Efficacy of high-throughput transthoracic ultrasonographic screening for on-farm detection of ovine pulmonary adenocarcinoma.

BACKGROUND: The aim of this study was to evaluate the efficacy of high-throughput on-farm transthoracic ultrasound (TUS) to screen for ovine pulmonary adenocarcinoma (OPA), an infectious ovine disease of increasing concern. No other routine diagnosis of preclinical OPA is available, or any vaccine or treatment. METHODS: More than 80,000 rapid TUS scans were applied on farms with a history of OPA. The TUS results from a convenience sample of 171 TUS-negative and 269 TUS-positive sheep were compared with postmortem histology/immunohistochemistry results, the 'gold standard' reference test for OPA diagnosis. These results, together with new data on within-flock prevalence, allowed estimation of the efficacy of rapid TUS screening to identify OPA (defined as tumours of larger than 1 cm) on-farm. RESULTS: The TUS screening had an estimated specificity of 0.998 (95% confidence interval [CI]: 0.998-0.999) and an estimated sensitivity of between 0.76 (95% CI: 0.72-0.79) and 0.99 (95% CI: 0.97-0.99) depending on the presumed false-negative rate applied to the calculation. CONCLUSION: High-throughput TUS should be considered for screening to identify individual sheep with OPA and has potential application to indicate flocks at low risk of OPA. However, lower efficacy is likely if conducted by less experienced persons.

Vat Photopolymerization of Reinforced Styrene-Butadiene Elastomers: A Degradable Scaffold Approach.

Vat photopolymerization (VP) is a high-throughput additive manufacturing modality that also offers exceptional feature resolution and surface finish; however, the process is constrained by a limited selection of processable photocurable resins. Low resin viscosity (<10 Pa·s) is one of the most stringent process-induced constraints on resin processability, which in turn limits the mechanical performance of printed resin systems. Recently, the authors created a VP-processable photosensitive latex resin, where compartmentalization of the high molecular weight polymer chains into discrete particles resulted in the decoupling of viscosity from molecular weight. However, the monomers used to form the hydrogel green body resulted in decreased ultimate material properties due to the high cross-link density. Herein, we report a novel scaffold that allows for facile UV-based AM and simultaneously enhances the final part's material properties. This is achieved with a chemically labile acetal-containing cross-linker in conjunction with N-vinylpyrrolidone, which forms a glassy polymer after photocuring. Subsequent reactive extraction cleaves the cross-links and liberates the glassy polymer, which provides mechanical reinforcement of the geometrically complex VP-printed elastomer. With only a 0.1 wt % loading of photoinitiator, G'/G'' crossover times of less than 1 s and green body plateau moduli nearing 105 Pa are obtained. In addition, removal of the hydrophilic and thermally labile scaffold results in decreased water uptake and increased thermal stability of the final printed part. Ultimate strain and stress values of over 650% and 8.5 MPa, respectively, are achieved, setting a new benchmark for styrene-butadiene VP elastomers.

Computerised medical record systems that guide and protect - reflections on the Bawa-Garba case.

Lawrence Weed proposed we develop computerised, problem orientated medical records that guide and teach.  The Bawa-Garba case outcomes might have been different if care had been supported by computerised medical record (CMR) systems. CMR systems can reduce prescribing errors and could be develop to flag gaps in supervision.   However, CMR systems are not a panacea and need to be fit for purpose.  Our informatics perspective on this case is to call for widespread use of CMR systems - designed to guide and protect.

An assessment of endocrine activity in Australian rivers using chemical and in vitro analyses.

Studies on endocrine disruption in Australia have mainly focused on wastewater effluents. Limited knowledge exists regarding the relative contribution of different potential sources of endocrine active compounds (EACs) to the aquatic environment (e.g., pesticide run-off, animal farming operations, urban stormwater, industrial inputs). In this study, 73 river sites across mainland Australia were sampled quarterly for 1 year. Concentrations of 14 known EACs including natural and synthetic hormones and industrial compounds were quantified by chemical analysis. EACs were detected in 88 % of samples (250 of 285) with limits of quantification (LOQ) ranging from 0.05 to 20 ng/l. Bisphenol A (BPA; LOQ = 20 ng/l) was the most frequently detected EAC (66 %) and its predicted no-effect concentration (PNEC) was exceeded 24 times. The most common hormone was estrone, detected in 28 % of samples (LOQ = 1 ng/l), and the PNEC was also exceeded 24 times. 17α-Ethinylestradiol (LOQ = 0.05 ng/l) was detected in 10 % of samples at concentrations ranging from 0.05 to 0.17 ng/l. It was detected in many samples with no wastewater influence, and the PNEC was exceeded 13 times. In parallel to the chemical analysis, endocrine activity was assessed using a battery of CALUX bioassays. Estrogenic activity was detected in 19 % (53 of 285) of samples (LOQ = 0.1 ng/l 17ß-estradiol equivalent; EEQ). Seven samples exhibited estrogenic activity (1-6.5 ng/l EEQ) greater than the PNEC for 17ß-estradiol. Anti-progestagenic activity was detected in 16 % of samples (LOQ = 8 ng/l mifepristone equivalents; MifEQ), but the causative compounds are unknown. With several compounds and endocrine activity exceeding PNEC values, there is potential risk to the Australian freshwater ecosystems.

Evaluating the potential of effluents and wood feedstocks from pulp and paper mills in Brazil, Canada, and New Zealand to affect fish reproduction: chemical profiling and in vitro assessments.

This study investigates factors affecting reproduction in fish exposed to pulp and paper mill effluents by comparing effluents from countries with varying levels of documented effects. To explore the hypothesis of wood as a common source of endocrine disrupting compounds, feedstocks from each country were analyzed. Analyses included in vitro assays for androgenic activity (binding to goldfish testis androgen receptors), estrogenic activity (yeast estrogen screen), and neurotransmitter enzyme inhibition (monoamine oxidase and glutamic acid decarboxylase). Chemical analyses included conventional extractives, known androgens, and gas chromatograph index (GCI) profiles. All effluents and wood contained androgenic activity, particularly in nonpolar fractions, although known androgens were undetected. Effluents with low suspended solids, having undergone conventional biotreatment had lower androgenic activities. Estrogenic activity was only associated with Brazilian effluents and undetected in wood. All effluents and wood inhibited neurotransmitter enzymes, predominantly in polar fractions. Kraft elemental chlorine free mills were associated with the greatest neurotransmitter inhibition. Effluent and wood GCI profiles were correlated with androgenic activity and neurotransmitter enzyme inhibition. Differences in feedstock bioactivities were not reflected in effluents, implying mill factors mitigate bioactive wood components. No differences in bioactivities could be discerned on the basis of country of origin, thus we predict effluents in regions lacking monitoring would affect fish reproduction and therefore recommend implementing such programs.

Compressive cervical myelopathy in young Texel and Beltex sheep.

BACKGROUND: This investigation was prompted by the referral of increasing numbers of young Texel and Beltex rams with ataxia and weakness, or wobbler syndrome. HYPOTHESIS: The study aims were to describe the clinical and pathologic findings in affected sheep. ANIMALS: The animals evaluated in this study included 7 Texel sheep (6 male and 1 female) and 3 Beltex sheep (2 male and 1 female) referred from pedigree flocks. Typically, the sheep were 15-18 months of age at referral. METHODS: Diagnostic investigations included radiographic and computed tomographic (CT) myelography followed by gross postmortem and histopathologic examinations. RESULTS: Clinical findings typical of cervical spinal cord compression were present in all sheep but varied in severity. Myelography confirmed dorsal spinal cord compression in the region of C6-C7. No bony abnormalities were identified as described in cases of canine and equine wobbler syndrome. Postmortem examinations revealed discrete, smooth, nodular to polypoid projections of adipose tissue apparently prolapsing through the dorsolateral intervertebral space at C6-C7 and causing localized spinal cord compression. Histopathology of the nodules confirmed that they were composed of well-differentiated adipocytes typical of fatty tissue. Spinal cord lesions were similar in all sheep with marked Wallerian degeneration at the site of compression and mild Wallerian degeneration present cranial and caudal to the lesion. CONCLUSIONS AND CLINICAL IMPORTANCE: The findings of this study suggest a novel cervical myelopathy in these sheep breeds caused by the presence of fatty nodules encroaching into the dorsal vertebral canal at C6-C7. Additional investigations are required to establish the etiology and possible hereditary risk factors for this unique clinicopathologic syndrome.

Integrin-alphavbeta6, a putative receptor for foot-and-mouth disease virus, is constitutively expressed in ruminant airways.

Evolved functions of integrin-alpha(v)beta(6) include roles in epithelial cell-extracellular matrix protein interactions and in the binding and activation of latent TGF-beta(1). Integrin-alpha(v)beta(6) is also exploited as a receptor by foot-and-mouth disease virus (FMDV) and may play a significant role in its transmission and pathogenesis. The ovine beta(6) integrin subunit was cloned and sequenced (EMBL accession no. AJ439062). Screening of normal ovine tissues by RT-PCR and immunocytochemistry confirmed that integrin-alphavbeta6 is restricted to sheep epithelial cells. Integrin-alphavbeta6 expression was detected in epithelia of the airways, oral cavity, gastrointestinal tract, kidney, sweat glands, hair follicle sheaths, and the epidermis of pedal coronary band (PB) but not of normal skin. Consistent with FMDV tropism, integrin-alphavbeta6 was detected within the basal layers of the stratified squamous epithelium of the oral mucosa and PB. In addition, integrin-alphavbeta6 appears to be constitutively expressed in the normal airways of both cattle and sheep. The latter finding suggests that ruminant airway epithelium presents a highly accessible target for initiation of infection with FMDV by inhalation.

Delineation of the function of a major gamma delta T cell subset during infection.

Gammadelta T cells play important but poorly defined roles in pathogen-induced immune responses and in preventing chronic inflammation and pathology. A major obstacle to defining their function is establishing the degree of functional redundancy and heterogeneity among gammadelta T cells. Using mice deficient in Vgamma1+ T cells which are a major component of the gammadelta T cell response to microbial infection, a specific immunoregulatory role for Vgamma1+ T cells in macrophage and gammadelta T cell homeostasis during infection has been established. By contrast, Vgamma1+ T cells play no significant role in pathogen containment or eradication and cannot protect mice from immune-mediated pathology. Pathogen-elicited Vgamma1+ T cells also display different functional characteristics at different stages of the host response to infection that involves unique and different populations of Vgamma1+ T cells. These findings, therefore, identify distinct and nonoverlapping roles for gammadelta T cell subsets in infection and establish the complexity and adaptability of a single population of gammadelta T cells in the host response to infection that is not predetermined, but is, instead, shaped by environmental factors.

From research to the road: the development of EMS specialty triage.

A recent study in the Journal of Neurosurgery demonstrates decreased mortality rates in patients with subarachnoid hemorrhage (SAH) treated at tertiary care centers with higher volumes of SAH patients.(1) As clinical research in emergency and critical care increases, so will its impact on transport systems. In recent years, advances in cardiology, interventional radiology, surgery, and emergency care all have had major influences in the triage and transport of critically ill and injured patients. The challenge facing modern transport systems is how to integrate research to improve patient care while respecting the logistic, financial, and political issues that are entwined in this process. This article discusses the process undertaken by one medical control zone in the triage and transport of prehospital patients with suspected ischemic stroke. It discusses the transition from initial research and national recommendations for emergent thrombolytic therapy through the development and implementation of prehospital triage protocols. The authors hope it will offer some guidance in dealing with these rapidly emerging and often complicated transport decisions.