Search

Mycosis fungoides (MF) is a subtype of CTCL with a low incidence and high medical need for novel treatments. The objective of this randomized, placebo-controlled, double-blinded, first-in-human study was to evaluate safety, efficacy, cutaneous and systemic pharmacokinetics (PK) of topical bimiralisib in healthy volunteers (HVs) and MF patients. In this trial, a total of 6 HVs and 19 early-stage MF patients were treated with 2.0% bimiralisib gel and/or placebo. Drug efficacy was assessed by the Composite Assessment of Index Lesion Severity (CAILS) score, supported by objective measuring methods to quantify lesion severity. PK blood samples were collected frequently and cutaneous PK was investigated in skin punch biopsies on the last day of treatment. Local distribution of bimiralisib in HVs showed a mean exposure of 2.54 µg/g in the epidermis. A systemic concentration was observed after application of a target dose of 2 mg/cm 2 on 400 cm 2, with a mean C avg of 0.96 ng/mL. Systemic exposure of bimiralisib was reached in all treated MF patients, and normalized plasma concentrations showed a 144% increased exposure compared to HVs, with an observed mean C avg of 4.49 ng/mL and a mean cutaneous concentration of 5.3 µg/g. No difference in CAILS or objective lesion severity quantification upon 42 days of once-daily treatment was observed in the MF patient group. In general, the treatment was well tolerated in terms of local reactions as well as systemic adverse events. In conclusion, we showed that topical bimiralisib treatment leads to (i) meaningful cutaneous drug levels and (ii) well-tolerated systemic drug exposure in MF patients and (iii) a lack of clinical efficacy, in need of further exploration due to numerous unknown factors, before depreciation of topical bimiralisib as a novel therapeutic drug for CTCLs.

Nintedanib and pirfenidone are approved treatments for idiopathic pulmonary fibrosis (IPF). This open-label, two-group trial investigated the pharmacokinetic drug–drug interaction between these two drugs in patients with IPF. Subjects not treated with antifibrotics at screening (group 1, n=20) received a single nintedanib dose (150 mg) followed by pirfenidone (titrated to 801 mg thrice daily) for 3 weeks, with a further single nintedanib dose (150 mg) on the last day (day 23). Subjects treated with pirfenidone at screening (group 2, n=17) continued to receive pirfenidone alone (801 mg thrice daily) for 7 days, then co-administered with nintedanib (150 mg twice daily) for a further 7 days, before single doses of both treatments on day 16. In group 1, adjusted geometric mean (gMean) ratios (with/without pirfenidone) were 88.6% and 80.6% for nintedanib area under the plasma concentration–time curve (AUC) and maximum plasma concentration (Cmax), respectively. In group 2, gMean ratios (with/without nintedanib) were 97.2% and 99.5% for pirfenidone AUC and Cmax, respectively. For all parameters, the 90% confidence intervals included 100%, suggesting similar exposure for administration alone and when co-administered. Both treatments were well tolerated. These data indicate there is no relevant pharmacokinetic drug–drug interaction between nintedanib and pirfenidone when co-administered in IPF patients.

© 2017 IEEE. Non-classical light sources, such as atoms and atom-like emitters play central roles in many areas of quantum information processing with applications as single photon generators, sources for nonlinearity and quantum memories. Solid-state quantum emitters have attracted growing interest due to the promise of combining remarkable optical properties with the convenience of scalability [1]. In recent years, there has been tremendous progress in developing quantum emitter systems based on crystallographic defects in wide-bandgap semiconductors. Nitrogen vacancies (NV) in diamond were among the first studied systems due to the well-defined optical transitions as well as electronic spin states that can be controlled optically. Quantum spins in diamond are among the most advanced systems in solid state for quantum based technologies such as quantum computing or quantum sensing [2]. Nevertheless, solid-state quantum emitters are not only limited to diamond and efforts to engineer single photon emitters (SPE) based on atom-like defects in scalable system have expanded beyond NV centers in diamond. Similar quantum emitters have been discovered in many other wide-bandgap host materials, including silicon carbide (SiC), III-nitride semiconductors such as gallium nitride (GaN) and aluminum nitride (AlN), and layered materials such as hexagonal boron nitride (hBN) [1]. Here, we will review our recent progress in developing and characterizing new quantum emitters in wide-bandgap semiconductors, and consider their applications as quantum light sources and sensors.

FLSmidth has been supplying gas suspension calciners (GSC) for alumina since 1984 with nameplate capacities of 820-4 500 tpd of smelter grade alumina. Several units have been supplied to China using coal gas as fuel, and the GSC technology is now used in almost all Chinese refineries built since 2005. The first two of seven new generation GSC units with name plate capacities of 2 500-3 500 tpd are now being commissioned at the Yarwun refinery in Australia. The units comprises four main sections, drying and pre-heating/pre-calcination, calcination furnace and furnace cyclone, four-stage cyclone cooler for heat recovery from alumina by direct cooling with air and fluidised bed cooler for indirect alumina cooling with water. The latest design incorporates a fluidised holding vessel with several minutes of solids retention time, allowing the calcination temperature in the gas suspension furnace/reactor to be reduced from about 1 050 to less than 950 degrees C. The physical-chemical processes involved in the calcination of alumina hydrate are described and the latest operating data with respect to alumina capacity and quality, environmental emissions and energy efficiency are presented., FLSmidth has been supplying gas suspension calciners (GSC) for alumina since 1984 with nameplate capacities of 820-4 500 tpd of smelter grade alumina. Several units have been supplied to China using coal gas as fuel, and the GSC technology is now used in almost all Chinese refineries built since 2005. The first two of seven new generation GSC units with name plate capacities of 2 500-3 500 tpd are now being commissioned at the Yarwun refinery in Australia. The units comprises four main sections, drying and pre-heating/pre-calcination, calcination furnace and furnace cyclone, four-stage cyclone cooler for heat recovery from alumina by direct cooling with air and fluidised bed cooler for indirect alumina cooling with water. The latest design incorporates a fluidised holding vessel with several minutes of solids retention time, allowing the calcination temperature in the gas suspension furnace/reactor to be reduced from about 1 050 to less than 950 degrees C. The physical-chemical processes involved in the calcination of alumina hydrate are described and the latest operating data with respect to alumina capacity and quality, environmental emissions and energy efficiency are presented.