Prospective external validation of an accelerated (2-h) acute coronary syndrome rule-out process using a contemporary troponin assay

Background: Recently there have been efforts to derive safe, efficient processes to rule out acute coronary syndrome (ACS) in emergency department (ED) chest pain patients. We aimed to prospectively validate an ACS assessment pathway (the 2-Hour Accelerated Diagnostic Protocol to Assess Patients with Chest Pain Symptoms Using Contemporary Troponins as the Only Biomarker (ADAPT) pathway) under pragmatic ED working conditions. Methods: This prospective cohort study included patients with atraumatic chest pain in whom ACS was suspected but who did not have clear evidence of ischaemia on ECG. Thrombolysis in myocardial infarction (TIMI) score and troponin (TnI Ultra) were measured at ED presentation, 2 h later and according to current national recommendations. The primary outcome of interest was the occurrence of major adverse cardiac events (MACE) including prevalent myocardial infarction (MI) at 30 days in the group who had a TIMI score of 0 and had presentation and 2-h TnI assays <99th percentile. Results: Eight hundred and forty patients were studied of whom 177 (21%) had a TIMI score of 0. There were no MI, MACE or revascularization in the per protocol and intention-to-treat 2-h troponin groups (0%, 95% confidence interval (CI) 0% to 4.5% and 0%, 95% CI 0% to 3.8%, respectively). The negative predictive value (NPV) was 100% (95% CI 95.5% to 100%) and 100% (95% CI 96.2% to 100%), respectively. Conclusions: A 2-h accelerated rule-out process for ED chest pain patients using electrocardiography, a TIMI score of 0 and a contemporary sensitive troponin assay accurately identifies a group at very low risk of 30-day MI or MACE.

Adjustable stiffness, external fixator for the rat femur osteotomy and segmental bone defect models

The mechanical environment around the healing of broken bone is very important as it determines the way the fracture will heal. Over the past decade there has been great clinical interest in improving bone healing by altering the mechanical environment through the fixation stability around the lesion. One constraint of preclinical animal research in this area is the lack of experimental control over the local mechanical environment within a large segmental defect as well as osteotomies as they heal. In this paper we report on the design and use of an external fixator to study the healing of large segmental bone defects or osteotomies. This device not only allows for controlled axial stiffness on the bone lesion as it heals, but it also enables the change of stiffness during the healing process in vivo. The conducted experiments have shown that the fixators were able to maintain a 5 mm femoral defect gap in rats in vivo during unrestricted cage activity for at least 8 weeks. Likewise, we observed no distortion or infections, including pin infections during the entire healing period. These results demonstrate that our newly developed external fixator was able to achieve reproducible and standardized stabilization, and the alteration of the mechanical environment of in vivo rat large bone defects and various size osteotomies. This confirms that the external fixation device is well suited for preclinical research investigations using a rat model in the field of bone regeneration and repair.

Open innovation in small and medium-sized enterprises (SMEs): External knowledge sourcing strategies and internal organizational facilitators

In this paper we explore how small and medium-sized enterprises (SMEs) engage in external knowledge sourcing, a form of inbound open innovation. We draw upon a sample of 1,411 SMEs and empirically conceptualize a typology of strategic types of external knowledge sourcing, namely minimal, supply-chain, technology-oriented, application-oriented, and full-scope sourcing. Each strategy reflects the nature of external interactions and is linked to a distinct mixture of four internal practices for managing innovation. Both full-scope and application-oriented sourcing offer performance benefits and are associated with a stronger focus on managing innovation. However, they differ in their managerial focus on strategic and operational aspects.

The new Vancouver Chest Pain Rule using troponin as the only biomarker: An external validation study

Objectives To externally evaluate the accuracy of the new Vancouver Chest Pain Rule and to assess the diagnostic accuracy using either sensitive or highly sensitive troponin assays. Methods Prospectively collected data from 2 emergency departments (EDs) in Australia and New Zealand were analysed. Based on the new Vancouver Chest Pain Rule, low-risk patients were identified using electrocardiogram results, cardiac history, nitrate use, age, pain characteristics and troponin results at 2 hours after presentation. The primary outcome was 30-day diagnosis of acute coronary syndrome (ACS), including acute myocardial infarction, and unstable angina. Sensitivity, specificity, positive predictive values and negative predictive values were calculated to assess the accuracy of the new Vancouver Chest Pain Rule using either sensitive or highly sensitive troponin assay results. Results Of the 1635 patients, 20.4% had an ACS diagnosis at 30 days. Using the highly sensitive troponin assay, 212 (13.0%) patients were eligible for early discharge with 3 patients (1.4%) diagnosed with ACS. Sensitivity was 99.1% (95% CI 97.4-99.7), specificity was 16.1 (95% CI 14.2-18.2), positive predictive values was 23.3 (95% CI 21.1-25.5) and negative predictive values was 98.6 (95% CI 95.9-99.5). The diagnostic accuracy of the rule was similar using the sensitive troponin assay. Conclusions The new Vancouver Chest Pain Rule should be used for the identification of low risk patients presenting to EDs with symptoms of possible ACS, and will reduce the proportion of patients requiring lengthy assessment; however we recommend further outpatient investigation for coronary artery disease in patients identified as low risk.

External auditors’ perceptions of cloud computing adoption in Australia

Adopting a multi-theoretical approach, I examine external auditors’ perceptions of the reasons why organizations do or do not adopt cloud computing. I interview forensic accountants and IT experts about the adoption, acceptance, institutional motives, and risks of cloud computing. Although the medium to large accounting firms where the external auditors worked almost exclusively used private clouds, both private and public cloud services were gaining a foothold among many of their clients. Despite the advantages of cloud computing, data confidentiality and the involvement of foreign jurisdictions remain a concern, particularly if the data are moved outside Australia. Additionally, some organizations seem to understand neither the technology itself nor their own requirements, which may lead to poorly negotiated contracts and service agreements. To minimize the risks associated with cloud computing, many organizations turn to hybrid solutions or private clouds that include national or dedicated data centers. To the best of my knowledge, this is the first empirical study that reports on cloud computing adoption from the perspectives of external auditors.

A road safety strategy for Norfolk Island, an Australian external territory

Norfolk Island is an Australian external territory in Oceania. The significant road safety reforms in Australia from the 1970s onward bypassed the island, and most road safety ‘silver bullets’ adopted in other Australian jurisdictions were not introduced. While legislative amendments in 2010 introduced mandatory seat belt wearing for vehicle occupants on Norfolk Island, other critical issues face the community including drink driving by residents and visitors, occupant protection for vehicle passengers, and the provision of a more protective road environment. The release of the first Norfolk Island road safety strategy 2014-2016 proposed, inter alia: • a lower BAC of 0.05 and the introduction of compulsory driver alcohol and drug testing by police; • targeted enforcement of occupant protection for vehicle passengers, particularly for passengers riding on vehicle tray backs; • education interventions to challenge values held by some members of the community that support unsafe road use; • ensuring that driver information, training and testing is adequate for all drivers; • identification and rectification of hazardous roadside infrastructure, particularly barrier protection at “high drop locations” within the road network; and • developing a specification for vehicle standards for vehicles imported into Norfolk Island. Norfolk Island is engaging in a process of integration with the Australian community, and wider issues relating to funding and resources have impacted on the implementation of the road safety strategy. The response to the strategy will be discussed, particularly in terms of current attempts to address drink driving and the provision of a safer road environment.

Submission to the External Independent Review of the United Nations Response to Allegations of Sexual Exploitation and Abuse and Other Serious Crimes by Members of Foreign Military Forces Not Under United Nations Command in the Central African Republic

In 2015 the UN Secretary-General established an External Independent Review to review how the United Nations has responded to allegations of child sexual exploitation and child sexual abuse, and to make recommendations concerning how the United Nations should respond to allegations in the future. This submission to the Review Panel draws on literature regarding children's rights, the nature of child sexual abuse, international instruments and policy, the nature of institutional child sexual abuse, and the CAR case itself. It makes recommendations for reform of UN protocols and procedures to better prevent child sexual abuse, and to improve responses to future occurrences.

Does PGA external stenting reduce compliance mismatch in venous grafts?

Background: Autogenous vein grafting is widely used in regular bypassing procedures. Due to its mismatch with the host artery in both mechanical property and geometry, the graft often over expands under high arterial blood pressure and forms a step-depth where eddy flow develops, thus causing restenosis, fibrous graft wall, etc. External stents, such as sheaths being used to cuff the graft, have been introduced to eliminate these mismatches and increase the patency. Although histological and immunochemical studies have shown some positive effects of the external stent, the mechanical mismatch under the protection of an external stent remains poorly analyzed. Methods: In this study, the jugular veins taken from hypercholesterolemic rabbits were transplanted into the carotid arteries, and non-woven polyglycolic acid (PGA) fabric was used to fabricate the external stents to study the effect of the biodegradable external stent. Eight weeks after the operation, the grafts were harvested to perform mechanical tests and histological examinations. An arc tangent function was suggested to describe the relationship between pressure and cross-sectional area to analyse the compliance of the graft. Results: The results from the mechanical tests indicated that grafts either with or without external stents displayed large compliance in the low-pressure range and were almost inextensible in the high-pressure range. This was very different from the behavior of the arteries or veins in vivo. The data from histological tests showed that, with external stents, collagen fibers were more compact, whilst those in the graft without protection were looser and thicker. No elastic fiber was found in either kind of grafts. Furthermore, grafts without protection were over-expanded which resulted in much bigger cross-sectional areas. Conclusion: The PGA external extent contributes little to the reduction of the mechanical mismatch between the graft and its host artery while remodeling develops. For the geometric mismatch, it reduces the cross-section area, therefore matching with the host artery much better. Although there are some positive effects, conclusively the PGA is not an ideal material for external stent.

External signal-activated liposomal drug delivery systems

Modern drug discovery gives rise to a great number of potential new therapeutic agents, but in some cases the efficient treatment of patient may not be achieved because the delivery of active compounds to the target site is insufficient. Thus, drug delivery is one of the major challenges in current pharmaceutical research. Numerous nanoparticle-based drug carriers, e.g. liposomes, have been developed for enhanced drug delivery and targeting. Drug targeting may enhance the efficiency of the treatment and, importantly, reduce unwanted side effects by decreasing drug distribution to non-target tissues. Liposomes are biocompatible lipid-based carriers that have been studied for drug delivery during the last 40 years. They can be functionalized with targeting ligands and sensing materials for triggered activation. In this study, various external signal-assisted liposomal delivery systems were developed. Signals can be used to modulate drug permeation or release from the liposome formulation, and they provide accurate control of time, place and rate of activation. The study involved three types of signals that were used to trigger drug permeation and release: electricity, heat and light. Electrical stimulus was utilized to enhance the permeation of liposomal DNA across the skin. Liposome/DNA complex-mediated transfections were performed in tight rat epidermal cell model. Various transfection media and current intensities were tested, and transfection efficiency was evaluated non-invasively by monitoring the concentration of secreted reporter protein in cell culture medium. Liposome/DNA complexes produced gene expression, but electrical stimulus did not enhance the transfection efficiency significantly. Heat-sensitive liposomal drug delivery system was developed by coating liposomes with biodegradable and thermosensitive poly(N-(2-hydroxypropyl) methacrylamide-mono/dilactate polymer. Temperature-triggered liposome aggregation and contents release from liposomes were evaluated. The cloud point temperature (CP) of the polymer was set to 42 °C. Polymer-coated liposome aggregation and contents release were observed above CP of the polymer, while non-coated liposomes remained intact. Polymer precipitates above its CP and interacts with liposomal bilayers. It is likely that this induces permeabilization of the liposomal membrane and contents release. Light-sensitivity was introduced to liposomes by incorporation of small (< 5 nm) gold nanoparticles. Hydrophobic and hydrophilic gold nanoparticles were embedded in thermosensitive liposomes, and contents release was investigated upon UV light exposure. UV light-induced lipid phase transitions were examined with small angle X-ray scattering, and light-triggered contents release was shown also in human retinal pigment epithelial cell line. Gold nanoparticles absorb light energy and transfer it into heat, which induces phase transitions in liposomes and triggers the contents release. In conclusion, external signal-activated liposomes offer an advanced platform for numerous applications in drug delivery, particularly in the localized drug delivery. Drug release may be localized to the target site with triggering stimulus that results in better therapeutic response and less adverse effects. Triggering signal and mechanism of activation can be selected according to a specific application.

Surface waves in the presence of external high frequency fields

The system equations of a collisionless, unmagnetized plasma, contained in a box where a high frequency (HF) electric field is incident, are solved in the electrostatic approximation. The surface modes of the plasma in the semi-infinite and box geometry are investigated. In thi high frequency limit, the mode frequencies are not significantly changed by the HF field but their group velocities can be quite different. Two long wavelength low frequency modes, which are not excited in the absence of HF field, are found. These modes are true surface modes (decaying on one wavelength from the surface) unlike the only low frequency ion acoustic mode in the zero field case. In the short wavelength limit the low frequency mode occurs at omega i/ square root 2, omega i being the ion plasma frequency, as a result similar to the case of no HF field.

Seismic reliability assessment of external stability of reinforced soil walls using pseudo-dynamic method

The paper presents a method for the evaluation of external stability of reinforced soil walls subjected to earthquakes in the framework of the pseudo-dynamic method. The seismic reliability of the wall is evaluated by considering the different possible failure modes such as sliding along the base, overturning about the toe point of the wall, bearing capacity and the eccentricity of the resultant force. The analysis is performed considering properties of the reinforced backfill, foundation soil below the base of the wall, length of the geosynthetic reinforcement and characteristics of earthquake ground motions such as shear wave and primary wave velocity as random variables. The optimum length of reinforcement needed to maintain stability against four modes of failure by targeting various component reliability indices is obtained. Differences between pseudo-static and pseudo-dynamic methods are clearly highlighted in the paper. A complete analysis of pseudo-static and pseudo-dynamic methodologies shows that the pseudodynamic method results in realistic design values for the length of geosynthetic reinforcement under earthquake conditions.

External administration in corporate insolvency and reorganisation: The insider alternative

This article considers the merits of alternative policy approaches to management of companies in insolvency administration, in particular from an identity economics theoretical perspective. The use of this perspective provides a novel assessment of the policy alternatives for insolvency administration, which can be characterized as either following the more flexible United States Chapter 11-style debtor-in-possession arrangement, or relying on the appointment of an external administrator or trustee to manage the insolvent company who automatically displaces incumbent management. This analysis indicates that stigma and reputational damage from automatic removal of managers in voluntary administration leaders to "identity loss" and that an insider alternative to the current external administration approach could be a beneficial policy change.

Social audit failure: Legal liability of external auditors

In this chapter, we look at the step beyond reporting, to the external audit or assurance function. The role of any audit engagement is to provide a professional opinion on a set of financial or non-financial assertions reported by an organization's management, based on an agreed evaluative framework. Any such opinion is not a guarantee that the underlying report is free from fraud or misstatement. Where an audit opinion on financial statements is incorrect, this is referred to as an audit failure. Specifically, the textbook definition of audit failure has two components: that the financial statements contain a serious error and that the auditor has failed to detect the error due to the auditor's failure during the audit process.

Surface waves in the presence of external high frequency fields

The system equations of a collisionless, unmagnetized plasma, contained in a box where a high frequency (h.f.1 electric field is incident, are solved in the electrostatic approximation. The surface modes of the plasma in the semi-infinite and box geometry are investigated. In the high frequency limit, the mode frequencies are not significantly changed by the h.f. field but their group velocities can be quite different. Two long wavelength low frequency modes, which are not excited in the absence of h.f. field, are found. These modes are true surface modes (decaying on one wavelength from the surface) unlike the only low frequency ion acoustic mode in the zero field case. In the short wavelength limit the low frequency mode occurs at &/2, oi being the ion plasma frequency, a result similar to the case of no h.f. field.

Structures of isopropylidene nucleoside derivatives - implications for ribose ring flexibility under external cyclic constraints

Crystal structures of six isopropylidene nucleoside derivatives are described. The results show that, under external cyclic constraints, the ribose assumes a variety of unusual conformations. In those compounds which possess a base-to-sugar cyclization through the C(4′) atom, the furanose pucker is predominantly C(4′)-endo, O(4′)-exo. The possible relevance of the sulphur geometry in two of the compounds to certain structural aspects of the action of the enzyme thymidylate synthetase is also pointed out.