Integration of Hot Isostatic Pressing and Heat Treatment for Advanced Modified γ-TiAl TNM Alloys

The conventional processing route of TNM (Ti-Nb-Mo) alloys combines casting and Hot Isostatic Pressing (HIP) followed by forging and multiple heat treatments to establish optimum properties. This is a time-consuming and costly process. In this study we present an advanced alternative TNM alloy processing route combining HIP and heat treatments into a single process, which we refer to as IHT (integrated HIP heat treatment), applied to a modified TNM alloy with 1.5B. A Quintus HIP lab unit with a quenching module was used, achieving fast and controlled cooling, which differs from the slow cooling rates of conventional HIP units. A Ti-42.5Al-3.5Nb-1Mo-1.5B (at.%) was subjected to an integrated two HIP steps at 200 MPa, one at 1250 °C for 3 h and another at 1260 °C for 1 h, both under a protective Ar atmosphere and followed by cooling at 30 K/min down to room temperature. The results were compared against the Ti-43.5Al-3.5Nb-1Mo-0.8B (at.%) thermomechanically processed in a conventional way. Applying IHT processing to the 1.5B alloy does indeed achieve good creep strength, and the secondary creep rate of the IHT processed materials is similar to that of conventionally forged TNM alloys. Thus, the proposed advanced IHT processing route could manufacture more cost-effective TiAl components.     

Vaccination with BNT162b2 and ChAdOx1 nCoV-19 Induces Cross-Reactive Anti-RBD IgG against SARS-CoV-2 Variants including Omicron

SARS-CoV-2 variants of concern (VOCs) have caused a significant increase in infections worldwide. Despite high vaccination rates in industrialized countries, the fourth VOC, Omicron, has outpaced the Delta variant and is causing breakthrough infections in individuals with two booster vaccinations. While the magnitude of morbidity and lethality is lower in Omicron, the infection rate and global spread are rapid. Using a specific IgG multipanel-ELISA with the spike protein’s receptor-binding domain (RBD) from recombinant Alpha, Gamma, Delta, and Omicron variants, sera from health-care workers from the Medical University of Vienna were tested pre-pandemic and post-vaccination (BNT162b2; ChAdOx1 nCoV-19). The cohort was continuously monitored by SARS-CoV-2 testing and commercial nucleocapsid IgG ELISA. RBD IgG ELISA showed significantly lower reactivity against the Omicron-RBD compared to the Alpha variant in all individuals (p < 0.001). IgG levels were independent of sex, but were significantly higher in BNT162b2 recipients <45 years of age for Alpha, Gamma, and Delta (p < 0.001; p = 0.040; p = 0.004, respectively). Pre-pandemic cross-reactive anti-Omicron IgG was detected in 31 individuals and was increased 8.78-fold after vaccination, regardless of vaccine type. The low anti-RBD Omicron IgG level could explain the breakthrough infections and their presence could also contribute to a milder COVID-19 course by cross-reactivity and broadening the adaptive immunity.     

Biocompatible fluorocarbon liquid underlays for in situ extraction of isoprenoids from microbial cultures

Microbial production of heterologous metabolites is now a mature technology in many host organisms, opening new avenues for green production processes of specialty chemicals. At lab scale, petroleum-based hydrophobic bio-compatible solvents like dodecane can be used as a second phase on top of microbial cultures to act as a physical sink for heterologous hydrocarbon products like isoprenoids. However, this approach has significant drawbacks at scale due to the difficulty of handling solvents and their potential contamination with unwanted byproducts of their manufacture. We discovered that synthetic perfluorocarbon liquids (FCs), commonly used for heat transfer, can also act as physical sinks for microbially produced isoprenoid compounds. FCs are stable, inert, and are amenable to direct liquid–liquid extraction with alcohols for rapid product isolation. These liquids are more dense than water and form a lower phase to microbial cultures rather than an upper phase as with other solvents. Their ability to form an under-layer or ‘underlay’ also enables the cultivation of microbes directly at the FC–culture medium interface via gravity settling, which could open their application for filamentous or mat-forming organisms. We present comparisons of the isoprenoid extraction potential of three commercial FCs: FC-3283, FC-40, and FC-770 with engineered green microalga cultures producing patchoulol, taxadiene, casbene, or 13R(+) manoyl oxide. We demonstrate that FCs are promising alternatives to traditional solvents and open new avenues in bio-process design for microbial heterologous metabolite milking.

A novel bioprocess to capture and purify terpenoids produced by engineered microbes using 2-phase cultivation of the algae with liquid perfluorocarbons followed by liquid–liquid extraction of the terpenoids with ethanol.     

Thermally stable mesoporous tetragonal zirconia through surfactant-controlled synthesis and Si-stabilization

Thermally stable, highly mesoporous Si-stabilized ZrO₂ was prepared by sol–gel-synthesis. By utilizing the surfactant dodecylamine (DDA), large mesopores with a pore width of ∼9.4 nm are formed. Combined with an NH₃-treatment on the hydrogel, a high specific surface area of up to 225 m² g⁻¹ and pore volume up to 0.46 cm³ g⁻¹ are obtained after calcination at 973 K. The individual contributions of Si-addition, DDA surfactant and the NH₃-treatment on the resulting pore system were studied by inductively coupled plasma with optical emission spectrometry (ICP-OES), X-ray diffraction (XRD), N₂ sorption, and transmission electron microscopy (TEM). Electron tomography was applied to visualize and investigate the mesopore network in 3D space. While Si prevents the growth of ZrO₂ crystallites and stabilizes the t-ZrO₂ phase, DDA generates a homogeneous mesopore network within the zirconia. The NH₃-treatment unblocks inaccessible pores, thereby increasing specific surface area and pore volume while retaining the pore width distribution.

Schematic representation of ZrO₂ crystallites; (a) monoclinic ZrO₂, (b) tetragonal ZrO₂ following Si-stabilization, (c) mesoporous t-ZrO₂ following Si-stabilization and use of surfactant dodecylamine.     

Using measures of reading time regularity (RTR) to quantify eye movement dynamics,and how they are shaped by linguistic information

In this article, we present the concept of reading time regularity (RTR) as a measure to capture reading process dynamics. The first study is concerned with examining one of the assumptions of RTR, namely, that process measures of reading, such as eye movement fluctuations and fixation durations, exhibit higher regularity when contingent on sequentially structured information, such as texts. To test this, eye movements of 26 German native speakers were recorded during reading-unrelated and reading-related tasks. To analyze the data, we used recurrence quantification analysis and sample entropy analysis to quantify the degree of temporal structure in time series of gaze steps and fixation durations. The results showed that eye movements become more regular in reading compared to nonreading conditions. These effects were most prominent when calculated on the basis of gaze step data. In a second study, eye movements of 27 native speakers of German were recorded for five conditions with increasing linguistic information. The results replicate the findings of the first study, verifying that these effects are not due to mere differences in task instructions between conditions. Implications for the concept of RTR and for future studies using these metrics in reading research are discussed.     

Use of Fertility Preservation Among a Cohort of Transgirls in the Netherlands

Purpose

The primary aims of the study are to examine the rate of attempted fertility preservation (FP) among a Dutch cohort of transgirls who started gonadotropin-releasing hormone analog treatment and the reasons why adolescents did or did not choose to attempt FP.

High‐dimensional propensity score algorithm in comparative effectiveness research with time‐varying interventions

The high‐dimensional propensity score (hdPS) algorithm was proposed for automation of confounding adjustment in problems involving large healthcare databases. It has been evaluated in comparative effectiveness research (CER) with point treatments to handle baseline confounding through matching or covariance adjustment on the hdPS. In observational studies with time‐varying interventions, such hdPS approaches are often inadequate to handle time‐dependent confounding and selection bias. Inverse probability weighting (IPW) estimation to fit marginal structural models can adequately handle these biases under the fundamental assumption of no unmeasured confounders. Upholding of this assumption relies on the selection of an adequate set of covariates for bias adjustment. We describe the application and performance of the hdPS algorithm to improve covariate selection in CER with time‐varying interventions based on IPW estimation and explore stabilization of the resulting estimates using Super Learning. The evaluation is based on both the analysis of electronic health records data in a real‐world CER study of adults with type 2 diabetes and a simulation study. This report (i) establishes the feasibility of IPW estimation with the hdPS algorithm based on large electronic health records databases, (ii) demonstrates little impact on inferences when supplementing the set of expert‐selected covariates using the hdPS algorithm in a setting with extensive background knowledge, (iii) supports the application of the hdPS algorithm in discovery settings with little background knowledge or limited data availability, and (iv) motivates the application of Super Learning to stabilize effect estimates based on the hdPS algorithm. Copyright © 2014 John Wiley & Sons, Ltd.     

Evolution of thrombolytic therapy in patients with HeartWare ventricular assist device thrombosis: a single-institutional experience

Open in a separate window OBJECTIVESPump thrombosis remains a major challenge in heart failure patients with left ventricular HeartWare assist device. Current International Society for Heart and Lung Transplantation recommendations favour surgical pump exchange over lysis because safety and efficacy of lysis has been controversially reported. This study summarizes our experience on our HeartWare thrombosis prevention strategy as well as thrombolysis through implementation of our institutional standardized HeartWare assist device protocol.METHODSOutcomes of all HeartWare thrombosis patients admitted between 2010 and 2020 were analysed. Thrombolysis therapy using tissue plasminogen activator was used as the first-line therapy in this study and thrombolysis therapy efficacy was defined as freedom from stroke, bleeding, recurrent HeartWare assist device thrombosis or surgical device exchange within 30 days after lysis application.RESULTSA total of 507 patients have been included in this study and 66 patients (13%) collectively developed a first HeartWare-thrombosis after a median of 12 months (8–22 months) after HeartWare implantation. Forty patients were treated with unstandardized lysis, of whom 7 patients had thrombolysis associated complications, such as incomplete thrombus resolution requiring surgical pump exchange in 4 patients, but also intracranial haemorrhage occurring in 3 patients. Three patients died in the non-protocol group. Eight device thrombosis patients were treated according to our protocol, showing no lysis-associated complication.CONCLUSIONSDespite current recommendations, preferring surgical HeartWare pump exchange in thrombosis, thrombolysis therapy for first HeartWare thrombosis can be safe and effective in a standardized protocol setting, including anticoagulation adjustment and intensified blood pressure control management.     

Neural processing associated with cognitive empathy in pedophilia and child sexual offending

Behavioral studies found evidence for superior cognitive empathy (CE) in pedophilic men without a history of child sexual offending (P − CSO) compared to pedophilic men with a history of child sexual offending (P + CSO). Functional magnetic resonance imaging (fMRI) studies also point to differences between P − CSO and P + CSO. Neural processing associated with CE has not yet been investigated. Therefore, the present study aimed to explore the neural correlates of CE in subjects with pedophilia with (P + CSO) and without (P − CSO) child sexual offending. 15 P + CSO, 15 P − CSO and 24 teleiophilic male controls (TC) performed a CE task during fMRI. We observed reduced activation in the left precuneus (Pcu) and increased activation in the left anterior cingulate cortex (ACC) in P − CSO compared to P + CSO. P − CSO also showed stronger connectivity between these regions, which might reflect a top-down modulation of the Pcu by the ACC toward an increased self-focused emotional reaction in social situations. There was also evidence for increased right superior temporal gyrus activation in P − CSO that might constitute a potentially compensatory recruitment due to the dampened Pcu activation. These findings provide first evidence for altered neural processing of CE in P − CSO and underline the importance of addressing CE in pedophilia and CSO in order to uncover processes relevant to effective prevention of child sexual abuse.     

Fulminant Adenoviral-Induced Hepatitis in Immunosuppressed Patients

Human adenovirus (HAdV) can often lead to fulminant hepatitis in immunocompromised patients, mostly after reactivation of HAdV. Different risk factors, e.g., transplantation and chemotherapy, increase the risk of developing a HAdV hepatitis. We retrospectively analyzed three patients who showed the characteristics of a HAdV hepatitis observed in disseminated disease. In addition to PCR, diagnosis could be proven by pathology, CT scan, and markedly elevated transaminases. All patients had a hemato-oncologic underlying disease. Two had received a stem-cell transplant, and one was under chemotherapy including rituximab. Despite therapy with cidofovir, all patients died. As the incidence of HAdV hepatitis is low, diagnosis may be easily overlooked. No treatment approaches have yet been established. HAdV hepatitis should be considered as a differential diagnosis, especially when risk factors are present. To avoid dissemination, treatment should be initiated as soon as possible.