Infections in recipients of liver homografts.

Seventeen patients received liver homografts between 1963 and May, 1968. The eight treated before July, 1967, died within 34 days; seven had progressive infections with gram-negative bacilli, Candida albicans and cytomegalovirus. The infections were similar to but more fulminating than those after renal homotransplantation. In nine later cases, there was more discriminating donor selection, improved immunosuppression, and better organ preservation. In the first five of these nine patients, all infants, lobar hepatic gangrene apparently secondary to delayed right hepatic arterial thrombosis developed. Two died within a few days, two and three and a half months after transplantation. The three who did not die immediately subsequently had multiple bacteremias, fungemias and cytomegalovirus pulmonary infections. One of these children is alive twelve months after transplantation; the others died after four and a half and six months. In contrast, the last four patients, in whom septic liver infarctions were avoided, have been free of serious infections for two to five and a half months

Absorbable versus silk sutures for surgical treatment of trachomatous trichiasis in Ethiopia: a randomised controlled trial.

BACKGROUND: Trachoma causes blindness through an anatomical abnormality called trichiasis (lashes touching the eye). Trichiasis can recur after corrective surgery. We tested the hypothesis that using absorbable sutures instead of silk sutures might reduce the risk of recurrent disease among patients with major trichiasis in a randomised trial. METHODS AND FINDINGS: 1,300 individuals with major trichiasis from rural villages in the Amhara Region of Ethiopia were recruited and assigned (1:1) by computer-generated randomisation sequence to receive trichiasis surgery using either an absorbable suture (polyglactin-910) or silk sutures (removed at 7-10 days) in an otherwise identical surgical technique. Participants were examined every 6 months for 2 years by clinicians masked to allocation. The primary outcome measure was recurrent trichiasis (≥one lash touching the eye) at 1 year. There was no difference in prevalence of recurrent trichiasis at 1 year (114 [18.2%] in the absorbable suture group versus 120 [19.7%] in the silk suture group; odds ratio = 0.90, 95% CI 0.68-1.20). The two groups also did not differ in terms of corneal opacification, visual acuity, conjunctival inflammation, and surgical complications. CONCLUSIONS: There was no evidence that use of absorbable polyglactin-910 sutures was associated with a lower prevalence of trichiasis recurrence at 1 year postsurgery than silk sutures. However, from a programmatic perspective, polyglactin-910 offers the major advantage that patients do not have to be seen soon after surgery for suture removal. The postoperative review after surgery using absorbable polyglactin-910 sutures can be delayed for 3-6 months, which might allow us to better determine whether a patient needs additional surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT00522860

Effects of trade barriers on development and growth

A basic definition of trade barriers could be ‘all factors that influence the amount of goods and services shipped across international borders’ (Feenstra and Taylor, 2017a). This definition is quite neutral, and it needs to be understood that the word ‘barrier’ has a negative connotation, which means that a trade barrier would be any instrument that limits or restrict trade between countries, as opposed to free trade. It is generally accepted that free trade is good for productivity and economic growth, but it is also true that most countries apply some sort of trade restriction, for different reasons

Mathematical and Statistical Techniques for Systems Medicine: The Wnt Signaling Pathway as a Case Study

The last decade has seen an explosion in models that describe phenomena in systems medicine. Such models are especially useful for studying signaling pathways, such as the Wnt pathway. In this chapter we use the Wnt pathway to showcase current mathematical and statistical techniques that enable modelers to gain insight into (models of) gene regulation, and generate testable predictions. We introduce a range of modeling frameworks, but focus on ordinary differential equation (ODE) models since they remain the most widely used approach in systems biology and medicine and continue to offer great potential. We present methods for the analysis of a single model, comprising applications of standard dynamical systems approaches such as nondimensionalization, steady state, asymptotic and sensitivity analysis, and more recent statistical and algebraic approaches to compare models with data. We present parameter estimation and model comparison techniques, focusing on Bayesian analysis and coplanarity via algebraic geometry. Our intention is that this (non exhaustive) review may serve as a useful starting point for the analysis of models in systems medicine.Comment: Submitted to 'Systems Medicine' as a book chapte

Pericardial effusion as the only manifestation of infection with Francisella tularensis: a case report

<p>Abstract</p> <p>Introduction</p> <p><it>Francisella tularensis</it>, a facultative intracellular Gram-negative bacterium, has rarely been reported as an agent of pericarditis, generally described as a complication of tularemia sepsis. <it>F. tularensis </it>is a fastidious organism that grows poorly on standard culture media and diagnosis is usually based on serological tests. However, cross-reactions may occur. Western blotting allows the correct diagnosis.</p> <p>Case presentation</p> <p>A non-smoking 53-year-old woman was admitted to hospital with a large posterior pericardial effusion. Serological tests showed a seroconversion in antibody titers to <it>F. tularensis </it>(IgG titer = 400) and <it>Legionella pneumophila </it>(IgG titer = 512). <it>F. tularensis </it>was identified by Western immunoblotting following cross-adsorption. The patient reported close contact with rabbits 2 weeks prior to the beginning of symptoms of pericarditis.</p> <p>Conclusion</p> <p>We report a rare case of pericardial effusion as the only manifestation of infection by <it>F. tularensis</it>. The etiological diagnosis is based on serology. Western blotting and cross-adsorption allow differential diagnosis.</p

A host transcriptional signature for presymptomatic detection of infection in humans exposed to influenza H1N1 or H3N2.

There is great potential for host-based gene expression analysis to impact the early diagnosis of infectious diseases. In particular, the influenza pandemic of 2009 highlighted the challenges and limitations of traditional pathogen-based testing for suspected upper respiratory viral infection. We inoculated human volunteers with either influenza A (A/Brisbane/59/2007 (H1N1) or A/Wisconsin/67/2005 (H3N2)), and assayed the peripheral blood transcriptome every 8 hours for 7 days. Of 41 inoculated volunteers, 18 (44%) developed symptomatic infection. Using unbiased sparse latent factor regression analysis, we generated a gene signature (or factor) for symptomatic influenza capable of detecting 94% of infected cases. This gene signature is detectable as early as 29 hours post-exposure and achieves maximal accuracy on average 43 hours (p = 0.003, H1N1) and 38 hours (p-value = 0.005, H3N2) before peak clinical symptoms. In order to test the relevance of these findings in naturally acquired disease, a composite influenza A signature built from these challenge studies was applied to Emergency Department patients where it discriminates between swine-origin influenza A/H1N1 (2009) infected and non-infected individuals with 92% accuracy. The host genomic response to Influenza infection is robust and may provide the means for detection before typical clinical symptoms are apparent

Epilation for minor trachomatous trichiasis: four-year results of a randomised controlled trial.

BACKGROUND: Trachomatous trichiasis (TT) needs to be managed to reduce the risk of vision loss. The long-term impact of epilation (a common traditional practice of repeated plucking of lashes touching the eye) in preventing visual impairment and corneal opacity from TT is unknown. We conducted a randomized controlled trial of epilation versus surgery for the management of minor TT (fewer than six lashes touching the eye) in Ethiopia. Here we report the four-year outcome and the effect on vision and corneal opacity. METHODOLOGY/ PRINCIPAL FINDINGS: 1300 individuals with minor TT were recruited and randomly assigned to quality trichiasis surgery or repeated epilation using high quality epilation forceps by a trained person with good near vision. Participants were examined six-monthly for two-years, and then at four-years after randomisation. At two-years all epilation arm participants were offered free surgery. At four-years 1151 (88.5%) were re-examined: 572 (88%) and 579 (89%) from epilation and surgery arms, respectively. At that time, 21.1% of the surgery arm participants had recurrent TT; 189/572 (33%) of the epilation arm had received surgery, while 383 (67%) declined surgery and had continued epilating ("epilation-only"). Among the epilation-only group, 207 (54.1%) fully controlled their TT, 166 (43.3%) had minor TT and 10 (2.6%) had major TT (&gt;5 lashes). There were no differences between participants in the epilation-only, epilation-to-surgery and surgery arm participants in changes in visual acuity and corneal opacity between baseline and four-years. CONCLUSIONS/ SIGNIFICANCE: Most minor TT participants randomised to the epilation arm continued epilating and controlled their TT. Change in vision and corneal opacity was comparable between surgery and epilation-only participants. This suggests that good quality epilation with regular follow-up is a reasonable second-line alternative to surgery for minor TT for individuals who either decline surgery or do not have immediate access to surgical treatment

Re-evaluation of mammary stem cell biology based on in vivo transplantation

Over nearly half a century, transplantation methods have been employed to regenerate the mammary gland in vivo. Recent highly cited reports claim to have demonstrated the regeneration of an entire functional mammary gland from a single mammary epithelial cell. Nevertheless, re-examination of the literature on the transplantation biology of mammary gland regeneration reveals that a complex, combinatorial interaction between variously differentiated mammary epithelial cells and the mammary fat pad stroma is indispensable to this process. In the present article, these issues are reviewed and discussed to provide a greater understanding of the complexity of these multiplex interactions

Mathematical modelling of polyamine metabolism in bloodstream-form trypanosoma brucei: An application to drug target identification

© 2013 Gu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedThis article has been made available through the Brunel Open Access Publishing Fund.We present the first computational kinetic model of polyamine metabolism in bloodstream-form Trypanosoma brucei, the causative agent of human African trypanosomiasis. We systematically extracted the polyamine pathway from the complete metabolic network while still maintaining the predictive capability of the pathway. The kinetic model is constructed on the basis of information gleaned from the experimental biology literature and defined as a set of ordinary differential equations. We applied Michaelis-Menten kinetics featuring regulatory factors to describe enzymatic activities that are well defined. Uncharacterised enzyme kinetics were approximated and justified with available physiological properties of the system. Optimisation-based dynamic simulations were performed to train the model with experimental data and inconsistent predictions prompted an iterative procedure of model refinement. Good agreement between simulation results and measured data reported in various experimental conditions shows that the model has good applicability in spite of there being gaps in the required data. With this kinetic model, the relative importance of the individual pathway enzymes was assessed. We observed that, at low-to-moderate levels of inhibition, enzymes catalysing reactions of de novo AdoMet (MAT) and ornithine production (OrnPt) have more efficient inhibitory effect on total trypanothione content in comparison to other enzymes in the pathway. In our model, prozyme and TSHSyn (the production catalyst of total trypanothione) were also found to exhibit potent control on total trypanothione content but only when they were strongly inhibited. Different chemotherapeutic strategies against T. brucei were investigated using this model and interruption of polyamine synthesis via joint inhibition of MAT or OrnPt together with other polyamine enzymes was identified as an optimal therapeutic strategy.The work was carried out under a PhD programme partly funded by Prof. Ray Welland, School of Computing Science, University of Glasgo