Sulphur-isotope compositions of pig tissues from a controlled feeding study

Sulphur-isotope determinations are becoming increasingly useful for palaeodietary reconstruction, but knowledge of isotopic discrimination between diet and various tissues remains inadequate. In this study, we explore the sensitivity of δ34Stissue values to changes in δ34Sdiet values, sulphur isotopic discrimination between diet and consumer, and the potential impact of terrestrial vs. marine protein consumption on these discrimination offsets. We present new δ34S values of bone collagen, muscle, liver, hair, milk and faeces from ten mature sows, ten piglets and fifteen adolescent pigs from a controlled feeding study. The δ34Stissue values were found to co-vary with the δ34Sdiet values, the δ34Stissue – δ34Sdiet isotopic offsets (Δ34Stissue-diet) are small but consistent, and dietary protein source does not systematically alter the Δ34Stissue-diet isotopic discrimination. The outcomes of this study are of particular relevance to questions that are difficult to resolve using carbon and nitrogen stable isotopes alone, and will also be useful in regions where terrestrial, freshwater, and marine resources could have all potentially contributed to human diet

Lab Hackathons to Overcome Laboratory Equipment Shortages in Africa: Opportunities and Challenges

Equipment shortages in Africa undermine Science, Technology, Engineering and Mathematics (STEM) Education. We have pioneered the LabHackathon (LabHack): a novel initiative that adapts the conventional hackathon and draws on insights from the Open Hardware movement and Responsible Research and Innovation (RRI). LabHacks are fun, educational events that challenge student participants to build frugal and reproducible pieces of laboratory equipment. Completed designs are then made available to others. LabHacks can therefore facilitate the open and sustainable design of laboratory equipment, in situ, in Africa. In this case study we describe the LabHackathon model, discuss its application in a pilot event held in Zimbabwe and outline the opportunities and challenges it presents

Cybercrime Investigators are Users Too! Understanding the Socio-Technical Challenges Faced by Law Enforcement

Cybercrime investigators face numerous challenges when policing online crimes. Firstly, the methods and processes they use when dealing with traditional crimes do not necessarily apply in the cyber-world. Additionally, cyber criminals are usually technologically-aware and constantly adapting and developing new tools that allow them to stay ahead of law enforcement investigations. In order to provide adequate support for cybercrime investigators, there needs to be a better understanding of the challenges they face at both technical and socio-technical levels. In this paper, we investigate this problem through an analysis of current practices and workflows of investigators. We use interviews with experts from government and private sectors who investigate cybercrimes as our main data gathering process. From an analysis of the collected data, we identify several outstanding challenges faced by investigators. These pertain to practical, technical, and social issues such as systems availability, usability, and in computer-supported collaborative work. Importantly, we use our findings to highlight research areas where user-centric workflows and tools are desirable. We also define a set of recommendations that can aid in providing a better foundation for future research in the field and allow more effective combating of cybercrimes

Antibiotic additives alter the static and viscoelastic properties of bone cements

Introduction: In arthroplasty antibiotics are added to bone cements to prevent deep infection. The static properties of plain and antibiotic laden cements have been extensively described in the literature [1]. Commercially available cements must perform above the minimum values set by ISO 5833:2002 [2]. However, no upper or lower limits are set for the viscoelastic properties of the cements, despite this being a recognised factor affecting the cement-implant performance [3]. The ability of acrylic bone cement to creep and stress relax in conjunction with forceclosed stems in hip arthroplasty affords protection of the vital bone-cement interface. With this design subsidence of the stem within the cement mantle over time does not lead to clinical failure [4]. Conversely, the clinical performance of shapeclosed stem designs can be negatively affected by cements demonstrating excessive creep. This study investigated the effect of antibiotic additives on the static and viscoelastic properties of PMMA cement. Materials and Methods: The mechanical and viscoelastic properties of Simplex P, Simplex Antibiotic and Simplex Tobramycin (Stryker, Limerick, IE) were investigated. This family of cements was chosen as they are characterised by the same polymeric base, that of Simplex P, the plain formulation, but contain different antibiotic additives. In particular Simplex Antibiotic contains 0.5g Erythromycin and 3 million I.U. Colistin, while in Simplex Tobramycin the only additive is 0.5g of Tobramycin. The static properties of the cements (compressive strength, bending strength and bending modulus) were assessed following ISO 5833:2002 [2], while stress relaxation and creep were assessed under quasi static conditions in a four pointbending configuration. The creep experiments were carried out using a custom made apparatus with the specimens positioned in a distilled water bath at 37 o

The Impairment of Macrophage-to-Feces Reverse Cholesterol Transport during Inflammation Does Not Depend on Serum Amyloid A

Studies suggest that inflammation impairs reverse cholesterol transport (RCT). We investigated whether serum amyloid A (SAA) contributes to this impairment using an established macrophage-to-feces RCT model. Wild-type (WT) mice and mice deficient in SAA1.1 and SAA2.1 (SAAKO) were injected intraperitoneally with 3H-cholesterol-labeled J774 macrophages 4 hr after administration of LPS or buffered saline. 3H-cholesterol in plasma 4 hr after macrophage injection was significantly reduced in both WT and SAAKO mice injected with LPS, but this was not associated with a reduced capacity of serum from LPS-injected mice to promote macrophage cholesterol efflux in vitro. Hepatic accumulation of 3H-cholesterol was unaltered in either WT or SAAKO mice by LPS treatment. Radioactivity present in bile and feces of LPS-injected WT mice 24 hr after macrophage injection was reduced by 36% (P \u3c 0.05) and 80% (P \u3c 0.001), respectively. In contrast, in SAAKO mice, LPS did not significantly reduce macrophage-derived 3H-cholesterol in bile, and fecal excretion was reduced by only 45% (P \u3c 0.05). Injection of cholesterol-loaded allogeneic J774 cells, but not syngeneic bone-marrow-derived macrophages, transiently induced SAA in C57BL/6 mice. Our study confirms reports that acute inflammation impairs steps in the RCT pathway and establishes that SAA plays only a minor role in this impairment

TIGIT Marks Exhausted T Cells, Correlates with Disease Progression, and Serves as a Target for Immune Restoration in HIV and SIV Infection.

HIV infection induces phenotypic and functional changes to CD8+ T cells defined by the coordinated upregulation of a series of negative checkpoint receptors that eventually result in T cell exhaustion and failure to control viral replication. We report that effector CD8+ T cells during HIV infection in blood and SIV infection in lymphoid tissue exhibit higher levels of the negative checkpoint receptor TIGIT. Increased frequencies of TIGIT+ and TIGIT+ PD-1+ CD8+ T cells correlated with parameters of HIV and SIV disease progression. TIGIT remained elevated despite viral suppression in those with either pharmacological antiretroviral control or immunologically in elite controllers. HIV and SIV-specific CD8+ T cells were dysfunctional and expressed high levels of TIGIT and PD-1. Ex-vivo single or combinational antibody blockade of TIGIT and/or PD-L1 restored viral-specific CD8+ T cell effector responses. The frequency of TIGIT+ CD4+ T cells correlated with the CD4+ T cell total HIV DNA. These findings identify TIGIT as a novel marker of dysfunctional HIV-specific T cells and suggest TIGIT along with other checkpoint receptors may be novel curative HIV targets to reverse T cell exhaustion

On the Clustering of Sub-millimeter Galaxies

We measure the angular two-point correlation function of sub-millimeter galaxies (SMGs) from 1.1-millimeter imaging of the COSMOS field with the AzTEC camera and ASTE 10-meter telescope. These data yields one of the largest contiguous samples of SMGs to date, covering an area of 0.72 degrees^2 down to a 1.26 mJy/beam (1-sigma) limit, including 189 (328) sources with S/N greater than 3.5 (3). We can only set upper limits to the correlation length r_0, modeling the correlation function as a power-law with pre-assigned slope. Assuming existing redshift distributions, we derive 68.3% confidence level upper limits of r_0 < 6-8 h^-1 Mpc at 3.7 mJy, and r_0 < 11-12 h^-1 Mpc at 4.2 mJy. Although consistent with most previous estimates, these upper limits imply that the real r_0 is likely smaller. This casts doubts on the robustness of claims that SMGs are characterized by significantly stronger spatial clustering, (and thus larger mass), than differently selected galaxies at high-redshift. Using Monte Carlo simulations we show that even strongly clustered distributions of galaxies can appear unclustered when sampled with limited sensitivity and coarse angular resolution common to current sub-millimeter surveys. The simulations, however, also show that unclustered distributions can appear strongly clustered under these circumstances. From the simulations, we predict that at our survey depth, a mapped area of two degrees^2 is needed to reconstruct the correlation function, assuming smaller beam sizes of future surveys (e.g. the Large Millimeter Telescope's 6" beam size). At present, robust measures of the clustering strength of bright SMGs appear to be below the reach of most observations.Comment: 23 pages, 8 figures, accepted for publication in The Astrophysical Journa

The Staphylococcus aureus Network Adaptive Platform Trial Protocol: New Tools for an Old Foe

Staphylococcus aureus bloodstream (SAB) infection is a common and severe infectious disease, with a 90-day mortality of 15%-30%. Despite this, <3000 people have been randomized into clinical trials of treatments for SAB infection. The limited evidence base partly results from clinical trials for SAB infections being difficult to complete at scale using traditional clinical trial methods. Here we provide the rationale and framework for an adaptive platform trial applied to SAB infections. We detail the design features of the Staphylococcus aureus Network Adaptive Platform (SNAP) trial that will enable multiple questions to be answered as efficiently as possible. The SNAP trial commenced enrolling patients across multiple countries in 2022 with an estimated target sample size of 7000 participants. This approach may serve as an exemplar to increase efficiency of clinical trials for other infectious disease syndromes