Continuous processing gains importance in the fine chemical and pharmaceutical industries where crystallization is an important downstream operation. Seeded cooling crystallization of the L-alanine/water system was investigated under similar conditions, i.e., temperature interval, cooling rate, and seed material, both in a stirred batch vessel and in a continuous plug flow crystallizer in the coiled flow inverter (CFI) design with horizontal helical tube coils (ID = 4 mm) and frequent 90°bends of the coils. Short-cut calculations based on characteristic time scales and the Damkoḧler number allow for comparing the batch and continuous crystallization processes. The experimental results reveal crystal growth and growth rate dispersion to be dominating on the product crystal size distribution (CSD). However, at low flow rates of approximately 31 g min −1 , a moving sediment flow of the slurry was present in the CFI crystallizer, resulting in further size dispersion effects. Elevated flow rates of approximately 40 g min −1 resulted in a more homogeneous suspension flow and a product CSD comparable to batch quality. Simulation studies based on a population balance equation model strengthen the hypothesis of the solid phase residence time distribution (RTD S ) to be more spread in the moving sediment flow regime, leading to a wider product CSD.

Numerically challenging, comprehensive benchmark cases are of great importance for researchers in the field of CFD. Numerical benchmark cases offer researchers frameworks to quantitatively explore limits of the computational tools and to validate them. Therefore, we focus on simulation of numerically challenging benchmark tests, laminar and transient 3D flows around a cylinder, and aim to establish a new comprehensive benchmark case by doing direct numerical simulations with three distinct CFD software packages. Although the underlying benchmark problems have been defined firstly in 1996, the first case which was a steady simulation of flow around a cylinder at Re = 20 could be accurately solved first in 2002 by John. Moreover, there is no precisely determined results for non-stationary case, the simulation of transient flow with time varying Reynolds number. The benchmark problems are studied with three CFD software packages, OpenFOAM, Ansys-CFX and FeatFlow which employ different numerical approaches to the discretization of the incompressible Navier-Stokes equations, namely finite volume method, element based finite volume method and finite element method respectively. The first benchmark test is considered as the "necessary condition" for the software tools, then they are compared according to their accuracy and performance in the second benchmark test. All the software tools successfully pass the first test and show well agreeing results for the second case such that the benchmark result was precisely determined. As a main result, the CFD software package with high order finite element approximation has been found to be computationally more efficient and accurate than the ones adopting low order space discretization methods.

Even in the era of PCR‐based monitoring, prophylaxis, and preemptive therapy, Cytomegalovirus (CMV) viremia remains a relevant cause of non‐relapse mortality (NRM) after allogeneic hematopoietic cell transplantation (HCT). However, studies using binary analysis (presence/absence of CMV) reported contradicting data for NRM, overall survival and leukemia relapse. Here, we analyzed CMV replication kinetics in 11 508 whole blood PCR samples of 705 patients with HCT between 2012 and 2017. Using two independent models based on CMV peak titers and on the time point of first CMV reactivation, we stratified patients into risk cohorts. Each cohort had distinct cellular immune reconstitution profiles and differentiated for relevant clinical outcomes. Patients with high CMV peak titers had significantly reduced overall survival (HR 2.13, 95% CI 1.53–2.96; p < .0001), due to high NRM. Early impaired T cell reconstitution was a risk factor for high CMV peak titers, however relevant CMV viremia also related to boosted T cell reconstitution. Importantly, intermediate CMV peak titers associated with a significantly reduced relapse probability (HR 0.53, 95% CI 0.31–0.91; p = .022). In short, CMV kinetics models distinguished relevant clinical outcome cohorts beyond the R+ serostatus with distinct immune reconstitution patterns and resolve in part contradicting results of previous studies exclusively focused on the presence or absence of CMV.

The implementation of traditional sensors is a drawback when investigating mass transfer phenomena within microstructured devices, since they disturb the flow and reactor characteristics. An Arduino based slider setup is developed, which is equipped with a computer-vision system to track gas-liquid slug flow. This setup is combined with an optical analytical method allowing to compare experimental results against CFD simulations and investigate the entire lifetime of a single liquid slug with high spatial and temporal resolution. Volumetric mass transfer coefficients are measured and compared with data from literature and the mass transfer contribution of the liquid film is discussed. K E Y W O R D SArduino based microcontroller, gas-liquid capillary flow, local mass transfer, noninvasive measurement, numerical simulation

No abstract

Steroid-resistant acute graft-versus-host disease (GVHD) of the gastrointestinal tract associates with important morbidity and mortality. While high-dose steroids are the established first-line therapy in GVHD, no second-line therapy is generally accepted. In this analysis of 65 consecutive patients with severe, steroid-resistant, intestinal GVHD (92% stage 4), additional ileostomy surgery significantly reduced overall mortality (hazard ratio 0.54; 95% confidence interval, 0.36-0.81; p = 0.003) compared to conventional GVHD therapy. Median overall survival was 16 months in the ileostomy cohort compared to 4 months in the conventional therapy cohort. In the ileostomy cohort, both infectious-and GVHD-associated mortality were reduced (40% versus 77%). Significantly declined fecal volumes (p = 0.001) after surgery provide evidence of intestinal adaptation following ileostomy. Correlative studies indicated ileostomy-induced immune-modulation with a > 50% decrease of activated T cells (p = 0.04) and an increase in regulatory T cells. The observed alterations of the patients' gut microbiota may also contribute to ileostomy's therapeutic effect. These data show that ileostomy induced significant clinical responses in patients with steroidresistant GVHD along with a reduction of pro-inflammatory immune cells and changes of the intestinal microbiota. Ileostomy is a treatment option for steroid-resistant acute GVHD of the gastrointestinal tract that needs further validation in a prospective clinical trial.

Prophylaxis of graft‐versus‐host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HCT) remains challenging. Because prospective randomized trials of in‐vivo T cell depletion using anti‐T‐lymphocyte globulin (ATLG) in addition to a calcineurin inhibitor and methotrexate (MTX) led to conflicting outcome results, we evaluated the impact of ATLG on clinical outcome, lymphocyte‐ and immune reconstitution survival models. In total, 1500 consecutive patients with hematologic malignancies received matched unrelated donor (MUD) HCT with cyclosporin and MTX (N = 723, 48%) or with additional ATLG (N = 777, 52%). In the ATLG cohort, grades III‐IV acute (12% vs 23%) and extensive chronic GVHD (18% vs 34%) incidences were significantly reduced (P < .0001). Nonrelapse mortality (27% vs 45%) and relapse (30% vs 22%) differed also significantly. Event‐free and overall survival estimates at 10 years were 44% and 51% with ATLG and 33% and 35% without ATLG (P < .002 and <.0001). A dose‐dependent ATLG effect on lymphocyte‐ and neutrophil reconstitution was observed. At ATLG exposure, lymphocyte counts and survival associated through a logarithmically increasing function. In this survival model, the lymphocyte count optimum range at exposure was between 0.4 and 1.45/nL (P = .001). This study supports additional ATLG immune prophylaxis and is the first study to associate optimal lymphocyte counts with survival after MUD‐HCT.

No abstract