A Pharmacogenetics Study in Mozambican Patients Treated with Nevirapine: Full Resequencing of TRAF3IP2 Gene Shows a Novel Association with SJS/TEN Susceptibility

Steven–Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are severe adverse drug reactions, characterized by extensive epidermal detachment and erosions of mucous membrane. SJS/TEN is one of the most serious adverse reactions to Nevirapine (NVP) treatment, commonly used in developing countries as first-line treatment of human immunodeficiency virus infection. In the last years TRAF3IP2 gene variants had been described as associated with susceptibility to several diseases such as psoriasis and psoriatic arthritis. We hypothesized that this gene, involved in immune response and in NF-κB activation, could also be implicated in the SJS/TEN susceptibility. We performed a full resequencing of TRAF3IP2 gene in a population of patients treated with NVP. Twenty-seven patients with NVP-induced SJS/TEN and 78 controls, all from Mozambique, were enrolled. We identified eight exonic and three intronic already described variants. The case/control association analysis highlighted an association between the rs76228616 SNP in exon 2 and the SJS/TEN susceptibility. In particular, the variant allele (C) resulted significantly associated with a higher risk to develop SJS/TEN (p = 0.012 and OR = 3.65 (95% CI 1.33–10.01)). A multivariate analysis by logistic regression confirmed its significant contribution (p = 0.027, OR = 4.39 (95% CI 1.19–16.23)). In conclusion, our study suggests that a variant in TRAF3IP2 gene could be involved in susceptibility to SJS/TEN.     

Disentangling Phase and Morphological Evolution During the Formation of the Lithium Superionic Conductor Li10GeP2S12

The structural and morphological changes of the Lithium superionic conductor Li₁₀GeP₂S₁₂, prepared via a widely used ball milling-heating method over a comprehensive heat treatment range (50 – 700 °C), are investigated. Based on the phase composition, the formation process can be distinctly separated into four zones: Educt, Intermediary, Formation, and Decomposition zone. It is found that instead of Li₄GeS₄–Li₃PS₄ binary crystallization process, diversified intermediate phases, including GeS₂ in different space groups, multiphasic lithium phosphosulfides (Li_xP_yS_z), and cubic Li₇Ge₃PS₁₂ phase, are involved additionally during the formation and decomposition of Li₁₀GeP₂S₁₂. Furthermore, the phase composition at temperatures around the transition temperatures of different formation zones shows a significant deviation. At 600 °C, Li₁₀GeP₂S₁₂ is fully crystalline, while the sample decomposed to complex phases at 650 °C with 30 wt.% impurities, including 20 wt.% amorphous phases. These findings over such a wide temperature range are first reported and may help provide previously lacking insights into the formation and crystallinity control of Li₁₀GeP₂S₁₂.     

Evaluation of tritium diffusion through the Neutral Beam Injector calorimeter panel

The Neutral Beam Test Facility (NBTF) to be realized in Padoa will test the Neutral Beam Injection (NBI), one of the Heating and Current Drive Systems foreseen for ITER. The NBI is based on the acceleration of hydrogen or deuterium negative ions up to 1 MeV. This work has been aimed at assessing the tritium release from the NBTF in order to provide data for the safety analysis. In particular, the diffusion of the tritium through the neutral beam target material (the CuCrZr alloy calorimeter panels) has been assessed by using literature data of the diffusion coefficient. The tritium generated inside the calorimeter panels moves into both the vacuum and water side: the tritium diffusion flux has been evaluated during the beam-on (200 °C) and the beam-off (20 °C) phases of the NBTF experiments consisting of an interim campaign and a final test. The penetration depth of the tritium through the 2 mm thick CuCrZr alloy material has been also evaluated by using a Monte-Carlo code. As main result, the assessed diffusion flux of tritium during both the beam-on and the beam-off phases are modest. In fact, at the end of the interim campaign (100 days), about the 96% of the all generated tritium (626.5 MBq) exits the calorimeter while the residual tritium inventory (25 MBq) leaves the copper alloy with a diffusion time of about 1 month. At the end of the final test (14 days) about the 99% of the total generated tritium (1.023 × 10⁴ MBq) leaves the copper alloy and the remaining tritium inventory (152.2 MBq) is released by about 32 days. In both the interim campaign and the final test, more than the 99% of the total tritium is transferred into the vacuum side of the calorimeter panel while negligible tritium amounts enter the cooling water system thus showing a very low impact on the environment.     

Progress in control and data acquisition for the ITER neutral beam test facility

SPIDER, the ion source test bed in the ITER neutral beam test facility, is under construction and its operation is expected to start in 2014. Control and data acquisition for SPIDER are undergoing final design. SPIDER CODAS, as the control and data acquisition system is referred to, is requested to manage 25 plant units, to acquire 1000 analogue signals with sampling rates ranging from a few S/s to 10 MS/s, to acquire images with up to 100 frames per second, to operate with long pulses lasting up to 1 h, and to sustain 200 MB/s data throughput into the data archive with an annual data storage amount of up to 50 TB. SPIDER CODAS software architecture integrates three open-source software frameworks each addressing specific system requirements. Slow control exploits the synergy among EPICS and Siemens S7 programmable controllers. Data handling is by MDSplus a data-centric framework that is geared towards the collection and organization of scientific data. Diagnostics based on imaging drive the design of data throughput and archive size. Fast control is implemented by using MARTe, a data-driven, object-oriented, real-time environment. The paper will describe in detail the progress of the system hardware and software architecture and will show how the software frameworks interact to provide the functions requested by SPIDER CODAS. The paper will focus on how the performance requirements can be met with the described SPIDER CODAS architecture, describing the progress achieved by carrying out prototyping activities.     

High-performance optical fiber polarizers based on long-period gratings in birefringent optical fibers

We have demonstrated the feasibility of achieving high-performance fiber polarizers (insertion loss <0.5 dB, extinction ratio >30 dB), based on polarization mode dispersion in a long-period grating. Chirped operation with 100-nm bandwidth has also been achieved, showing the possibility of a broad-band device.     

Multi layer structure for encapsulation of organic transistors

A novel encapsulation structure to protect organic thin film transistors against oxygen and moisture contaminations is presented. The sealing architecture is comprised of three-layers: aluminum oxide deposited by means of Atomic Layer Deposition is the actual capping layer, while cross-linked poly-vinylphenol and poly-vinylphenol prevent the contamination/damage of the underlying organic semiconductor during the oxide growth. The process has negligible impact on device mobility but it enables poly-3-hexylthiophene based transistors to operate with an on/off ratio in excess of 10³ even after 100 days of continuous ambient air exposure.     

Intraoperative laparoscope augmentation for port placement and resection planning in minimally invasive liver resection

In recent years, an increasing number of liver tumor indications were treated by minimally invasive laparoscopic resection. Besides the restricted view, two major intraoperative issues in laparoscopic liver resection are the optimal planning of ports as well as the enhanced visualization of (hidden) vessels, which supply the tumorous liver segment and thus need to be divided (e.g., clipped) prior to the resection. We propose an intuitive and precise method to plan the placement of ports. Preoperatively, self-adhesive fiducials are affixed to the patient's skin and a computed tomography (CT) data set is acquired while contrasting the liver vessels. Immediately prior to the intervention, the laparoscope is moved around these fiducials, which are automatically reconstructed to register the patient to its preoperative imaging data set. This enables the simulation of a camera flight through the patient's interior along the laparoscope's or instruments' axes to easily validate potential ports. Intraoperatively, surgeons need to update their surgical planning based on actual patient data after organ deformations mainly caused by application of carbon dioxide pneumoperitoneum. Therefore, preoperative imaging data can hardly be used. Instead, we propose to use an optically tracked mobile C-arm providing cone-beam CT imaging capability intraoperatively. After patient positioning, port placement, and carbon dioxide insufflation, the liver vessels are contrasted and a 3-D volume is reconstructed during patient exhalation. Without any further need for patient registration, the reconstructed volume can be directly augmented on the live laparoscope video, since prior calibration enables both the volume and the laparoscope to be positioned and oriented in the tracking coordinate frame. The augmentation provides the surgeon with advanced visual aid for the localization of veins, arteries, and bile ducts to be divided or sealed.     

Heterogeneous Catalysis for Fine Chemicals in Dense Phase Carbon Dioxide

An increasing number of fine chemicals is being produced using heterogeneously catalysed reactions in supercritical carbon dioxide with significant improvements in terms of process selectivity and purity of the products thereby obtained. A selection of examples and of recent findings shows the large potential of this technology for the synthetic chemistry of the future.