A Conventional Internal Combustion Engine Versus a Range Extended Electric Vehicle Under the Current Regulatory Regime in the United Kingdom

Transport accounts for 22% of greenhouse gas emissions in the United Kingdom and cars are expected tomore than double by 2050. Car manufacturers are continually aiming for a substantially reduced carbonfootprint through improved fuel efficiency and better powertrain performance due to the strict EuropeanUnion emissions standards. However, road tax, not just fuel efficiency, is a key consideration of consumerswhen purchasing a car. While measures have been taken to reduce emissions through stricter standards, infuture, alternative technologies will be used. Electric vehicles, hybrid vehicles and range extended electricvehicles have been identified as some of these future technologies. In this research a virtual test bed of aconventional internal combustion engine and a range extended electric vehicle family saloon car were builtin AVL’s vehicle and powertrain system level simulation tool, CRUISE, to simulate the New EuropeanDrive Cycle and the results were then soft-linked to a techno-economic model to compare the effectivenessof current support mechanisms over the full life cycle of both cars. The key finding indicates that althoughcarbon emissions are substantially reduced, switching is still not financially the best option for either theconsumer or the government in the long run.

Estimating biomass, fishing mortality, and "total allowable discards" for surveyed non-target fish

Demersal fisheries targeting a few high-value species often catch and discard other "non-target" species. It is difficult to quantify the impact of this incidental mortality when population biomass of a non-target species is unknown. We calculate biomass for 14 demersal fish species in ICES Area VIIg (Celtic Sea) by applying species-and length-based catchability corrections to catch records from the Irish Groundfish Survey (IGFS). We then combine these biomass estimates with records of commercial discards (and landings for marketable non-target species) to calculate annual harvesting rates (HR) for each study species. Uncertainty is incorporated into estimates of both biomass andHR. Our survey-based HR estimates for cod and whiting compared well with HR-converted fishing mortality (F) estimates from analytical assessments for these two stocks. Of the non-target species tested, red gurnard (Chelidonichthys cuculus) recorded some annual HRs greater than those for cod or whiting; challenging "Pope's postulate" that F on non-target stocks in an assemblage will not exceed that on target stocks. We relate HR for each species to two corresponding maximum sustainable yield (MSY) reference levels; six non-target species (including three ray species) show annual HRs >= HRMSY. This result suggests that it may not be possible to conserve vulnerable non-target species when F is coupled to that of target species. Based on biomass, HR, and HRMSY, we estimate "total allowable catch" for each non-target species.

Improving appropriate polypharmacy for older people in primary care: selecting components of an evidence-based intervention to target prescribing and dispensing.

Background
The use of multiple medicines (polypharmacy) is increasingly common in older people. Ensuring that patients receive the most appropriate combinations of medications (appropriate polypharmacy) is a significant challenge. The quality of evidence to support the effectiveness of interventions to improve appropriate polypharmacy is low. Systematic identification of mediators of behaviour change, using the Theoretical Domains Framework (TDF), provides a theoretically robust evidence base to inform intervention design. This study aimed to (1) identify key theoretical domains that were perceived to influence the prescribing and dispensing of appropriate polypharmacy to older patients by general practitioners (GPs) and community pharmacists, and (2) map domains to associated behaviour change techniques (BCTs) to include as components of an intervention to improve appropriate polypharmacy in older people in primary care.

Methods
Semi-structured interviews were conducted with members of each healthcare professional (HCP) group using tailored topic guides based on TDF version 1 (12 domains). Questions covering each domain explored HCPs’ perceptions of barriers and facilitators to ensuring the prescribing and dispensing of appropriate polypharmacy to older people. Interviews were audio-recorded and transcribed verbatim. Data analysis involved the framework method and content analysis. Key domains were identified and mapped to BCTs based on established methods and discussion within the research team.

Results
Thirty HCPs were interviewed (15 GPs, 15 pharmacists). Eight key domains were identified, perceived to influence prescribing and dispensing of appropriate polypharmacy: ‘Skills’, ‘Beliefs about capabilities’, ‘Beliefs about consequences’, ‘Environmental context and resources’, ‘Memory, attention and decision processes’, ‘Social/professional role and identity’, ‘Social influences’ and ‘Behavioural regulation’. Following mapping, four BCTs were selected for inclusion in an intervention for GPs or pharmacists: ‘Action planning’, ‘Prompts/cues’, ‘Modelling or demonstrating of behaviour’ and ‘Salience of consequences’. An additional BCT (‘Social support or encouragement’) was selected for inclusion in a community pharmacy-based intervention in order to address barriers relating to interprofessional working that were encountered by pharmacists.

Conclusions
Selected BCTs will be operationalised in a theory-based intervention to improve appropriate polypharmacy for older people, to be delivered in GP practice and community pharmacy settings. Future research will involve development and feasibility testing of this intervention.

Choline Kinase Alpha as an Androgen Receptor Chaperone and Prostate Cancer Therapeutic Target

BACKGROUND: The androgen receptor (AR) is a major drug target in prostate cancer (PCa). We profiled the AR-regulated kinome to identify clinically relevant and druggable effectors of AR signaling.

METHODS: Using genome-wide approaches, we interrogated all AR regulated kinases. Among these, choline kinase alpha (CHKA) expression was evaluated in benign (n = 195), prostatic intraepithelial neoplasia (PIN) (n = 153) and prostate cancer (PCa) lesions (n = 359). We interrogated how CHKA regulates AR signaling using biochemical assays and investigated androgen regulation of CHKA expression in men with PCa, both untreated (n = 20) and treated with an androgen biosynthesis inhibitor degarelix (n = 27). We studied the effect of CHKA inhibition on the PCa transcriptome using RNA sequencing and tested the effect of CHKA inhibition on cell growth, clonogenic survival and invasion. Tumor xenografts (n = 6 per group) were generated in mice using genetically engineered prostate cancer cells with inducible CHKA knockdown. Data were analyzed with χ(2) tests, Cox regression analysis, and Kaplan-Meier methods. All statistical tests were two-sided.

RESULTS: CHKA expression was shown to be androgen regulated in cell lines, xenografts, and human tissue (log fold change from 6.75 to 6.59, P = .002) and was positively associated with tumor stage. CHKA binds directly to the ligand-binding domain (LBD) of AR, enhancing its stability. As such, CHKA is the first kinase identified as an AR chaperone. Inhibition of CHKA repressed the AR transcriptional program including pathways enriched for regulation of protein folding, decreased AR protein levels, and inhibited the growth of PCa cell lines, human PCa explants, and tumor xenografts.

CONCLUSIONS: CHKA can act as an AR chaperone, providing, to our knowledge, the first evidence for kinases as molecular chaperones, making CHKA both a marker of tumor progression and a potential therapeutic target for PCa.

Real-time estimation of battery internal temperature based on a simplified thermoelectric model

Li-ion batteries have been widely used in the EVs, and the battery thermal management is a key but challenging part of the battery management system. For EV batteries, only the battery surface temperature can be measured in real-time. However, it is the battery internal temperature that directly affects the battery performance, and large temperature difference may exist between surface and internal temperatures, especially in high power demand applications. In this paper, an online battery internal temperature estimation method is proposed based on a novel simplified thermoelectric model. The battery thermal behaviour is first described by a simplified thermal model, and battery electrical behaviour by an electric model. Then, these two models are interrelated to capture the interactions between battery thermal and electrical behaviours, thus offer a comprehensive description of the battery behaviour that is useful for battery management. Finally, based on the developed model, the battery internal temperature is estimated using an extended Kalman filter. The experimental results confirm the efficacy of the proposed method, and it can be used for online internal temperature estimation which is a key indicator for better real-time battery thermal management.

Wishful Thinking: Lessons from the internal and external evaluations of an innovatory education project in Northern Ireland

From March 1999 to August 2000, the authors were involved in simultaneous internal and external evaluations of the social civic and political education (SCaPE) project in Northern Ireland. This project was a major initiative established by the Citizenship Foundation, the Northern Ireland Council for the Curriculum, Examination and Assessment (CCEA), and the School of Education at the University of Ulster at Coleraine. It was a 2-year project in 25 secondary schools established to design, develop, pilot and evaluate a new programme of social, civic and political education for Northern Ireland. It also aimed to serve as a model for future Citizenship curriculum developments throughout Northern Ireland and elsewhere. This paper describes the background to the project, the design and conduct of the two evaluations, and the links between them. It outlines the main conclusions of each evaluation and describes the way SCaPE has since evolved into a mainstream curriculum development project. The final part of the paper analyses the key opportunities, tensions and challenges involved in running such evaluations at a critical time in the history of Northern Ireland – a time when innovation is both necessary and controversial. It argues that, especially in such circumstances, evaluation cannot be conducted from a neutral, objective standpoint, and that it is incumbent on evaluators to recognise the emotional, personal and political commitment they make to the projects in which they are engaged.

Progressing from internal to supply chain level environmental strategies: The influence of internal support processes

The need for companies to consider the environmental impact of their operations and supply chains has been highlighted in the literature. However, few studies appear to consider how companies’ progress from proactive environmental strategies implemented at the internal, operations level to proactive environmental strategies implemented at the supply chain level. This study assesses the implementation process through the lens of the natural resource-based view and dynamic capabilities perspective. First, the link between the internal strategy ‘pollution prevention’ and the supply chain strategy ‘process stewardship’ is assessed. Second, the mediating influence of the internal support processes ‘integration’ and ‘learning’ on the implementation process is considered. Data collected from a sample of 1200 UK-based food manufacturing companies is analysed using multiple regression analysis. The findings suggest that the progression to environmental efforts at the supply chain level begins with internally-based environmental efforts and that the integration of these efforts and experience gained from them are important supporting factors in this progression.

Protein disulphide isomerase as a target for nanoparticle-mediated sensitisation of cancer cells to radiation

Radiation resistance and toxicity in normal tissues are limiting factors in the efficacy of radiotherapy. Gold nanoparticles (GNPs) have been shown to be effective at enhancing radiation-induced cell death, and were initially proposed to physically enhance the radiation dose deposited. However, biological responses of GNP radiosensitization based on physical assumptions alone are not predictive of radiosensitisation and therefore there is a fundamental research need to determine biological mechanisms of response to GNPs alone and in combination with ionising radiation. This study aimed to identify novel mechanisms of cancer cell radiosensitisation through the use of GNPs, focusing on their ability to induce cellular oxidative stress and disrupt mitochondrial function. Using N-acetyl-cysteine, we found mitochondrial oxidation to be a key event prior to radiation for the radiosensitisation of cancer cells and suggests the overall cellular effects of GNP radiosensitisation are a result of their interaction with protein disulphide isomerase (PDI). This investigation identifies PDI and mitochondrial oxidation as novel targets for radiosensitisation.

Measurement of Fast Electrons Spectra Generated by Interaction between Solid Target and Peta Watt Laser

Fast electron energy spectra have been measured for a range of intensities between 1018 Wcm−2 and 1021 Wcm−2 and for different target materials using electron spectrometers. Several experimental campaigns were conducted on peta watt laser facilities at the Rutherford Appleton Laboratory and Osaka University. In these experimental campaigns, the pulse duration was varied from 0.5 ps to 5 ps. The laser incident angle was also changed from normal incidence to 40° in p-polarized. The results show a reduction from the ponderomotive scaling on fast electrons over 1020 Wcm−2.