The growth of galaxies in cosmological simulations of structure formation

We use hydrodynamic simulations to examine how the baryonic components of galaxies are assembled, focusing on the relative importance of mergers and smooth accretion in the formation of ~L_* systems. In our primary simulation, which models a (50\hmpc)^3 comoving volume of a Lambda-dominated cold dark matter universe, the space density of objects at our (64-particle) baryon mass resolution threshold, M_c=5.4e10 M_sun, corresponds to that of observed galaxies with L~L_*/4. Galaxies above this threshold gain most of their mass by accretion rather than by mergers. At the redshift of peak mass growth, z~2, accretion dominates over merging by about 4:1. The mean accretion rate per galaxy declines from ~40 M_sun/yr at z=2 to ~10 M_sun/yr at z=0, while the merging rate peaks later (z~1) and declines more slowly, so by z=0 the ratio is about 2:1. We cannot distinguish truly smooth accretion from merging with objects below our mass resolution threshold, but extrapolating our measured mass spectrum of merging objects, dP/dM ~ M^a with a ~ -1, implies that sub-resolution mergers would add relatively little mass. The global star formation history in these simulations tracks the mass accretion rate rather than the merger rate. At low redshift, destruction of galaxies by mergers is approximately balanced by the growth of new systems, so the comoving space density of resolved galaxies stays nearly constant despite significant mass evolution at the galaxy-by-galaxy level. The predicted merger rate at z<~1 agrees with recent estimates from close pairs in the CFRS and CNOC2 redshift surveys.Comment: Submitted to ApJ, 35 pp including 15 fig

The effects of a supermarket-based intervention on the nutritional quality of private-label foods: a prospective study

Private-label products, products owned by supermarkets, are a growing area of the food supply. The aim of this study was to assess the effect of an intervention that provided an Australian supermarket ('intervention supermarket') with comparative nutrition data to improve the healthiness of their private-label range. Between 2015 and 2016, the intervention supermarket received reports that ranked the nutritional quality of their products against competitors. Changes in the nutrient content (sodium, sugar, saturated fat, energy and Health Star Rating) of products from the intervention supermarket between 2015 and 2018 were compared against changes achieved for three comparators (private-label products from two other supermarkets and branded products). The intervention supermarket achieved a significantly greater reduction in the sodium content of their products relative to all three comparators, which ranged between -104 and -52 mg/100 g (all p 0.05). Providing comparative nutrition information to a supermarket may be ineffective in improving the healthiness of their private-label products, likely due to competing factors that play a role in the decision-making process behind product reformulation and product discontinuation/innovation

Mechanisms of action of the sodium-glucose cotransporter-2 (SGLT2) inhibitor canagliflozin on tubular inflammation and damage: A post hoc mediation analysis of the CANVAS trial

Aims: To test the hypothesis that the reduction in urinary kidney injury molecule-1 (KIM-1) observed with the sodium-glucose cotransporter-2 (SGLT2) inhibitor canagliflozin is mediated through its effects on urine albumin to creatinine ratio (UACR) and monocyte chemoattractant protein-1 (MCP-1) by assessing the proportion of the effect of canagliflozin on KIM-1 that is mediated through its effects on MCP-1 and UACR in patients with type 2 diabetes and albuminuric kidney disease. Material and methods: We measured KIM-1 and MCP-1 levels in urine samples from the CANVAS trial at baseline and Week 52 with the Mesoscale QuickPlex SQ 120 platform. KIM-1 and MCP-1 were standardized by urinary creatinine (Cr). The proportion of the effect of canagliflozin that is mediated through UACR and MCP-1/Cr on KIM-1/Cr was estimated with G-computation. Results: In total, 763 patients with micro- or macroalbuminuria (17.6% of the total cohort) were included. Baseline characteristics were well balanced between the canagliflozin and placebo group. At Year 1, canagliflozin compared to placebo reduced UACR, MCP-1/Cr and KIM-1/Cr by 40.4% (95% CI 31.0, 48.4), 18.1% (95% CI 8.9, 26.4) and 30.9% (95% CI 23.0, 38.0), respectively. The proportion of the effect of canagliflozin on KIM-1/Cr mediated by its effect on UACR and in turn on MCP-1/Cr was 15.2% (95% CI 9.4, 24.5). Conclusion: Canagliflozin reduces urinary KIM-1, suggesting decreased tubular damage. This effect was partly mediated through a reduction in MCP-1, indicative of reduced tubular inflammation, which was in turn mediated by a reduction in UACR. This post hoc analysis suggests that urinary albumin leakage may lead to tubular inflammation and induction of injury, and provide mechanistic insight for how canagliflozin may ameliorate tubular damage, but further research is required to confirm these findings

Projected effects on salt purchases following implementation of a national salt reduction policy in South Africa.

OBJECTIVE: To assess the contribution of different food groups to total salt purchases and to evaluate the estimated reduction in salt purchases if mandatory maximum salt limits in South African legislation were being complied with. DESIGN: This study conducted a cross-sectional analysis of purchasing data from Discovery Vitality members. Data were linked to the South African FoodSwitch database to determine the salt content of each food product purchased. Food category and total annual salt purchases were determined by summing salt content (kg) per each unit purchased across a whole year. Reductions in annual salt purchases were estimated by applying legislated maximum limits to product salt content. SETTING: South Africa. PARTICIPANTS: The study utilised purchasing data from 344 161 households, members of Discovery Vitality, collected for a whole year between January and December 2018. RESULTS: Vitality members purchased R12·8 billion worth of food products in 2018, representing 9562 products from which 264 583 kg of salt was purchased. The main contributors to salt purchases were bread and bakery products (23·3 %); meat and meat products (19 %); dairy (12·2 %); sauces, dressings, spreads and dips (11·8 %); and convenience foods (8·7 %). The projected total quantity of salt that would be purchased after implementation of the salt legislation was 250 346 kg, a reduction of 5·4 % from 2018 levels. CONCLUSIONS: A projected reduction in salt purchases of 5·4 % from 2018 levels suggests that meeting the mandatory maximum salt limits in South Africa will make a meaningful contribution to reducing salt purchases

OMEX metadata specification (version 1.2).

A standardized approach to annotating computational biomedical models and their associated files can facilitate model reuse and reproducibility among research groups, enhance search and retrieval of models and data, and enable semantic comparisons between models. Motivated by these potential benefits and guided by consensus across the COmputational Modeling in BIology NEtwork (COMBINE) community, we have developed a specification for encoding annotations in Open Modeling and EXchange (OMEX)-formatted archives. This document details version 1.2 of the specification, which builds on version 1.0 published last year in this journal. In particular, this version includes a set of initial model-level annotations (whereas v 1.0 described exclusively annotations at a smaller scale). Additionally, this version uses best practices for namespaces, and introduces omex-library.org as a common root for all annotations. Distributing modeling projects within an OMEX archive is a best practice established by COMBINE, and the OMEX metadata specification presented here provides a harmonized, community-driven approach for annotating a variety of standardized model representations. This specification acts as a technical guideline for developing software tools that can support this standard, and thereby encourages broad advances in model reuse, discovery, and semantic analyses

Protocol for a novel sodium and blood pressure reduction intervention targeting online grocery shoppers with hypertension – the SaltSwitch Online Grocery Shopping randomized trial

Background: High dietary sodium intake is a leading cause of hypertension. A major source of dietary sodium is salt added to processed food products available in retail food environments. The fast-growing online grocery shopping setting provides new opportunities for salt reduction interventions that support consumers in choosing healthier options. Methods: The SaltSwitch Online Grocery Shopping randomized controlled trial is investigating the feasibility, acceptability, and effectiveness of a novel intervention for lowering salt consumption and blood pressure amongst people with hypertension who shop for groceries online. The intervention is based on a bespoke web browser extension that interfaces with a major retailer's online store to highlight and interpret product sodium content and suggest similar but lower-sodium alternatives. The primary outcome of interest is change in mean systolic blood pressure between individuals randomized (1:1) to the intervention and control (usual online shopping) arms at 12 weeks. Secondary outcomes are diastolic blood pressure, spot urinary sodium and sodium:potassium ratio, sodium purchases, and dietary intake. Intervention implementation and lessons for future uptake will be assessed using a mixed methods process evaluation. Participants with hypertension who shop online for groceries and exhibit high sodium purchasing behavior are being recruited across Australia. A target sample size of 1,966 provides 80% power (2-sided alpha = 0.05) to detect a 2 mm Hg difference in systolic blood pressure between groups, assuming a 15 mm Hg standard deviation, after allowing for a 10% dropout rate. Discussion: This trial will provide evidence on an innovative intervention to potentially reduce salt intake and blood pressure in people with hypertension. The intervention caters to individual preferences by encouraging sustainable switches to similar but lower-salt products. If effective, the intervention will be readily scalable at low cost by interfacing with existing online retail environments

Multiple agency perspective, family control, and private information abuse in an emerging economy

Using a comprehensive sample of listed companies in Hong Kong this paper investigates how family control affects private information abuses and firm performance in emerging economies. We combine research on stock market microstructure with more recent studies of multiple agency perspectives and argue that family ownership and control over the board increases the risk of private information abuse. This, in turn, has a negative impact on stock market performance. Family control is associated with an incentive to distort information disclosure to minority shareholders and obtain private benefits of control. However, the multiple agency roles of controlling families may have different governance properties in terms of investors’ perceptions of private information abuse. These findings contribute to our understanding of the conflicting evidence on the governance role of family control within a multiple agency perspectiv

Harmonizing semantic annotations for computational models in biology

Life science researchers use computational models to articulate and test hypotheses about the behavior of biological systems. Semantic annotation is a critical component for enhancing the interoperability and reusability of such models as well as for the integration of the data needed for model parameterization and validation. Encoded as machine-readable links to knowledge resource terms, semantic annotations describe the computational or biological meaning of what models and data represent. These annotations help researchers find and repurpose models, accelerate model composition and enable knowledge integration across model repositories and experimental data stores. However, realizing the potential benefits of semantic annotation requires the development of model annotation standards that adhere to a community-based annotation protocol.Without such standards, tool developers must account for a variety of annotation formats and approaches, a situation that can become prohibitively cumbersome and which can defeat the purpose of linking model elements to controlled knowledge resource terms. Currently, no consensus protocol for semantic annotation exists among the larger biological modeling community. Here, we report on the landscape of current annotation practices among the Computational Modeling in BIology NEtwork community and provide a set of recommendations for building a consensus approach to semantic annotation

Antileishmanial High-Throughput Drug Screening Reveals Drug Candidates with New Scaffolds

Drugs currently available for leishmaniasis treatment often show parasite resistance, highly toxic side effects and prohibitive costs commonly incompatible with patients from the tropical endemic countries. In this sense, there is an urgent need for new drugs as a treatment solution for this neglected disease. Here we show the development and implementation of an automated high-throughput viability screening assay for the discovery of new drugs against Leishmania. Assay validation was done with Leishmania promastigote forms, including the screening of 4,000 compounds with known pharmacological properties. In an attempt to find new compounds with leishmanicidal properties, 26,500 structurally diverse chemical compounds were screened. A cut-off of 70% growth inhibition in the primary screening led to the identification of 567 active compounds. Cellular toxicity and selectivity were responsible for the exclusion of 78% of the pre-selected compounds. The activity of the remaining 124 compounds was confirmed against the intramacrophagic amastigote form of the parasite. In vitro microsomal stability and cytochrome P450 (CYP) inhibition of the two most active compounds from this screening effort were assessed to obtain preliminary information on their metabolism in the host. The HTS approach employed here resulted in the discovery of two new antileishmanial compounds, bringing promising candidates to the leishmaniasis drug discovery pipeline