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Background: Quisinostat is a hydroxamate, second-generation, orally available pan-histone deacetylase inhibitor. Objectives: To evaluate the efficacy and safety of oral quisinostat in patients with previously treated cutaneous T-cell lymphoma (CTCL). Methods: Patients received quisinostat 8 mg or 12 mg on days 1, 3 and 5 of each week in 21-day treatment cycles. Primary efficacy end point was cutaneous response rate (RR) based on the modified Severity Weighted Assessment Tool (mSWAT). Secondary end points included global RR, duration of response (DOR) in skin, progression-free survival (PFS), pruritus relief, safety and pharmacodynamic markers. Results: Eight of 26 (25 evaluable) patients achieved ≥ 50% reduction in mSWAT score at least once, with confirmed cutaneous response in six (RR 24%). There was a low global RR of 8%. DOR in skin ranged from 2·8 to 6·9 months. Median PFS was 5·1 months. Pruritus relief was more frequent in cutaneous responders (67%) than nonresponders (32%). Serial tumour biopsies revealed an increase in acetylated tubulin, indicating a target effect of histone deacetylase 6. Twenty-one of 26 (81%) patients were withdrawn from the study before or at clinical cut-off; five (19%) continued to receive treatment with quisinostat. The most common drug-related adverse events were nausea, diarrhoea, asthenia, hypertension, thrombocytopenia and vomiting. Grade 3 drug-related adverse events included hypertension, lethargy, pruritus, chills, hyperkalaemia and pyrexia. Conclusions: Quisinostat 12 mg three times weekly is active in the treatment of patients with relapsed or refractory CTCL, with an acceptable safety profile. Combination therapy with other drugs active in CTCL may be appropriate.

© 2015 American Chemical Society. Recent trends in legislation across the world are aimed toward the reduction of the levels of sulfur in fuel oils to less than 10 ppm (ultra low sulfur diesel, ULSD) due to its toxic and environmental effects. Hydrodesulfurization (HDS) is the current method used for desulfurization and faces technical challenges, due to the extreme conditions and energy consumption necessary to reach low sulfur levels. Recently, ionic liquid (IL) technology has been proposed as a possible solution toward achieving ULSD. ILs represent a new class of "green" solvents that are gaining popularity due to their favorable properties and have recently been shown to be effective extractants for desulfurization on a laboratory scale. In this work, the feasibility of industrial scale IL-extractive processing of ULSD has been examined via the simulation and optimization of a conceptual process in ASPEN Plus. The widely used [Cnmim] [NTF2] series of ionic liquids have been employed, due to their favorable properties and the availability of experimental data in literature. User-defined ionic liquid components have been created within ASPEN Plus, incorporating several thermodynamic and physical property parameters derived from literature, to allow the process to be simulated via the UNIFAC thermodynamic method. On the basis of the technical analysis, it is proposed that the most feasible process configuration consists of HDS as a preliminary treatment, followed by IL extraction as intermediate treatment to reduce the sulfur content to 50 ppm, with adsorption as the final treatment to achieve ULSD levels.

© 2014 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim. This paper is on the design, fabrication, and testing of skins and sleeves for soft robotics with the focus on the mechanical features of the microstructure of these skins, drawing inspiration from nature and architecture. Biological inspirations drawn from animals are used for designing skin membranes or skin structures for soft robotic actuators, in particular pneumatic actuators that protect, guide, and contribute to the development of the actuated shape. The results presented in this paper will be a new step toward advancing the state-of-the-art of biologically inspired soft robots for minimally invasive surgery. Inspirations from architecture are of particular interest in the areas of formability of design and continuous flow. The report presents a trade-off study using various skin and sleeve technologies of innovative fiber structures and combinations of different materials in different innovative designs, surrounding a pneumatically actuated, soft robot of variable stiffness.

This paper investigates different types of crimped, braided sleeve used for a soft arm for robotic abdominal surgery, with the sleeve required to contain balloon expansion in the pneumatically actuating arm while it follows the required bending, elongation and diameter reduction of the arm.Three types of crimped, braided sleeves from PET (BraidPET) or nylon (BraidGreyNylon and BraidNylon, with different monofilament diameters) were fabricated and tested including geometrical and microstructural characterisation of the crimp and braid, mechanical tests and medical scratching tests for organ damage of domestic pigs.BraidPET caused some organ damage, sliding under normal force of 2-5 N; this was attributed to the high roughness of the braid pattern, the higher friction coefficient of polyethylene terephthalate (PET) compared to nylon, and the high frequency of the crimp peaks for this sleeve. No organ damage was observed for the BraidNylon, attributed to both the lower roughness of the braid pattern and the low friction coefficient of nylon. BraidNylon also required the lowest tensile force during its elongation to similar maximum strain as that of BraidPET, translating to low power requirements.BraidNylon is recommended for the crimped sleeve of the arm designed for robotic abdominal surgery.

BACKGROUND: Bortezomib and rituximab have shown additive activity in preclinical models of lymphoma, and have been shown to be active and generally well tolerated in a randomised phase 2 study in patients with follicular and marginal zone lymphoma. We compared the efficacy and safety of rituximab alone or combined with bortezomib in patients with relapsed or refractory follicular lymphoma in a phase 3 setting. METHODS: In this multicentre phase 3 trial, rituximab-naive or rituximab-sensitive patients aged 18 years or older with relapsed grade 1 or 2 follicular lymphoma were randomly assigned (1:1) to receive five 35-day cycles consisting of intravenous infusions of rituximab 375 mg/m(2) on days 1, 8, 15, and 22 of cycle 1, and on day 1 of cycles 2-5, either alone or with bortezomib 1·6 mg/m(2), administered by intravenous injection on days 1, 8, 15, and 22 of all cycles. Randomisation was stratified by FLIPI score, previous use of rituximab, time since last therapy, and region. Treatment assignment was based on a computer-generated randomisation schedule prepared by the sponsor. Patients and treating physicians were not masked to treatment allocation. The primary endpoint was progression-free survival analysed by intention to treat. This trial has been completed and is registered with ClinicalTrials.gov, number NCT00312845. FINDINGS: Between April 10, 2006, and Aug 12, 2008, 676 patients were randomised to receive rituximab (n=340) or bortezomib plus rituximab (n=336). After a median follow-up of 33·9 months (IQR 26·4-39·7), median progression-free survival was 11·0 months (95% CI 9·1-12·0) in the rituximab group and 12·8 months (11·5-15·0) in the bortezomib plus rituximab group (hazard ratio 0·82, 95% CI 0·68-0·99; p=0·039). The magnitude of clinical benefit was not as large as the anticipated prespecified improvement of 33% in progression-free survival. Patients in both groups received a median of five treatment cycles (range 1-5); 245 of 339 (72%) and 237 of 334 (71%) patients in the rituximab and bortezomib plus rituximab groups, respectively, completed five cycles. Of patients who did not complete five cycles, most discontinued early because of disease progression (77 [23%] patients in the rituximab group, and 56 [17%] patients in the bortezomib plus rituximab group). Rates of adverse events of grade 3 or higher (70 [21%] of 339 rituximab-treated patients vs 152 [46%] of 334 bortezomib plus rituximab treated patients), and serious adverse events (37 [11%] patients vs 59 [18%] patients) were lower in the rituximab group than in the combination group. The most common adverse events of grade 3 or higher were neutropenia (15 [4%] patients in the rituximab group and 37 [11%] patients in the bortezomib plus rituximab group), infection (15 [4%] patients and 36 [11%] patients, respectively), diarrhoea (no patients and 25 [7%] patients, respectively), herpes zoster (one [