Microneedle-mediated vaccine delivery:harnessing cutaneous immunobiology to improve efficacy

INTRODUCTION: Breaching the skin's stratum corneum barrier raises the possibility of the administration of vaccines, gene vectors, antibodies and even nanoparticles, all of which have at least their initial effect on populations of skin cells. AREAS COVERED: Intradermal vaccine delivery holds enormous potential for improved therapeutic outcomes for patients, particularly those in the developing world. Various vaccine-delivery strategies have been employed, which are discussed in this review. The importance of cutaneous immunobiology on the effect produced by microneedle-mediated intradermal vaccination is also discussed. EXPERT OPINION: Microneedle-mediated vaccines hold enormous potential for patient benefit. However, in order for microneedle vaccine strategies to fulfill their potential, the proportion of an immune response that is due to the local action of delivered vaccines on skin antigen-presenting cells, and what is due to a systemic effect from vaccines reaching the systemic circulation, must be determined. Moreover, industry will need to invest significantly in new equipment and instrumentation in order to mass-produce microneedle vaccines consistently. Finally, microneedles will need to demonstrate consistent dose delivery across patient groups and match this to reliable immune responses before they will replace tried-and-tested needle-and-syringe-based approaches.

Comparison of teleconsultations and face-to-face consultations:preliminary results of a United Kingdom multicentre teledermatology study

The objective of this multicentre study was to undertake a systematic comparison of face-to-face consultations and teleconsultations performed using low-cost videoconferencing equipment. One hundred and twenty-six patients were enrolled by their general practitioners across three sites. Each patient underwent a teleconsultation with a distant dermatologist followed by a traditional face-to-face consultation with a dermatologist. The main outcome measures were diagnostic concordance rates, management plans and patient and doctor satisfaction. One hundred and fifty-five diagnoses were identified by the face-to-face consultations from the sample of 126 patients. Identical diagnoses were recorded from both types of consultation in 59% of cases. Teledermatology consultations missed a secondary diagnosis in 6% of cases and were unable to make a useful diagnosis in 11% of cases. Wrong diagnoses were made by the teledermatologist in 4% of cases. Dermatologists were able to make a definitive diagnosis by face-to-face consultations in significantly more cases than by teleconsultations (P = 0.001). Where both types of consultation resulted in a single diagnosis there was a high level of agreement (kappa = 0.96, lower 95% confidence limit 0.91-1.00). Overall follow-up rates from both types of consultation were almost identical. Fifty per cent of patients seen could have been managed using a single videoconferenced teleconsultation without any requirement for further specialist intervention. Patients reported high levels of satisfaction with the teleconsultations. General practitioners reported that 75% of the teleconsultations were of educational benefit. This study illustrates the potential of telemedicine to diagnose and manage dermatology cases referred from primary care. Once the problem of image quality has been addressed, further studies will be required to investigate the cost-effectiveness of a teledermatology service and the potential consequences for the provision of dermatological services in the U.K.

Structural testing and numerical simulation of a 34 m composite wind turbine blade

A full-scale 34 m composite wind turbine blade was tested to failure under flap-wise loading. Local displacement measurement equipment was developed and displacements were recorded throughout the loading history.

Ovalization of the load carrying box girder was measured in the full-scale test and simulated in non-linear FE-calculations. The nonlinear Brazier effect is characterized by a crushing pressure which causes the ovalization. To capture this effect, non-linear FE-analyses at different scales were employed. A global non-linear FE-model of the entire blade was prepared and the boundaries to a more detailed sub-model were extracted. The FE-model was calibrated based on full-scale test measurements.

Local displacement measurements helped identify the location of failure initiation which lead to catastrophic failure. Comparisons between measurements and FE-simulations showed that delamination of the outer skin was the initial failure mechanism followed by delamnination buckling which then led to collapse. 

Resource utilization and cost analyses of home-based palliative care service provision:The Niagara West End-of-Life Shared-Care Project

Background: Increasing emphasis is being placed on the economics of health care service delivery - including home-based palliative care. Aim: This paper analyzes resource utilization and costs of a shared-care demonstration project in rural Ontario (Canada) from the public health care system's perspective. Design: To provide enhanced end-of-life care, the shared-care approach ensured exchange of expertise and knowledge and coordination of services in line with the understood goals of care. Resource utilization and costs were tracked over the 15 month study period from January 2005 to March 2006. Results: Of the 95 study participants (average age 71 years), 83 had a cancer diagnosis (87%); the non-cancer diagnoses (12 patients, 13%) included mainly advanced heart diseases and COPD. Community Care Access Centre and Enhanced Palliative Care Team-based homemaking and specialized nursing services were the most frequented offerings, followed by equipment/transportation services and palliative care consults for pain and symptom management. Total costs for all patient-related services (in 2007 CAN) were 1,625,658.07 - or 17,112.19 per patient/117.95 per patient day. Conclusion: While higher than expenditures previously reported for a cancer-only population in an urban Ontario setting, the costs were still within the parameters of the US Medicare Hospice Benefits, on a par with the per diem funding assigned for long-term care homes and lower than both average alternate level of care and hospital costs within the Province of Ontario. The study results may assist service planners in the appropriate allocation of resources and service packaging to meet the complex needs of palliative care populations. © 2012 The Author(s).

Surrogate-based analysis and optimization for the design of heat sinks with jet impingement

Heat sinks are widely used for cooling electronic devices and systems. Their thermal performance is usually determined by the material, shape, and size of the heat sink. With the assistance of computational fluid dynamics (CFD) and surrogate-based optimization, heat sinks can be designed and optimized to achieve a high level of performance. In this paper, the design and optimization of a plate-fin-type heat sink cooled by impingement jet is presented. The flow and thermal fields are simulated using the CFD simulation; the thermal resistance of the heat sink is then estimated. A Kriging surrogate model is developed to approximate the objective function (thermal resistance) as a function of design variables. Surrogate-based optimization is implemented by adaptively adding infill points based on an integrated strategy of the minimum value, the maximum mean square error approach, and the expected improvement approaches. The results show the influence of design variables on the thermal resistance and give the optimal heat sink with lowest thermal resistance for given jet impingement conditions. 

The interaction between adsorbed OH and O-2 on TiO2 surfaces

Reduced TiO2 (110) surfaces usually have OH groups as a result of H2O dissociation at oxygen vacancy defects. Because of excess electrons due to OH adsorption, OH/TiO2. exhibit interesting properties favorable to further O-2 or H2O adsorption. Both O-2 and H2O can adsorb and easily diffuse on the OH/TiO2 surface; such behavior plays a significant role in photocatalysis, heterogeneous catalysis, electronic devices and sensors. Indeed, the processes of H2O dissociation, O-2 and H2O diffusion on Such TiO2 surfaces, in the presence of OH groups, are important issues in their own right. Herein, the most recent experimental and theoretical progresses in understanding the interactions between adsorbed OH groups and O-2, or H2O, over TiO2 (110) surfaces and their implications will be reviewed. (c) 2009 Elsevier Ltd. All rights reserved.

The potential of electron beam irradiation for simultaneous surface modification and bioresorption control of PLLA for medical device applications

Bioresorbable polymers have been widely investigated as materials exhibiting significant potential for successful application in the medical fields of bone fixation devices and drug delivery. Further to the ability to control degradation, surface engineering of polymers has been highlighted as a key method central to their development. Previous work has demonstrated the ability of electron beam (e-beam) technology to control the degradation profiles and bioresorption of a number of commercially relevant bioresorbable polymers (poly-l-lactic acid (PLLA), L-lactide/ DL-lactide co-polymer (PLDL) and poly(lactic-co-glycolic acid) (PLGA). This work investigates the further potential of e-beam technology to impart added biofunctionality through the manipulation of polymer (PLLA) surface properties. A Dynamatron Continuous DC e-beam unit (Synergy Health, UK), with beam energies of 0.5, 0.75, and 1.5 MeV, was used for the irradiation of PLLA samples with delivered surface doses of 150 or 500 kGy at each energy level. The chosen conditions reflect the need to achieve a specific surface modification for the control of surface degradation as demonstrated in previous work. Surface characterization was then performed using contact angle analysis, X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and atomic force microscopy.
Results demonstrated a significant increase in surface wettability post e-beam treatment. In correlation with this, XPS data showed the introduction of oxygen-containing functional groups to the surface of PLLA. Raman spectroscopy indicated chain scission in the near surface region of PLLA. E-beam irradiation did not seem to affect the surface roughness of PLLA as a direct consequence of the treatment. In conclusion electron beam surface modification has been found to modify both the surface-to-bulk bioresorption profile and the surface hydrophilicity. Both could provide benefits in relation to the performance of implantable medical devices.

Design and results of a dual-gas Quasi-Phase matching (QPM) foil target

Quasi-phase matching (QPM) can be used to increase the conversion efficiency of the high harmonic generation (HHG) process. We observed QPM with an improved dual-gas foil target with a 1 kHz, 10 mJ, 30 fs laser system. Phase tuning and enhancement were possible within a spectral range from 17 nm to 30 nm. Furthermore analytical calculations and numerical simulations were carried out to distinguish QPM from other effects, such as the influence of adjacent jets on each other or the laser gas interaction. The simulations were performed with a 3 dimensional code to investigate the phase matching of the short and long trajectories individually over a large spectral range.

Control energy consumption and system performance in vector control of voltage source converters

Power electronics plays an important role in the control and conversion of modern electric power systems. In particular, to integrate various renewable energies using DC transmissions and to provide more flexible power control in AC systems, significant efforts have been made in the modulation and control of power electronics devices. Pulse width modulation (PWM) is a well developed technology in the conversion between AC and DC power sources, especially for the purpose of harmonics reduction and energy optimization. As a fundamental decoupled control method, vector control with PI controllers has been widely used in power systems. However, significant power loss occurs during the operation of these devices, and the loss is often dissipated in the form of heat, leading to significant maintenance effort. Though much work has been done to improve the power electronics design, little has focused so far on the investigation of the controller design to reduce the controller energy consumption (leading to power loss in power electronics) while maintaining acceptable system performance. This paper aims to bridge the gap and investigates their correlations. It is shown a more thoughtful controller design can achieve better balance between energy consumption in power electronics control and system performance, which potentially leads to significant energy saving for integration of renewable power sources.

Social housing tenants, Climate Change and sustainable living: A study of awareness, behaviours and willingness to adapt

Despite a focus in the UK on providing sustainable housing in recent years, it is unlikely that targets set to reduce resource consumption in housing will be achieved without a greater focus on human behaviour. It is necessary to understand the actions of people occupying dwellings, as it is invariably the occupants rather than the buildings that decided whether or not to consume resources. In this paper the authors present a pilot study where 53 social housing tenant households in Northern Ireland were interviewed to ascertain their perceptions of Climate Change, their current behaviours and their willingness to reduce energy and water consumption in the home. The intention was to explore links between perceptions and reported behaviour as well as perceptions and willingness to reduce resource consumption. Results show that 77% of tenants believed Climate Change to be an important issue; 57% accepted that it is up to the individual to take responsibility for tackling Climate Change; and demonstrated a strong desire to make a difference to reduce their impact. The researchers identified both passive (devices) and active (behaviours) resource savings currently in place and established where further resource reduction was feasible based on tenants' willingness to alter their behaviours.

Pet population management and public health:A web service based tool for the improvement of dog traceability

The risks associated with zoonotic infections transmitted by companion animals are a serious public health concern: the control of zoonoses incidence in domestic dogs, both owned and stray, is hence important to protect human health. Integrated dog population management (DPM) programs, based on the availability of information systems providing reliable data on the structure and composition of the existing dog population in a given area, are fundamental for making realistic plans for any disease surveillance and action system. Traceability systems, based on the compulsory electronic identification of dogs and their registration in a computerised database, are one of the most effective ways to ensure the usefulness of DPM programs. Even if this approach provides many advantages, several areas of improvement have emerged in countries where it has been applied. In Italy, every region hosts its own dog register but these are not compatible with one another. This paper shows the advantages of a web-based-application to improve data management of dog regional registers. The approach used for building this system was inspired by farm animal traceability schemes and it relies on a network of services that allows multi-channel access by different devices and data exchange via the web with other existing applications, without changing the pre-existing platforms. Today the system manages a database for over 300,000 dogs registered in three different Italian regions. By integrating multiple Web Services, this approach could be the solution to gather data at national and international levels at reasonable cost and creating a traceability system on a large scale and across borders that can be used for disease surveillance and development of population management plans. © 2012 Elsevier B.V.

Validity of model devices used to assess canine temperament in behavioral tests

Temperament tests are widely accepted as instruments for profiling behavioral variability in dogs, and they are applied in numerous areas of investigation (e.g. suitability for adoption or for breeding). During testing, to elicit a dog's reaction toward novel stimuli and predict its behavior in everyday life, model devices such as a child-like doll, or a fake dog, are often employed. However, the reliability of these devices to accurately stimulate dogs' reactions to children or dogs, is unknown and perhaps overestimated. This may be a particular concern in the case of aggressive behavior toward humans, a significant public health issue. The aim of this study was to: (1) evaluate the correlation between dogs' reactions to these devices, and owners' reports of their dog's aggression history (using the C-BARQ ??); (2) compare reactions toward the devices of dogs with and without histories of aggression. Subjects were selected among those visiting for behavioral consultation at the Veterinary Hospital of the University of Pennsylvania, and previously categorized as aggressive toward unfamiliar children, conspecifics, or as non-aggressive dogs (control). The test consisted of different components: an unfamiliar female tester approaching the dog; the presentation of a child-like doll, an ambiguous object, and a fake plastic dog. All tests were videotaped and durations of behaviors were later analyzed on the basis of a specified ethogram. Dogs' reactions were compared to C-BARQ scores, and interesting correlations emerged for 'dog-directed aggression/fear' (R = 0.48, P = 0.004), and 'stranger-directed aggression' (R = 0.58, P <0.001) factors. Dogs differed in their reactions toward the devices: the child-like doll and the fake dog elicited more social behaviors than the ambiguous object used as a control stimulus. Issues concerning the reliability of these tools to assess canine temperament are discussed. ?? 2012 Elsevier B.V. All rights reserved.

Achieving Energy Saving through Proxying Applications on behalf of Idle Devices

Several studies in the past have revealed that network end user devices are left powered up 24/7 even when idle just for the sake of maintaining Internet connectivity. Network devices normally support low power states but are kept inactive due to their inability to maintain network connectivity. The Network Connectivity Proxy (NCP) has recently been proposed as an effective mechanism to impersonate network connectivity on behalf of high power devices and enable them to sleep when idle without losing network presence. The NCP can efficiently proxy basic networking protocol, however, proxying of Internet based applications have no absolute solution due to dynamic and non-predictable nature of the packets they are sending and receiving periodically. This paper proposes an approach for proxying Internet based applications and presents the basic software architectures and capabilities. Further, this paper also practically evaluates the proposed framework and analyzes expected energy savings achievable under-different realistic conditions.

WLAN Security Processor

A novel wireless local area network (WLAN) security processor is described in this paper. It is designed to offload security encapsulation processing from the host microprocessor in an IEEE 802.11i compliant medium access control layer to a programmable hardware accelerator. The unique design, which comprises dedicated cryptographic instructions and hardware coprocessors, is capable of performing wired equivalent privacy, temporal key integrity protocol, counter mode with cipher block chaining message authentication code protocol, and wireless robust authentication protocol. Existing solutions to wireless security have been implemented on hardware devices and target specific WLAN protocols whereas the programmable security processor proposed in this paper provides support for all WLAN protocols and thus, can offer backwards compatibility as well as future upgrade ability as standards evolve. It provides this additional functionality while still achieving equivalent throughput rates to existing architectures. © 2006 IEEE.

Hardware Performance Analysis of the SHACAL-2 Encryption Algorithm

A hardware performance analysis of the SHACAL-2 encryption algorithm is presented in this paper. SHACAL-2 was one of four symmetric key algorithms chosen in the New European Schemes for Signatures, Integrity and Encryption (NESSIE) initiative in 2003. The paper describes a fully pipelined encryption SHACAL-2 architecture implemented on a Xilinx Field Programmable Gate Array (FPGA) device that achieves a throughput of over 25 Gbps. This is the fastest private key encryption algorithm architecture currently available. The SHACAL-2 decryption algorithm is also defined in the paper as it was not provided in the NESSIE submission.