Numerical simulation of blood flow and pressure drop in the pulmonary arterial and venous circulation

A novel multiscale mathematical and computational model of the pulmonary circulation is presented and used to analyse both arterial and venous pressure and flow. This work is a major advance over previous studies by Olufsen et al. (Ann Biomed Eng 28:1281–1299, 2012) which only considered the arterial circulation. For the first three generations of vessels within the pulmonary circulation, geometry is specified from patient-specific measurements obtained using magnetic resonance imaging (MRI). Blood flow and pressure in the larger arteries and veins are predicted using a nonlinear, cross-sectional-area-averaged system of equations for a Newtonian fluid in an elastic tube. Inflow into the main pulmonary artery is obtained from MRI measurements, while pressure entering the left atrium from the main pulmonary vein is kept constant at the normal mean value of 2 mmHg. Each terminal vessel in the network of ‘large’ arteries is connected to its corresponding terminal vein via a network of vessels representing the vascular bed of smaller arteries and veins. We develop and implement an algorithm to calculate the admittance of each vascular bed, using bifurcating structured trees and recursion. The structured-tree models take into account the geometry and material properties of the ‘smaller’ arteries and veins of radii ≥ 50 μ m. We study the effects on flow and pressure associated with three classes of pulmonary hypertension expressed via stiffening of larger and smaller vessels, and vascular rarefaction. The results of simulating these pathological conditions are in agreement with clinical observations, showing that the model has potential for assisting with diagnosis and treatment for circulatory diseases within the lung

Gravito-electromagnetic analogies

We reexamine and further develop different gravito-electromagnetic (GEM) analogies found in the literature, and clarify the connection between them. Special emphasis is placed in two exact physical analogies: the analogy based on inertial fields from the so-called "1+3 formalism", and the analogy based on tidal tensors. Both are reformulated, extended and generalized. We write in both formalisms the Maxwell and the full exact Einstein field equations with sources, plus the algebraic Bianchi identities, which are cast as the source-free equations for the gravitational field. New results within each approach are unveiled. The well known analogy between linearized gravity and electromagnetism in Lorentz frames is obtained as a limiting case of the exact ones. The formal analogies between the Maxwell and Weyl tensors are also discussed, and, together with insight from the other approaches, used to physically interpret gravitational radiation. The precise conditions under which a similarity between gravity and electromagnetism occurs are discussed, and we conclude by summarizing the main outcome of each approach.Comment: 60 pages, 2 figures. Improved version (compared to v2) with some re-write, notation improvements and a new figure that match the published version; expanded compared to the published version to include Secs. 2.3 and

Co-infection of Influenza B and Streptococci causing severe pneumonia and septic shock in healthy women

<p>Abstract</p> <p>Background</p> <p>Since the Influenza A pandemic in 1819, the association between the influenza virus and <it>Streptococcus pneumoniae </it>has been well described in literature. While a leading role has been so far attributed solely to Influenza A as the primary infective pathogen, Influenza B is generally considered to be less pathogenic with little impact on morbidity and mortality of otherwise healthy adults. This report documents the severe synergistic pathogenesis of Influenza B infection and bacterial pneumonia in previously healthy persons not belonging to a special risk population and outlines therapeutic options in this clinical setting.</p> <p>Case Presentation</p> <p>During the seasonal influenza epidemic 2007/2008, three previously healthy women presented to our hospital with influenza-like symptoms and rapid clinical deterioration. Subsequent septic shock due to severe bilateral pneumonia necessitated intensive resuscitative measures including the use of an interventional lung assist device. Microbiological analysis identified severe dual infections of Influenza B with <it>Streptococcus pyogenes </it>in two cases and <it>Streptococcus pneumoniae </it>in one case. The patients presented with no evidence of underlying disease or other known risk factors for dual infection such as age (< one year, > 65 years), pregnancy or comorbidity.</p> <p>Conclusions</p> <p>Influenza B infection can pose a risk for severe secondary infection in previously healthy persons. As patients admitted to hospital due to severe pneumonia are rarely tested for Influenza B, the incidence of admission due to this virus might be greatly underestimated, therefore, a more aggressive search for influenza virus and empirical treatment might be warranted. While the use of an interventional lung assist device offers a potential treatment strategy for refractory respiratory acidosis in addition to protective lung ventilation, the combined empiric use of a neuraminidase-inhibitor and antibiotics in septic patients with pulmonary manifestations during an epidemic season should be considered.</p

Cost-effectiveness of High-Intensity Interval Training (HIIT) vs Moderate Intensity Steady-State (MISS) Training in UK Cardiac Rehabilitation

Objective: To perform a cost-effectiveness analysis of high-intensity interval training (HIIT) compared with moderate intensity steady-state (MISS) training in people with coronary artery disease (CAD) attending cardiac rehabilitation (CR). Design: Secondary cost-effectiveness analysis of a prospective, assessor-blind, parallel group, multi-center RCT. Setting: Six outpatient National Health Service cardiac rehabilitation centers in England and Wales, UK. Participants: 382 participants with CAD (N=382). Interventions: Participants were randomized to twice-weekly usual care (n=195) or HIIT (n=187) for 8 weeks. Usual care was moderate intensity continuous exercise (60%-80% maximum capacity, MISS), while HIIT consisted of 10 × 1-minute intervals of vigorous exercise (>85% maximum capacity) interspersed with 1-minute periods of recovery. Main Outcome Measures: We conducted a cost-effectiveness analysis of the HIIT or MISS UK trial. Health related quality of life was measured with the EQ-5D-5L to estimate quality-adjusted life years (QALYs). Costs were estimated with health service resource use and intervention delivery costs. Cost-utility analysis measured the incremental cost-effectiveness ratio (ICER). Bootstrapping assessed the probability of HIIT being cost-effective according to the UK National Institute for Health and Care Excellence (NICE) threshold value (£20,000 per QALY). Missing data were imputed. Uncertainty was estimated using probabilistic sensitivity analysis. Assumptions were tested using univariate/1-way sensitivity analysis. Results: 124 (HIIT, n=59; MISS, n=65) participants completed questionnaires at baseline, 8 weeks, and 12 months. Mean combined health care use and delivery cost was £676 per participant for HIIT, and £653 for MISS. QALY changes were 0.003 and -0.013, respectively. For complete cases, the ICER was £1448 per QALY for HIIT compared with MISS. At a willingness-to-pay threshold of £20,000 per QALY, the probability of HIIT being cost-effective was 96% (95% CI, 0.90 to 0.95). Conclusion: For people with CAD attending CR, HIIT was cost-effective compared with MISS. These findings are important to policy makers, commissioners, and service providers across the health care sector

Safety of liver resection and effect on quality of life in patients with benign hepatic disease: Single center experience

<p>Abstract</p> <p>Background</p> <p>Although liver resection has long been established for selected patients with benign hepatic disease, the success of surgical treatment of these patients cannot be evaluated exclusively through postoperative morbidity and mortality. Therefore, the aim of the study was to prove the safety of liver resection in the treatment of benign liver tumors and to evaluate the effect of surgical treatment on the patients' qauality of life.</p> <p>Methods</p> <p>A total of 146 patients who underwent liver resection because of benign liver tumors were included in this study. Postoperative outcome was assessed and patients evaluated their quality of life before surgery and at the present time using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ C-30).</p> <p>Results</p> <p>The rate of serious (> grade 2) complications was 4.1% with no postoperative death. The quality of life assessment revealed an overall improvement of general health status after resection (0.7 vs. 0.56, p < 0.001) and additionally a significant reduction of 6 out of 9 symptoms. Furthermore, compelling benefits in the patients' social and emotional coping could be detected after surgery.</p> <p>Conclusions</p> <p>Liver resection for benign liver disease is a safe procedure and leads to a significant improvement of quality of life in selected patients.</p

Family history of cancer as a risk factor for second malignancies after Hodgkin's lymphoma

This study estimated the risk of second primary malignancies after Hodgkin's lymphoma (HL) in relation to family history of cancer, age at diagnosis and latency, among 6946 patients treated for HL in Sweden in 1965–1995 identified through the Swedish Cancer Register (SCR). First-degree relatives (FDRs) to the HL patients and their malignancies were then ascertained together with their malignancies through the Multi-Generation Registry and SCR. The HL patient cohort was stratified on the number of FDRs with cancer, and standardised incidence ratios (SIRs) of developing SM were analysed. In the HL cohort, 781 SM were observed 1 year or longer after HL diagnosis. The risk for developing SM increased with the number of FDRs with cancer, SIRs being 2.26, 3.01, and 3.45 with 0, 1, or ⩾2 FDRs with cancer, respectively. Hodgkin's lymphoma long-term survivors treated at a young age with a family history of cancer carry an increased risk for developing SM and may represent a subgroup where standardised screening for the most common cancer sites could be offered in a stringent surveillance programme

Metformin treatment in diabetes and heart failure: when academic equipoise meets clinical reality

<p>Abstract</p> <p>Objective</p> <p>Metformin has had a 'black box' contraindication in diabetic patients with heart failure (HF), but many believe it to be the treatment of choice in this setting. Therefore, we attempted to conduct a pilot study to evaluate the feasibility of undertaking a large randomized controlled trial with clinical endpoints.</p> <p>Study Design</p> <p>The pilot study was a randomized double blinded placebo controlled trial. Patients with HF and type 2 diabetes were screened in hospitals and HF clinics in Edmonton, Alberta, Canada (population ~1 million). Major exclusion criteria included the current use of insulin or high dose metformin, decreased renal function, or a glycosylated hemoglobin <7%. Patients were to be randomized to 1500 mg of metformin daily or matching placebo and followed for 6 months for a variety of functional outcomes, as well as clinical events.</p> <p>Results</p> <p>Fifty-eight patients were screened over a six month period and all were excluded. Because of futility with respect to enrollment, the pilot study was abandoned. The mean age of screened patients was 77 (SD 9) years and 57% were male. The main reasons for exclusion were: use of insulin therapy (n = 23; 40%), glycosylated hemoglobin <7% (n = 17; 29%) and current use of high dose metformin (n = 12; 21%). Overall, contraindicated metformin therapy was the most commonly prescribed oral antihyperglycemic agent (n = 27; 51%). On average, patients were receiving 1,706 mg (SD 488 mg) of metformin daily and 12 (44%) used only metformin.</p> <p>Conclusion</p> <p>Despite uncertainty in the scientific literature, there does not appear to be clinical uncertainty with regards to the safety or effectiveness of metformin in HF making a definitive randomized trial virtually impossible.</p> <p>Trial registration</p> <p>ClinicalTrials.gov Identifier: NCT00325910</p

Electrophysiological Evidence for Spatiotemporal Flexibility in the Ventrolateral Attention Network

Successful completion of many everyday tasks depends on interactions between voluntary attention, which acts to maintain current goals, and reflexive attention, which enables responding to unexpected events by interrupting the current focus of attention. Past studies, which have mostly examined each attentional mechanism in isolation, indicate that volitional and reflexive orienting depend on two functionally specialized cortical networks in the human brain. Here we investigated how the interplay between these two cortical networks affects sensory processing and the resulting overt behavior. By combining measurements of human performance and electrocortical recordings with a novel analytical technique for estimating spatiotemporal activity in the human cortex, we found that the subregions that comprise the reflexive ventrolateral attention network dissociate both spatially and temporally as a function of the nature of the sensory information and current task demands. Moreover, we found that together with the magnitude of the early sensory gain, the spatiotemporal neural dynamics accounted for the high amount of the variance in the behavioral data. Collectively these data support the conclusion that the ventrolateral attention network is recruited flexibly to support complex behaviors