Effects of switching to PI monotherapy on measures of lipoatrophy: meta-analysis of six randomized HIV clinical trials

Background: Switching from triple combination treatment to protease inhibitor (PI) monotherapy may prevent or reverse adverse events related to long-term nucleoside analogues. Lipoatrophy is associated with long-term use of thymidine analogues (zidovudine and stavudine). Methods: A detailed MEDLINE search was conducted to identify randomised clinical trials of triple combination treatment versus PI monotherapy. Summary results from analysis of changes in body composition (DEXA analysis) were collected: the mean change in limb fat and trunk fat to Week 48 or 96, and the percentage of patients with lipoatrophy (20% reduction from baseline in limb fat) or lipohypertrophy (20% rise from baseline in trunk fat). Results: Six randomised trials of PI monotherapy versus triple therapy with data on body composition changes, measured by DEXA scanning at baseline and Week 48 or 96, were identified: Abbott-613 (LPV/r vs ZDV/3TC/EFV, induction-maintenance trial, n=105), Monark (LPV/r vs ZDV/3TC/LPV/r, first-line trial, n=63), Kalesolo (LPV/r vs LPV/r +2NRTIs, switch trial, n=42), MONOI (DRV/r vs DRV/r + 2NRTIs, switch trial, n=156), MONARCH (DRV/r vs DRV/r + 2NRTIs, switch trial, n=30) and KRETA (LPV/r vs LPV/r + ABC/3TC, switch trial, n=74). In the meta-analysis, there were greater rises in limb fat in the PI monotherapy arms than the triple therapy arms (mean difference =277g, 95% CI=+36 to+517g, p=0.024). The percentage of patients with lipoatrophy was significantly lower in the PI monotherapy arms (4%) than the triple therapy arms (20%), (p=0.0005). There was no difference between PI monotherapy and triple therapy for mean change in trunk fat (mean difference=−73g, 95% CI = −621 to +475g, p=ns). There was also no significant difference in the risk of lipohypertrophy between the PI monotherapy arms (32%) and the triple therapy arms (27%) (p=ns). In each of the four analyses, there was no evidence for heterogeneity of treatment effects between the trials (Cochran's Q tests, p=ns for each comparison). Conclusions: In this meta-analysis, the risk of lipoatrophy was significantly lower for patients taking PI monotherapy, compared to triple therapy. There was no significant difference between the arms for lipohypertrophy. However, several of the trials included zidovudine in the control arm, which carries a higher risk of lipoatrophy than tenofovir and abacavir, which are now more widely used

Nonsaturating magnetoresistance and nontrivial band topology of type-II Weyl semimetal NbIrTe4

Weyl semimetals, characterized by nodal points in the bulk and Fermi arc states on the surface, have recently attracted extensive attention due to the potential application on low energy consumption electronic materials. In this report, the thermodynamic and transport properties of a theoretically predicted Weyl semimetal NbIrTe4 is measured in high magnetic fields up to 35 T and low temperatures down to 0.4 K. Remarkably, NbIrTe4 exhibits a nonsaturating transverse magnetoresistance which follows a power-law dependence in B. Low-field Hall measurements reveal that hole-like carriers dominate the transport for T $>$ 80 K, while the significant enhancement of electron mobilities with lowering T results in a non-negligible contribution from electron-like carriers which is responsible for the observed non-linear Hall resistivity at low T. The Shubnikov-de Haas oscillations of the Hall resistivity under high B give the light effective masses of charge carriers and the nontrivial Berry phase associated with Weyl fermions. Further first-principles calculations confirm the existence of 16 Weyl points located at kz = 0, $\pm$0.02 and $\pm$0.2 planes in the Brillouin zone.Comment: 5 figures, 1 tabl

Stability investigation of polyPOSS-imide membranes for H2 purification and their application in the steel industry

In the present work, the high-temperature and long-term hydrothermal stability of novel polyPOSS-imide membranes for high-temperature hydrogen separation is investigated. The polyPOSS-imide membranes are found to exhibit an appropriate stability up to 300 C. Above this temperature the membrane selectivity rapidly decreases, which is seemingly related to changes in the molecular structure coupled to silanol condensation forming siloxane groups. Surprisingly, the exposure of the membrane to temperatures of up to 300 C even increases the H2 permeance together with the selective feature of the polyPOSS-imide layer. Subsequently, the long-term hydrothermal stability of the polyPOSS-imide membranes was investigated over a period of close to 1000 h at 250 C exposing the membrane to 10 mol% steam in the feed. An increase in H2/CH4 selectivity was observed upon water addition, and even though a minor drop was noticed over time during the hydrothermal operation, the selectivity exceeds the initial selectivity obtained in the dry feed atmosphere. After the removal of steam from the feed, the performance returns to its original state prior to the exposure to any steam showing appropriate steam stability of the polyPOSS-imide membranes. A conceptual process design and assessment was performed for application of these membranes involving a combination of carbon reuse and electrification of the steel making process with co-production of hydrogen. The results indicate a CO2 avoidance of 14%. The CO2 reduction achieved using renewable electricity in the proposed scheme is a factor 2.76 higher compared to a situation where the same renewable electricity would be fed in the electricity grid.publishedVersio

Free radical scavenging and formation by multi-walled carbon nanotubes in cell free conditions and in human bronchial epithelial cells

Background: Certain multi-walled carbon nanotubes (MWCNTs) have been shown to elicit asbestos-like toxicological effects. To reduce needs for risk assessment it has been suggested that the physicochemical characteristics or reactivity of nanomaterials could be used to predict their hazard. Fibre-shape and ability to generate reactive oxygen species (ROS) are important indicators of high hazard materials. Asbestos is a known ROS generator, while MWCNTs may either produce or scavenge ROS. However, certain biomolecules, such as albumin – used as dispersants in nanomaterial preparation for toxicological testing in vivo and in vitro - may reduce the surface reactivity of nanomaterials. Methods: Here, we investigated the effect of bovine serum albumin (BSA) and cell culture medium with and without BEAS 2B cells on radical formation/scavenging by five MWCNTs, Printex 90 carbon black, crocidolite asbestos, and glass wool, using electron spin resonance (ESR) spectroscopy and linked this to cytotoxic effects measured by trypan blue exclusion assay. In addition, the materials were characterized in the exposure medium (e.g. for hydrodynamic size-distribution and sedimentation rate). Results: The test materials induced highly variable cytotoxic effects which could generally be related to the abundance and characteristics of agglomerates/aggregates and to the rate of sedimentation. All carbon nanomaterials were found to scavenge hydroxyl radicals (•OH) in at least one of the solutions tested. The effect of BSA was different among the materials. Two types of long, needle-like MWCNTs (average diameter >74 and 64.2 nm, average length 5.7 and 4.0 µm, respectively) induced, in addition to a scavenging effect, a dose-dependent formation of a unique, yet unidentified radical in both absence and presence of cells, which also coincided with cytotoxicity. Conclusions: Culture medium and BSA affects scavenging/production of •OH by MWCNTs, Printex 90 carbon black, asbestos and glass-wool. An unidentified radical is generated by two long, needle-like MWCNTs and these two CNTs were more cytotoxic than the other CNTs tested, suggesting that this radical could be related to the adverse effects of MWCNTs

Mesoscopic Fluctuations in Quantum Dots in the Kondo Regime

Properties of the Kondo effect in quantum dots depend sensitively on the coupling parameters and so on the realization of the quantum dot -- the Kondo temperature itself becomes a mesoscopic quantity. Assuming chaotic dynamics in the dot, we use random matrix theory to calculate the distribution of both the Kondo temperature and the conductance in the Coulomb blockade regime. We study two experimentally relevant cases: leads with single channels and leads with many channels. In the single-channel case, the distribution of the conductance is very wide as $T_K$ fluctuates on a logarithmic scale. As the number of channels increases, there is a slow crossover to a self-averaging regime.Comment: 4 pages, 3 figure

Quantum phase transition in a two-channel-Kondo quantum dot device

We develop a theory of electron transport in a double quantum dot device recently proposed for the observation of the two-channel Kondo effect. Our theory provides a strategy for tuning the device to the non-Fermi-liquid fixed point, which is a quantum critical point in the space of device parameters. We explore the corresponding quantum phase transition, and make explicit predictions for behavior of the differential conductance in the vicinity of the quantum critical point