The stars of the Milky Way carry the chemical history of our Galaxy in their atmospheres as they journey through its vast expanse. Like barcodes, we can extract the chemical fingerprints of stars from high-resolution spectroscopy. The fourth data release (DR4) of the Galactic Archaeology with HERMES (GALAH) Survey, based on a decade of observations, provides the chemical abundances of up to 32 elements for 917 588 stars that also have exquisite astrometric data from the Gaia satellite. For the first time, these elements include life-essential nitrogen to complement carbon, and oxygen as well as more measurements of rare-earth elements critical to modern-life electronics, offering unparalleled insights into the chemical composition of the Milky Way. For this release, we use neural networks to simultaneously fit stellar parameters and abundances across the whole wavelength range, leveraging synthetic grids computed with Spectroscopy Made Easy. These grids account for atomic line formation in non-local thermodynamic equilibrium for 14 elements. In a two-iteration process, we first fit stellar labels to all 1 085 520 spectra, then co-add repeated observations and refine these labels using astrometric data from Gaia and 2MASS photometry, improving the accuracy and precision of stellar parameters and abundances. Our validation thoroughly assesses the reliability of spectroscopic measurements and highlights key caveats. GALAH DR4 represents yet another milestone in Galactic archaeology, combining detailed chemical compositions from multiple nucleosynthetic channels with kinematic information and age estimates. The resulting dataset, covering nearly a million stars, opens new avenues for understanding not only the chemical and dynamical history of the Milky Way but also the broader questions of the origin of elements and the evolution of planets, stars, and galaxies.

Multidimensional probabilistic models of behavior following similarity and choice judgements have proven to be useful in representing multidimensional percepts in Euclidean and non-Euclidean spaces. With few exceptions, these models are generally computationally intense because they often require numerical work with multiple integrals. This paper focuses attention on a particularly general triad and preferential choice model previously requiring the numerical evaluation of a 2n-fold integral, where n is the number of elements in the vectors representing the psychological magnitudes. Transforming this model to an indefinite quadratic form leads to a single integral. The significance of this form to multidimensional scaling and computational efficiency is discussed.

Multivariate models for the triangular and duo-trio methods are described in this paper. In both cases, the mathematical formulation of Euclidean models for these methods is derived and evaluated for the bivariate case using numerical quadrature. Theoretical results are compared with those obtained using Monte Carlo simulation which is validated by comparison with previously published theoretical results for univariate models of these methods. This work is discussed in light of its importance to the development of a new theory for multidimensional scaling in which the traditional assumption can be eliminated that proximity measures and perceptual distances are monotonically related.

We present high-resolution observations of nearby ($z\lesssim0.1$) galaxies that have hosted Type Ia supernovae to measure systemic spectroscopic redshifts using the wide field spectrograph (WiFeS) instrument on the Australian National University 2.3 m telescope at Siding Spring Observatory. While most of the galaxies targeted have previous spectroscopic redshifts, we provide demonstrably more accurate and precise redshifts with competitive uncertainties, motivated by potential systematic errors that could bias estimates of the Hubble constant ($H_0$). The WiFeS instrument is remarkably stable; after calibration, the wavelength solution varies by $\lesssim$0.5 Å in red and blue with no evidence of a trend over the course of several years. By virtue of the $25\times 38$ arcsec field of view, we are always able to measure the redshift of the galactic core, or the entire galaxy in the cases where its angular extent is smaller than the field of view, reducing any errors due to galaxy rotation. We observed 185 southern SN Ia host galaxies and measured the redshift of each via at least one spatial region of (a) the core and (b) the average over the full-field/entire galaxy. Overall, we find stochastic differences between historical redshifts and our measured redshifts on the order of $\lesssim10^{-3}$ with a mean offset of 4.3${\times 10^{-5}}$ and normalised median absolute deviation of 1.2${\times 10^{-4}}$. We show that a systematic redshift offset at this level is not enough to bias cosmology, as $H_0$ shifts by $+0.1$ km s$^{-1}$ Mpc$^{-1}$ when we replace Pantheon+ redshifts with our own, but the occasional large differences are interesting to note.

Operationalization guidance is needed to support health technology assessment (HTA) bodies considering implementing lifecycle HTA (LC-HTA) approaches. The 2022 Health Technology Assessment International (HTAi) Global Policy Forum (GPF) established a Task Force to develop a position paper on LC-HTA. In its first paper, the Task Force established a definition and framework for LC-HTA in order to tailor it to specific decision problems. This second paper focused on the provision of practical operational guidance to implement LC-HTA. Detailed descriptions of the three LC-HTA operational steps are provided (defining the decision problem, sequencing of HTA activities, and developing optimization criteria) and accompanied by worked examples and an operationalization checklist with 20 different questions for HTA bodies to consider when developing an LC-HTA approach. The questions were designed to be applicable across different types of HTA and scenarios, and require adaptation to local jurisdictions, remits, and context.

The 2022 Health Technology Assessment International (HTAi) Global Policy Forum (GPF) established the goal of developing a position statement and framework for lifecycle HTA (LC-HTA), through a Task Force leveraging multi-stakeholder monthly discussions and GPF member input. The Task Force developed a working definition: LC-HTA is a systematic process utilizing sequential HTA activities to inform decision making where the evidence base, the health technology itself, or the context in which it is applied, has a potential to meaningfully change at different points in its LC. Four key scenarios were identified where it was considered that an LC-HTA approach would add sufficient value to HTA bodies and their key stakeholders to justify the additional resource burden. Based on the four scenarios, a high-level LC-HTA framework was developed consisting of (i) defining the decision problem, (ii) sequencing of HTA activities, and (iii) developing optimization criteria. Subsequently, the Task Force developed operationalization guidance for LC-HTA in a companion paper.

New technologies and disruptions related to Coronavirus disease-2019 have led to expansion of decentralized approaches to clinical trials. Remote tools and methods hold promise for increasing trial efficiency and reducing burdens and barriers by facilitating participation outside of traditional clinical settings and taking studies directly to participants. The Trial Innovation Network, established in 2016 by the National Center for Advancing Clinical and Translational Science to address critical roadblocks in clinical research and accelerate the translational research process, has consulted on over 400 research study proposals to date. Its recommendations for decentralized approaches have included eConsent, participant-informed study design, remote intervention, study task reminders, social media recruitment, and return of results for participants. Some clinical trial elements have worked well when decentralized, while others, including remote recruitment and patient monitoring, need further refinement and assessment to determine their value. Partially decentralized, or “hybrid” trials, offer a first step to optimizing remote methods. Decentralized processes demonstrate potential to improve urban-rural diversity, but their impact on inclusion of racially and ethnically marginalized populations requires further study. To optimize inclusive participation in decentralized clinical trials, efforts must be made to build trust among marginalized communities, and to ensure access to remote technology.

In a survey of infection prevention programs, leaders reported frequent clinical and infection prevention practice modifications to avoid coronavirus disease 2019 (COVID-19) exposure that exceeded national guidance. Future pandemic responses should emphasize balanced approaches to precautions, prioritize educational campaigns to manage safety concerns, and generate an evidence-base that can guide appropriate infection prevention practices.

Precision Medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle. Autoimmune diseases are those in which the body’s natural defense system loses discriminating power between its own cells and foreign cells, causing the body to mistakenly attack healthy tissues. These conditions are very heterogeneous in their presentation and therefore difficult to diagnose and treat. Achieving precision medicine in autoimmune diseases has been challenging due to the complex etiologies of these conditions, involving an interplay between genetic, epigenetic, and environmental factors. However, recent technological and computational advances in molecular profiling have helped identify patient subtypes and molecular pathways which can be used to improve diagnostics and therapeutics. This review discusses the current understanding of the disease mechanisms, heterogeneity, and pathogenic autoantigens in autoimmune diseases gained from genomic and transcriptomic studies and highlights how these findings can be applied to better understand disease heterogeneity in the context of disease diagnostics and therapeutics.

OBJECTIVES/GOALS: Recent research has attempted to identify diagnostic, prognostic, and predictive biomarkers, however, currently, no biomarkers can accurately diagnose GBC and predict patients prognosis. Using machine learning, we can utilize high-throughput RNA sequencing with clinicopathologic data to develop a predictive tool for GBC prognosis. METHODS/STUDY POPULATION: Current predictive models for GBC outcomes often utilize clinical data only. We aim to build a superior algorithm to predict overall survival in GBC patients with advanced disease, using machine learning approaches to prioritize biomarkers for GBC prognosis. We have identified over 80 fresh frozen GBC tissue samples from Rochester, Minnesota, Daegu, Korea, Vilnius, Lithuania, and Calgary, Canada. We will perform next-generation RNA sequencing on these tissue samples. The patients clinical, pathologic and survival data will be abstracted from the medical record. Random forests, support vector machines, and gradient boosting machines will be applied to train the data. Standard 5-fold cross validation will be used to assess performance of each ML algorithm. RESULTS/ANTICIPATED RESULTS: Our preliminary analysis of next generation RNA sequencing from 18 GBC tissue samples identified recurrent mutations in genes enriched in pathways in cytoskeletal signaling, cell organization, cell movement, extracellular matrix interaction, growth, and proliferation. The top three most significantly altered pathways, actin cytoskeleton signaling, hepatic fibrosis/hepatic stellate cell activation, and epithelial adherens junction signaling, emphasized a molecular metastatic and invasive fingerprint in our patient cohort. This molecular fingerprint is consistent with the previous knowledge of the highly metastatic nature of gallbladder tumors and is also manifested physiologically in the patient cohort. DISCUSSION/SIGNIFICANCE: Integrative analysis of molecular and clinical characterization of GBC has not been fully established, and minimal improvement has been made to the survival of these patients. If overall survival can be better predicted, we can gain a greater understanding of key biomarkers driving the tumor phenotype.

Introduction. Exercise interventions may assist smoking cessation attempts. One such publicly available 10-week program, Walk or Run to Quit (WRTQ), demonstrated success in smoking cessation and physical activity (PA) outcomes. However, initial WRTQ participants (2016-2017) were fairly homogenous in their demographic profile. To increase diversity, subsidies for participation were offered in 2018. This study assessed how the subsidies affected participant demographics, running frequency, smoking cessation, intention to quit, and program attendance and completion. Methods. The $70 registration fee was subsidized for 41% of participants in 2018. A pre-postdesign was used, with participants completing surveys on their demographics and smoking and physical activity behaviours. Descriptive statistics compared the year subsidies were available (2018) and unsubsidized years (2016-2017) and subsidized and unsubsidized participants’ data from 2018. Results. The 2018 participants had lower average attendance and program completion rates compared to 2016-2017 and no statistically significant differences in demographics or smoking cessation and PA outcomes. There were no differences in smoking cessation, run frequency, or demographic variables between the subsidized and unsubsidized participants in 2018. Conclusions. Offering subsidies did not diversify the participant profile. Subsidies did not have a negative impact on attendance nor primary outcomes. Subsidies may not have addressed barriers that prevented a more diverse sample from participating in WRTQ, such as program location, timing, and design. Equitable access to smoking cessation programs remains essential. As subsidies may play a role in reducing financial barriers disproportionately faced by marginalized groups, the implementation of, and recruitment for, such subsidized programs requires further investigation.

Extra virgin olive oil is often associated with anti-inflammatory and antioxidant properties. Its effects on inflammatory conditions such as ulcerative colitis (UC), however, have yet to be defined. As such, we aimed to conduct a systematic review and meta-analysis of studies investigating olive-based interventions in UC. A comprehensive database search for randomised controlled trials was performed between 9 July 2018 and 16 August 2018. Studies identified from search alerts were included up to 22 June 2020. Both individuals living with UC at any disease stage and murine models of UC were included in this review. No human trials meeting the eligibility criteria were identified, while nineteen animal studies comprised 849 murine models of UC were included in this review. Pooling of the data could not be performed due to heterogeneous outcomes; however, general trends favouring olive-based interventions were identified. Milder disease expression including weight maintenance, reduced rectal bleeding and well-formed stools favouring olive-based interventions was statistically significant in 16/19 studies, with moderate-to-large effect sizes (−0·66 (95 % CI −1·56, 0·24) to −12·70 (95 % CI −16·8, −8·7)). Olive-based interventions did not prevent the development of colitis-like pathologies in any study. In conclusion, effects of olive-based interventions on murine models of UC appear promising, with milder disease outcomes favouring the intervention in most trials and effect sizes suggesting potential clinical relevance. However, the lack of published randomised controlled human trials warrants further investigation to determine if these effects would translate to individuals living with UC.

The Maintain Your Brain (MYB) trial is one of the largest internet-delivered multidomain randomised controlled trial designed to target modifiable risk factors for dementia. It comprises four intervention modules: physical activity, nutrition, mental health and cognitive training. This paper explains the MYB Nutrition Module, which is a fully online intervention promoting the adoption of the ‘traditional’ Mediterranean Diet (MedDiet) pattern for those participants reporting dietary intake that does not indicate adherence to a Mediterranean-type cuisine or those who have chronic diseases/risk factors for dementia known to benefit from this type of diet. Participants who were eligible for the Nutrition Module were assigned to one of the three diet streams: Main, Malnutrition and Alcohol group, according to their medical history and adherence to the MedDiet at baseline. A short dietary questionnaire was administered weekly during the first 10 weeks and then monthly during the 3-year follow-up to monitor whether participants adopted or maintained the MedDiet pattern during the intervention. As the Nutrition Module is a fully online intervention, resources that promoted self-efficacy, self-management and process of change were important elements to be included in the module development. The Nutrition Module is unique in that it is able to individualise the dietary advice according to both the medical and dietary history of each participant; the results from this unique intervention will contribute substantively to the evidence that links the Mediterranean-type diet with cognitive function and the prevention of dementia and will increase our understanding of the benefits of a MedDiet in a Western country.

Introduction. Smoking prevalence is disproportionately high among Asian American immigrant men with limited English proficiency. Understanding the role of family support may provide insights into culturally acceptable strategies to promote smoking cessation. Aims. This study examined how family support was associated with readiness to consider smoking cessation among Chinese and Vietnamese American male daily smokers. Methods. We analyzed baseline data (N = 340) from a cluster randomized trial of a family-based healthy lifestyle intervention. We assessed the frequency of receiving family support in various forms (encouraging use of cessation resources, praising efforts, checking in, and reminding of familial role). Multiple regression analysis was used to determine associations between family support areas and readiness to consider smoking cessation, controlling for covariates. Results/Findings. Reporting a higher frequency of receiving praise and encouragement for one’s efforts to quit was positively associated with readiness to consider cessation. Other areas of family support were not significant. Conclusions. These findings provide evidence to explore specific areas of family support in enhancing Asian American smokers’ readiness to consider cessation. As there is high interest from Asian American family members to support their smokers for quitting, culturally specific and acceptable strategies are needed to promote smoking cessation among Asian Americans.

Dietary protein is a pre-requisite for the maintenance of skeletal muscle mass; stimulating increases in muscle protein synthesis (MPS), via essential amino acids (EAA), and attenuating muscle protein breakdown, via insulin. Muscles are receptive to the anabolic effects of dietary protein, and in particular the EAA leucine, for only a short period (i.e. about 2–3 h) in the rested state. Thereafter, MPS exhibits tachyphylaxis despite continued EAA availability and sustained mechanistic target of rapamycin complex 1 signalling. Other notable characteristics of this ‘muscle full’ phenomenon include: (i) it cannot be overcome by proximal intake of additional nutrient signals/substrates regulating MPS; meaning a refractory period exists before a next stimulation is possible, (ii) it is refractory to pharmacological/nutraceutical enhancement of muscle blood flow and thus is not induced by muscle hypo-perfusion, (iii) it manifests independently of whether protein intake occurs in a bolus or intermittent feeding pattern, and (iv) it does not appear to be dependent on protein dose per se. Instead, the main factor associated with altering muscle full is physical activity. For instance, when coupled to protein intake, resistance exercise delays the muscle full set-point to permit additional use of available EAA for MPS to promote muscle remodelling/growth. In contrast, ageing is associated with blunted MPS responses to protein/exercise (anabolic resistance), while physical inactivity (e.g. immobilisation) induces a premature muscle full, promoting muscle atrophy. It is crucial that in catabolic scenarios, anabolic strategies are sought to mitigate muscle decline. This review highlights regulatory protein turnover interactions by dietary protein, exercise, ageing and physical inactivity.

Deliberative processes are a well-established part of health technology assessment (HTA) programs in a number of high- and middle-income countries, and serve to combine complex sets of evidence, perspectives, and values to support open, transparent, and accountable decision making. Nevertheless, there is little documentation and research to inform the development of effective and efficient deliberative processes, and to evaluate their quality. This article summarizes the 2020 HTAi Global Policy Forum (GPF) discussion on deliberative processes in HTA.

Through a combination of small and large group discussion and successive rounds of polling, the GPF members reached strong agreement on three core principles for deliberative processes in HTA: transparency, inclusivity, and impartiality. In addition, discussions revealed other important principles, such as respect, reviewability, consistency, and reasonableness, that may supplement the core set. A number of associated supporting actions for each of the principles are also described in order to make each principle realizable in a given HTA setting. The relative importance of the principles and actions are context-sensitive and must be considered in light of the political, legislative, and operational factors that may influence the functioning of any particular HTA environment within which the deliberative process is situated. The paper ends with suggested concrete next steps that HTA agencies, researchers, and stakeholders might take to move the field forward. The proposed principles and actions, and the next steps, provide a springboard for further research and better documentation of important aspects of deliberation that have historically been infrequently studied.