The Falerii Novi Project represents a newly formed archaeological initiative to explore the Roman city of Falerii Novi. The project forms a collaboration of the British School at Rome with a multinational team of partner institutions. Thanks to a rich legacy of geophysical work on both the site and its territory, Falerii Novi presents an exceptional opportunity to advance understanding of urbanism in ancient and medieval Italy. The Falerii Novi Project employs a range of methodologies, integrating continued site-scale survey with new campaigns of stratigraphic excavation, archival research and environmental archaeology. The project aims to present a more expansive and holistic urban history of this key Tiber Valley settlement by focusing on long-run socio-economic processes both within Falerii Novi and as they linked the city to its wider landscape.

This review describes a computational approach for modeling the development of speech motor control in infants. We address the development of two levels of control: articulation of individual speech sounds (defined here as phonemes, syllables, or words for which there is an optimized motor program) and production of sound sequences such as phrases or sentences. We describe the DIVA model of speech motor control and its application to the problem of learning individual sounds in the infant’s native language. Then we describe the GODIVA model, an extension of DIVA, and how chunking of frequently produced phoneme sequences is implemented within it.

For a Galois extension $K/F$ with $\text {char}(K)\neq 2$ and $\mathrm {Gal}(K/F) \simeq \mathbb {Z}/2\mathbb {Z}\oplus \mathbb {Z}/2\mathbb {Z}$ , we determine the $\mathbb {F}_{2}[\mathrm {Gal}(K/F)]$ -module structure of $K^{\times }/K^{\times 2}$ . Although there are an infinite number of (pairwise nonisomorphic) indecomposable $\mathbb {F}_{2}[\mathbb {Z}/2\mathbb {Z}\oplus \mathbb {Z}/2\mathbb {Z}]$ -modules, our decomposition includes at most nine indecomposable types. This paper marks the first time that the Galois module structure of power classes of a field has been fully determined when the modular representation theory allows for an infinite number of indecomposable types.

OBJECTIVES/GOALS: Osteoarthritis (OA) is a cartilage destroying disease. We are investigating abaloparatide (ABL) activation of parathyroid hormone receptor type 1 (PTH1R), which is expressed by articular chondrocytes in OA. We propose ABL treatment is chondroprotective in murine PTOA via stimulation of matrix production and inhibition of chondrocyte maturation. METHODS/STUDY POPULATION: 16-week-old C57BL/6 male mice received destabilization of the medial meniscus (DMM) surgery to induce knee PTOA. Beginning 2 weeks post-DMM, 40 μg/kg of ABL (or saline) was administered daily via subcutaneous injection and tissues were harvested after 6 weeks of daily injections and 8 weeks after DMM surgery. Harvested joint tissues were used for histological and molecular assessment of OA using three 5 μm thick sagittal sections from each joint, 50 μm apart, cut from the medial compartment of injured knees. Safranin O/Fast Green tissue staining and immunohistochemistry-based detection of type 10 collagen (Col10) and lubricin (Prg4) was performed using standard methods. Histomorphometric quantification of tibial cartilage area and larger hypertrophic-like cells was performed using the Osteomeasure system. RESULTS/ANTICIPATED RESULTS: Safranin O/Fast Green stained sections showed a decreased cartilage loss in DMM joints from ABL-treated versus saline-treated mice. Histomorphometric analysis of total tibial cartilage area revealed preservation of cartilage tissue on the tibial surface. Immunohistochemical analyses showed that upregulation of Col10 in DMM joints was mitigated in the cartilage of ABL-treated mice, and chondrocyte expression of Prg4 was increased in uncalcified cartilage areas in ABL-treated group. The Prg4 finding suggests a matrix anabolic effect that may counter OA cartilage loss. Quantification of chondrocytes in uncalcified and calcified tibial cartilage areas revealed a reduction in the number of larger hypertrophic-like cells in ABL treated mice, suggesting deceleration of hypertrophic differentiation. DISCUSSION/SIGNIFICANCE: Cartilage preservation/regeneration therapies would fill a critical unmet need. We demonstrate that an osteoporosis drug targeting PTH1R decelerates PTOA in mice. ABL treatment was associated with preservation of cartilage, decreased Col10, increased Prg4, and decreased number of large hypertrophic-like chondrocytes in the tibial cartilage.

ABSTRACT IMPACT: Our data reveal a histone modifying enzyme involved in regulating inflammation that may be a novel target for treating non-healing diabetic wounds. OBJECTIVES/GOALS: We investigate molecular mechanisms that regulate the inflammatory phenotype of macrophages in normal and diabetic wound healing. Our goal is to identify novel pathways that may be used to better treat diabetic patients with non-healing wounds. METHODS/STUDY POPULATION: We utilize normal and transgenic murine models on standard chow or high-diet to identify chromatin modifying enzymes involved in regulating macrophage function during wound healing. We validate our murine studies with human blood monocytes or wound macrophages from diabetic patients undergoing limb amputation surgery. RESULTS/ANTICIPATED RESULTS: We have identified the histone methyltransferase SETDB2 as a regulator inflammation in normal and diabetic wound macrophages. We found that SETDB2 was dependent on IFNβ singaling and that both IFNβ and Setdb2 expression were impaired in diabetic wound macrophages. Further, we show that SETDB2 regulates inflammatory response and immune cell trafficking pathways. We also show that SETDB2 genomic localization is dependent on *NFκΒ deposition of the promoter. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our results indicate that SETDB2 is a regulator of macrophage plasticity and that SETDB2 expression is impaired in diabetic wound macrophages leading to hyper-inflammatory response and delayed wound healing. These data provide a novel potential therapeutic pathway for treating non-healing diabetic wounds.

Darwin's frogs Rhinoderma darwinii and Rhinoderma rufum are the only known species of amphibians in which males brood their offspring in their vocal sacs. We propose these frogs as flagship species for the conservation of the Austral temperate forests of Chile and Argentina. This recommendation forms part of the vision of the Binational Conservation Strategy for Darwin's Frogs, which was launched in 2018. The strategy is a conservation initiative led by the IUCN SSC Amphibian Specialist Group, which in 2017 convened 30 governmental, non-profit and private organizations from Chile, Argentina and elsewhere. Darwin's frogs are iconic examples of the global amphibian conservation crisis: R. rufum is categorized as Critically Endangered (Possibly Extinct) on the IUCN Red List, and R. darwinii as Endangered. Here we articulate the conservation planning process that led to the development of the conservation strategy for these species and present its main findings and recommendations. Using an evidence-based approach, the Binational Conservation Strategy for Darwin's Frogs contains a comprehensive status review of Rhinoderma spp., including critical threat analyses, and proposes 39 prioritized conservation actions. Its goal is that by 2028, key information gaps on Rhinoderma spp. will be filled, the main threats to these species will be reduced, and financial, legal and societal support will have been achieved. The strategy is a multi-disciplinary, transnational endeavour aimed at ensuring the long-term viability of these unique frogs and their particular habitat.

Glycemic, insulinemic and lipemic postprandial responses are multi-factorial and contribute to diabetes, obesity and CVD. The aim of the PREDICT I study is to assess the genetic, metabolic, metagenomic, and meal-context contribution to postprandial responses, integrating the metabolic burden and gut microbiome to predict individual responses to food using a machine learning algorithm.

A multi-center postprandial study of 1,000 individuals from the UK (unrelated, identical and non-identical twins) and 100 unrelated individuals from the US, assessed postprandial (0–6h) metabolic responses to sequential mixed-nutrient dietary challenges (50 g fat and 85 g carbohydrate at 0 h; 22 g fat and 71 g carbohydrate at 4h) in a clinic setting. Glycemic responses to 5 duplicate isocaloric meals of different macronutrient content and self-selected meals (> 100,000), were tested at home using a continuous glucose monitor (CGM). Baseline factors included metabolomics, genomics, gut metagenomics and body composition. Genetic contributions to postprandial responses were determined by classical twin methods.

Inter-individual variability in postprandial responses (glucose, insulin and triacylglycerol (TG)) was high in the clinic setting: iAUC IQR (median) was (n = 644); glucose (0–2h) 1.97 (1.89) mmol/L.h, insulin (0–2h) 45.6 (67.7) mIU/L.h and TG (0–6h) 2.37 (2.42) mmol/L.h. The unadjusted genetic contribution for glucose, insulin and TG responses were 54%, 29% and 27% respectively. Within-individual concordance (ICC) in glucose responses (iAUC 0–2h) for at home duplicate isocaloric meals was moderate-to-high, depending on the test meal: ICC (95%CI) was; high carbohydrate 0.62 (0.58,0.66), (carbohydrate = 95g/76% energy; n = 764), average lunch 0.57 (0.53, 0.62) (carbohydrate = 68g/54% energy; n = 763), OGTT 0.65 (0.61,0.70) (carbohydrate = 75 g; n = 754), high fat 0.35 (0.28, 0.41) (fat = 40g/71% energy; n = 576) and high protein 0.56, (0.48,0.62) (protein = 41g/32% energy; n = 364). An interim machine learning algorithm predicted 46% of the variation in glycemic responses based on meal content, meal context and participant's baseline characteristics, excluding genetic and microbiome features. Only 29% of variation could be explained by the macronutrient content of the meal.

This is the most comprehensive postprandial study performed to date. The large and modifiable variation in metabolic responses to identical meals in healthy people explains why ‘one size fits all’ nutritional guidelines are problematic. The genetic component to these responses is moderate, leaving the majority of the variation potentially modifiable. By collecting information on glucose responses to > 100,000 meals, alongside environmental, genetic and microbiome variables, we will have excellent power to use machine learning to optimise and predict individual responses to foods.

Postprandial lipemia is an independent risk factor for CVD, due to effects on lipoprotein remodelling, oxidative stress, inflammation, haemostasis and endothelial dysfunction. However, it is unknown whether the total, peak or duration of the lipemic response determines risk. The PREDICT I study is the largest study to date to measure postprandial lipemic responses and intermediary acutely changing cardiometabolic risk factors at multiple time points using a standardized test meal model.

A multi-center postprandial study of 1,000 individuals from the UK (unrelated, identical and non-identical twins) and 100 unrelated individuals from the US, assessed postprandial (hourly 0–6h) metabolic responses to sequential mixed-nutrient dietary challenges (50 g fat, 85 g carbohydrate at 0 h; 22 g fat, 71 g carbohydrate at 4h) in a clinic setting. We investigated the relationship of different postprandial triacylglycerol (TG) measures (4 and 6 h TG iAUC, 4 and 6 h TG concentration, 4 and 6 h TG increase from fasting) with lipoprotein remodelling (XXL-VLDL (including chylomicron remnants and VLDL particles) and XL-VLDL particle concentrations (average diameters > 75, 64 nm respectively), HDL-C) and levels of glycosylated acute phase proteins (GlycA; marker of cardiovascular inflammation), all of which have been implicated as independent predictors of CVD risk.

Following adjustment (for use of medication, demographic characteristics, fasting TG, insulin and glucose levels), all six postprandial TG measures (4 and 6 h TG iAUC, 4 and 6 h TG concentration, 4 and 6 h TG increase from fasting) were strongly correlated with markers of atherogenic lipoprotein remodelling and the marker of cardiovascular inflammation (GlycA). The strongest correlation (interim analysis) was observed for the 6 h TG increase from fasting (all P < 0.001, Pearson's coefficient r = 0.94 [95%CI's; 0.93, 0.95] for XXL-VLDL-P; r = 0.95 [95%CI's; 0.95, 0.96] for XL-VLDL-P; r = 0.89 [95%CI's; 0.88, 0.91] for GlycA ; r = -0.61 [95%CI's; -0.66, -0.55] for HDL-C). Inter-individual variability in postprandial lipemic responses was high in the tightly controlled clinic setting (interim analysis, n = 656); IQR (median) was; iAUC (0–6h) 2.39 (2.31) mmol/L.h; Cmax 1.32 (2.06) mmol/L; Tmax 30.0 (300) min; and increase above fasting at 6 h 0.78 (0.62) mmol/L.

This is the most detailed postprandial study performed to date and suggests that identifying predictors of the postprandial 6 h TG rise will have the highest CVD relevance. Ongoing exploration in PREDICT I of the determinants of postprandial lipemic responses considering environmental, genetic and microbiome variables will significantly advance our ability to predict an individual's postprandial response and its links to cardiovascular risk.

The COVID-19 pandemic has raised significant concerns for population mental health and the effective provision of mental health services in the light of increased demands and barriers to service delivery [1]. Particular attention is being directed toward the possible neuropsychiatric sequelae of both COVID-19 and of the stringent societal mitigation steps deployed by national governments, concerns that are informed by historical increases in the incidence of psychotic disorders following influenza pandemics [2]. However, so far there has been scant attention paid to other important areas of psychiatry during COVID-19, including medico-legal aspects and human rights. In this paper, we discuss the legal implications for psychiatry of the COVID-19 pandemic and report a novel situation in which psychiatric patients may experience diminution of their statutory protections. We believe that this represents a paradigm shift in psychiatric care and that the consideration of the fundamental rights of psychiatric patients as “less important” than infection control measures compel mental health professionals to “advocate for … patients and their caregivers” in this time of crisis [1].

Tomasello's account of the origins and nature of moral obligation rightly emphasises the key roles of social relations and a cooperative sense of “we.” However, we suggest that it overlooks the complexity of those social relations and the resulting prevalence of a divided “we” in moral social groups. We argue that the social identity dynamics that arise can lead to competing obligations in a single group, and this has implications for the evolution of obligation.