Barrett’s oesophagus (BE) is the precursor of oesophageal adenocarcinoma, which has become the most common type of oesophageal cancer in many Western populations. Existing evidence on diet and risk of BE predominantly comes from case–control studies, which are subject to recall bias in measurement of diet. We aimed to investigate the potential effect of diet, including macronutrients, carotenoids, food groups, specific food items, beverages and dietary scores, on risk of BE in over 20 000 participants of the Melbourne Collaborative Cohort Study. Diet at baseline (1990–1994) was measured using a food frequency questionnaire. The outcome was BE diagnosed between baseline and follow-up (2007–2010). Logistic regression models were used to estimate OR and 95 % CI for diet in relation to risk of BE. Intakes of leafy vegetables and fruit were inversely associated with risk of BE (highest v. lowest quartile: OR = 0·59; CI: 0·38, 0·94; P-trend = 0·02 and OR = 0·58; CI: 0·37, 0·93; P-trend = 0·02 respectively), as were dietary fibre and carotenoids. Stronger associations were observed for food than the nutrients found in them. Positive associations were observed for discretionary food (OR = 1·54; CI: 0·97, 2·44; P-trend = 0·04) and total fat intake (OR per 10 g/d = 1·11; CI: 1·00, 1·23), the association for fat was less robust in sensitivity analyses. No association was observed for meat, protein, dairy products or diet scores. Diet is a potential modifiable risk factor for BE. Public health and clinical guidelines that incorporate dietary recommendations could contribute to reduction in risk of BE and, thereby, oesophageal adenocarcinoma.

The Hierarchical Taxonomy of Psychopathology (HiTOP) has emerged out of the quantitative approach to psychiatric nosology. This approach identifies psychopathology constructs based on patterns of co-variation among signs and symptoms. The initial HiTOP model, which was published in 2017, is based on a large literature that spans decades of research. HiTOP is a living model that undergoes revision as new data become available. Here we discuss advantages and practical considerations of using this system in psychiatric practice and research. We especially highlight limitations of HiTOP and ongoing efforts to address them. We describe differences and similarities between HiTOP and existing diagnostic systems. Next, we review the types of evidence that informed development of HiTOP, including populations in which it has been studied and data on its validity. The paper also describes how HiTOP can facilitate research on genetic and environmental causes of psychopathology as well as the search for neurobiologic mechanisms and novel treatments. Furthermore, we consider implications for public health programs and prevention of mental disorders. We also review data on clinical utility and illustrate clinical application of HiTOP. Importantly, the model is based on measures and practices that are already used widely in clinical settings. HiTOP offers a way to organize and formalize these techniques. This model already can contribute to progress in psychiatry and complement traditional nosologies. Moreover, HiTOP seeks to facilitate research on linkages between phenotypes and biological processes, which may enable construction of a system that encompasses both biomarkers and precise clinical description.

OBJECTIVES/GOALS: A functional precision medicine platform to identify therapeutic targets for a glioblastoma patient with Li Fraumeni syndrome was performed. Comparative transcriptomics identified druggable targets and patient derived organoids and a 3D-PREDICT drug screening assay was used to validate the pipeline and identify further therapeutic targets. METHODS/STUDY POPULATION: A comparative transcriptomics pipeline was used to identify druggable genes that are uniquely overexpressed in our patient of interest relative to a cancer compendium of 12,747 tumor RNA sequencing datasets including 200 GBMs. Mini-ring patient derived organoid-based drug viability assays were performed to validate the comparative transcriptomics data. Additionally, a spheroid-based drug screening assay (3D-PREDICT) was performed and used to identify further therapeutic targets. RESULTS/ANTICIPATED RESULTS: Using comparative transcriptomics STAT1 and STAT2 were found to be significantly overexpressed in our patient, indicating ruxolitinib, a Janus kinase 1 and 2 inhibitor, as a potential therapy. Druggable pathways predicted using comparative transcriptomics corresponded with ruxolitinib sensitivity in a panel of patient derived organoids screened with this compound. Cells from the LFS patient were among the most sensitive to ruxolitinib compared to patient-derived cells with lower STAT1 and STAT2 expression levels. Additionally, 3D-PREDICT screening identified the mTOR inhibitor everolimus as a potential candidate. These two targeted therapies were selected for our patient and resulted in radiographic disease stability. DISCUSSION/SIGNIFICANCE: This research illustrates the use of comparative transcriptomics to identify druggable pathways irrespective of actionable DNA mutations present. Our results are promising and serve to highlight the importance of functional precision medicine in tailoring treatment regimes to specific patients.

The present study reports the validity of multiple assessment methods for tracking changes in body composition over time and quantifies the influence of unstandardised pre-assessment procedures. Resistance-trained males underwent 6 weeks of structured resistance training alongside a hyperenergetic diet, with four total body composition evaluations. Pre-intervention, body composition was estimated in standardised (i.e. overnight fasted and rested) and unstandardised (i.e. no control over pre-assessment activities) conditions within a single day. The same assessments were repeated post-intervention, and body composition changes were estimated from all possible combinations of pre-intervention and post-intervention data. Assessment methods included dual-energy X-ray absorptiometry (DXA), air displacement plethysmography, three-dimensional optical imaging, single- and multi-frequency bioelectrical impedance analysis, bioimpedance spectroscopy and multi-component models. Data were analysed using equivalence testing, Bland–Altman analysis, Friedman tests and validity metrics. Most methods demonstrated meaningful errors when unstandardised conditions were present pre- and/or post-intervention, resulting in blunted or exaggerated changes relative to true body composition changes. However, some methods – particularly DXA and select digital anthropometry techniques – were more robust to a lack of standardisation. In standardised conditions, methods exhibiting the highest overall agreement with the four-component model were other multi-component models, select bioimpedance technologies, DXA and select digital anthropometry techniques. Although specific methods varied, the present study broadly demonstrates the importance of controlling and documenting standardisation procedures prior to body composition assessments across distinct assessment technologies, particularly for longitudinal investigations. Additionally, there are meaningful differences in the ability of common methods to track longitudinal body composition changes.

Behavioral and psychological symptoms of dementia (BPSD), constitute a major clinical component of Alzheimer’s disease (AD). There is a growing interest in BPSD as they are responsible for a large share of the suffering of patients and caregivers, and they strongly determine the patient’s lifestyle and management. Better detection and understanding of these symptoms is essential to provide appropriate management. This article is a consensus produced by the behavioral group of the European Alzheimer’s Disease Consortium (EADC). The aim of this article is to present clinical description and biological correlates of the major behavioral and psychological symptomatology in AD. BPSD is not a unitary concept. Instead, it should be divided into several symptoms or more likely: groups of symptoms, each possibly reflecting a different prevalence, course over time, biological correlate and psychosocial determinants. There is some clinical evidence for clusters within groups of BPSD. Biological studies indicate that patients with AD and BPSD are associated with variations in the pathological features (atrophy, brain perfusion/metabolism, histopathology) when compared to people with AD without BPSD. An individually tailored approach taking all these aspects into account is warranted as it may offer more, and better, pharmacological and non-pharmacological treatment opportunities.

We introduce Hypercat, a large set of 2-d AGN torus images computed with the state-of-the-art clumpy radiative transfer code Clumpy. The images are provided as a 9-dimensional hypercube, in addition to a smaller hypercube of corresponding projected dust distribution maps. Hypercat also comprises a software suite for easy use of the hypercubes, quantification of image morphology, and simulation of synthetic observations with single-dish telescopes, interferometers, and Integral Field Units. We apply Hypercat to NGC 1068 and find that it can be spatially resolved in Near- and Mid-IR, for the first time with single-dish apertures, on the upcoming generation of 25–40m class telescopes. We also find that clumpy AGN torus models within a range of the parameter space can explain on scales of several parsec the recently reported polar elongation of MIR emission in several sources, while not upending basic assumptions about AGN unification.

Drawing on a landscape analysis of existing data-sharing initiatives, in-depth interviews with expert stakeholders, and public deliberations with community advisory panels across the U.S., we describe features of the evolving medical information commons (MIC). We identify participant-centricity and trustworthiness as the most important features of an MIC and discuss the implications for those seeking to create a sustainable, useful, and widely available collection of linked resources for research and other purposes.

As the IAU heads towards its second century, many changes have simultaneously transformed Astronomy and the human condition world-wide. Amid the amazing recent discoveries of exoplanets, primeval galaxies, and gravitational radiation, the human condition on Earth has become blazingly interconnected, yet beset with ever-increasing problems of over-population, pollution, and never-ending wars. Fossil-fueled global climate change has begun to yield perilous consequences. And the displacement of people from war-torn nations has reached levels not seen since World War II.

The Astroinformatics Program is funded by the Chilean Economy Ministry’s (FIE Grant FIE-2016-V022, CORFO Grant 16IFI6626) with the mission to identify and initiate investments to foster Chilean Digital Economy, using Astronomy data-centric tools (known as astroinformatics). Over 2017 we worked with communities across sectors identifying opportunities to achieve the program mission, the Data Observatory vision emerged from that work and will guide design activities throughout 2018.

Introduction: Each year about two thirds of U.S. smokers make a quit attempt. Yet, less than 5% remain abstinent three months post-quit date. One factor that may affect abstinence is negative feelings about the self-associated with being a smoker (disequilibrium), particularly if smoking is important to the sense of self and one is trying to quit.

Aims: We evaluated a multivariate structural equation model proposing that smoking's subjective importance to a smoker would influence carbon monoxide verified smoking abstinence at 24 weeks (post-quit date). Further, we assessed whether the relation would be moderated by the smoker's experience of disequilibrium.

Methods: Participants were 440 regular smokers taking part in a clinical trial assessing the effectiveness of different durations of nicotine replacement therapy use. Participants completed the subjective importance of smoking survey at baseline and were assessed for carbon monoxide verified seven-day point prevalence abstinence at 24 weeks

Results: Using exploratory structural equation modelling, the subjective importance of smoking was associated with point prevalence abstinence at 24 weeks, but only for smokers with high disequilibrium.

Conclusions: The results of this study suggest that experiencing negative feelings about being a smoker could motivate smokers to remain abstinent, despite the importance of smoking to the smoker's sense of self.

Protected areas have been established historically in residual places where the potential for extractive uses is low, implying that places at risk are usually under-protected. Argentina is no exception, with few protected areas established in productive regions that are prone to conversion. Here, using reptiles as a study group and considering the most important human threats in north-western Argentina, we estimated priority conservation areas where we expect species to persist in the face of climate change and land conversion. Protected areas cover no more than 9% of the study region, but represent less than 15% of reptile distributions. There are great opportunities for improving the conservation status in the region by protecting only 8% more of north-western Argentina, with the level of species protection inside the protected area network increasing almost four-fold, reaching 43% of species distributions on average and 59% of the distributions of threatened reptiles. Fortunately, the highest diversity of reptiles in the region does not match the places targeted for agriculture expansion. Our findings suggest that future prioritization schemes should embrace other groups that are especially diverse in the Chaco ecoregion, which overlaps with our study area.

We studied neuroinflammation in individuals with late-life, depression, as a risk factor for dementia, using [11C]PK11195 positron emission tomography (PET). Five older participants with major depression and 13 controls underwent PET and multimodal 3T magnetic resonance imaging (MRI), with blood taken to measure C-reactive protein (CRP). We found significantly higher CRP levels in those with late-life depression and raised [11C]PK11195 binding compared with controls in brain regions associated with depression, including subgenual anterior cingulate cortex, and significant hippocampal subfield atrophy in cornu ammonis 1 and subiculum. Our findings suggest neuroinflammation requires further investigation in late-life depression, both as a possible aetiological factor and a potential therapeutic target.