High dose bystander effects in spatially fractionated radiation therapy

Traditional radiotherapy of bulky tumors has certain limitations. Spatially fractionated radiation therapy (GRID) and intensity modulated radiotherapy (IMRT) are examples of advanced modulated beam therapies that help in significant reductions in normal tissue damage. GRID refers to the delivery of a single high dose of radiation to a large treatment area that is divided into several smaller fields, while IMRT allows improved dose conformity to the tumor target compared to conventional three-dimensional conformal radiotherapy. In this review, we consider spatially fractionated radiotherapy approaches focusing on GRID and IMRT, and present complementary evidence from different studies which support the role of radiation induced signaling effects in the overall radiobiological rationale for these treatments.

Tracking smart grid hackers

The next-generation smart grid will rely highly on telecommunications infrastructure for data transfer between various systems. Anywhere we have data transfer in a system is a potential security threat. When we consider the possibility of smart grid data being at the heart of our critical systems infrastructure it is imperative that we do all we can to ensure the confidentiality, availability and integrity of the data. A discussion on security itself is outside the scope of this paper, but if we assume the network to be as secure as possible we must consider what we can do to detect when that security fails, or when the attacks comes from the inside of the network. One way to do this is to setup a hacker-trap, or honeypot. A honeypot is a device or service on a network which appears legitimate, but is in-fact a trap setup to catch breech attempts. This paper identifies the different types of honeypot and describes where each may be used. The authors have setup a test honeypot system which has been live for some time. The test system has been setup to emulate a device on a utility network. The system has had many hits, which are described in detail by the authors. Finally, the authors discuss how larger-scale systems in utilities may benefit from honeypot placement.

Securing the smart grid

The availability of electricity is fundamental to modern society. It is at the top of the list of critical infrastructures and its interruption can have severe consequences. This highly important system is now evolving to become more reliable, efficient, and clean. This evolving infrastructure has become known as the smart grid; and these future smart grid systems will rely heavily on ICT. This infrastructure will require many servers and due to the nature of the grid, many of these systems will be geographically diverse requiring communication links. At the heart of this ICT infrastructure will be security. At each level of the smart grid from smart metering right through to remote sensing and control networks, security will be a key factor for system design consideration. With an increased number of ICT systems in place the security risk also increases. In this paper the authors discuss the changing nature of security in relation to the smart grid by looking at the move from legacy systems to more modern smart grid systems. The potential planes of attack for future smart grid systems are identified, and the general anatomy of a cyber-attack is presented. The authors then introduce the various threat levels of different types of attack and the mitigation techniques that could be put in place for each. Finally, the authors' introduce a Phasor Measurement Unit (PMU) communication system (operated by the authors) that can be used as a test-bed for some of the proposed future security research.

A smart load appliance application using a single compressor fridge-freezer to support grid operations

This paper describes a fridge-freezer smart load model, which responds to external signals from the wholesale electricity market to support grid operations while switching the fridge-freezer on and off to maintain optimum operations for the owner. The key parameters of the model are the appliance dimensions, thermal mass, the fridge and freezer thermal time constants and the compressor power consumption. The model demonstrates that control strategies help to minimise load at times when the grid is under stress from high demand, and shift some load to a lower wholesale price or when there is excess renewable power. Three control strategies are proposed, based on peak shaving and valley filling, price signals and wind availability.

New multi-stage DC-DC converters for grid-connected photovoltaic systems

Renewable energy is high on international and national agendas. Currently, grid-connected photovoltaic (PV) systems are a popular technology to convert solar energy into electricity. Existing PV panels have a relatively low and varying output voltage so that the converter installed between the PVs and the grid should be equipped with high step-up and versatile control capabilities. In addition, the output current of PV systems is rich in harmonics which affect the power quality of the grid. In this paper, a new multi-stage hysteresis control of a step-up DC-DC converter is proposed for integrating PVs into a single-phase power grid. The proposed circuitry and control method is experimentally validated by testing on a 600W prototype converter. The developed technology has significant economic implications and could be applied to many distributed generation (DG) systems, especially for the developing countries which have a large number of small PVs connected to their single-phase distribution network. 

Role of the receptor for advanced glycation endproducts (RAGE) in retinal vasodegenerative pathology during diabetes in mice

Aims/hypothesis
The receptor for AGEs (RAGE) is linked to proinflammatory pathology in a range of tissues. The objective of this study was to assess the potential modulatory role of RAGE in diabetic retinopathy.
Methods
Diabetes was induced in wild-type (WT) and Rage −/− mice (also known as Ager −/− mice) using streptozotocin while non-diabetic control mice received saline. For all groups, blood glucose, HbA1c and retinal levels of methylglyoxal (MG) were evaluated up to 24 weeks post diabetes induction. After mice were killed, retinal glia and microglial activation, vasopermeability, leucostasis and degenerative microvasculature changes were determined. 

Results
Retinal expression of RAGE in WT diabetic mice was increased after 12 weeks (p < 0.01) but not after 24 weeks. Rage −/− mice showed comparable diabetes but accumulated less MG and this corresponded to enhanced activity of the MG-detoxifying enzyme glyoxalase I in their retina when compared with WT mice. Diabetic Rage −/− mice showed significantly less vasopermeability, leucostasis and microglial activation (p < 0.05–0.001). Rage −/− mice were also protected against diabetes-related retinal acellular capillary formation (p < 0.001) but not against pericyte loss. 

Conclusions/interpretation Rage −/− in diabetic mice is protective against many retinopathic lesions, especially those related to innate immune responses. Inhibition of RAGE could be a therapeutic option to prevent diabetic retinopathy.

System flexibility provision using short term grid scale storage

This paper presents a novel analysis of the utilisation of small grid scale energy storage to mitigate negative system operational impacts due to high penetrations of wind power. This was investigated by artificially lowering the minimum stable generation level of a gas thermal generating unit coupled to a storage device over a five hour storage charging window using a unit commitment and economic dispatch model. The key findings of the analysis were a 0.18% reduction in wind curtailment, a 2.35 MW/min reduction in the ramping rate required to be met by all generators in the test system during a representative period and a total generation cost reduction of €6.5 million.

Secure Communications in Smart Grid: Networking and Protocols

The key attributes of a smarter power grid include: pervasive interconnection of smart devices; extensive data generation and collection; and rapid reaction to events across a widely dispersed physical infrastructure. Modern telecommunications technologies are being deployed across power systems to support these monitoring and control capabilities. To enable interoperability, several new communications protocols and standards have been developed over the past 10 to 20 years. These continue to be refined, even as new systems are rolled out.

This new hyper-connected communications infrastructure provides an environment rich in sub-systems and physical devices that are attractive to cyber-attackers. Indeed, as smarter grid operations become dependent on interconnectivity, the communications network itself becomes a target. Consequently, we examine cyber-attacks that specifically target communications, particularly state-of-the-art standards and protocols. We further explore approaches and technologies that aim to protect critical communications networks against intrusions, and to monitor for, and detect, intrusions that infiltrate Smart Grid systems.

Implementation Experiences from Smart Grid Security Applications and Outlook on Future Research

Experiences from smart grid cyber-security incidents in the past decade have raised questions on the applicability and effectiveness of security measures and protection mechanisms applied to the grid. In this chapter we focus on the security measures applied under real circumstances in today’s smart grid systems. Beginning from real world example implementations, we first review cyber-security facts that affected the electrical grid, from US blackout incidents, to the Dragonfly cyber-espionage campaign currently focusing on US and European energy firms. Provided a real world setting, we give information related to energy management of a smart grid looking also in the optimization techniques that power control engineers perform into the grid components. We examine the application of various security tools in smart grid systems, such as intrusion detection systems, smart meter authentication and key management using Physical Unclonable Functions, security analytics and resilient control algorithms. Furthermore we present evaluation use cases of security tools applied on smart grid infrastructure test-beds that could be proved important prior to their application in the real grid, describing a smart grid intrusion detection system application and security analytics results. Anticipated experimental results from the use-cases and conclusions about the successful transitions of security measures to real world smart grid operations will be presented at the end of this chapter.

Immune modulation in advanced radiotherapies: Targeting out-of-field effects

By virtue of being a localized treatment modality, radiotherapy is unable to deliver a tumoricidal radiation dose to tissues outside of the irradiated field. Nevertheless, ionizing radiation may result in radiation damage mediated by a bystander like effect away from the irradiated field, but this response is likely to be modest when radiotherapy is the sole treatment modality. Over the last decade there has been a re-emergence of immune modulating therapies as anti-cancer treatment modalities. Clinical trials on vaccines have on the whole been largely disappointing, but greater response rates have been observed from the immune checkpoint modulators. A clinical benefit of using such agents has been shown in disease sites such as melanoma and non-small cell lung cancer. There is growing pre-clinical data and a number of case reports which suggest the presence of abscopal effects when radiotherapy is co-administered with immune checkpoint inhibitors, suggesting that this combination may lead to an enhanced tumour response outside of the primary treatment field. In this review, the mechanisms of such an enhanced out-of-field tumour response, the potential clinical utilities, the optimal radiotherapy delivery and considerations for clinical follow-up following treatment are discussed.

Impact of finite element idealisation on the prediction of welded fuselage stiffened panel buckling

Lap joints are widely used in the manufacture of stiffened panels and influence local panel sub-component stability, defining buckling unit dimensions and boundary conditions. Using the Finite Element method it is possible to model joints in great detail and predict panel buckling behaviour with accuracy. However, when modelling large panel structures such detailed analysis becomes computationally expensive. Moreover, the impact of local behaviour on global panel performance may reduce as the scale of the modelled structure increases. Thus this study presents coupled computational and experimental analysis, aimed at developing relationships between modelling fidelity and the size of the modelled structure, when the global static load to cause initial buckling is the required analysis output. Small, medium and large specimens representing welded lap-joined fuselage panel structure are examined. Two element types, shell and solid-shell, are employed to model each specimen, highlighting the impact of idealisation on the prediction of welded stiffened panel initial skin buckling.

Advanced design optimization of cold-formed steel portal frame buildings

The design optimization of cold-formed steel portal frame buildings is considered in this paper. The objective function is based on the cost of the members for the main frame and secondary members (i.e., purlins, girts, and cladding for walls and roofs) per unit area on the plan of the building. A real-coded niching genetic algorithm is used to minimize the cost of the frame and secondary members that are designed on the basis of ultimate limit state. It iis shown that the proposed algorithm shows effective and robust capacity in generating the optimal solution, owing to the population's diversity being maintained by applying the niching method. In the optimal design, the cost of purlins and side rails are shown to account for 25% of the total cost; the main frame members account for 27% of the total cost, claddings for the walls and roofs accounted for 27% of the total cost.

Development and Application of Medication Appropriateness Indicators for Persons with Advanced Dementia: A Feasibility Study

Background: No studies have been conducted in the UK context to date that categorise medications in terms of appropriateness for patients with advanced dementia, or that examine medication use in these vulnerable patients.

Objectives: The objectives of this study were to categorise the appropriateness of a comprehensive list of medications and medication classes for use in patients with advanced dementia; examine the feasibility of conducting a longitudinal prospective cohort study to collect clinical and medication use data; and determine the appropriateness of prescribing for nursing home residents with advanced dementia in Northern Ireland (NI), using the categories developed.

Methods: A three-round Delphi consensus panel survey of expert clinicians was used to categorise the appropriateness of medications for patients with advanced dementia [defined as having Functional Assessment Staging (FAST) scores ranging from 6E to 7F]. This was followed by a longitudinal prospective cohort feasibility study that was conducted in three nursing homes in NI. Clinical and medication use for participating residents with advanced dementia (FAST scores ranging from 6E to 7F) were collected and a short test of dementia severity administered. These data were collected at baseline and every 3 months for up to 9 months or until death. For those residents who died during the study period, data were also collected within 14 days of death. The appropriateness ratings from the consensus panel survey were retrospectively applied to residents’ medication data at each data collection timepoint to determine the appropriateness of medications prescribed for these residents.

Results: Consensus was achieved for 87 (90 %) of the 97 medications and medication classes included in the survey. Fifteen residents were recruited to participate in the longitudinal prospective cohort feasibility study, four of whom died during the data collection period. Mean numbers of medications prescribed per resident were 16.2 at baseline, 19.6 at 3 months, 17.4 at 6 months and 16.1 at 9 months. Fourteen residents at baseline were taking at least one medication considered by the consensus panel to be never appropriate, and approximately 25 % of medications prescribed were considered to be never appropriate. Post-death data collection indicated a decrease in the proportion of never appropriate medications and an increase in the proportion of always appropriate medications for those residents who died.

Conclusions: This study is the first to develop and apply medication appropriateness indicators for patients with advanced dementia in the UK setting. The Delphi consensus panel survey of expert clinicians was a suitable method of developing such indicators. It is feasible to collect information on quality of life, functional performance, physical comfort, neuropsychiatric symptoms and cognitive function for this subpopulation of nursing home residents with advanced dementia.