OBJECTIVES/GOALS: Current approaches to drug development for the aggressive triple negative breast cancer rely on current 2D and 3D in vitro models which have limited capabilities. We have developed a translational microphysiological system that can maintain the human breast microenvironment to capture the complex interaction with the tumor microenvironment. METHODS/STUDY POPULATION: Three different TNBC cell lines were seeded in BC-MPS: MDA-MB-231 parental cell line, MDA-MB-231wiht the gene, LKB1 overexpressed, which is a tumor suppressor, and MDA-MB-231 with the enzyme, ERK5, an enzyme associated with increased metastasis and drug resistance, knocked out. These three TNBC cell lines were cultured in a standard 2D 96-well plate and in BC-MPS. Time-lapse videos were taken to track cellular mobility. RNA-sequencing was performed to compare different expression levels of various cancer related genes of the cell lines cultured in standard 2D and BC-MPS. RESULTS/ANTICIPATED RESULTS: The LKB1 overexpressed MDA-MB-231 and the ERK5-ko MDA-MB-231 cell lines are expected to have decreased mobility compared to the parental cells. The cell lines are expected to have increased expression of cancer related genes when cultured in BC-MPS than when cultured in standard 2D due to the presence of human breast tissue. DISCUSSION/SIGNIFICANCE: BC-MPS is a promising new translational MPS that facilitates studying long term interactions between real human breast tissue and cancer cells. The BC-MPS systems ability to support the growth of established cell lines has been demonstrated. Future studies will focus on developing the model for personalized medicine.

This article uses thing theory to interrogate literary portrayals of ancient statues in Africa. It argues that Victorian colonists adopted a “rhetoric of thinghood” to portray these statues’ history and purpose as forever lost to time. By treating them as “things”—singular, incomprehensible, sublime—the statues could be decoupled from the indigenous cultures that made them. Victorians could thus avoid acknowledging the evidence that the objects’ appearance and manufacture provided of the existence of Black civilization, which Victorian race theory denied to Black Africans. Starting with an overview of the nineteenth-century European concept of fetishism, this article traces the development of that rhetorical sleight-of-hand through the real-world integration of the bust of Younger Memnon (now Ramses II) and other Egyptian antiquities into Eurocentric notions of world history: an integration that spurred a variety of interpretive methods intended to negate their racialized appearance. Nonetheless, many African artifacts, particularly those with human likenesses, remained sites of hegemonic destabilization, which authors like Haggard and Wells interrogated in their imperial romances. Under the assumed scrutiny of ancient statues—portrayed as pseudo-animate sentinels bearing silent witness to the unfolding of history—the justifications for colonial expansion corrode, triggering a more hostile and xenophobic mind-set in the Victorian protagonist.

Multiple micronutrient deficiencies are widespread in Ethiopia. However, the distribution of Se and Zn deficiency risks has previously shown evidence of spatially dependent variability, warranting the need to explore this aspect for wider micronutrients. Here, blood serum concentrations for Ca, Mg, Co, Cu and Mo were measured (n 3102) on samples from the Ethiopian National Micronutrient Survey. Geostatistical modelling was used to test spatial variation of these micronutrients for women of reproductive age, who represent the largest demographic group surveyed (n 1290). Median serum concentrations were 8·6 mg dl−1 for Ca, 1·9 mg dl−1 for Mg, 0·4 µg l−1 for Co, 98·8 µg dl−1 for Cu and 0·2 µg dl−1 for Mo. The prevalence of Ca, Mg and Co deficiency was 41·6 %, 29·2 % and 15·9 %, respectively; Cu and Mo deficiency prevalence was 7·6 % and 0·3 %, respectively. A higher prevalence of Ca, Cu and Mo deficiency was observed in north western, Co deficiency in central and Mg deficiency in north eastern parts of Ethiopia. Serum Ca, Mg and Mo concentrations show spatial dependencies up to 140–500 km; however, there was no evidence of spatial correlations for serum Co and Cu concentrations. These new data indicate the scale of multiple mineral micronutrient deficiency in Ethiopia and the geographical differences in the prevalence of deficiencies suggesting the need to consider targeted responses during the planning of nutrition intervention programmes.

Yarkoni's analysis clearly articulates a number of concerns limiting the generalizability and explanatory power of psychological findings, many of which are compounded in infancy research. ManyBabies addresses these concerns via a radically collaborative, large-scale and open approach to research that is grounded in theory-building, committed to diversification, and focused on understanding sources of variation.

The Variables and Slow Transients Survey (VAST) on the Australian Square Kilometre Array Pathfinder (ASKAP) is designed to detect highly variable and transient radio sources on timescales from 5 s to $\sim\!5$ yr. In this paper, we present the survey description, observation strategy and initial results from the VAST Phase I Pilot Survey. This pilot survey consists of $\sim\!162$ h of observations conducted at a central frequency of 888 MHz between 2019 August and 2020 August, with a typical rms sensitivity of $0.24\ \mathrm{mJy\ beam}^{-1}$ and angular resolution of $12-20$ arcseconds. There are 113 fields, each of which was observed for 12 min integration time, with between 5 and 13 repeats, with cadences between 1 day and 8 months. The total area of the pilot survey footprint is 5 131 square degrees, covering six distinct regions of the sky. An initial search of two of these regions, totalling 1 646 square degrees, revealed 28 highly variable and/or transient sources. Seven of these are known pulsars, including the millisecond pulsar J2039–5617. Another seven are stars, four of which have no previously reported radio detection (SCR J0533–4257, LEHPM 2-783, UCAC3 89–412162 and 2MASS J22414436–6119311). Of the remaining 14 sources, two are active galactic nuclei, six are associated with galaxies and the other six have no multi-wavelength counterparts and are yet to be identified.

We present the data and initial results from the first pilot survey of the Evolutionary Map of the Universe (EMU), observed at 944 MHz with the Australian Square Kilometre Array Pathfinder (ASKAP) telescope. The survey covers $270 \,\mathrm{deg}^2$ of an area covered by the Dark Energy Survey, reaching a depth of 25–30 $\mu\mathrm{Jy\ beam}^{-1}$ rms at a spatial resolution of $\sim$ 11–18 arcsec, resulting in a catalogue of $\sim$ 220 000 sources, of which $\sim$ 180 000 are single-component sources. Here we present the catalogue of single-component sources, together with (where available) optical and infrared cross-identifications, classifications, and redshifts. This survey explores a new region of parameter space compared to previous surveys. Specifically, the EMU Pilot Survey has a high density of sources, and also a high sensitivity to low surface brightness emission. These properties result in the detection of types of sources that were rarely seen in or absent from previous surveys. We present some of these new results here.

In view of the increasing complexity of both cardiovascular implantable electronic devices (CIEDs) and patients in the current era, practice guidelines, by necessity, have become increasingly specific. This document is an expert consensus statement that has been developed to update and further delineate indications and management of CIEDs in pediatric patients, defined as ≤21 years of age, and is intended to focus primarily on the indications for CIEDs in the setting of specific disease categories. The document also highlights variations between previously published adult and pediatric CIED recommendations and provides rationale for underlying important differences. The document addresses some of the deterrents to CIED access in low- and middle-income countries and strategies to circumvent them. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by class of recommendation and level of evidence. Several questions addressed in this document either do not lend themselves to clinical trials or are rare disease entities, and in these instances recommendations are based on consensus expert opinion. Furthermore, specific recommendations, even when supported by substantial data, do not replace the need for clinical judgment and patient-specific decision-making. The recommendations were opened for public comment to Pediatric and Congenital Electrophysiology Society (PACES) members and underwent external review by the scientific and clinical document committee of the Heart Rhythm Society (HRS), the science advisory and coordinating committee of the American Heart Association (AHA), the American College of Cardiology (ACC), and the Association for European Paediatric and Congenital Cardiology (AEPC). The document received endorsement by all the collaborators and the Asia Pacific Heart Rhythm Society (APHRS), the Indian Heart Rhythm Society (IHRS), and the Latin American Heart Rhythm Society (LAHRS). This document is expected to provide support for clinicians and patients to allow for appropriate CIED use, appropriate CIED management, and appropriate CIED follow-up in pediatric patients.

Older persons experiencing a longer length of stay (LOS) or delayed discharge (DD) may see a decline in their health and well-being, generating significant costs. This review aimed to identify evidence on the impact of cognitive impairment (CI) on acute care hospital LOS/DD. A scoping review of studies examining the association between CI and LOS/DD was performed. We searched six databases; two reviewers independently screened references until November 2019. A narrative synthesis was used to answer the research question; 58 studies were included of which 33 found a positive association between CI and LOS or DD, 8 studies had mixed results, 3 found an inverse relationship, and 14 showed an indirect link between CI-related syndromes and LOS/DD. Thus, cognitive impairment seemed to be frequently associated with increased LOS/DD. Future research should consider CI together with other risks for LOS/DD and also focus on explaining the association between the two.

We performed a prospective study of 501 patients, regardless of symptoms, admitted to the hospital, to estimate the predictive value of a negative nasopharyngeal swab for severe acute respiratory coronavirus virus 2 (SARS-CoV-2). At a positivity rate of 10.2%, the estimated negative predictive value (NPV) was 97.2% and the NPV rose as prevalence decreased during the study.

Previous genetic association studies have failed to identify loci robustly associated with sepsis, and there have been no published genetic association studies or polygenic risk score analyses of patients with septic shock, despite evidence suggesting genetic factors may be involved. We systematically collected genotype and clinical outcome data in the context of a randomized controlled trial from patients with septic shock to enrich the presence of disease-associated genetic variants. We performed genomewide association studies of susceptibility and mortality in septic shock using 493 patients with septic shock and 2442 population controls, and polygenic risk score analysis to assess genetic overlap between septic shock risk/mortality with clinically relevant traits. One variant, rs9489328, located in AL589740.1 noncoding RNA, was significantly associated with septic shock (p = 1.05 × 10–10); however, it is likely a false-positive. We were unable to replicate variants previously reported to be associated (p < 1.00 × 10–6 in previous scans) with susceptibility to and mortality from sepsis. Polygenic risk scores for hematocrit and granulocyte count were negatively associated with 28-day mortality (p = 3.04 × 10–3; p = 2.29 × 10–3), and scores for C-reactive protein levels were positively associated with susceptibility to septic shock (p = 1.44 × 10–3). Results suggest that common variants of large effect do not influence septic shock susceptibility, mortality and resolution; however, genetic predispositions to clinically relevant traits are significantly associated with increased susceptibility and mortality in septic individuals.

Vitamin K has important physiological functions which relate to blood coagulation (its classical role), bone health, inhibition of arterial calcification, as well as anti-inflammatory effects. National nutrition survey data have shown that over half of all adults in Ireland and the UK have low vitamin K1 intakes (£1 μg/kg body weight/d). Vitamin K biofortification of food may be an important complementary food-based approach for improving vitamin K intakes. Our study aimed to explore the feasibility of producing vitamin K-biofortified eggs via increasing the vitamin K3 content of the hen diet, and to examine any effects on hen performance and egg/eggshell quality parameters. A 12-week hen feeding trial was conducted in the Agri-Food and Biosciences Institute, Belfast, UK. Hyline chickens (n = 128) were randomized into 4 treatment (T) groups (n = 32 hens/group) and fed diets containing 3 (T1-industry standard), 12.9 (T2), 23.7 (T3) and 45.7 (T4) mg vitamin K3/kg of feed. Hens were provided feed ad libitum and feed intake was recorded weekly. Eggs were collected daily and weighed. While egg quality and vitamin K content was assessed at week 0, 4, 6, 8 and 12, the trial endpoint (week 12) data was prioritized for the current analysis. Total vitamin K content (i.e., vitamin K1 plus menaquinone (MK)-4 and MK-7) of composite samples (n = 12 eggs/treatment), measured using a novel, sensitive liquid chromatography-mass spectrometry method at Teagasc, increased from 22.4 μg/100 g (whole egg) in T1 (control and commercial level of vitamin K3) to 57.8 μg/100 g in T4. MK-4 was the most abundant form of vitamin K found in the eggs. Eggshell weight and eggshell thickness in T2 and T3 (but not T4) were significantly higher than in T1 (by 20–28%, P < 0.05). Likewise, based on colourimetric assessment, yellowness (parameter b*) of the egg yolk in all three biofortified groups was significantly higher compared to T1 (by 27–45%, P < 0.05). Haugh unit of the eggs and hen performance parameters, such as feed intake, feed conversion ratio and egg production, were unaffected by vitamin K-biofortification. In conclusion, increasing the level of addition of vitamin K3 to hen feed significantly increased the total vitamin K content of eggs, and without any evidence of negative effects on egg quality or hen performance. Consumption of an average sized (60 g) vitamin K-biofortified egg could contribute an additional 35 μg total vitamin K. The effects on eggshell parameters could be of importance in terms of revenue loss due to breakages.

Chronic aggression and violence in schizophrenia are rare, but receive disproportionate negative media coverage. This contributes to the stigma of mental illness and reduces accessibility to mental health services. Substance Use Disorders (SUD), antisocial behavior, non-adherence and recidivism are known risk factors for violence. Treatment with antipsychotic medication can reduce violence. Aside from clozapine, long-acting injectable antipsychotics (LAI) appear to be superior to oral antipsychotics for preventing violence, addressing adherence and recidivism. LAI also facilitate the implementation of functional skills training. For the high-risk recidivist target population with schizophrenia, better life skills have the potential to also reduce the risk for contact with the legal system, including an improved ability to live independently in supported environments and interact appropriately with others. High-risk patients who are resistant to treatment with other antipsychotics should receive treatment with clozapine due to its direct positive effects on impulsive violence, along with a reduction in comorbid risk factors such as SUDs.