The Host Immune Response to Tissue-Engineered Organs: Current Problems and Future Directions

As the global health burden of chronic disease increases, end-stage organ failure has become a costly and intractable problem. De novo organ creation is one of the long-term goals of the medical community. One of the promising avenues is that of tissue engineering: the use of biomaterials to create cells, structures, or even whole organs. Tissue engineering has emerged from its nascent stage, with several proof-of-principle trials performed across various tissue types. As tissue engineering moves from the realm of case trials to broader clinical study, three major questions have emerged: (1) Can the production of biological scaffolds be scaled up accordingly to meet current and future demands without generating an unfavorable immune response? (2) Are biological scaffolds plus or minus the inclusion of cells replaced by scar tissue or native functional tissue? (3) Can tissue-engineered organs be grown in children and adolescents given the different immune profiles of children? In this review, we highlight current research in the immunological response to tissue-engineered biomaterials, cells, and whole organs and address the answers to these questions

Wegener's granulomatosis of the orbit: two cases requiring endoscopic surgical decompression

We report two unusual and contrasting cases of Wegener's granulomatosis involving the orbit, requiring urgent endoscopic orbital decompression surgery

Understanding consumer demand for new transport technologies and services, and implications for the future of mobility

The transport sector is witnessing unprecedented levels of disruption. Privately owned cars that operate on internal combustion engines have been the dominant modes of passenger transport for much of the last century. However, recent advances in transport technologies and services, such as the development of autonomous vehicles, the emergence of shared mobility services, and the commercialization of alternative fuel vehicle technologies, promise to revolutionise how humans travel. The implications are profound: some have predicted the end of private car dependent Western societies, others have portended greater suburbanization than has ever been observed before. If transport systems are to fulfil current and future needs of different subpopulations, and satisfy short and long-term societal objectives, it is imperative that we comprehend the many factors that shape individual behaviour. This chapter introduces the technologies and services most likely to disrupt prevailing practices in the transport sector. We review past studies that have examined current and future demand for these new technologies and services, and their likely short and long-term impacts on extant mobility patterns. We conclude with a summary of what these new technologies and services might mean for the future of mobility.Comment: 15 pages, 0 figures, book chapte

Achieving flying colours in surgical safety: audit of World Health Organization 'Surgical Safety Checklist' compliance

Objective: The World Health Organization 'Surgical Safety Checklist' has been adopted by UK surgical units following National Patient Safety Agency guidance. Our aim was to assess compliance with our local version of this Checklist. Methods: Otolaryngology trainee doctors prospectively assessed compliance with the local Checklist over a six-week period. A staff educational intervention was implemented and the audit was repeated 12 months later. Results: A total of 72 cases were assessed. The initial audit found that: 44 per cent of procedures were undocumented at 'Sign in'; 'Time out' was inappropriately interrupted in 39 per cent of cases; the procedure started before Checklist completion in 33 per cent of cases; and the 'Sign out' was not read out in 94 per cent of cases and was not fully documented in 42 per cent of cases. Following education, re-audit indicated that overall compliance had improved from 63.7 per cent (±8.9 per cent standard error of the mean) to 90.4 per cent (±2.7 per cent standard error of the mean). Conclusion: Our completed audit cycle demonstrated a significant improvement in Checklist compliance following educational intervention. We discuss barriers to compliance, as well as strategies for quality improvement, and we call for other surgeons to similarly publish their Checklist experience and assess its impact on surgical outcomes

Prospective, randomised controlled trial comparing intense endoscopic cleaning versus minimal intervention in the early post-operative period following functional endoscopic sinus surgery

There is currently no standardised management protocol following functional endoscopic sinus surgery. This study assessed frequent endoscopic cleaning versus minimal intervention in the early post-operative period following such surgery

Appetite suppressants and valvular heart disease - a systematic review

Background Although appetite suppressants have been implicated in the development of valvular heart disease, the exact level of risk is still uncertain. Initial studies suggested that as many as 1 in 3 exposed patients were affected, but subsequent research has yielded substantially different figures. Our objective was to systematically assess the risk of valvular heart disease with appetite suppressants. Methods We accepted studies involving obese patients treated with any of the following appetite suppressants: fenfluramine, dexfenfluramine, and phentermine. Three types of studies were reviewed: controlled and uncontrolled observational studies, and randomized controlled trials. Outcomes of interest were echocardiographically detectable aortic regurgitation of mild or greater severity, or mitral regurgitation of moderate or greater severity. Results Of the 1279 patients evaluated in seven uncontrolled cohort studies, 236 (18%) and 60 (5%) were found to have aortic and mitral regurgitation, respectively. Pooled data from six controlled cohort studies yielded, for aortic regurgitation, a relative risk ratio of 2.32 (95% confidence intervals 1.79 to 3.01, p < 0.00001) and an attributable rate of 4.9%, and for mitral regurgitation, a relative risk ratio of 1.55 (95% confidence intervals 1.06 to 2.25, p = 0.02) with an attributable rate of 1.0%. Only one case of valvular heart disease was detected in 57 randomized controlled trials, but this was judged unrelated to drug therapy. Conclusions The risk of valvular heart disease is significantly increased by the appetite suppressants reviewed here. Nevertheless, when considering all the evidence, valvulopathy is much less common than suggested by the initial, less methodologically rigorous studies

Platelet count and Interleukin 6 Gene polymorphism in healthy subjects

BACKGROUND: Interleukin 6 (IL-6) is thought to play important roles in the development of reactive thrombocytosis caused by inflammation by its stimulatory effect on megakaryocytopoiesis. A G/C polymorphism of the IL-6 gene at position -174 has been found to be associated to different transcription rates. Specifically, subjects with the CC genotype showed lower plasma IL-6 levels compared with GC or GG subjects. Given this difference in transcription rates of IL-6 we speculated on different platelet count according to this IL-6 polymorphism. METHODS: The G/C polymorphism of the IL-6 gene at position -174, serum IL-6 concentration and platelet count were prospectively analyzed in 59 (25 women) consecutive healthy subjects. RESULTS: Subjects who were homozygotes for the C allele at position -174 of the IL-6 gene (Sfa NI genotype) showed significantly lower platelet count than carriers of the G allele, despite similar age, sex, body mass index and proportion of smokers (205400 ± 44088 vs 239818 ± 60194, p = 0.047). This was in parallel to differences in peripheral white blood cell count (5807 ± 1671 vs 6867 ± 1192 × 10(9)/ml, p = 0.01). CONCLUSION: This is the first description, to our knowledge, of a genetical influence on basal platelet counts, which appears to be partially dependent on a polymorphism of the IL-6 gene, even in the absence of inflammation

The developmental dynamics of terrorist organizations

We identify robust statistical patterns in the frequency and severity of violent attacks by terrorist organizations as they grow and age. Using group-level static and dynamic analyses of terrorist events worldwide from 1968-2008 and a simulation model of organizational dynamics, we show that the production of violent events tends to accelerate with increasing size and experience. This coupling of frequency, experience and size arises from a fundamental positive feedback loop in which attacks lead to growth which leads to increased production of new attacks. In contrast, event severity is independent of both size and experience. Thus larger, more experienced organizations are more deadly because they attack more frequently, not because their attacks are more deadly, and large events are equally likely to come from large and small organizations. These results hold across political ideologies and time, suggesting that the frequency and severity of terrorism may be constrained by fundamental processes.Comment: 28 pages, 8 figures, 4 tables, supplementary materia

An Exactly Solvable Model for the Integrability-Chaos Transition in Rough Quantum Billiards

A central question of dynamics, largely open in the quantum case, is to what extent it erases a system's memory of its initial properties. Here we present a simple statistically solvable quantum model describing this memory loss across an integrability-chaos transition under a perturbation obeying no selection rules. From the perspective of quantum localization-delocalization on the lattice of quantum numbers, we are dealing with a situation where every lattice site is coupled to every other site with the same strength, on average. The model also rigorously justifies a similar set of relationships recently proposed in the context of two short-range-interacting ultracold atoms in a harmonic waveguide. Application of our model to an ensemble of uncorrelated impurities on a rectangular lattice gives good agreement with ab initio numerics.Comment: 29 pages, 5 figure