Heterogeneity in susceptibility dictates the order of epidemiological models

The fundamental models of epidemiology describe the progression of an infectious disease through a population using compartmentalized differential equations, but do not incorporate population-level heterogeneity in infection susceptibility. We show that variation strongly influences the rate of infection, while the infection process simultaneously sculpts the susceptibility distribution. These joint dynamics influence the force of infection and are, in turn, influenced by the shape of the initial variability. Intriguingly, we find that certain susceptibility distributions (the exponential and the gamma) are unchanged through the course of the outbreak, and lead naturally to power-law behavior in the force of infection; other distributions often tend towards these "eigen-distributions" through the process of contagion. The power-law behavior fundamentally alters predictions of the long-term infection rate, and suggests that first-order epidemic models that are parameterized in the exponential-like phase may systematically and significantly over-estimate the final severity of the outbreak

Partial anomalous pulmonary venous return mimics arterial positioning after central line placement for plasmapheresis

Case: A 61-year-old male who was status post right single lung transplant complicated by grade three primary graft dysfunction was admitted and mechanically ventilated for hypoxic respiratory failure. Donor specific antibody testing to human leukocyte antigens was positive. The protocol for antibody-mediated transplant rejection was initiated. One aspect of the protocol was a series of plasmapheresis procedures. In advance of the first plasmapheresis, central line placement was attempted via the left internal jugular vein. A chest x-ray showed a line that terminated to the left of the midline and raised concern for arterial placement (Figure 1). Blood gases from the line were: pH 7.72, pCO2 21 mmHg, pO2 369 mmHg, bicarbonate 28.4 mmol/L.Alex J. Griffith (Department of Pathology and Laboratory Medicine, University of Wisconsin Hospital), Victoria Ray (MD, Department of Anesthesiology, University of Wisconsin Hospital), William N. Rose (MD, Department of Emergency Medicine, University of Wisconsin Hospital)Includes bibliographical reference

Medicago PhosphoProtein Database: a repository for Medicago truncatula phosphoprotein data

The ability of legume crops to fix atmospheric nitrogen via a symbiotic association with soil rhizobia makes them an essential component of many agricultural systems. Initiation of this symbiosis requires protein phosphorylation-mediated signaling in response to rhizobial signals named Nod factors. Medicago truncatula (Medicago) is the model system for studying legume biology, making the study of its phosphoproteome essential. Here, we describe the Medicago PhosphoProtein Database (MPPD; http://phospho.medicago.wisc.edu), a repository built to house phosphoprotein, phosphopeptide, and phosphosite data specific to Medicago. Currently, the MPPD holds 3,457 unique phosphopeptides that contain 3,404 non-redundant sites of phosphorylation on 829 proteins. Through the web-based interface, users are allowed to browse identified proteins or search for proteins of interest. Furthermore, we allow users to conduct BLAST searches of the database using both peptide sequences and phosphorylation motifs as queries. The data contained within the database are available for download to be investigated at the user’s discretion. The MPPD will be updated continually with novel phosphoprotein and phosphopeptide identifications, with the intent of constructing an unparalleled compendium of large-scale Medicago phosphorylation data

Clot Characterization in Acute Ischemic Stroke

Background: In the treatment of acute ischemic stroke (AIS) with mechanical thrombectomy, revascularization depends upon integration of the thrombus into the retrieval device. The histologic and mechanical characteristics of thrombi are key determinants of effective thrombus-device interaction. Thrombi with greater calcium and fibrin content have been associated with more challenging thrombus retrievals. Objective: To develop thrombus analogs with histologic and mechanical characteristics similar to those of challenging clinical thrombi for thrombectomy device testing. Methods: Fifty thrombi were retrieved from twenty-nine patients with AIS. Clinical thrombi underwent histologic analysis to determine erythrocyte and fibrin content. Nine clinical thrombi underwent dynamic mechanical analysis to determine thrombus stiffness, which was defined as a function of stress variation at low and high strains. Results from the clinical thrombi were used to determine the key mechanical characteristics of the challenging thrombus analogs, the calcium apatite-rich and fibrin-rich thrombus analogs. Results: Of the twenty-nine AIS cases, fifteen required multiple pass attempts. The average histologic composition of the challenging clinical thrombi was 26% erythrocyte, 54% fibrin, and 20% mixed. The average stiffness of the challenging clinical thrombi was found to be similar to that of the fibrin-rich thrombus analogs. Addition of calcium apatite increased the stiffness of the thrombus analogs at low strain approximately five-fold. Conclusions: Thrombus analogs with mechanical characteristics similar to those of challenging clinical thrombi were successfully developed. The calcium apatite-rich thrombus analogs were found to be stiffer than the fibrin-rich red thrombus analogs

Potential regulatory phosphorylation sites in a Medicago truncatula plasma membrane proton pump implicated during early symbiotic signaling in roots

AbstractIn plants and fungi the plasma membrane proton pump generates a large proton-motive force that performs essential functions in many processes, including solute transport and the control of cell elongation. Previous studies in yeast and higher plants have indicated that phosphorylation of an auto-inhibitory domain is involved in regulating pump activity. In this report we examine the Medicago truncatula plasma membrane proton pump gene family, and in particular MtAHA5. Yeast complementation assays with phosphomimetic mutations at six candidate sites support a phosphoregulatory role for two residues, suggesting a molecular model to explain early Nod factor-induced changes in the plasma membrane proton-motive force of legume root cells

1000 Norms Project: Protocol of a cross-sectional study cataloging human variation

Background Clinical decision-making regarding diagnosis and management largely depends on comparison with healthy or ‘normal’ values. Physiotherapists and researchers therefore need access to robust patient-centred outcome measures and appropriate reference values. However there is a lack of high-quality reference data for many clinical measures. The aim of the 1000 Norms Project is to generate a freely accessible database of musculoskeletal and neurological reference values representative of the healthy population across the lifespan. Methods/design In 2012 the 1000 Norms Project Consortium defined the concept of ‘normal’, established a sampling strategy and selected measures based on clinical significance, psychometric properties and the need for reference data. Musculoskeletal and neurological items tapping the constructs of dexterity, balance, ambulation, joint range of motion, strength and power, endurance and motor planning will be collected in this cross-sectional study. Standardised questionnaires will evaluate quality of life, physical activity, and musculoskeletal health. Saliva DNA will be analysed for the ACTN3 genotype (‘gene for speed’). A volunteer cohort of 1000 participants aged 3 to 100 years will be recruited according to a set of self-reported health criteria. Descriptive statistics will be generated, creating tables of mean values and standard deviations stratified for age and gender. Quantile regression equations will be used to generate age charts and age-specific centile values. Discussion This project will be a powerful resource to assist physiotherapists and clinicians across all areas of healthcare to diagnose pathology, track disease progression and evaluate treatment response. This reference dataset will also contribute to the development of robust patient-centred clinical trial outcome measures