Supply chain security presents numerous challenges to governments interested in defending against terrorist threats. While most approaches stress technological solutions, scholars and policy-makers tend to overlook economics, labour market issues, and industrial relations. Applying agency theory from behavioural economics, this article analyses threats to the US supply chain and opportunities for efficient solutions. Using data from a sophisticated web-based survey of owner-operator cost-of-operations, it shows that drayage drivers are among the lowest paid truck drivers and workers in the US. We provide evidence that low pay is associated with both safety and security risk. Low-wage labour and subcontracting present challenges to US and foreign supply-chain security because the market attracts workers who have few other employment options. In this environment, principals and agents currently make inefficient and inequitable contracts because markets do not reflect the complete costs associated with low-probability/high-impact events like cargo theft and transport security.

This paper examines the privatisation of Sydney Airport and the regime of ‘light-handed’ monitoring of service quality and airport charges that followed the sale in 2002. The arguments for privatisation are reviewed, in particular the need for increased competition and/or appropriate regulation where a former public monopoly, such as Sydney Airport, is sold. The aftermath of the privatisation of the airport has led to complaints by the major airlines and consumers of ever increasing charges for use of the airfield and for car parking and other services. This highlights that the ‘light-handed’ monitoring regime has not constrained the airport’s ability to charge monopoly rents. The aftermath of privatisation has resulted in labour shedding, outsourcing and a focus on cost minimisation by the airport’s management.

People are often more likely to accept risky monetary gambles with positive expected values when the gambles will be played more than once. We investigated whether this distinction between single-play and multiple-play gambles extends to medical treatments for individual patients and groups of patients. Resident physicians and medical students (n = 69) and undergraduates (n = 99) ranked 9 different flu shots and a no-flu-shot option in 1 of 4 combinations of perspective (individual patient vs. group of 1000 patients) and uncertainty frame (probability vs. frequency). The rank of the no-flu-shot option (a measure of preference for treatment vs. no treatment) was not significantly related to perspective or participant population. The main effect of uncertainty frame and the interaction between perspective and uncertainty frame approached significance (0.1 > p > 0.05), with the no-flu-shot option faring particularly poorly (treatment faring particularly well) when decisions about many patients were based on frequency information. Undergraduate participants believed that the no-flu-shot option would be less attractive (treatment would be more attractive) in decisions about many patients, but these intuitions were inconsistent with the actual ranks. These results and those of other studies suggest that medical treatments for individuals and groups are not analogous to single-play and multiple-play monetary gambles, perhaps because many people are unwilling to aggregate treatment outcomes over patients in the same way that they would compute net gains or losses over monetary gambles.

In lottery gambling, the common phenomenon of risk aversion shows up as preference of the option with the higher win probability, even if a riskier alternative offers a greater expected value. Because riskier choices would optimize profitability in such cases, the present study investigates the visual format, with which lotteries are conveyed, as potential instrument to modulate risk attitudes. Previous research has shown that enhanced attention to graphical compared to numerical probabilities can increase risk aversion, but evidence for the reverse effect — reduced risk aversion through a graphical display of outcomes — is sparse. We conducted three experiments, in which participants repeatedly selected one of two lotteries. Probabilities and outcomes were either presented numerically or in a graphical format that consisted of pie charts (Experiment 1) or icon arrays (Experiment 2 and 3). Further, expected values were either higher in the safer or in the riskier lottery, or they did not differ between the options. Despite a marked risk aversion in all experiments, our results show that presenting outcomes as graphs can reduce — albeit not eliminate — risk aversion (Experiment 3). Yet, not all formats prove suitable, and non-intuitive outcome graphs can even enhance risk aversion (Experiment 1). Joint analyses of choice proportions and response times (RTs) further uncovered that risk aversion leads to safe choices particularly in fast decisions. This pattern is expressed under graphical probabilities, whereas graphical outcomes can weaken the rapid dominance of risk aversion and the variability over RTs (Experiment 1 and 2). Together, our findings demonstrate the relevance of information format for risky decisions.