Risk assessment with gene expression markers in sepsis development.

Infection is a commonplace, usually self-limiting, condition but can lead to sepsis, a severe life-threatening dysregulated host response. We investigate the individual phenotypic predisposition to developing uncomplicated infection or sepsis in a large cohort of non-infected patients undergoing major elective surgery. Whole-blood RNA sequencing analysis was performed on preoperative samples from 267 patients.

Presymptomatic diagnosis of postoperative infection and sepsis using gene expression signatures.

Purpose: Early accurate diagnosis of infection ± organ dysfunction (sepsis) remains a major challenge in clinical practice. Utilizing effective biomarkers to identify infection and impending organ dysfunction before the onset of clinical signs and symptoms would enable earlier investigation and intervention. To our knowledge, no prior study has specifically examined the possibility of pre-symptomatic detection of sepsis.

Stochastic dynamics of Francisella tularensis infection and replication.

We study the pathogenesis of Francisella tularensis infection with an experimental mouse model, agent-based computation and mathematical analysis. Following inhalational exposure to Francisella tularensis SCHU S4, a small initial number of bacteria enter lung host cells and proliferate inside them, eventually destroying the host cell and releasing numerous copies that infect other cells. Our analysis of disease progression is based on a stochastic model of a population of infectious agents inside one host cell, extending the birth-and-death process by the occurrence of catastrophes: cell rupture events that affect all bacteria in a cell simultaneously.

The use of data science to analyse physiology of oxygen delivery in the extracorporeal circulation.

Background: Recent scientific reports have brought into light a new concept of goal-directed perfusion (GDP) that aims to recreate physiological conditions in which the risk of end-organ malperfusion is minimalized. The aim of our study was to analyse patients' interim physiology while on cardiopulmonary bypass based on the haemodynamic and tissue oxygen delivery measurements. We also aimed to create a universal formula that may help in further implementation of the GDP concept.

Common Host Responses in Murine Aerosol Models of Infection Caused by Highly Virulent Gram-Negative Bacteria from the Genera Burkholderia, Francisella and Yersinia.

Highly virulent bacterial pathogens cause acute infections which are exceptionally difficult to treat with conventional antibiotic therapies alone. Understanding the chain of events that are triggered during an infection of a host has the potential to lead to new therapeutic strategies. For the first time, the transcriptomic responses within the lungs of Balb/C mice have been compared during an acute infection with the intracellular pathogens , and .

Nonintrusive Appliance Load Monitoring: An Overview, Laboratory Test Results and Research Directions.

Nonintrusive appliance load monitoring (NIALM) allows disaggregation of total electricity consumption into particular appliances in domestic or industrial environments. NIALM systems operation is based on processing of electrical signals acquired at one point of a monitored area. The main objective of this paper was to present the state-of-the-art in NIALM technologies for the smart home.

Multiple metabolic pathways are predictive of ricin intoxication in a rat model.

Introduction: Exposure to ricin can be lethal and treatments that are under development have short windows of opportunity for administration after exposure. It is therefore essential to achieve early detection of ricin exposure to provide the best prognosis for exposed individuals. Ricin toxin can be detected in clinical samples via several antibody-based techniques, but the efficacy of these can be limited due to the rapid processing and cellular uptake of toxin in the body and subsequent low blood ricin concentrations.

Continuous flash suppression operates in local spatial zones: Effects of mask size and contrast.

Continuous flash suppression (CFS) is a technique in which presenting one eye with a dynamic Mondrian sequence prevents a low-contrast target in the other eye from being perceived for many seconds. Frequently used to study unconscious visual processing, CFS bears many similarities with binocular rivalry (BR), another popular dichoptic stimulation technique. It is therefore puzzling that the effect of mask size and contrast seem to differ between CFS and BR.

Observations on the Inactivation Efficacy of a MALDI-TOF MS Chemical Extraction Method on Bacillus anthracis Vegetative Cells and Spores.

A chemical (ethanol; formic acid; acetonitrile) protein extraction method for the preparation of bacterial samples for matrix assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS) identification was evaluated for its ability to inactivate bacterial species. Initial viability tests (with and without double filtration of the extract through 0.2 μM filters), indicated that the method could inactivate Escherichia coli MRE 162 and Klebsiella pneumoniae ATCC 35657, with or without filtration, but that filtration was required to exclude viable, avirulent, Bacillus anthracis UM23CL2 from extracts.

Developing and understanding biofluid vibrational spectroscopy: a critical review.

Vibrational spectroscopy can provide rapid, label-free, and objective analysis for the clinical domain. Spectroscopic analysis of biofluids such as blood components (e.g.

Polymerase Chain Reaction on a Viral Nanoparticle.

The field of synthetic biology includes studies that aim to develop new materials and devices from biomolecules. In recent years, much work has been carried out using a range of biomolecular chassis including α-helical coiled coils, β-sheet amyloids and even viral particles. In this work, we show how hybrid bionanoparticles can be produced from a viral M13 bacteriophage scaffold through conjugation with DNA primers that can template a polymerase chain reaction (PCR).

Control of intracellular Francisella tularensis by different cell types and the role of nitric oxide.

Reactive nitrogen is critical for the clearance of Francisella tularensis infections. Here we assess the role of nitric oxide in control of intracellular infections in two murine macrophage cell lines of different provenance: the alveolar macrophage cell line, MH-S, and the widely used peritoneal macrophage cell line, J774A.1.

Targeting the "Rising DAMP" during a Francisella tularensis Infection.

Antibiotic efficacy is greatly enhanced the earlier it is administered following infection with a bacterial pathogen. However, in a clinical setting antibiotic treatment usually commences following the onset of symptoms, which in some cases (e.g.

The ability of CpG oligonucleotides to protect mice against Francisella tularensis live vaccine strain but not fully virulent F. tularensis subspecies holarctica is reflected in cell-based assays.

CpG DNA is a potent activator of the innate immune system. Here the protective effects of CpG DNA are assessed against the facultative intracellular pathogen Francisella tularensis. Dosing of mice with CpG DNA provided protection against disease caused by F.

The use of colorimetric sensor arrays to discriminate between pathogenic bacteria.

A colorimetric sensor array is a high-dimensional chemical sensor that is cheap, compact, disposable, robust, and easy to operate, making it a good candidate technology to detect pathogenic bacteria, especially potential bioterrorism agents like Yersinia pestis and Bacillus anthracis which feature on the Center for Disease Control and Prevention's list of potential biothreats. Here, a colorimetric sensor array was used to continuously monitor the volatile metabolites released by bacteria in solid media culture in an Advisory Committee on Dangerous Pathogen Containment Level 3 laboratory. At inoculum concentrations as low as 8 colony-forming units per plate, 4 different bacterial species were identified with 100% accuracy using logistic regression to classify the kinetic profile of sensor responses to culture headspace gas.

Targeting the "cytokine storm" for therapeutic benefit.

Inflammation is the body's first line of defense against infection or injury, responding to challenges by activating innate and adaptive responses. Microbes have evolved a diverse range of strategies to avoid triggering inflammatory responses. However, some pathogens, such as the influenza virus and the Gram-negative bacterium Francisella tularensis, do trigger life-threatening "cytokine storms" in the host which can result in significant pathology and ultimately death.

Gene expression following low dose inhalational Francisella tularensis (SchuS4) exposure in Balb/c mice and the potential role of the epithelium and cell adhesion.

Interactions between Francisella tularensis and the host are slowly being elucidated. Microarray technology was used to further characterise the response of Balb/c mice after inhalation of the virulent F. tularensis, SchuS4.

Neutrophils are the predominant cell-type to associate with Burkholderia pseudomallei in a BALB/c mouse model of respiratory melioidosis.

A variety of studies have implicated neutrophils and the rapid induction of cytokine in the host response in melioidosis. Here a BALB/c mouse model of infection with aerosolised Burkholderia pseudomallei K96243 has been used to understand the immune response to infection in this model and verify other infection models that show rapid growth of bacteria, colonisation of tissues and periphery, induction of cytokines and influx of neutrophils. Uniquely, this study has also determined the association of B.

Combining vaccination and postexposure CpG therapy provides optimal protection against lethal sepsis in a biodefense model of human melioidosis.

The Gram-negative bacterium Burkholderia pseudomallei is the causative agent of melioidosis, a major cause of lethal sepsis and morbidity in endemic areas of Southeast Asia and a potential bioterrorism threat. We have used susceptible BALB/c mice to evaluate the potential of targeting vaccination and generic immunotherapy to the lung for optimal protection against respiratory challenge. Intranasal vaccination with live attenuated B.