ING116070: a study of the pharmacokinetics and antiviral activity of dolutegravir in cerebrospinal fluid in HIV-1-infected, antiretroviral therapy-naive subjects.

BackgroundDolutegravir (DTG), a once-daily, human immunodeficiency virus type 1 (HIV-1) integrase inhibitor, was evaluated for distribution and antiviral activity in cerebrospinal fluid (CSF).MethodsING116070 is an ongoing, single-arm, open-label, multicenter study in antiretroviral therapy-naive, HIV-1-infected adults. Subjects received DTG (50 mg) plus abacavir/lamivudine (600/300 mg) once daily. The CSF and plasma (total and unbound) DTG concentrations were measured at weeks 2 and 16. The HIV-1 RNA levels were measured in CSF at baseline and weeks 2 and 16 and in plasma at baseline and weeks 2, 4, 8, 12, and 16.ResultsThirteen white men enrolled in the study; 2 withdrew prematurely, 1 because of a non-drug-related serious adverse event (pharyngitis) and 1 because of lack of treatment efficacy. The median DTG concentrations in CSF were 18 ng/mL (range, 4-23 ng/mL) at week 2 and 13 ng/mL (4-18 ng/mL) at week 16. Ratios of DTG CSF to total plasma concentration were similar to the unbound fraction of DTG in plasma. Median changes from baseline in CSF (n = 11) and plasma (n = 12) HIV-1 RNA were -3.42 and -3.04 log10 copies/mL, respectively. Nine of 11 subjects (82%) had plasma and CSF HIV-1 RNA levels <50 copies/mL and 10 of 11 (91%) had CSF HIV-1 RNA levels <2 copies/mL at week 16.ConclusionsThe DTG concentrations in CSF were similar to unbound plasma concentrations and exceeded the in vitro 50% inhibitory concentration for wild-type HIV (0.2 ng/mL), suggesting that DTG achieves therapeutic concentrations in the central nervous system. The HIV-1 RNA reductions were similar in CSF and plasma. Clinical Trials Registration. NCT01499199

Phase separation of binary fluids with dynamic temperature

Phase separation of binary fluids quenched by contact with cold external walls is considered. Navier-Stokes, convection-diffusion, and energy equations are solved by lattice Boltzmann method coupled with finite-difference schemes. At high viscosity, different morphologies are observed by varying the thermal diffusivity. In the range of thermal diffusivities with domains growing parallel to the walls, temperature and phase separation fronts propagate towards the inner of the system with power-law behavior. At low viscosity hydrodynamics favors rounded shapes, and complex patterns with different lengthscales appear. Off-symmetrical systems behave similarly but with more ordered configurations.Comment: Accepted for publication in Phys. Rev. E, 11 figures, best quality figures available on reques

Study of a high spatial resolution 10B-based thermal neutron detector for application in neutron reflectometry: the Multi-Blade prototype

Although for large area detectors it is crucial to find an alternative to detect thermal neutrons because of the 3He shortage, this is not the case for small area detectors. Neutron scattering science is still growing its instruments' power and the neutron flux a detector must tolerate is increasing. For small area detectors the main effort is to expand the detectors' performances. At Institut Laue-Langevin (ILL) we developed the Multi-Blade detector which wants to increase the spatial resolution of 3He-based detectors for high flux applications. We developed a high spatial resolution prototype suitable for neutron reflectometry instruments. It exploits solid 10B-films employed in a proportional gas chamber. Two prototypes have been constructed at ILL and the results obtained on our monochromatic test beam line are presented here

Time dynamics of background noise in geoelectrical and geochemical signals: an application in a seismic area of Southern Italy

We analyse geoelectrical and geochemical time series jointly measured by means of a multiparametric automatic station close to an anomalous fluid emission in Val d’Agri (Basilicata, Italy). The investigated area is located on Southern Apennine chain that in past and recent years was interested by destructive earthquakes. After a complete pre-processing of time series, we analyse the fluctuations triggered by the seasonal cycles and focus our attention on the possible link between geoelectrical and geochemical signals. In order to extract quantitative dynamical information from experimental time series, we detect scaling laws in power spectra that are typical fingerprints of fractional Brownian processes. After this analysis, the problem of the identification of extreme events in the time series has been approached. We consider significant anomalous patterns only when more consecutive values are above/below a fixed threshold in almost two of the time series jointly measured. We give the first preliminary results about the comparison between anomalous patterns detected in geoelectrical and geochemical parameters and the local seismic activity and, finally, analyse the implications with the earthquake prediction problem