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Mass asymptomatic SARS-CoV-2 nucleic acid amplified testing of healthcare personnel (HCP) was performed at a large tertiary health system. A low period-prevalence of positive HCP was observed. Of those who tested positive, half had mild symptoms in retrospect. HCP with even mild symptoms should be isolated and tested.
Rapid infant growth increases the risk for adult obesity. The gut microbiome is associated with early weight status; however, no study has examined how interactions between microbial and host ribonucleic acid (RNA) expression influence infant growth. We hypothesized that dynamics in infant stool micro-ribonucleic acids (miRNAs) would be associated with both microbial activity and infant growth via putative metabolic targets. Stool was collected twice from 30 full-term infants, at 1 month and again between 6 and 12 months. Stool RNA were measured with high-throughput sequencing and aligned to human and microbial databases. Infant growth was measured by weight-for-length z-score at birth and 12 months. Increased RNA transcriptional activity of Clostridia (R = 0.55; Adj p = 3.7E-2) and Burkholderia (R = −0.820, Adj p = 2.62E-3) were associated with infant growth. Of the 25 human RNAs associated with growth, 16 were miRNAs. The miRNAs demonstrated significant target enrichment (Adj p < 0.05) for four metabolic pathways. There were four associations between growth-related miRNAs and growth-related phyla. We have shown that longitudinal trends in gut microbiota activity and human miRNA levels are associated with infant growth and the metabolic targets of miRNAs suggest these molecules may regulate the biosynthetic landscape of the gut and influence microbial activity.
We develop a deep autoencoder architecture that can be used to find a coordinate transformation which turns a non-linear partial differential equation (PDE) into a linear PDE. Our architecture is motivated by the linearising transformations provided by the Cole–Hopf transform for Burgers’ equation and the inverse scattering transform for completely integrable PDEs. By leveraging a residual network architecture, a near-identity transformation can be exploited to encode intrinsic coordinates in which the dynamics are linear. The resulting dynamics are given by a Koopman operator matrix K. The decoder allows us to transform back to the original coordinates as well. Multiple time step prediction can be performed by repeated multiplication by the matrix K in the intrinsic coordinates. We demonstrate our method on a number of examples, including the heat equation and Burgers’ equation, as well as the substantially more challenging Kuramoto–Sivashinsky equation, showing that our method provides a robust architecture for discovering linearising transforms for non-linear PDEs.
OBJECTIVES/GOALS: The objective of this study is to define the molecular mechanisms that control survival of malignant stem cells in acute myeloid leukemia (AML). Leukemia stem cells (LSCs) are not effectively eradicated by standard treatment and lead to resistance and relapse, which contribute to poor survival rates. METHODS/STUDY POPULATION: The recently FDA approved venetoclax, a BCL2 inhibitor, with azacitidine, a hypomethylating agent leads to a 70% response rate in AML patients. Analysis of patients treated with this regimen showed direct targeting of LSCs. BCL2 has a non-canonical function in regulation of intracellular calcium. To determine how BCL2 mediated calcium signaling plays a role in LSC biology, we used LSCs isolated from venetoclax/azacitidine (ven/aza) sensitive and resistant patient samples to measure expression of calcium channels via RNA seq. BIO-ID, siRNA, flow cytometry, seahorse assays, calcium measurements and colony assays were used to determine the effects of calcium channel perturbation on LSC biology. RESULTS/ANTICIPATED RESULTS: BCL2 inhibition leads to decreased OXPHOS activity in primary AML specimens. BIO-ID studies revealed cation/metal ion transporters, ER membrane proteins and ER membrane organization as top enriched pathways interacting with BCL2. RNA-seq data showed increased expression of genes involved in calcium influx into the ER in ven/aza sensitive LSCs and increased expression of genes involved in calcium efflux from the ER in ven/aza resistant samples. Ven/Aza resistant LSCs have increased mitochondrial calcium content, consistent with their increased OXPHOS activity as calcium is required for OXPHOS. Perturbation of these channels leads to decreased OXPHOS activity and decreased viability in LSCs. DISCUSSION/SIGNIFICANCE OF IMPACT: We postulate that a deeper understanding of the mechanisms behind ven/aza targeting of LSCs will lead to the development of novel therapies for patients who do not respond to ven/aza. Our data show targeting intracellular calcium signaling could be a viable therapeutic strategy for AML patients.
Art may be made as a guide to understanding sense of place, and also as a pathway to understanding and valuing scientific ideas. Here we consider this connection in the context of a selected history of artists working in Antarctica, from early explorers to the modern era. This provides a parallel trajectory for the nature, realisation and purpose of the art. We then consider the interaction between art and science and the nature of interdisciplinary work by looking at work produced in a sea ice-based science field camp by an artist collecting data – both scientific and art focused. The artist participated in two field campaigns a year apart, allowing comparison of the evolution of both the artistic practice and the science data collection. Furthermore, the collection of data that served both needs provides a unique point of connection between two fields of endeavour, which are typically considered as separate.
The Drygalski Ice Tongue presents an ~80 km long floating obstacle to alongshore flows in the Victoria Land coastal ocean region of the Western Ross Sea. Here we use oceanographic data from near to the tongue to explore the interplay between the floating glacier and the local currents and stratification. A vessel-based circuit of the glacier, recording ocean temperature and salinity profiles, reveals the southwest corner to be the coldest and most complex in terms of vertical structure. The southwest corner structure beneath the surface warm, salty layer sustains a block of very cold water extending to 200 m depth. In this same location there was a distinct layer at 370 m not seen anywhere else of water at ~−1.93°C. The new observations broadly, but not directly, support the presence of a coherent Victoria Land Coastal Current. The data suggest the northward moving coastal current turns against the Coriolis force and works its way anticlockwise around the glacier, but with leakage beneath the glacier through the highly ‘rippled’ underside, resulting in a spatially heterogeneous supply to the Terra Nova Bay Polynya region – an important location for the formation of high-salinity shelf water.
The advent of managed care as a system driving purchasing in the health sector has brought with it an emphasis on purchasing outcomes rather than inputs. Although any change in purchasing schemes will have an effect on service providers, it should not prove to be too disruptive for those of us in rehabilitation since rehabilitation as a service system has always been outcome driven. In fact, our entire system is driven by needs based assessment and directed toward the meeting individually identified goals for service. These goals reflect the desired outcome of the service we provide for each individual served. The challenge we face, then, is translating our emphasis on goal directed, outcome driven services to meet the language, understanding and expectations of our funding agents as they begin to adopt a regime of outcome based contracts. The purpose of this paper is to argue the validity of individually determined outcomes as opposed to institutionally determined measures and to propose one method of measuring those outcomes in a manner that is applicable to the needs of the purchaser.
Tomato product consumption and estimated lycopene intake are hypothesised to reduce the risk of prostate cancer. To define the impact of typical servings of commercially available tomato products on resultant plasma and prostate lycopene concentrations, men scheduled to undergo prostatectomy (n 33) were randomised either to a lycopene-restricted control group ( < 5 mg lycopene/d) or to a tomato soup (2–2¾ cups prepared/d), tomato sauce (142–198 g/d or 5–7 ounces/d) or vegetable juice (325–488 ml/d or 11–16·5 fluid ounces/d) intervention providing 25–35 mg lycopene/d. Plasma and prostate carotenoid concentrations were measured by HPLC. Tomato soup, sauce and juice consumption significantly increased plasma lycopene concentration from 0·68 (sem 0·1) to 1·13 (sem 0·09) μmol/l (66 %), 0·48 (sem 0·09) to 0·82 (sem 0·12) μmol/l (71 %) and 0·49 (sem 0·12) to 0·78 (sem 0·1) μmol/l (59 %), respectively, while the controls consuming the lycopene-restricted diet showed a decline in plasma lycopene concentration from 0·55 (sem 0·60) to 0·42 (sem 0·07) μmol/l ( − 24 %). The end-of-study prostate lycopene concentration was 0·16 (sem 0·02) nmol/g in the controls, but was 3·5-, 3·6- and 2·2-fold higher in tomato soup (P= 0·001), sauce (P= 0·001) and juice (P= 0·165) consumers, respectively. Prostate lycopene concentration was moderately correlated with post-intervention plasma lycopene concentrations (r 0·60, P =0·001), indicating that additional factors have an impact on tissue concentrations. While the primary geometric lycopene isomer in tomato products was all-trans (80–90 %), plasma and prostate isomers were 47 and 80 % cis, respectively, demonstrating a shift towards cis accumulation. Consumption of typical servings of processed tomato products results in differing plasma and prostate lycopene concentrations. Factors including meal composition and genetics deserve further evaluation to determine their impacts on lycopene absorption and biodistribution.
Maternal nutritional status during pregnancy has been reported to be associated with childhood asthma and atopic disease. The Avon Longitudinal Study of Parents and Children has reported associations between reduced umbilical cord Fe status and childhood wheeze and eczema; however, follow-up was short and lung function was not measured. In the present study, the associations between maternal Fe status during pregnancy and childhood outcomes in the first 10 years of life were investigated in a subgroup of 157 mother–child pairs from a birth cohort with complete maternal, fetal ultrasound, blood and child follow-up data. Maternal Fe intake was assessed using FFQ at 32 weeks of gestation and Hb concentrations and serum Fe status (ferritin, soluble transferrin receptor and TfR-F (transferrin receptor:ferritin) index) were measured at 11 weeks of gestation and at delivery. Maternal Fe intake, Hb concentrations and serum Fe status were found to be not associated with fetal or birth measurements. Unit increases in first-trimester maternal serum TfR concentrations (OR 1·44, 95 % CI 1·05, 1·99) and TfR-F index (OR 1·42, 95 % CI 1·10, 1·82) (i.e. decreasing Fe status) were found to be associated with an increased risk of wheeze, while unit increases in serum ferritin concentrations (i.e. increasing Fe status) were found to be associated with increases in standardised mean peak expiratory flow (PEF) (β 0·25, 95 % CI 0·09, 0·42) and forced expiratory volume in the first second (FEV1) (β 0·20, 95 % CI 0·08, 0·32) up to 10 years of age. Increasing maternal serum TfR-F index at delivery was found to be associated with an increased risk of atopic sensitisation (OR 1·35, 95 % CI 1·02, 1·79). The results of the present study suggest that reduced maternal Fe status during pregnancy is adversely associated with childhood wheeze, lung function and atopic sensitisation, justifying further studies on maternal Fe status and childhood asthma and atopic disease.
We present an unconditionally energy stable and uniquely solvable finite difference scheme for the Cahn-Hilliard-Brinkman (CHB) system, which is comprised of a Cahn-Hilliard-type diffusion equation and a generalized Brinkman equation mod-eling fluid flow. The CHB system is a generalization of the Cahn-Hilliard-Stokes model and describes two phase very viscous flows in porous media. The scheme is based on a convex splitting of the discrete CH energy and is semi-implicit. The equations at the implicit time level are nonlinear, but we prove that they represent the gradient of a strictly convex functional and are therefore uniquely solvable, regardless of time step size. Owing to energy stability, we show that the scheme is stable in the time and space discrete and norms. We also present an efficient, practical nonlinear multigrid method . comprised of a standard FAS method for the Cahn-Hilliard part, and a method based on the Vanka smoothing strategy for the Brinkman part . for solving these equations. In particular, we provide evidence that the solver has nearly optimal complexity in typical situations. The solver is applied to simulate spinodal decomposition of a viscous fluid in a porous medium, as well as to the more general problems of buoyancy- and boundary-driven flows.
The Supplemental Nutrition Assistance Program (SNAP) is the largest nutritional assistance program addressing food insecurity in the United States. Due to the program's reach, SNAP has been called upon to address other nutrition-related challenges facing low-income Americans, including childhood obesity. This study considers the effect of SNAP participation on child weight outcomes after controlling for household financial stress, an important determinant of child overweight status that disproportionately affects low-income households. Using data from the Survey of Household Finances and Childhood Obesity and instrumental variable methods, we find that SNAP participation is negatively associated with obesity among eligible children.
Invasive plants continue to spread in riparian ecosystems, causing both ecological and economic damage. This research investigated the impacts of common reed, purple loosestrife, riparian shrubland, and riparian woodlands on the quality and quantity of sandhill crane roosting habitat in the central Platte River, Nebraska, using a discrete choice model. A more detailed investigation of the impacts of common reed on sandhill crane roosting habitat was performed by forecasting a spread or contraction of this invasive plant. The discrete choice model indicates that riparian woodlands had the largest negative impact on sandhill crane roosting habitat. The forecasting results predict that a contraction of common reed could increase sandhill crane habitat availability by 50%, whereas an expansion could reduce the availability by as much as 250%. This suggests that if the distribution of common reed continues to expand in the central Platte River the availability of sandhill crane roosting habitat would likely be greatly reduced.