In vitro anti-HIV and -HSV activity and safety of sodium rutin sulfate as a microbicide candidate

Sodium rutin sulfate (SRS) is a sulfated rutin modified from the natural flavonol glycoside rutin. Here, we investigated its in vitro anti-HIV and -HSV activities and its cytotoxic profile. Fifty percent inhibitory concentration (IC50) values of SRS against HIV-1 X4 virus IIIB, HIV-1 R5 isolates Ada-M and Ba-L were 2.3 +/- 0.2, 4.5 +/- 2.0 and 8.5 +/- 3.8 mu M with a selectivity index (SI) of 563, 575 and 329, respectively. Its IC50 against primary R5 HIV-1 isolate from Yunnan province in China was 13.1 +/- 5.5 mu M, with a Sl of 197. In contrast, unsulfated rutin had no activity against any of the HIV-1 isolates tested. Further study indicated that SRS blocked viral entry and virus-cell fusion likely through interacting with the HIV- I envelope glycoprotein. SRS also demonstrated some activity against human herpes simplex virus (HSV) with an IC50 of 88.3 +/- 0.1 mu M and a Sl of 30. The 50% cytotoxicity concentration (CC50) of SRS was >3.0 mM, as determined in human genital ME 180, HeLa and primary human foreskin fibroblast cells. Minimum inhibitory concentration of SRS for vaginal lactobacilli was >3.0 mM. These results collectively indicate that SRS represents a novel candidate for anti-HIV-1/HSV microbicide development. (C) 2007 Elsevier B.V. All rights reserved.

Stress on the ward: evidence of safety tipping points in hospitals

Do hospitals experience safety tipping points as utilization increases, and if so, what are the implications for hospital operations management? We argue that safety tipping points occur when managerial escalation policies are exhausted and workload variability buffers are depleted. Front-line clinical staff is forced to ration resources and, at the same time, becomes more error prone as a result of elevated stress hormone levels. We confirm the existence of safety tipping points for in-hospital mortality using the discharge records of 82,280 patients across six high-mortality-risk conditions from 256 clinical departments of 83 German hospitals. Focusing on survival during the first seven days following admission, we estimate a mortality tipping point at an occupancy level of 92.5%. Among the 17% of patients in our sample who experienced occupancy above the tipping point during the first seven days of their hospital stay, high occupancy accounted for one in seven deaths. The existence of a safety tipping point has important implications for hospital management. First, flexible capacity expansion is more cost-effective for safety improvement than rigid capacity, because it will only be used when occupancy reaches the tipping point. In the context of our sample, flexible staffing saves more than 40% of the cost of a fully staffed capacity expansion, while achieving the same reduction in mortality. Second, reducing the variability of demand by pooling capacity in hospital clusters can greatly increase safety in a hospital system, because it reduces the likelihood that a patient will experience occupancy levels beyond the tipping point. Pooling the capacity of nearby hospitals in our sample reduces the number of deaths due to high occupancy by 34%.

Safety implications of reactivity variations in fast thorium ADSRs

Nuclear power generation offers a reliable, low-impact and large-scale alternative to fossil fuels. However, concerns exist over the safety and sustainability of this method of power production, and it remains unpopular with some governments and pressure groups throughout the world. Fast thorium fuelled accelerator-driven sub-critical reactors (ADSRs) offer a possible route to providing further re-assurance regarding these concerns on account of their properties of enhanced safety through sub-critical operation combined with reduced actinide waste production from the thorium fuel source. The appropriate sub-critical margin at which these reactors should operate is the subject of continued debate. Commercial interests favour a small sub-critical margin in order to minimise the size of the accelerator needed for a given power output, whilst enhanced safety would be better satisfied through larger sub-critical margins to further minimise the possibility of a criticality excursion. Against this background, this paper examines some of the issues affecting reactor safety inherent within thorium fuel sources resulting from the essential Th90232→Th90233→Pa91233→U92233 breeding chain. Differences in the decay half-lives and fission and capture cross-sections of 233Pa and 233U can result in significant changes in the reactivity of the fuel following changes in the reactor power. Reactor operation is represented using a homogeneous lumped fast reactor model that can simulate the evolution of actinides and reactivity variations to first-order accuracy. The reactivity of the fuel is shown to increase significantly following a loss of power to the accelerator. Where the sub-critical operating margins are small this can result in a criticality excursion unless some form of additional intervention is made, for example through the insertion of control rods. © 2012 Elsevier Ltd. All rights reserved.

Visual retrieval of concrete crack properties for automated post-earthquake structural safety evaluation

The safety of post-earthquake structures is evaluated manually through inspecting the visible damage inflicted on structural elements. This process is time-consuming and costly. In order to automate this type of assessment, several crack detection methods have been created. However, they focus on locating crack points. The next step, retrieving useful properties (e.g. crack width, length, and orientation) from the crack points, has not yet been adequately investigated. This paper presents a novel method of retrieving crack properties. In the method, crack points are first located through state-of-the-art crack detection techniques. Then, the skeleton configurations of the points are identified using image thinning. The configurations are integrated into the distance field of crack points calculated through a distance transform. This way, crack width, length, and orientation can be automatically retrieved. The method was implemented using Microsoft Visual Studio and its effectiveness was tested on real crack images collected from Haiti.

Automated Detection of Exposed Reinforcement in Post-Earthquake Safety and Structural Evaluations

Post-earthquake structural safety evaluations are currently performed manually by a team of certified inspectors and/or structural engineers. This process is time-consuming and costly, keeping owners and occupants from returning to their businesses and homes. Automating these evaluations would enable faster, and potentially more consistent, relief and response processes. In order to do this, the detection of exposed reinforcing steel is of utmost significance. This paper presents a novel method of detecting exposed reinforcement in concrete columns for the purpose of advancing practices of structural and safety evaluation of buildings after earthquakes. Under this method, the binary image of the reinforcing area is first isolated using a state-of-the-art adaptive thresholding technique. Next, the ribbed regions of the reinforcement are detected by way of binary template matching. Finally, vertical and horizontal profiling are applied to the processed image in order to filter out any superfluous pixels and take into consideration the size of reinforcement bars in relation to that of the structural element within which they reside. The final result is the combined binary image disclosing only the regions containing rebar overlaid on top of the original image. The method is tested on a set of images from the January 2010 earthquake in Haiti. Preliminary test results convey that most exposed reinforcement could be properly detected in images of moderately-to-severely damaged concrete columns.

Automated Detection of Exposed Reinforcement in Post-Earthquake Safety and Structural Evaluations

The world is at the threshold of emerging technologies, where new systems in construction, materials, and civil and architectural design are poised to make the world better from a structural and construction perspective. Exciting developments, that are too many to name individually, take place yearly, affecting design considerations and construction practices. This edited book brings together modern methods and advances in structural engineering and construction, fulfilling the mission of ISEC Conferences, which is to enhance communication and understanding between structural and construction engineers for successful design and construction of engineering projects. The articles in this book are those accepted for publication and presentation at the 6th International Structural Engineering and Construction Conference in Zurich. The 6th ISEC Conference in Zurich, Switzerland, follows the overwhelming reception and success of previous ISEC conference in Las Vegas, USA in 2009; Melbourne, Australia in 2007; Shunan, Japan in 2005; Rome, Italy in 2003; and Honolulu, USA in 2001. Many topics are covered in this book, ranging from legal affairs and contracting, to innovations and risk analysis in infrastructure projects, analysis and design of structural systems, materials, architecture, and construction. The articles here are a lasting testimony to the excellent research being undertaken around the world. These articles provide a platform for the exchange of ideas, research efforts and networking in the structural engineering and construction communities. We congratulate and thank the authors for these articles that were selected after intensive peer-review, and our gratitude extends to all reviewers and members of the International Technical Committee. It is their combined contributions that have made this book a reality.

Comprehensive Property Retrieval and Measurement of Concrete Spalling Using Machine Vision for Post-Earthquake Safety Assessments

Active vibration control (AVC) is a relatively new technology for the mitigation of annoying human-induced vibrations in floors. However, recent technological developments have demonstrated its great potential application in this field. Despite this, when a floor is found to have problematic floor vibrations after construction the unfamiliar technology of AVC is usually avoided in favour of more common techniques, such as Tuned Mass Dampers (TMDs) which have a proven track record of successful application, particularly for footbridges and staircases. This study aims to investigate the advantages and disadvantages that AVC has, when compared with TMDs, for the application of mitigation of pedestrian-induced floor vibrations in offices. Simulations are performed using the results from a finite element model of a typical office layout that has a high vibration response level. The vibration problems on this floor are then alleviated through the use of both AVC and TMDs and the results of each mitigation configuration compared. The results of this study will enable a more informed decision to be made by building owners and structural engineers regarding suitable technologies for reducing floor vibrations.

Live Attenuated S. Typhimurium Vaccine with Improved Safety in Immuno-Compromised Mice

Live attenuated vaccines are of great value for preventing infectious diseases. They represent a delicate compromise between sufficient colonization-mediated adaptive immunity and minimizing the risk for infection by the vaccine strain itself. Immune defects can predispose to vaccine strain infections. It has remained unclear whether vaccine safety could be improved via mutations attenuating a vaccine in immune-deficient individuals without compromising the vaccine's performance in the normal host. We have addressed this hypothesis using a mouse model for Salmonella diarrhea and a live attenuated Salmonella Typhimurium strain (ssaV). Vaccination with this strain elicited protective immunity in wild type mice, but a fatal systemic infection in immune-deficient cybb-/-nos2-/- animals lacking NADPH oxidase and inducible NO synthase. In cybb-/-nos2-/- mice, we analyzed the attenuation of 35 ssaV strains carrying one additional mutation each. One strain, Z234 (ssaV SL1344_3093), was >1000-fold attenuated in cybb-/-nos2-/- mice and ≈100 fold attenuated in tnfr1-/- animals. However, in wt mice, Z234 was as efficient as ssaV with respect to host colonization and the elicitation of a protective, O-antigen specific mucosal secretory IgA (sIgA) response. These data suggest that it is possible to engineer live attenuated vaccines which are specifically attenuated in immuno-compromised hosts. This might help to improve vaccine safety. © 2012 Periaswamy et al.

Rapid entropy-based detection and properties measurement of concrete spalling with machine vision for post-earthquake safety assessments

The current procedures in post-earthquake safety and structural assessment are performed manually by a skilled triage team of structural engineers/certified inspectors. These procedures, and particularly the physical measurement of the damage properties, are time-consuming and qualitative in nature. This paper proposes a novel method that automatically detects spalled regions on the surface of reinforced concrete columns and measures their properties in image data. Spalling has been accepted as an important indicator of significant damage to structural elements during an earthquake. According to this method, the region of spalling is first isolated by way of a local entropy-based thresholding algorithm. Following this, the exposure of longitudinal reinforcement (depth of spalling into the column) and length of spalling along the column are measured using a novel global adaptive thresholding algorithm in conjunction with image processing methods in template matching and morphological operations. The method was tested on a database of damaged RC column images collected after the 2010 Haiti earthquake, and comparison of the results with manual measurements indicate the validity of the method.

Stakeholder challenges in purchasing medical devices for patient safety.

OBJECTIVE: This study identifies the stakeholders who have a role in medical device purchasing within the wider system of health-care delivery and reports on their particular challenges to promote patient safety during purchasing decisions. METHODS: Data was collected through observational work, participatory workshops, and semi-structured qualitative interviews, which were analyzed and coded. The study takes a systems-based and engineering design approach to the study. Five hospitals took part in this study, and the participants included maintenance, training, clinical end-users, finance, and risk departments. RESULTS: The main stakeholders for purchasing were identified to be staff from clinical engineering (Maintenance), device users (Clinical), device trainers (Training), and clinical governance for analyzing incidents involving devices (Risk). These stakeholders display varied characteristics in terms of interpretation of their own roles, competencies for selecting devices, awareness and use of resources for purchasing devices, and attitudes toward the purchasing process. The role of "clinical engineering" is seen by these stakeholders to be critical in mediating between training, technical, and financial stakeholders but not always recognized in practice. CONCLUSIONS: The findings show that many device purchasing decisions are tackled in isolation, which is not optimal for decisions requiring knowledge that is currently distributed among different people within different departments. The challenges expressed relate to the wider system of care and equipment management, calling for a more systemic view of purchasing for medical devices.

Initial phase modelling in numerical explosion applied to process safety

The utilisation of computational fluid dynamics (CFD) in process safety has increased significantly in recent years. The modelling of accidental explosion via CFD has in many cases replaced the classical Multi Energy and Brake Strehlow methods. The benefits obtained with CFD modelling can be diminished if proper modelling of the initial phase of explosion is neglected. In the early stages of an explosion, the flame propagates in a quasi-laminar regime. Proper modelling of the initial laminar phase is a key aspect in order to predict the peak pressure and the time to peak pressure. The present work suggests a modelling approach for the initial laminar phase in explosion scenarios. Findings are compared with experimental data for two classical explosion test cases which resemble the common features in chemical process areas (confinement and congestion). A detailed analysis of the threshold for the transition from laminar to turbulent regime is also carried out. The modelling is implemented in a fully 3D Navier-Stokes compressible formulation. Combustion is treated using a laminar flamelet approach based on the Bray, Moss and Libby (BML) formulation. A novel modified porosity approach developed for the unstructured solver is also considered. Results agree satisfactorily with experiments and the modelling is found to be robust. © 2013 The Institution of Chemical Engineers.

Improving the safety and security of the pharmaceutical supply chain

This paper discusses various techniques that may be used to combat counterfeiting in the pharmaceutical supply chain. These include the use of electronic pedigrees (to ensure the integrity of the supply chain), together with mass-serialization (to provide for a unique lifecycle history of each individual package) and authentication of the product (to check for any discrepancies in the various attributes of the product and its packaging are as intended for that individual package). Management of the pedigree process and product authentication is discussed in some detail, together with various other learnings from the Drug Security Network, including identification of some remaining vulnerabilities and suggestions for tightening these loopholes. © 2008 Springer-Verlag Berlin Heidelberg.