A Randomized Trial of Drug Route in Out-of-Hospital Cardiac Arrest.

Background: In patients with out-of-hospital cardiac arrest, the effectiveness of drugs such as epinephrine is highly time-dependent. An intraosseous route of drug administration may enable more rapid drug administration than an intravenous route; however, its effect on clinical outcomes is uncertain.

Methods: We conducted a multicenter, open-label, randomized trial across 11 emergency medical systems in the United Kingdom that involved adults in cardiac arrest for whom vascular access for drug administration was needed.

Connecting livestock disease dynamics to human learning and biosecurity decisions.

The acceleration of animal disease spread worldwide due to increased animal, feed, and human movement has driven a growing body of epidemiological research as well as a deeper interest in human behavioral studies aimed at understanding their interconnectedness. Biosecurity measures can reduce the risk of infection, but human risk tolerance can hinder biosecurity investments and compliance. Humans may learn from hardship and become more risk averse, but sometimes they instead become more risk tolerant because they forget negative experiences happened in the past or because they come to believe they are immune.

Assessing strategic, tactical, and operational decision-making and risk in a livestock production chain through experimental simulation platforms.

This paper provides a research summary of a series of serious games and simulations that form the basis of an experimental platform for the study of human decision-making and behavior associated with biosecurity across complex livestock production chains. This platform is the first of its kind to address the challenges associated with scaling micro-behavior of biosecurity decision-making to macro-patterns of disease spread across strategic, tactical and operational levels, capturing the roles that facility managers and front-line workers play in making biosecurity decisions under risk and uncertainty. Informational and incentive treatments are tested within each game and simulation.

Manure management strategies are interconnected with complexity across U.S. dairy farms.

Among one of the key challenges in dairy production is the management of manure in a way that is beneficial for agricultural production, with minimal environmental and public health impacts. Manure management systems (MMS)-the entire system of handling, storage, and application of manure-are diverse in countries with developed dairy industries such as the United States, enabled by a number of different technologies. The ways in which dairy farmers manage manure is driven by varying tradeoffs, including economic, social, and environmental; however, existing research has not examined the relationships between components of MMS.

Twice Bitten, Thrice Shy: A Case of Recurrent Isolated Cardiac Sarcoidosis in the Transplanted Heart.

We present a case of recurrent isolated cardiac sarcoidosis, 3 years post-heart transplantation. The case highlights the scarcity of data on the utility of immunosuppression in cardiac sarcoidosis and, in particular, raises questions about the optimal immunosuppression regimen in transplant recipients. (.

Creation of an anthropomorphic CT head phantom for verification of image segmentation.

Purpose: Many methods are available to segment structural magnetic resonance (MR) images of the brain into different tissue types. These have generally been developed for research purposes but there is some clinical use in the diagnosis of neurodegenerative diseases such as dementia. The potential exists for computed tomography (CT) segmentation to be used in place of MRI segmentation, but this will require a method to verify the accuracy of CT processing, particularly if algorithms developed for MR are used, as MR has notably greater tissue contrast.

Willingness to Comply With Biosecurity in Livestock Facilities: Evidence From Experimental Simulations.

Disease in U.S. animal livestock industries annually costs over a billion dollars.

Decision-making in livestock biosecurity practices amidst environmental and social uncertainty: Evidence from an experimental game.

Livestock industries are vulnerable to disease threats, which can cost billions of dollars and have substantial negative social ramifications. Losses are mitigated through increased use of disease-related biosecurity practices, making increased biosecurity an industry goal. Currently, there is no industry-wide standard for sharing information about disease incidence or on-site biosecurity strategies, resulting in uncertainty regarding disease prevalence and biosecurity strategies employed by industry stakeholders.

Vitamin C deficiency in an Australian cohort of metropolitan surgical patients.

Vitamin C is an essential micronutrient in the human diet. While large population studies measuring vitamin C have been performed in other countries, there are few studies of deficiency in the Australian population. This study aimed to quantify vitamin C deficiency, identify scorbutic symptoms and examine dietary associations in a cohort of preoperative general surgical patients.

Using an agent-based model to evaluate the effect of producer specialization on the epidemiological resilience of livestock production networks.

An agent-based computer model that builds representative regional U.S. hog production networks was developed and employed to assess the potential impact of the ongoing trend towards increased producer specialization upon network-level resilience to catastrophic disease outbreaks.

Transancestral fine-mapping of four type 2 diabetes susceptibility loci highlights potential causal regulatory mechanisms.

To gain insight into potential regulatory mechanisms through which the effects of variants at four established type 2 diabetes (T2D) susceptibility loci (CDKAL1, CDKN2A-B, IGF2BP2 and KCNQ1) are mediated, we undertook transancestral fine-mapping in 22 086 cases and 42 539 controls of East Asian, European, South Asian, African American and Mexican American descent. Through high-density imputation and conditional analyses, we identified seven distinct association signals at these four loci, each with allelic effects on T2D susceptibility that were homogenous across ancestry groups. By leveraging differences in the structure of linkage disequilibrium between diverse populations, and increased sample size, we localised the variants most likely to drive each distinct association signal.

Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.

We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation.

Unusual presentation of left sided acute appendicitis in elderly male with asymptomatic midgut malrotation.

Introduction: Acute appendicitis in the setting of midgut malrotation is uncommon. Midgut malrotation commonly presents within the first month of life. A minority remain asymptomatic and may present with concomitant abdominal pathology making diagnosis difficult.

Cyclosporine A Treatment Inhibits Abcc6-Dependent Cardiac Necrosis and Calcification following Coxsackievirus B3 Infection in Mice.

Coxsackievirus type B3 (CVB3) is a cardiotropic enterovirus. Infection causes cardiomyocyte necrosis and myocardial inflammation. The damaged tissue that results is replaced with fibrotic or calcified tissue, which can lead to permanently altered cardiac function.

Discovery and Fine-Mapping of Glycaemic and Obesity-Related Trait Loci Using High-Density Imputation.

Reference panels from the 1000 Genomes (1000G) Project Consortium provide near complete coverage of common and low-frequency genetic variation with minor allele frequency ≥0.5% across European ancestry populations. Within the European Network for Genetic and Genomic Epidemiology (ENGAGE) Consortium, we have undertaken the first large-scale meta-analysis of genome-wide association studies (GWAS), supplemented by 1000G imputation, for four quantitative glycaemic and obesity-related traits, in up to 87,048 individuals of European ancestry.

Mapping of a quantitative trait locus controlling susceptibility to Coxsackievirus B3-induced viral hepatitis.

The pathogenesis of coxsackieviral infection is a multifactorial process involving host genetics, viral genetics and the environment in which they interact. We have used a mouse model of Coxsackievirus B3 infection to characterize the contribution of host genetics to infection survival and to viral hepatitis. Twenty-five AcB/BcA recombinant congenic mouse strains were screened.

Reduced MCMV Δm157 viral clearance in the absence of TSAd.

The T cell specific adapter protein (TSAd) is expressed in activated T cells and NK cells. While TSAd is beginning to emerge as a critical regulator of Lck and Itk activity in T cells, its role in NK cells has not yet been explored. Here we have examined susceptibility to virus infections in a murine model using various viral infection models.

Unc93b1 -Dependent Endosomal Toll-Like Receptor Signaling Regulates Inflammation and Mortality during Coxsackievirus B3 Infection.

Coxsackievirus strain B serotype 3 (CVB3)-induced myocarditis is an important human disease that causes permanent tissue damage and can lead to death from acute infection or long-term morbidity caused by chronic inflammation. The timing and magnitude of immune activation following CVB3 infection can mediate a positive host outcome or increase tissue pathology. To better elucidate the role of endosomal Toll-like receptor (TLR) signaling in acute CVB3 infection, we studied mice with a loss-of-function mutation, known as Letr for 'loss of endosomal TLR response', in Unc93b1, which is a chaperone protein for TLR3, TLR7 and TLR9.

Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.

To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci.

A comprehensive investigation of variants in genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1/R2), and their association with serum adiponectin, type 2 diabetes, insulin resistance and the metabolic syndrome.

Background: Low levels of serum adiponectin have been linked to central obesity, insulin resistance, metabolic syndrome, and type 2 diabetes. Variants in ADIPOQ, the gene encoding adiponectin, have been shown to influence serum adiponectin concentration, and along with variants in the adiponectin receptors (ADIPOR1 and ADIPOR2) have been implicated in metabolic syndrome and type 2 diabetes. This study aimed to comprehensively investigate the association of common variants in ADIPOQ, ADIPOR1 and ADIPOR2 with serum adiponectin and insulin resistance syndromes in a large cohort of European-Australian individuals.

Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes.

To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D.

Plain Radiography May Be Safely Omitted for Selected Major Trauma Patients Undergoing Whole Body CT: Database Study.

Introduction. Whole body CT is being used increasingly in the primary survey of major trauma patients. We evaluated whether omitting plain films of the chest and pelvis in the primary survey was safe.

Genetic control of high density lipoprotein-cholesterol in AcB/BcA recombinant congenic strains of mice.

Epidemiological studies show that high HDL-cholesterol (HDLc) decreases the risk of cardiovascular disease. To map genes controlling lipid metabolism, particularly HDLc levels, we screened the plasma lipids of 36 AcB/BcA RC mouse strains subjected to either a normal or a high-fat/cholesterol diet. Strains BcA68 and AcB65 showed deviant HDLc plasma levels compared with the parental A/J and C57BL/6J strains; they were thus selected to generate informative F2 crosses.

Impact of the Reelin signaling cascade (ligands-receptors-adaptor complex) on cognition in schizophrenia.

Our previous neurocognitive studies of schizophrenia outlined two clusters of affected subjects--cognitively spared (CS) and cognitive deficit (CD), the latter's characteristics pointing to developmental origins and impaired synaptic plasticity. Here we investigate the contribution of polymorphisms in major regulators of these processes to susceptibility to schizophrenia and to CD in patients. We examine variation in genes encoding proteins at the gateway of Reelin signaling: ligands RELN and APOE, their common receptors APOER2 and VLDLR, and adaptor DAB1.