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Reporting on outcomes of a UK Antimicrobial Resistance research initiative into the infection control offered by downward flow laminar ventilation in operating theatres. Pre-cooled air is forced down onto the patient with the intention of diverting airborne pathogens from the surgical wound. The concept was commercialised in the early 1970s as the Ultra Clean Ventilation (UCV) system, a commonly applied contemporary solution. Data collected by the authors in unoccupied UCV theatres in a recently completed acute hospital indicates that as the warming air descends into the occupied zone it may be subject to recirculation within the suite of spaces. This phenomenon is confirmed by the authors’ experimental modelling. Increasing the residence time of microorganisms will increase the probability of Surgical Site Infection (SSI). An alternative up flow displacement ventilation scheme is proposed in combination with a localised source of filtered air to ventilate the wound as required. Likely ventilation flows are modelled experimentally and compared with those of the downdraught ventilated UCV type. The alternative arrangement appears to provide lower risk of Surgical Site Infection, while requiring less energy to drive the ventilation system. The concept is developed into a novel surgical theatre proposal in which background airflows are driven by natural buoyancy. (196)

Contemporary spaces for surgery are highly energy intensive, with much of this energy driving powerful air conditioning systems intended to force pre-cooled air down onto the patient, surgical staff and instruments to keep airborne pathogens from sedimenting on the patient and equipment during surgery and to drive them up and out through high level exhausts. The carbon footprint from these systems is prodigious in a service required to dramatically cut emissions. Sufficient doubts have arisen from experimental modelling and data collected in such surgical theatres that pathogens are expelled efficiently to encourage broader speculation about the fundamental configuration of spaces for surgery. One prospective avenue is the investigation of the aseptic movement’s operating room designs of the late nineteenth and early twentieth centuries before the adoption of air conditioning. Historical review and testing of theatre design, as part of the Excising Infections in Surgical Environments (ExISE) project, identified a particularly carefully designed and innovative operating room in Hamburg’s general hospital of 1897. The St. Georg’s Operationshaus (1899) is reconstructed digitally, analysed theoretically and modelled experimentally to determine modern utility as a green theatre. Results are promising but are affected fundamentally by the parallel intent to introduce prodigious natural daylighting; however, the effects of this on the air flow patterns in the space could be managed by modern materials and control technologies.

Background Cardiac interventions account for a significant share of overall healthcare spending and have been the focus of several large-scale interventions to develop effective bundled payments. To date, however, none have proven successful in commercially insured populations. In 2018, we worked with Hawaii Medical Service Association (HMSA), the Blue Cross Blue Shield of Hawaii, to design a novel commercial bundled payment for percutaneous coronary interventions, the Percutaneous Coronary Intervention Episode Payment Model (PCI EPM). Methods Descriptive analysis of HMSA's PCI EPM, including its inclusion criteria , contents of the bundle, target prices, shared savings model, and incentivized quality metrics. We also compare HMSA's PCI EPM to Medicare's Bundled Payment for Care Improvement programs and the cancelled Cardiac Care Model. Results HMSA's PCI EPM was designed through an iterative process with cardiologists and is the first commercial bundle to specifically target a cardiac procedure. PCI EPM incorporates site neutrality and incentivizes providers to shift care to the outpatient setting when medically permissible. Compared to existing non-commercial models, PCI EPM incorporate first-dollar shared savings and incentivized fewer quality metrics. Conclusions Reviewing features of the Percutaneous Coronary Intervention Episode Payment Model in comparison to existing Medicare programs is intended to help guide health plan and health policymakers when designing programs and policies related to cardiac interventions. Implications Bundled commercial payments for interventional cardiology procedures are promising and should continue to be further explored. Level of evidence VI.

We consider a toy model of interacting extrovert and introvert agents introduced earlier by Liu et al [Europhys. Lett. {\bf 100} (2012) 66007]. The number of extroverts, and introverts is $N$ each. At each time step, we select an agent at random, and allow her to modify her state. If an extrovert is selected, she adds a link at random to an unconnected introvert. If an introvert is selected, she removes one of her links. The set of $N^2$ links evolves in time, and may be considered as a set of Ising spins on an $N \times N$ square-grid with single-spin-flip dynamics. This dynamics satisfies detailed balance condition, and the probability of different spin configurations in the steady state can be determined exactly. The effective hamiltonian has long-range multi-spin couplings that depend on the row and column sums of spins. If the relative bias of choosing an extrovert over an introvert is varied, this system undergoes a phase transition from a state with very few links to one in which most links are occupied. We show that the behavior of the system can be determined exactly in the limit of large $N$. The behavior of large fluctuations in the total numer of links near the phase transition is determined. We also discuss two variations, called egalitarian and elitist agents, when the agents preferentially add or delete links to their least/ most-connected neighbor. These shows interesting cooperative behavior., Comment: Minor correction in one equation

The aim of inhaled corticosteroid (ICS) therapy is to achieve optimal drug targeting by producing pulmonary effects with a minimum of systemic side effects. To achieve a favorable safety and efficacy profile, an ICS should possess the necessary pharmacokinetic and pharmacodynamic characteristics. Ideally, an ICS would have high pulmonary deposition efficiency, high systemic clearance, negligible oral bioavailability, sustained pulmonary residence time, selective binding to the corticosteroid receptor, and high plasma protein binding. Recent developments in ICS therapy have used these concepts in producing more effective compounds resulting in drugs with a very high therapeutic index. Additional developments may consider exploring improvements in delivery devices and drug formulations to improve pulmonary residence time.

This laboratory is investigating the use of anti-methotrexate IgG (AMI) and anti-methotrexate Fab fragments (AMF) within an inverse targeting strategy that is designed to enhance the pharmacokinetic selectivity of intraperitoneal (i.p.) chemotherapy. The goal of this study was to develop enzyme-linked immunosorbent assays (ELISAs) to determine concentrations of AMI and AMF in mouse and rat plasma. An antigen-specific ELISA was developed for AMI and AMF in mouse and rat plasma. The assay was validated with respect to precision and accuracy by evaluating the recovery of AMI and AMF from mouse and rat plasma samples. Preliminary pharmacokinetic studies of AMI and AMF were performed in Sprague-Dawley rats and Swiss Webster mice. The animals were instrumented with a jugular vein cannula and administered AMI or AMF, 15 mg kg(-1) via the cannula. Plasma samples were taken at various time points and analyzed using the ELISA, and the observed concentration vs. time profiles were subjected to non-compartmental pharmacokinetic analyses. Standard curves for the ELISAs were found to be linear over concentration ranges of 0-250 and 0-350 ng mL(-1) for AMI and AMF, respectively. Intra-assay and inter-assay recovery of AMI and AMF from plasma samples were found to be within 15% of theoretical values. Preliminary pharmacokinetic investigations of AMI allowed estimation of AMI clearance to be 0.017 mL kg(-1) min(-1) in the rat and 0.043 mL kg(-1) min(-1) in the mouse. AMF clearance was estimated to be 0.038 and 1.93 mL kg(-1) min(-1) in the mouse and rat, respectively. In conclusion, ELISAs have been developed and validated for quantitation of AMI and AMF in rat and mouse plasma. The assays will allow further investigations of AMI and AMF pharmacokinetics.

The occurrence of follicular bronchiolitis (FB), lymphoid hyperplasia of the bronchus-associated lymphoid tissue, is reported in association with several systemic rheumatic diseases. However, the occurrence of FB in patients with giant cell arteritis (GCA) is not described. A 64-year-old man with long-standing GCA subsequently presented with haemoptysis. A mass in the lower lobe of the left lung was seen on chest x-ray and computed tomography. A wedge resection was performed, and histological examination revealed bronchiectasis, granulation tissue and hyperplasia of peribronchiolar lymphoid aggregates, consistent with FB. FB should be included in the differential diagnosis of haemoptysis in patients with systemic rheumatic diseases.

We study a simple model of dynamic networks, characterized by a set preferred degree, $\kappa$. Each node with degree $k$ attempts to maintain its $\kappa$ and will add (cut) a link with probability $w(k;\kappa)$ ($1-w(k;\kappa)$). As a starting point, we consider a homogeneous population, where each node has the same $\kappa$, and examine several forms of $w(k;\kappa)$, inspired by Fermi-Dirac functions. Using Monte Carlo simulations, we find the degree distribution in steady state. In contrast to the well-known Erd\H{o}s-R\'{e}nyi network, our degree distribution is not a Poisson distribution; yet its behavior can be understood by an approximate theory. Next, we introduce a second preferred degree network and couple it to the first by establishing a controllable fraction of inter-group links. For this model, we find both understandable and puzzling features. Generalizing the prediction for the homogeneous population, we are able to explain the total degree distributions well, but not the intra- or inter-group degree distributions. When monitoring the total number of inter-group links, $X$, we find very surprising behavior. $X$ explores almost the full range between its maximum and minimum allowed values, resulting in a flat steady-state distribution, reminiscent of a simple random walk confined between two walls. Both simulation results and analytic approaches will be discussed., Comment: Accepted by JSTAT

Inhaled therapy with either glucocorticoids and/or beta(2)-adrenergic drugs remains the mainstay of asthma treatment. In the last few years, a number of new products have been introduced into the market with the goal of improving efficacy and safety. This review article summarises the pharmacokinetic and pharmacodynamic properties of inhaled drugs for topical delivery necessary to achieve this goal. Pharmacokinetic properties include a high pulmonary deposition, low oral bioavailability, optimised pulmonary residence time and a very high systemic clearance. Optimisation of pharmacodynamic properties, such as receptor selectivity, may also yield drugs with improved pulmonary selectivity. As existing drugs also provide high efficacy and safety profiles, future developments will represent only slight improvements and quantum leap improvements are unlikely to occur.

We present long Monte Carlo simulations of a simple model of biological macroevolution in which births, deaths, and mutational changes in the genome take place at the level of individual organisms. The model displays punctuated equilibria and flicker noise with a 1/f-like power spectrum, consistent with some current theories of evolutionary dynamics., Comment: 3 pages RevTex4, 2 included eps figures

During operation of the microporous membrane oxygenators at some conditions, gas microbubbles penetrate into the blood. This effect, so-called spontaneous bubbling, takes place even when the blood pressure is higher than the gas pressure. This phenomenon was confirmed experimentally both in a model cell with hydrophobic microporous hollow fibers being used in the oxygenators and in in vitro tests on the actual microporous hollow fiber oxygenator. We proposed a mechanism of spontaneous gas bubbling into liquid that contains dissolved gases. Because of a partial pressure gradient, the dissolved gases and water vapors are transported from blood into the gas pore. This causes Stefans gas flow directed from the liquid-gas interface. Because of the high hydraulic resistance of the micropores, gas pressure at the meniscus increases up to gas bubbling. A mishandled priming of the oxygenator as well as the blood pressure pulsation caused by the roller pump operation contribute to spontaneous gas bubbling in the microporous oxygenators. The flow and pressure in the hydrophobic pores were calculated for various gases.

A 68-year-old man, who underwent a left lower lobectomy for a typical carcinoid tumor 30 years previously, presented with a 2-year history of left-sided chest pain. A computed tomographic scan, an octreotide scan, and pleural biopsy all showed recurrence of carcinoid tumor in the pleura. He underwent left chest wall resection, and histopathologic examination confirmed the diagnosis of typical carcinoid tumor. A review of the literature indicates that this is only the second reported case of pleural recurrence after previous complete resection of typical pulmonary carcinoid tumor. This case is even more unusual in that the recurrence presented so long after surgery.

Based on a high temperature expansion, we compute the two-point correlation function and the critical line of an Ising lattice gas driven into a non-equilibrium steady state by a uniform bias E. The lowest nontrivial order already reproduces the key features, i.e., the discontinuity singularity of the structure factor and the (qualitative) E-dependence of the critical line. Our approach is easily generalized to other non-equilibrium lattice models and provides a simple analytic tool for the study of the high temperature phase and its boundaries., Comment: 17 pages, no figures. Some typos corrected. To appear in J. Stat. Phys. (May 1998)