Paediatric drug development:reformulation, in vitro, genomic and in vivo evaluation

Angiotensin converting enzyme (ACE) inhibitors lisinopril and ramipril were selected from EMA/480197/2010 and the potassium-sparing diuretic spironolactone was selected from the NHS specials list for November 2011 drug tariff with the view to produce oral liquid formulations providing dosage forms targeting paediatrics. Lisinopril, ramipril and spironolactone were chosen for their interaction with transporter proteins in the small intestine. Formulation limitations such as poor solubility or pH sensitivity needed consideration. Lisinopril was formulated without extensive development as drug and excipients were water soluble. Ramipril and spironolactone are both insoluble in water and strategies combating this were employed. Ramipril was successfully solubilised using low concentrations of acetic acid in a co-solvent system and also via complexation with hydroxypropyl-β-cyclodextrin. A ramipril suspension was produced to take formulation development in a third direction. Spironolactone dosages were too high for solubilisation techniques to be effective so suspensions were developed. A buffer controlled pH for the sensitive drug whilst a precisely balanced surfactant and suspending agent mix provided excellent physical stability. Characterisation, stability profiling and permeability assessment were performed following formulation development. The formulation process highlighted current shortcomings in techniques for taste assessment of pharmaceutical preparations resulting in early stage research into a novel in vitro cell based assay. The formulations developed in the initial phase of the research were used as model formulations investigating microarray application in an in vitro-in vivo correlation for carrier mediated drug absorption. Caco-2 cells were assessed following transport studies for changes in genetic expression of the ATP-binding cassette and solute carrier transporter superfamilies. Findings of which were compared to in vitro and in vivo permeability findings. It was not possible to ascertain a correlation between in vivo drug absorption and the expression of individual genes or even gene families, however there was a correlation (R2 = 0.9934) between the total number of genes with significantly changed expression levels and the predicted human absorption.

Nonlinear inverse synthesis technique for optical links with lumped amplification

The nonlinear inverse synthesis (NIS) method, in which information is encoded directly onto the continuous part of the nonlinear signal spectrum, has been proposed recently as a promising digital signal processing technique for combating fiber nonlinearity impairments. However, because the NIS method is based on the integrability property of the lossless nonlinear Schrödinger equation, the original approach can only be applied directly to optical links with ideal distributed Raman amplification. In this paper, we propose and assess a modified scheme of the NIS method, which can be used effectively in standard optical links with lumped amplifiers, such as, erbium-doped fiber amplifiers (EDFAs). The proposed scheme takes into account the average effect of the fiber loss to obtain an integrable model (lossless path-averaged model) to which the NIS technique is applicable. We found that the error between lossless pathaveraged and lossy models increases linearly with transmission distance and input power (measured in dB). We numerically demonstrate the feasibility of the proposed NIS scheme in a burst mode with orthogonal frequency division multiplexing (OFDM) transmission scheme with advanced modulation formats (e.g., QPSK, 16QAM, and 64QAM), showing a performance improvement up to 3.5 dB; these results are comparable to those achievable with multi-step per span digital backpropagation.

Criminals and terrorists in partnership:unholy alliance

The nexus between terrorism and organised crime consists in a strategic alliance between two non-state actors, able to exploit illegal markets, threaten the security of individuals, and influence policy-making on a global level. Recent Europol reports have pointed towards the importance of studying the links between organised crime and terrorist groups, and have underlined that the nature and extent of these connections have seldom been addressed from an academic perspective. Considering the degree of dangerousness that both organised crime and terrorism currently represent in the world, the collusion between these two phenomena is of urgent contemporary interest. Basing itself on geographical case-studies, this edited volume aims at contributing to the existing literature in three ways: by enriching the empirical knowledge on the nature of the crime-terror nexus and its evolution; by exploring the impact of the nexus within different economic, political and societal contexts; and by expanding on its theoretical conceptualization.

Fibre impairment compensation using artificial neural network equalizer for high-capacity coherent optical OFDM signals

We propose an artificial neural network (ANN) equalizer for transmission performance enhancement of coherent optical OFDM (C-OOFDM) signals. The ANN equalizer showed more efficiency in combating both chromatic dispersion (CD) and single-mode fibre (SMF)-induced non-linearities compared to the least mean square (LMS). The equalizer can offer a 1.5 dB improvement in optical signal-to-noise ratio (OSNR) compared to LMS algorithm for 40 Gbit/s C-OOFDM signals when considering only CD. It is also revealed that ANN can double the transmission distance up to 320 km of SMF compared to the case of LMS, providing a nonlinearity tolerance improvement of ∼0.7 dB OSNR.

Optimization of relay selection in DF cooperative systems with outdated CSI

Relay selection has been considered as an effective method to improve the performance of cooperative communication. However, the Channel State Information (CSI) used in relay selection can be outdated, yielding severe performance degradation of cooperative communication systems. In this paper, we investigate the relay selection under outdated CSI in a Decode-and-Forward (DF) cooperative system to improve its outage performance. We formulize an optimization problem, where the set of relays that forwards data is optimized to minimize the probability of outage conditioned on the outdated CSI of all the decodable relays’ links. We then propose a novel multiple-relay selection strategy based on the solution of the optimization problem. Simulation results show that the proposed relay selection strategy achieves large improvement of outage performance compared with the existing relay selection strategies combating outdated CSI given in the literature.

The external dimension of the EU’s fight against organized crime:the search for coherence between rhetoric and practice

SSince the external dimension of the European Union’s Justice and Home Affairs (JHA) began to be considered, a substantial amount of literature has been dedicated to discussing how the EU is cooperating with non-member states in order to counter problems such as terrorism, organized crime and illegal migration. According to the EU, the degree of security interconnectedness has become so relevant that threats can only be adequately controlled if there is effective concerted regional action. This reasoning has led the EU to develop a number of instruments, which have resulted in the exporting of certain elements of its JHA policies, either through negotiation or socialization. Although the literature has explored how this transfer has been applied to the field of terrorism and immigration, very little has been written on the externalisation of knowledge, practice and norms in the area of organized crime. This article proposes to bridge this gap by looking at EU practice in the development of the external dimension of organized crime policies, through the theoretical lens of the EU governance framework.

Native language identification (NLID) for forensic authorship analysis of weblogs

This chapter introduces Native Language Identification (NLID) and considers the casework applications with regard to authorship analysis of online material. It presents findings from research identifying which linguistic features were the best indicators of native (L1) Persian speakers blogging in English, and analyses how these features cope at distinguishing between native influences from languages that are linguistically and culturally related. The first chapter section outlines the area of Native Language Identification, and demonstrates its potential for application through a discussion of relevant case history. The next section discusses a development of methodology for identifying influence from L1 Persian in an anonymous blog author, and presents findings. The third part discusses the application of these features to casework situations as well as how the features identified can form an easily applicable model and demonstrates the application of this to casework. The research presented in this chapter can be considered a case study for the wider potential application of NLID.

Mechatronic solutions for measuring disturbance levels within a cochlea

Hearing implants are an important devices for combating deafness over the next 15 years. In this paper, we focus on the means to determine the sensitivity of the hearing organ to disturbances produced by implants and other interventions, and those induced by implantation. The preservation of residual hearing is an important aspect to be considered, however, the sensitivity of this to the process of implantation, device location and power levels is not well understood. Within this paper, a new experimental set-up to contrast the merits of different implantation techniques, implant location and power transmission are discussed and the initial results regarding disturbance levels using different surgical techniques are described.