Objectives/Goals: Osteosarcoma (OS) is the most common primary bone malignancy in humans and dogs. >40% of children and >90% of dogs succumb to metastatic disease. We hypothesize MYC overexpression in metastatic canine and human OS contributes to an immunosuppressive tumor environment by driving tumor-associated macrophage influx and T lymphocyte exclusion. Methods/Study Population: To characterize the role of oncogenic MYC signaling in the canine metastatic tumor immune microenvironment (TIME), 42 archived FFPE lung metastatic canine OS samples were evaluated for MYC copy number variation (CNV), mRNA, and protein expression via ddPCR, nanostring analysis, and immunohistochemistry (IHC). Seven samples also underwent GeoMX spatial profiling to more specifically evaluate T cell and macrophage transcriptional profiles based on MYC status. To determine the role of MYC target modulation as a potential therapeutic option, canine and human OS cell lines were treated with a novel MYC inhibitor (MYCi975) and assessed for effects on survival, proliferation, and cytokine profiles. Results/Anticipated Results: We demonstrate that copy number gains are not a key driver of MYC hyperactivity in canine metastatic OS. However, stratification based on MYC protein expression demonstrates that “MYC-high” tumors are associated with downregulation of cytotoxic effector T-cell associated transcripts and upregulation of tumor-associated macrophage (TAM) and extracellular matrix remodeling transcripts. We also report that MYCi975 treatment of canine and human OS cell lines results in significant inhibition of OS cell survival and proliferation at concentrations that are pharmacologically achievable in mice. Furthermore, we demonstrate MYC inhibition by MYCi975 is associated with reduced pro-inflammatory cytokine secretion in OS cell culture models. Discussion/Significance of Impact: While MYC overactivity in metastatic canine OS may not be genomically driven, other mechanisms that lead to increased MYC protein expression are associated with transcriptomic profiles supportive of local immunosuppression. Pharmacologic targeting of MYC may serve as a strategy to bolster immunotherapeutic options in metastatic OS treatment.

Objectives/Goals: The extracellular matrix (ECM) of the sinoatrial node (SAN) is critical for maintaining automaticity in hiPSC-derived pacemaking cardiomyocytes (PCMs) under cyclic strain. We aim to determine the ECM ligands responsible for cell-ECM mediated mechanotransduction and the resulting phenotype in PCMs. Methods/Study Population: HiPSCs are differentiated to PCM and replated on substrate with 5 or 15 kPa PDMS that are coated with 5 or 25 ug/cm of either collagen I or fibronectin at sub-confluent density to restrict junction engagement to only costameres. Then, PCM are subjected to 10% cyclic mechanical strain at 1 Hz for 48 hours, with static culture as control. PCMs from all conditions are subsequently fixed and stained for cardiomyocyte-specific troponin T (TnT), pacemaking HCN4 channel, and pro-pacemaking transcription factors (Shox2, Isl1, Tbx3, Tbx18). Additionally, PCM cell size will also be assessed. Results/Anticipated Results: Considering the amount of hypertrophy and myofilament in CMs correlates with mechanical strain, we expect a reduced degree of mechanotransduction in hiPSC-PCM on collagen I with a stiffness 15 kPa to induce smaller cell size with fewer myofilament and an upregulation of HCN4 and pro-pacemaking transcription factors than those on 5 kPa and those on fibronectin of either 5 or 15 kPa after cyclic strain. This is because COL1 is reported to have a lower signaling threshold but a limited sensitivity to force which contributes to the diminished mechanotransduction signaling. Discussion/Significance of Impact: Effects of the microenvironment on hiPSC-PCMs via costamere mechanotransduction may provide insights for engineering biopacemakers with a suitable ECM, to potentially preserve automaticity in hiPSC-PCMs and sustain long-term pacemaking function, making biopacemakers a step closer to reality.

Farm advisors provide knowledge and support to farmers, to help them change their on-farm practices or behaviours, with a view to improving the farm’s overall sustainability and competitiveness(1,2). In this way, advisors can be viewed as agents of change(3). In order to fulfil their role as agents of change, advisors must possess sufficient knowledge of human psychology and behavioural science, which is the discipline involved with understanding, predicting and changing behaviour(4,5). Despite this, within advisory education and professional development, it is considered that greater emphasis is given to advisory technical knowledge acquisition, than how to work effectively with others to support learning and change(6). Accordingly, this study aims to implement a behaviour change communication training programme for farm advisors and evaluate its efficacy. As much work within the health and social care field has been undertaken to support health related behaviour change, this study aims to adapt a behaviour change communication training programme originally developed for use within this field to the advisory setting(7,8).

A mixed-methods case study under the pragmatic worldview was conducted. Ethical approval was obtained from the Faculty of Medicine, Health and Life Sciences Research Ethics Committee at Queen’s University Belfast. The programme was adapted from the ‘MAP of Health Behaviour Change Learning Programme’ (MAP) created by NHS Education for Scotland(9). Eight farm advisors completed the programme delivered by health psychologists, which involved the completion of a 40-minute online module and a one-day in-person workshop about the principles of person-centred communication and behaviour change techniques. The Brinkerhoff training evaluation model guided the evaluation(10). Quantitative questionnaire data, including perceived knowledge and confidence, was descriptively analysed. Qualitative data including surveys, logs and focus group/interview data was thematically analysed.

Descriptive analysis found advisors scored highly in perceived knowledge (mean: 5.5) and confidence (mean: 5.5) post-training (measured on 6-point Likert scale). Thematic analysis determined three themes: valuable activities, takeaways, and programme evolution. Advisors valued open discussions and role-playing activities. A key takeaway was how to structure conversations about change; firstly, identifying a person’s stage of change, then delivering behaviour change techniques tailored to that stage. Further training on how to support individuals to explore and build motivation towards change was deemed beneficial.

MAP was shown to be an effective training programme with applications in agriculture. This study offers insights for those involved in advisory education. Incorporating behaviour change communication courses into advisory programmes helps advisors develop knowledge surrounding the psychology behind behaviour change and additional competencies in supporting behaviour change at the farm level.

This study surveyed 190 healthcare professionals to examine attitudes towards reusable surgical gowns, aiming to reduce medical waste. Comfort (scoring 5.32 out of 7) and misconceptions about gowns serving as personal protective equipment (87% hold this belief) are crucial influencers. External motivators, trust, emotions, and workload also impact perceptions. The study recommends enhancing reusable gown design for comfort, multifunctionality, and hygiene trust. It calls for communication strategies to normalise reusables in healthcare and urges a transition to sustainable practices.

The trend toward the “humanization” of international law reflects a greater emphasis on individuals rather than simply states as objects of concern. The advance of human rights law (HRL) has been an important impetus for this trend. Some observers suggest that humanization can be furthered even more by applying HRL rather than international humanitarian law (IHL) to hostilities between states and nonstate armed groups, unless a state explicitly declares that it is engaged in an armed conflict. This essay argues, however, that a court should not defer to a state's characterization of hostilities, but should base its analysis on whether hostilities meet the criteria for an armed conflict. Applying HRL to hostilities that effectively are an armed conflict but not acknowledged as such risks diluting the legitimacy and normative force of HRL. On the one hand, if a court applies conventional stringent HRL standards, this body of law may be seen as unrealistic and is likely to be ignored. On the other hand, a court that adapts HRL standards to armed conflict may need to take a consequentialist approach at odds with HRL's deontological foundations. Clearly differentiating between HRL and IHL may thus best promote the humanization of warfare.

The COVID-19 pandemic and Black Lives Matter movement have brought ethnic and racial inequalities to the forefront of public conversation on both sides of the Atlantic. However, research shows that people routinely overestimate the progress made towards equality and underestimate disparities between racial and ethnic majority and minority groups. Common among the American public is a naive belief in equal opportunity that stands in sharp contrast to the reality of structural racial inequity. Across the Atlantic, Dutch people’s self-perception of a tolerant, progressive, and egalitarian society means that racism and discrimination are topics often avoided, rendering invisible the stigmatization of ethnic and racial minorities. The result is racism of omission: ethnic and racial disparities are minimized and attributed to factors other than discrimination, which leads to legitimize inequities and justify non-intervention. Against this background, we field an internationally comparative randomized survey experiment to study whether (willful) ignorance about racial and ethnic inequality can be addressed through the provision of information. We find that facts about ethnic and racial inequality, on the whole, (1) have the greatest impact on people’s perceptions of inequality as compared to their explanations of inequality and policy attitudes, (2) register most strongly with majority-group White participants as compared to participants from minority groups, (3) cut across partisan lines, and (4) effect belief change most consistently in the Netherlands, as compared to the United States. We make sense of these findings through the lens of how ‘shocking’ the information provided was to different groups of participants.

As the origin story of the present world political order the globalization of international society serves as a unifying frame for the discipline of international relations. This paper considers the consequences of the shift from the ‘expansion’ to the ‘globalization’ of international society in relation to two main texts: Hedley Bull's The Anarchical Society and Tim Dunne and Christian Reus-Smit's The Globalization of International Society. The analysis shows that Bull's conception of world order depends on a key distinction between aggregate and system which marks the difference between an aggregate of local political orders and a systematically unified world political order (a global international system). Because recent histories of the globalization of international society remain guided by Bull's distinction, they are unable to explain this transition in historical terms without transforming the global international order from the explanandum of the globalization of international society to its explanans. As a result, global histories of the globalization of international society grant a global international system a structural permanence the original expansion story was meant to contest. In doing so they change profoundly the kind of questions that can be asked regarding the origins, character, and future of political order on earth.

The objective of this study was to assess the effect of providing mats in the farrowing pen on behaviour and lesions in sows (n = 38) and piglets. Nineteen of the sows and their litters housed in farrowing crates with metal slatted floors were provided with mats, the remaining 19 acting as controls. Sow skin was inspected pre-farrowing and at weaning: the skin and feet of piglets were examined when they were 6 days old. Skin lesions were scored (on a scale of 0 to 6) according to severity. Total lesion scores per sow and median total lesion scores per litter were calculated. Sow behaviour was recorded by direct observation at feeding. Usage of a heat pad for lying in the presence or absence of mats was assessed over a 2hr observation period. Median skin lesion scores of sows did not differ between treatments. Litters from the control treatment had lower skin lesion scores (median [range] 8 [2-12] vs 10 [5-21]; P < 0.05). Median lesion scores of the front legs tended to be higher for piglets on mats (median [range] 8 [1.5-13] vs 4 [1.5-8]; ns). Sows on metal flooring went from kneeling to lowering their hindquarters faster (median [range] 15 [2—45] s) than sows on mats (23 [11—54] s) (P < 0.05). Furthermore, they slipped more on their front (median [range] 2.7 [0-8.7] vs 0 [0-1.3] slips min1; P < 0.001) and hind (median [range] 5.3 [0.3-31.7] vs 1.9 [0-33.3] slips min1; P < 0.05) feet while standing, than sows on mats. More piglets lay on the heat pad when it was covered by a mat (mean ± SEM 45.97 ± 4.49 %) than when no mat was provided (29.29 ± 4.47 %)(P < 0.05). Mats improve sow comfort and reduce slipping. They encourage piglets to lie on the heat pad but cause damage to the skin of the front legs. Providing pigs with mats in the farrowing house could greatly improve welfare on slatted floors, but further research is needed to identify materials that are less abrasive.

The COVID-19 crisis has forced healthcare professionals to make tragic decisions concerning which patients to save. Furthermore, The COVID-19 crisis has foregrounded the influence of self-serving bias in debates on how to allocate scarce resources. A utilitarian principle favors allocating scarce resources such as ventilators toward younger patients, as this is expected to save more years of life. Some view this as ageist, instead favoring age-neutral principles, such as “first come, first served”. Which approach is fairer? The “veil of ignorance” is a moral reasoning device designed to promote impartial decision-making by reducing decision-makers’ use of potentially biasing information about who will benefit most or least from the available options. Veil-of-ignorance reasoning was originally applied by philosophers and economists to foundational questions concerning the overall organization of society. Here we apply veil-of-ignorance reasoning to the COVID-19 ventilator dilemma, asking participants which policy they would prefer if they did not know whether they were younger or older. Two studies (pre-registered; online samples; Study 1, N=414; Study 2 replication, N=1,276) show that veil-of-ignorance reasoning shifts preferences toward saving younger patients. The effect on older participants is dramatic, reversing their opposition toward favoring the young, thereby eliminating self-serving bias. These findings provide guidance on how to remove self-serving biases to healthcare policymakers and frontline personnel charged with allocating scarce medical resources during times of crisis.