Long-Term Efficacy of Intranasal Esketamine in Treatment-Resistant Major Depression: A Systematic Review

Esketamine (ESK) has been approved as a rapid-acting intranasal treatment for treatment-resistant depression (TRD). Although existing studies have investigated the efficacy of ESK in the 4-week induction phase, our knowledge about long-term ESK efficacy remains poor. The aim of this systematic review was to summarize the available data on long-term ESK efficacy for TRD. A systematic search was performed including articles in English, up to 31 March 2021. The search found 7 relevant studies, involving 1024 adult TRD patients. Continuing treatment with ESK after the 4-week induction phase may be associated with stable efficacy in relapse prevention among TRD patients. Conversely, the long-term antidepressant effectiveness upon discontinuation of ESK might be limited, although data from three studies had a moderate to high risk of bias. Overall, the results on the effectiveness of this compound in the long term are mixed. According to our findings, ESK treatment should be continued following the induction phase to reach a stable efficacy in relapse prevention, while the long-term antidepressant and anti-suicidal effects of ESK after discontinuation are inconsistent. Currently, the level of proof of ESK efficacy in long-term TRD treatment remains low and more RCTs with larger sample sizes and active comparators are needed.     

Local electron heating in nanoscale conductors

The electron current density in nanoscale junctions is typically several orders of magnitude larger than the corresponding one in bulk electrodes. Consequently, the electron-electron scattering rate increases substantially in the junction. This leads to local electron heating of the underlying Fermi sea in analogy to the local ionic heating that is due to the increased electron-phonon scattering rates. We predict the bias dependence of local electron heating in quasi-ballistic nanoscale conductors and its effect on ionic heating and discuss possible experimental tests of our results.     

A k, k-ε optimality selection based multi objective genetic algorithm with applications to vehicle engineering

In the paper, a multi objective genetic algorithm based on the concept of k-optimality and k-ε-optimality (KEMOGA) is introduced and applied. Pareto optimality alone is not always adequate for selecting a final solution because the Pareto optimal set can be very large. The k-optimality approach and the more general k-ε-optimality method, can be used to rank the Pareto-optimal solutions. The two methods have been included into a genetic algorithm selection procedure. The k-optimality method searches for points which remain Pareto-optimal when all of the subsets of n-k objectives (n is the number of objective functions) are optimised. The k-ε approach considers not only if an objective is worse than the others but also the entity of this variation through the introduction of a vector of indifference thresholds. The KEMOGA has been applied for the solution of two engineering problems. The selection of the stiffness and damping of a passively suspended vehicle in order to get the best compromise between discomfort, road holding and working space and a complex problem related to the optimisation of the tyre/suspension system of a sport car. The final design solution, found by means of the KEMOGA seems consistent with the solution selected by skilled suspensions specialists. The proposed approach has been tested and validated on a complex optimization problem. The solved problem deals with the optimization of the tyre/suspension system of a sport car. The proposed approach (KEMOGA) has shown to be very effective in terms of computational efficiency and accuracy.     

The identification and characterization of fusogenic domains in herpes virus glycoprotein B molecules

The molecular mechanism of entry of herpes viruses requires a multicomponent fusion system. Virus entry and cell-cell fusion of Herpes simplex virus (HSV) requires four glycoproteins: gD, gB and gH/gL. The role of gB remained elusive until recently, when the crystal structure of HSV-1 gB became available. Glycoprotein B homologues represent the most highly conserved group of herpes virus glycoproteins; however, despite the high degree of sequence and structural conservation, differences in post-translational processing are observed for different members of this virus family. Whereas gB of HSV is not proteolytically processed after oligomerization, most other gB homologues are cleaved by a cellular protease into subunits that remain linked through disulfide bonds. Proteolytic cleavage is common for activation of many other viral fusion proteins, so it remains difficult to envisage a common role for different herpes virus gB structures in the fusion mechanism. We selected bovine herpes virus type 1 (BoHV-1) and herpes simplex virus type 1 (HSV-1) as representative viruses expressing cleaved and uncleaved gBs, and have screened their amino acid sequences for regions of highly interfacial hydrophobicity. Synthetic peptides corresponding to such regions were tested for their ability to induce the fusion of large unilamellar vesicles and to inhibit herpes virus infection. These results underline that several regions of the gB protein are involved in the mechanism of membrane interaction.     

Flow instabilities in rheotens experiments: Analysis of the impacts of the process conditions through neural network modeling

Fiber spinning experiments are conducted with a capillary rheometer and a Rheotens tester on linear styrene‐isoprene‐styrene copolymer samples by varying extrusion temperature and drawdown velocity in a wide range of values, also covering the occurrence of instability phenomena. Tensile stress is measured during the experiences, and the experimental time series are then analyzed by means of a new methodology. The proposed approach is based on Neural Network modeling of the time series, coupled with Principal Component Analysis postprocessing of the results. The methodology is able to identify and quantify the effects of process condition on the dynamical behavior of the system. POLYM. ENG. SCI., 2013. © 2012 Society of Plastics Engineers     

Synthesis,size-dependent optoelectronic and charge transport properties of thieno(bis)imide end-substituted molecular semiconductors

The synthesis of two new thieno(bis)imide (TBI, N) end functionalized oligothiophene semiconductors is reported. In particular, trimer (NT3N) and pentamer (NT5N) have been synthesized and characterized. Two different synthetic approaches for their preparation were tested and compared namely conventional Stille cross coupling and direct arylation reaction via C–H activation. Theoretical calculations, optical and electrochemical characterization allowed us to assess the role of the π-conjugation extent, i.e., of the oligomer size on the optoelectronic properties of these materials. In both TBI ended compounds, due to the strong localization of the LUMO orbital on the TBI unit, the LUMO energy is almost insensitive to the oligomer size, this being crucial for the fine-tailoring of the energy and the distribution of the frontier orbitals. Surprisingly, despite its short size and contrarily to comparable TBI-free analogues, NT3N shows electron charge transport with mobility up to μ_N = 10⁻⁴ cm² V⁻¹ s⁻¹, while increasing the oligomer size to NT5N promotes ambipolar behavior and electroluminescence properties with mobility up to μ_N = 0.14 cm² V⁻¹ s⁻¹ and to μ_P = 10⁻⁵ cm² V⁻¹ s⁻¹.     

Modelling of Chillers for Energy Performance Assessment of HVAC Systems

The reliable assessment of the annual energy demand has become necessary in view of building energy performance certification. Accurate models must be used to simulate the behaviour of HVAC （heating, ventilation and air conditioning） components in real operation, usually characterized by a wide variation of building loads. In this context, this paper deals with the development and validation of an algorithm aimed at the assessment of part load performance of various kinds of controls for vapour compresion based heat pumps and chillers, in particular referring to on-off, inverter-driven and multi-stage vapour compression. The reliability of this algorithm in the calculation of seasonal performances is checked against monitoring of heat pumps and chillers operating under real conditions.