Effect of schottky barrier alteration on the low-frequency noise of InP based HEMTs

For the first time the effect of increasing the Schottky barrier's Al content of InP-based InAlAs-InGaAs HEMTs from 48 to 60% on the low-frequency (LF) drain and gate current noise is investigated. It is shown that the LF gate current noise SIG(f) for the 60% case decreases by almost three decades, while the LF drain current noise S IDS(f) stays at the same level. From small coherence values, it can be concluded that drain and gate noise sources can be treated separately which facilitates the LF noise modeling of these HEMT

Embedded macrophages induce intravascular coagulation in 3D blood vessel-on-chip

Macrophages are innate immune cells that prevent infections and help in wound healing and vascular inflammation. While these cells are natural helper cells, they also contribute to chronic diseases, e.g., by infiltrating the endothelial layer in early atherosclerosis and by promoting vascular inflammation. There is a crosstalk between inflammatory pathways and key players in thrombosis, such as platelets and endothelial cells – a phenomenon known as ‘thromboinflammation’. The role of the embedded macrophages in thromboinflammation in the context of vascular disease is incompletely understood. Blood vessels-on-chips, which are microfluidic vascular cell culture models, have been used extensively to study aspects of vascular disease, like permeability, immune cell adhesion and thrombosis. Blood perfusion assays in blood vessel-on-chip models benefit from multiple unique aspects of the models, such as control of microvessel structure and well-defined flow patterns, as well as the ability to perform live imaging. However, due to their simplified nature, blood vessels-on-chip models have not yet been used to capture the complex cellular crosstalk that is important in thromboinflammation. Using induced pluripotent stem cell-derived endothelial cells and polarized THP-1 monocytes, we have developed and systematically set up a 3D blood vessel-on-chip with embedded (lipid-laden) macrophages, which is created using sequential cell seeding in viscous finger patterned collagen hydrogels. We have set up a human whole blood perfusion assay for these 3D blood vessels-on-chip. An increased deposition of fibrin in the blood vessel-on-chip models containing lipid-laden macrophages was observed. We anticipate the future use of this advanced vascular in vitro model in drug development for early atherosclerosis or aspects of other vascular diseases

Sub-electron Charge Relaxation via 2D Hopping Conductors

We have extended Monte Carlo simulations of hopping transport in completely disordered 2D conductors to the process of external charge relaxation. In this situation, a conductor of area $L \times W$ shunts an external capacitor $C$ with initial charge $Q_i$. At low temperatures, the charge relaxation process stops at some "residual" charge value corresponding to the effective threshold of the Coulomb blockade of hopping. We have calculated the r.m.s$.$ value $Q_R$ of the residual charge for a statistical ensemble of capacitor-shunting conductors with random distribution of localized sites in space and energy and random $Q_i$, as a function of macroscopic parameters of the system. Rather unexpectedly, $Q_{R}$ has turned out to depend only on some parameter combination: $X_0 \equiv L W \nu_0 e^2/C$ for negligible Coulomb interaction and $X_{\chi} \equiv LW \kappa^2/C^{2}$ for substantial interaction. (Here $\nu_0$ is the seed density of localized states, while $\kappa$ is the dielectric constant.) For sufficiently large conductors, both functions $Q_{R}/e =F(X)$ follow the power law $F(X)=DX^{-\beta}$, but with different exponents: $\beta = 0.41 \pm 0.01$ for negligible and $\beta = 0.28 \pm 0.01$ for significant Coulomb interaction. We have been able to derive this law analytically for the former (most practical) case, and also explain the scaling (but not the exact value of the exponent) for the latter case. In conclusion, we discuss possible applications of the sub-electron charge transfer for "grounding" random background charge in single-electron devices.Comment: 12 pages, 5 figures. In addition to fixing minor typos and updating references, the discussion has been changed and expande

Chemical and mechanical influence of root canal irrigation on biofilm removal from lateral morphological features of simulated root canals, dentine discs and dentinal tubules

Aim To investigate the anti-biofilm efficacy of irrigation using a simulated root canal model, the chemical effect of irrigants against biofilms grown on dentine discs and their impact on biofilm viscoelasticity, the efficacy of the irrigants in decontaminating infected dentinal tubules and the capacity of bacteria to regrow. Methodology Biofilm removal, viscoelastic analysis of remaining biofilms and bacterial viability were evaluated using a simulated root canal model with lateral morphological features, dentine discs and a dentinal tubule model, respectively. Experiments were conducted using a two-phase irrigation protocol. Phase 1: a modified salt solution (RISA) and sodium hypochlorite (NaOCl) were used at a low flow rate to evaluate the chemical action of the irrigants. Ultrasonic activation (US) of a chemically inert solution (buffer) was used to evaluate the mechanical efficacy of irrigation. Phase 2: a final irrigation with buffer at a high flow rate was performed for all groups. Optical coherence tomography (OCT), low load compression testing (LLCT) and confocal scanning laser microscopy analysis were used in the different models. One-way analysis of variance (anova) was performed for the OCT and LLCT analysis, whilst Kruskal-Wallis and Wilcoxon ranked tests for the dentinal tubule model. Results US and high flow rate removed significantly more biofilm from the artificial lateral canal. For biofilm removal from the artificial isthmus, no significant differences were found between the groups. Within-group analysis revealed significant differences between the steps of the experiment, with the exception of NaOCl. For the dentine discs, no significant differences regarding biofilm removal and viscoelasticity were detected. In the dentinal tubule model, NaOCl exhibited the greatest anti-biofilm efficacy. Conclusions The mechanical effect of irrigation is important for biofilm removal. An extra high flow irrigation rate resulted in greater biofilm removal than US in the artificial isthmus. The mechanical effect of US seemed to be more effective when the surface contact biofilm-irrigant was small. After the irrigation procedures, the remaining biofilm could survive after a 5-day period. RISA and NaOCl seemed to alter post-treatment remaining biofilms

Time-trends in disease characteristics and comorbidities in patients with chronic hepatitis B in the period 1980–2020

Background & aims: The incidence of chronic hepatitis B (CHB) is declining due to successful implementation of vaccination programs and widespread use of antiviral therapy. We aimed to study time-trends in disease characteristics and comorbidities in newly referred CHB patients. Methods: : We collected information on hepatitis B virus (HBV) related disease characteristics (including hepatitis B e-antigen (HBeAg) status, viremia, stage of liver fibrosis and indication for treatment and/or hepatocellular carcinoma (HCC) surveillance) and presence of comorbidities in all CHB patients referred to our center from 1980 through 2020. Patient characteristics were compared according to referral date (before 2000, between 2000 and 2010 and after 2010). Results: : We identified 1515 eligible patients. Patients referred after 2010 were older (36 versus 34 years, p < 0.001), more often non-Caucasian (82.3% versus 55.0%, p < 0.001) and more frequently HBeAg negative (81.5% versus 49.8%, p < 0.001) when compared to patients referred before 2000. Adjusted for ethnicity, sex and age, patients referred after 2010 were less likely to have significant fibrosis (adjusted odds ratio [aOR]:0.178, p < 0.001) or indication for antiviral therapy (aOR:0.342, p < 0.001) but were more likely to be affected by the metabolic syndrome (aOR:1.985, p = 0.013), hepatic steatosis (aOR:1.727, p < 0.001) and metabolic dysfunction associated fatty liver disease (MAFLD) (aOR:1.438, p = 0.013). Conclusions: : The characteristics of the CHB populations are changing. Newly referred patients are older, have less active HBV related liver disease but are more likely to be co-affected by MAFLD. These findings provide guidance for adequate allocation of resources to cope with the changing characteristics of the CHB population

Sex Proportionality in Pre-clinical and Clinical Trials: An Evaluation of 22 Marketing Authorization Application Dossiers Submitted to the European Medicines Agency

This study assessed to what extent women were included in all phases of drug development; whether the clinical studies in the marketing authorization application dossiers include information per sex; and explored whether there are differences between women and men in the drugs' efficacy and safety. Data were extracted from dossiers submitted to the European Medicines Agency. Twenty-two dossiers of drugs approved between 2011 and 2015 for the treatment of various diseases were included. Female animals were included in only 9% of the pharmacodynamics studies, but female and male animals were included in all toxicology studies. Although fewer women than men were included in the clinical studies used to evaluate pharmacokinetics (PK) (29 to 40% women), all dossiers contained sex-specific PK parameter estimations. In the phase III trials, inclusion of women was proportional to disease prevalence for depression, epilepsy, thrombosis, and diabetes [participation to prevalence ratio (PPR) range: 0.91–1.04], but women were considered underrepresented for schizophrenia, hepatitis C, hypercholesterolemia, HIV, and heart failure (PPR range: 0.49-0.74). All dossiers contained sex-specific subgroup analyses of efficacy and safety. There seemed to be higher efficacy for women in one dossier and a trend toward lower efficacy in another dossier. More women had adverse events in both treatment (73.0 vs. 70.6%, p < 0.001) and placebo groups (69.5 vs. 65.5%, p < 0.001). In conclusion, women were included throughout all phases of clinical drug research, and sex-specific information was available in the evaluated dossiers. The included number of women was, however, not always proportional to disease prevalence rates