Optical coherence tomography is a valuable tool in the study of the effects of microneedle geometry on skin penetration characteristics and in-skin dissolution.

In this study, we used optical coherence tomography (OCT) to extensively investigate, for the first time, the effect that microneedle (MN) geometry (MN height, and MN interspacing) and force of application have upon penetration characteristics of soluble poly(methylvinylether-co-maleic anhydride, PMVE/MA) MN arrays into neonatal porcine skin in vitro. The results from OCT investigations were then used to design optimal and suboptimal MN-based drug delivery systems and evaluate their drug delivery profiles cross full thickness and dermatomed neonatal porcine skin in vitro. It was found that increasing the force used for MN application resulted in a significant increase in the depth of penetration achieved within neonatal porcine skin. For example, MN of 600 µm height penetrated to a depth of 330 µm when inserted at a force of 4.4 N/array, while the penetration increased significantly to a depth of 520 µm, when the force of application was increased to 16.4 N/array. At an application force of 11.0 N/array it was found that, in each case, increasing MN height from 350 to 600 µm to 900 µm led to a significant increase in the depth of MN penetration achieved. Moreover, alteration of MN interspacing had no effect upon depth of penetration achieved, at a constant MN height and force of application. With respect to MN dissolution, an approximate 34% reduction in MN height occurred in the first 15 min, with only 17% of the MN height remaining after a 3-hour period. Across both skin models, there was a significantly greater cumulative amount of theophylline delivered after 24 h from an MN array of 900 µm height (292.23 ± 16.77 µg), in comparison to an MN array of 350 µm height (242.62 ± 14.81 µg) (p < 0.001). Employing full thickness skin significantly reduced drug permeation in both cases. Importantly, this study has highlighted the effect that MN geometry and application force have upon the depth of penetration into skin. While it has been shown that MN height has an important role in the extent of drug delivered across neonatal porcine skin from a soluble MN array, further studies to evaluate the full significance of MN geometry on MN mediated drug delivery are now underway. The successful use of OCT in this study could prove to be a key development for polymeric MN research, accelerating their commercial exploitation.

Understanding New Product Project Performance

Purpose – The purpose of this paper is to summarize the accumulated body of knowledge on the performance of new product projects and provide directions for further research. Design/methodology/approach – Using a refined classification of antecedents of new product project performance the research results are meta-analyzed in the literature in order to identify the strength and stability of predictor-performance relationships. Findings – The results reveal that 22 variables have a significant relationship with new product project performance, of which only 12 variables have a sizable relationship. In order of importance these factors are the degree of organizational interaction, R&D and marketing interface, general product development proficiency, product advantage, financial/business analysis, technical proficiency, management skill, marketing proficiency, market orientation, technology synergy, project manager competency and launch activities. Of the 34 variables 16 predictors show potential for moderator effects. Research limitations/implications – The validity of the results is constrained by publication bias and heterogeneity of performance measures, and directions for the presentation of data in future empirical publications are provided. Practical implications – This study helps new product project managers in understanding and managing the performance of new product development projects. Originality/value – This paper provides unique insights into the importance of predictors of new product performance at the project level. Furthermore, it identifies which predictor-performance relations are contingent on other factors.

Impact of gate-source/drain channel architecture on the performance of an operational transconductance amplifier (OTA)

In this work, we report on the significance of gate-source/drain extension region (also known as underlap design) optimization in double gate (DG) FETs to improve the performance of an operational transconductance amplifier (OTA). It is demonstrated that high values of intrinsic voltage gain (A(VO_OTA)) > 55 dB and unity gain frequency (f(T_OTA)) similar to 57 GHz in a folded cascode OTA can be achieved with gate-underlap channel design in 60 nm DG MOSFETs. These values correspond to 15 dB improvement in A(VO_OTA) and three fold enhancement in f(T_OTA) over a conventional non-underlap design. OTA performance based on underlap single gate SOI MOSFETs realized in ultra-thin body (UTB) and ultra-thin body BOX (UTBB) technologies is also evaluated. A(VO_OTA) values exhibited by a DG MOSFET-based OTA are 1.3-1.6 times higher as compared to a conventional UTB/UTBB single gate OTA. f(T_OTA) values for DG OTA are 10 GHz higher for UTB OTAs whereas a twofold improvement is observed with respect to UTBB OTAs. The simultaneous improvement in A(VO_OTA) and f(T_OTA) highlights the usefulness of underlap channel architecture in improving gain-bandwidth trade-off in analog circuit design. Underlap channel OTAs demonstrate high degree of tolerance to misalignment/oversize between front and back gates without compromising the performance, thus relaxing crucial process/technology-dependent parameters to achieve 'idealized' DG MOSFETs. Results show that underlap OTAs designed with a spacer-to-straggle (s/sigma) ratio of 3.2 and operated below a bias current (IBIAS) of 80 mu A demonstrate optimum performance. The present work provides new opportunities for realizing future ultra-wide band OTA design with underlap DG MOSFETs.

Networks for systems biology: conceptual connection of data and function

The purpose of this study is to survey the use of networks and network-based methods in systems biology. This study starts with an introduction to graph theory and basic measures allowing to quantify structural properties of networks. Then, the authors present important network classes and gene networks as well as methods for their analysis. In the last part of this study, the authors review approaches that aim at analysing the functional organisation of gene networks and the use of networks in medicine. In addition to this, the authors advocate networks as a systematic approach to general problems in systems biology, because networks are capable of assuming multiple roles that are very beneficial connecting experimental data with a functional interpretation in biological terms.

Firms and Innovative Conflict Management Systems in Ireland

This article examines the practices adopted by firms in the Republic of Ireland to manage conflict involving groups of employees, focusing in particular on the uptake of 'alternative dispute resolution practices'. The article reveals that conflict management practices take the form of 'systems', and it estimates the incidence of innovative conflict management systems, incorporating alternative dispute resolution (ADR) practices, as involving about 30 per cent of firms. A series of influences are shown to be associated with innovative, ADR-based conflict management systems, especially commitment-oriented HRM practices and whether unions are recognized. © Blackwell Publishing Ltd/London School of Economics 2010.

The Diffusion of Risks in Public Private Partnership Contracts

Purpose The UK government argues that the benefits of public private partnership (PPP) in delivering public infrastructure stem from: transferring risks to the private sector within a structure in which financiers put their own capital at risk; and, the performance based payment mechanism, reinforced by the due diligence requirements imposed by the lenders financing the projects (HM Treasury, 2010). Prior studies of risk in PPPs have investigated ‘what’ risks are allocated and to ‘whom’, that is to the public or the private sector. The purpose of this study is to examine ‘how’ and ‘why’ PPP risks are diffused by their financiers. Design/methodology/approach This study focuses on the financial structure of PPPs and on their financiers. Empirical evidence comes from interviews conducted with equity and debt financiers. Findings The findings show that the financial structure of the deals generates risk aversion in both debt and equity financiers and that the need to attract affordable finance leads to risk diffusion through a network of companies using various means that include contractual mitigation through insurance, performance support guarantees, interest rate swaps and inflation hedges. Because of the complexity this process generates, both procurers and suppliers need expensive expert advice. The risk aversion and diffusion and the consequent need for advice add cost to the projects impacting on the government’s economic argument for risk transfer. Limitations and implications The empirical work covers the private finance initiative (PFI) type of PPP arrangements and therefore the risk diffusion mechanisms may not be generalisable to other forms of PPP, especially those that do not involve the use of high leverage or private finance. Moreover, the scope of this research is limited to exploring the diffusion of risk in the private sector. Further research is needed on how risk is diffused in other settings and on the value for money implication of risk diffusion in PPP contracts. Originality/value The expectation inherent in PPP is that the private sector will better manage those risks allocated to it and because private capital is at risk, financiers will perform due diligence with the ultimate outcome that only viable projects will proceed. This paper presents empirical evidence that raises questions about these expectations. Key words: public private partnership, risk management, diffusion, private finance initiative, financiers

A Systems Biology Approach Identifies SART1 as a Novel Determinant of Both 5-Fluorouracil and SN38 Drug Resistance in Colorectal Cancer

Chemotherapy response rates for advanced colorectal cancer remain disappointingly low, primarily because of drug resistance, so there is an urgent need to improve current treatment strategies. To identify novel determinants of resistance to the clinically relevant drugs 5-fluorouracil (5-FU) and SN38 (the active metabolite of irinotecan), transcriptional profiling experiments were carried out on pretreatment metastatic colorectal cancer biopsies and HCT116 parental and chemotherapy-resistant cell line models using a disease-specific DNA microarray. To enrich for potential chemoresistance-determining genes, an unsupervised bioinformatics approach was used, and 50 genes were selected and then functionally assessed using custom-designed short interfering RNA(siRNA) screens. In the primary siRNA screen, silencing of 21 genes sensitized HCT116 cells to either 5-FU or SN38 treatment. Three genes (RAPGEF2, PTRF, and SART1) were selected for further analysis in a panel of 5 colorectal cancer cell lines. Silencing SART1 sensitized all 5 cell lines to 5-FU treatment and 4/5 cell lines to SN38 treatment. However, silencing of RAPGEF2 or PTRF had no significant effect on 5-FU or SN38 sensitivity in the wider cell line panel. Further functional analysis of SART1 showed that its silencing induced apoptosis that was caspase-8 dependent. Furthermore, silencing of SART1 led to a downregulation of the caspase-8 inhibitor, c-FLIP, which we have previously shown is a key determinant of drug resistance in colorectal cancer. This study shows the power of systems biology approaches for identifying novel genes that regulate drug resistance and identifies SART1 as a previously unidentified regulator of c-FLIP and drug-induced activation of caspase-8. Mol Cancer Ther; 11(1); 119-31. (C) 2011 AACR.

In conclusion

This paper will consider ‘the purpose and relevance, process and method, audience and effect of contemporary architectural research in Ireland’ through the lens of one ongoing project, first presented in the paper ‘Vinegar and Chips, Concrete and Linen’ at AIARG Conference in 2012.
The paper however will not reopen the subject of last year’s paper; rather it will deliver the conclusion that the author failed to deliver within the given time. The paper will thus cover ‘a discussion of the contexts of this research i.e. academic, practice-based, craft and commercial’, placing particular emphasis on how these contexts relate to one another and more particularly ‘architectural research’. It will briefly relate the academic discussions that have evolved from the work (digital crafting; feminist forms of practice and technology; design methodology), but will chiefly focus on the meaning and purpose of research; the development of a practice based research methodology; the myth, mist and missed opportunities of peer review and dissemination (including the disclosure of intellectual property); and the significance of funding.

Effectiveness of granular columns in containing settlement

Laboratory-based research studies and full-scale evaluations of the behaviour of ground improved with granular columns are ample regarding bearing capacity, but limited in respect to the settlement response. This paper presents a laboratory model study that considers the settlement performance of isolated pad footings bearing on reinforced sand deposits under the influence of a fluctuating groundwater table. This is a particularly onerous condition for loose sand deposits in coastal areas which may undergo significant collapse settlement over time. Loose and dense experimental sand beds were constructed and the performance of rigid footings under a maintained load and bearing on sand incorporating different column configurations were monitored under cycling of the water table over a period of 28 days, with one filling/empting cycle every 18 h. It was found that settlement, while greatly reduced compared with unreinforced footings, was ongoing and typically occurred at a much greater rate for loose sand than dense sand. Also, settlement rates were slightly higher for fully penetrating than partially penetrating columns and also for footings reinforced by a column group rather than a single column. This was attributed to the migration of sand grains into the larger column voids.

Participatory Action Research with and within community activist groups: capturing the collective experience of Ireland's Community and Voluntary Pillar

The inclusion of community activists in policy planning is increasingly recognized at the highest international level. This article shows how the use of Participatory Action Research (PAR) can present a deeper and more holistic picture of the experiences of Civil Society Organizations (CSOs) in shaping national-level social policy. By utilizing action-based research, the Community and Voluntary Pillar (CVP) of Ireland’s system of social partnership is shown to be an important agent in deliberating national bargaining outcomes (known as the Towards 2016 national agreement). The key contribution of this research is the reflective methodological considerations in terms of PAR design, execution and participant integration in the research process as a way to enrich and develop a deeper and more informed community of practice.

On the Exploitation of the Inherent Error Resilience of Wireless Systems under Unreliable Silicon

In this paper, we investigate the impact of circuit misbehavior due to parametric variations and voltage scaling on the performance of wireless communication systems. Our study reveals the inherent error resilience of such systems and argues that sufficiently reliable operation can be maintained even in the presence of unreliable circuits and manufacturing defects. We further show how selective application of more robust circuit design techniques is sufficient to deal with high defect rates at low overhead and improve energy efficiency with negligible system performance degradation.

Key performance indicators – A new approach for specifying concrete and assessing state of health of concrete structure

The focus of this paper is to outline a method for consolidating and implementing the work on performance-based specification and testing. First part of the paper will review the mathematical significance of the variables used in common service life models. The aim is to identify a set of significant variables that influence the ingress of chloride ions into concrete. These variables are termed as Key Performance Indicators (KPI’s). This will also help to reduce the complexity of some of the service life models and make them more appealing for practicing engineers. The second part of the paper presents a plan for developing a database based on these KPI’s so that relationships can then be drawn between common concrete mix parameters and KPI’s. This will assist designers in specifying a concrete with adequate performance for a particular environment. This, collectively, is referred to as the KPI based approach and the concluding remarks will outline how the authors envisage the KPI theory to relate to performance assessment and monitoring.

The performance of concrete exposed to marine environments: predictive modelling and use of laboratory/on site test methods

This paper reports an approach by which laboratory based testing and numerical modelling can be combined to predict the long term performance of a range of concretes exposed to marine environments. Firstly, a critical review of the test methods for assessing the chloride penetration resistance of concrete is given. The repeatability of the different test results is also included. In addition to the test methods, a numerical simulation model is used to explore the test data further to obtain long-term chloride ingress trends. The combined use of testing and modelling is validated with the help of long-term chloride ingress data from a North Sea exposure site. In summary, the paper outlines a methodology for determining the long term performance of concrete in marine environments.

Pre-operative fasting for intravenous conscious sedation used in dental treatment: are conclusions based on relative risk management or evidence?

Intravenous sedation is a widely used pharmacological method of patient management commonly used in dental surgery for the treatment of anxious patients. Variety exists in fasting regimes between different centres offering dental sedation, with some advocating starvation in line with general anaesthesia protocols and others not enforcing starvation at all. The currently available guidelines on fasting protocols are ambiguous and open to interpretation partly because they are based on expert opinion rather than evidence-based research. This article reviews the available evidence on the subject of pre-operative fasting and discusses current guidelines.