Restoring efficiency, removing sound

Increased renewable power generation, HVDC interconnections and geomagnetic effects all bias the AC grid with small direct currents which leads to two negative effects on transformers (theory of half-cycle saturation) increased noise and increased no-load losses. A unique solution is the DC compensation system, which is an add-on to a transformer which eliminates the DC effects. Furthermore, there are dedicated steps available, from pure detection of the problem, preparation of the transformer and measurement, all the way up to a full compensation system

Restoring efficiency, removing sound

Increased renewable power generation, HVDC interconnections and geomagnetic effects all bias the AC grid with small direct currents which leads to two negative effects on transformers (theory of half-cycle saturation) increased noise and increased no-load losses. A unique solution is the DC compensation system, which is an add-on to a transformer which eliminates the DC effects. Furthermore, there are dedicated steps available, from pure detection of the problem, preparation of the transformer and measurement, all the way up to a full compensation system

The Challenge of Human Mesenchymal Stromal Cell Expansion: Current and Prospective Answers

In the field of cell therapy, allogenic human mesenchymal stromal cells (hMSCs) are often used in clinical trials, creating a demand for cell mass production using efficient dynamic bioreactor systems. As an advanced therapy medicinal product (ATMP), such cells should meet certain special requirements, including product specifications requiring a production process compatible with good manufacturing practice (GMP). The development of processes in which the cells are the product therefore remains a significant challenge. This chapter describes the requirements at different steps in the upstream and downstream phases of such dynamic processes. Potential solutions are presented and future prospects are discussed, including the selection of media and carriers for the strictly adherent growing cells, allowing efficient cell adhesion and detachment. Strategies for dynamic cultivation in bioreactors are described in detail for fixed‐bed and stirred‐tank reactors based on GMP requirements and the integration of process analytical technology (PAT). Following cell harvest, separation and purification, the formulation and storage of the product are also described. Finally, the chapter covers important cell quality characteristics necessary for the approval of ATMPs

DIRECT CURRENT COMPENSATION – FIELD EXPERIENCE UNDER SERVICE CONDITIONS

Modern grain oriented core steel used in power transformers has a very high magnetic conductivity. This advanced material makes the transformer susceptible even for small direct current (DC) in the power grid. Already minor DC increases the no-load noise and no-load losses of the transformer considerably. This effect is known as half-cycle saturation. In order to overcome these parasitic DC an active compensation method called “DC compensation” (DCC) was recently developed by Siemens [1]. The question about the origin of the DC is not fully answered yet. However the following sources have been already identified: power electronics, renewable power generation (wind, solar), HVDC transmission lines and DC operated railroad or subway systems. The parasitic direct currents can flow over the power lines to ground or asymmetrically in the power line phases only. In this paper field data, a four-month DC load profile, of single-phase core type transformers, equipped with active DC compensation, are shown. The discussed unit, a bank of three single-phase autotransformers, is in service mainly exposed to DC flowing from the overhead lines through the windings to the common neutral. DC magnitude varies from 0.05 A to about 0.2 A DC per phase throughout the day. From factory tests we know that only 0.2 A DC causes a noise increase of 5.6 dB(A) compared to the noise level without any DC compensation. This might cause troubles at the substation when noise has to be below a guaranteed level. Data analysis of the field data shows that the DC throughout the day follows a clear profile with its highest level during midnight and lunch time. This might indicate a correlation to the load and / or switching operations in the grid to adjust to the actual needed load. However, the DC compensation equipment fully eliminates the direct flux in the core and thus the DC caused increase in noise

Manufacturing of Human Umbilical Cord Mesenchymal Stromal Cells on Microcarriers in a Dynamic System for Clinical Use

Citation: Florian Petry, J. Robert Smith, Jasmin Leber, Denise Salzig, Peter Czermak, and Mark L. Weiss, “Manufacturing of Human Umbilical Cord Mesenchymal Stromal Cells on Microcarriers in a Dynamic System for Clinical Use,” Stem Cells International, vol. 2016, Article ID 4834616, 12 pages, 2016. doi:10.1155/2016/4834616The great properties of human mesenchymal stromal cells (hMSCs) make these cells an important tool in regenerative medicine. Because of the limitations of hMSCs derived from the bone marrow during isolation and expansion, hMSCs derived from the umbilical cord stroma are a great alternative to overcome these issues. For a large expansion of these cells, we performed a process transfer from static culture to a dynamic system. For this reason, a microcarrier selection out of five microcarrier types was made to achieve a suitable growth surface for the cells. The growth characteristics and metabolite consumption and production were used to compare the cells growth in 12-well plate and spinner flask. The goal to determine relevant process parameters to transfer the expansion process into a stirred tank bioreactor was achieved

Attachment, Growth, and Detachment of Human Mesenchymal Stem Cells in a Chemically Defined Medium

Citation: Denise Salzig, Jasmin Leber, Katharina Merkewitz, Michaela C. Lange, Natascha Köster, and Peter Czermak, “Attachment, Growth, and Detachment of Human Mesenchymal Stem Cells in a Chemically Defined Medium,” Stem Cells International, vol. 2016, Article ID 5246584, 10 pages, 2016. doi:10.1155/2016/5246584The manufacture of human mesenchymal stem cells (hMSCs) for clinical applications requires an appropriate growth surface and an optimized, preferably chemically defined medium (CDM) for expansion. We investigated a new protein/peptide-free CDM that supports the adhesion, growth, and detachment of an immortalized hMSC line (hMSC-TERT) as well as primary cells derived from bone marrow (bm-hMSCs) and adipose tissue (ad-hMSCs). We observed the rapid attachment and spreading of hMSC-TERT cells and ad-hMSCs in CDM concomitant with the expression of integrin and actin fibers. Cell spreading was promoted by coating the growth surface with collagen type IV and fibronectin. The growth of hMSC-TERT cells was similar in CDM and serum-containing medium whereas the lag phase of bm-hMSCs was prolonged in CDM. FGF-2 or surface coating with collagen type IV promoted the growth of bm-hMSCs, but laminin had no effect. All three cell types retained their trilineage differentiation capability in CDM and were detached by several enzymes (but not collagenase in the case of hMSC-TERT cells). The medium and coating did not affect detachment efficiency but influenced cell survival after detachment. CDM combined with cell-specific surface coatings and/or FGF-2 supplements is therefore as effective as serum-containing medium for the manufacture of different hMSC types

Consensus recommendations for mrd testing in adult b-cell acute lymphoblastic leukemia in ontario

Measurable (minimal) residual disease (MRD) is an established, key prognostic factor in adult B-cell acute lymphoblastic leukemia (B-ALL), and testing for MRD is known to be an important tool to help guide treatment decisions. The clinical value of MRD testing depends on the accuracy and reliability of results. Currently, there are no Canadian provincial or national guidelines for MRD testing in adult B-ALL, and consistent with the absence of such guidelines, there is no uniform Ontario MRD testing consensus. Moreover, there is great variability in Ontario in MRD testing with respect to where, when, and by which technique, MRD testing is performed, as well as in how the results are interpreted. To address these deficiencies, an expert multidisciplinary working group was convened to define consensus recommendations for improving the provision of such testing. The expert panel recommends that MRD testing should be implemented in a centralized manner to ensure expertise and accuracy in testing for this low volume indication, thereby to provide accurate, reliable results to clinicians and patients. All adult patients with B-ALL should receive MRD testing after induction chemotherapy. Philadelphia chromosome (Ph)-positive patients should have ongoing monitoring of MRD during treatment and thereafter, while samples from Ph-negative B-ALL patients should be tested at least once later during treatment, ideally at 12 to 16 weeks after treatment initiation. In Ph-negative adult B-ALL patients, standardized, ideally centralized, protocols must be used for MRD testing, including both flow cytometry and immunoglobulin (Ig) heavy chain and T-cell receptor (TCR) gene rearrangement analysis. For Ph-positive B-ALL patients, MRD testing using a standardized protocol for reverse transcription real-time quantitative PCR (RT-qPCR) for the BCR-ABL1 gene fusion transcript is recommended, with Ig/TCR gene rearrangement analysis done in parallel likely providing additional clinical information

Secondary Sclerosing Cholangitis in Critically Ill Patients Alters the Gut–Liver Axis: A Case Control Study

Secondary sclerosing cholangitis in critically ill patients (SC-CIP) occurs after long-term intensive care treatment. This study aimed to assess the gut–liver axis in SC-CIP. Stool microbiome composition, gut permeability, bacterial translocation and serum bile acid profiles of 18 SC-CIP patients compared to 11 patients after critical illness without liver disease (CIP controls), 21 patients with cirrhosis and 21 healthy controls were studied. 16S rDNA was isolated from stool and sequenced using the Illumina technique. Diamine oxidase, zonulin, soluble CD14 (sCD14) and lipopolysaccharide binding protein were measured in serum and calprotectin in stool. Serum bile acids were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS). Reduced microbiome alpha diversity and altered beta diversity were seen in SC-CIP, CIP controls and cirrhosis compared to healthy controls. SC-CIP patients showed a shift towards pathogenic taxa and an oralization. SC-CIP, CIP controls and cirrhotic patients presented with impaired gut permeability, and biomarkers of bacterial translocation were increased in SC-CIP and cirrhosis. Total serum bile acids were elevated in SC-CIP and cirrhosis and the bile acid profile was altered in SC-CIP, CIP controls and cirrhosis. In conclusions, observed alterations of the gut–liver axis in SC-CIP cannot solely be attributed to liver disease, but may also be secondary to long-term intensive care treatment

Evaluating the impact of post-trial implementation of RHIVA nurse-led HIV screening on HIV testing, diagnosis and earlier diagnosis in general practice in London, UK.

BACKGROUND: UK and European guidelines recommend HIV testing in general practice. We report on the implementation of the Rapid HIV Assessment trial (RHIVA2) promoting HIV screening in general practice into routine care. METHODS: Interrupted time-series, difference-in-difference analysis and Pearson-correlation on three cohorts comprising 42 general practices in City & Hackney (London, UK); covering three periods: pre-trial (2009-2010), trial (2010-2012) and implementation (2012-2014). Cohorts comprised practices receiving: "trial intervention" only (n = 19), "implementation intervention" only (n = 13); and neither ("comparator") (n = 10). Primary outcomes were HIV testing and diagnosis rates per 1000 people and CD4 at diagnosis. FINDINGS: Overall, 55,443 people were tested (including 38,326 among these cohorts), and 101 people were newly diagnosed HIV positive (including 65 among these cohorts) including 74 (73%) heterosexuals and 69 (68%) people of black African/Caribbean background; with mean CD4 count at diagnosis 357 (SD=237). Among implementation intervention practices, testing rate increased by 85% (from 1·798 (95%CI=(1·657,1·938) at baseline to 3·081 (95%CI=(2·865,3·306); p = 0·0000), diagnosis rate increased by 34% (from 0·0026 (95%CI=(0·0004,0·0037)) to 0·0035 (95%CI=(0·0007,0·0062); p = 0·736), and mean CD4 count at diagnosis increased by 55% (from 273 (SD=372) to 425 (SD=274) cells per μL; p = 0·433). Implementation intervention and trial intervention practices achieved similar testing rates (3·764 vs. 3·081; 6% difference; 95% CI=(-5%,18%); p = 0·358), diagnosis rates (0·0035 vs. 0·0081; -13% difference; 95%CI=(-77%,244%; p = 0·837), and mean CD4 count (425 (SD=274) vs. 351 (SD=257); 69% increase; 95% CI=(-61%,249%); p = 0·359). HIV testing was positively correlated with diagnosis (r = 0·114 (95% CI=[0·074,0·163])), and diagnosis with CD4 count at diagnosis (r = 0·011 (95% CI=[-0·177,0·218])). INTERPRETATION: Implementation of the RHIVA programme promoting nurse-led HIV screening into routine practice in inner-city practices with high HIV prevalence increased HIV testing, and may be associated with increased and earlier diagnosis. HIV screening in primary care should be considered a key strategy to reduce undiagnosed infection particularly among high risk persons not attending sexual health services. FUNDING: National Institute for Health Research ARC North Thames, and Barts and The London School of Medicine and Dentistry

Comparison of automated interval measurements by widely used algorithms in digital electrocardiographs

Background: Automated measurements of electrocardiographic (ECG) intervals by current-generation digital electrocardiographs are critical to computer-based ECG diagnostic statements, to serial comparison of ECGs, and to epidemiological studies of ECG findings in populations. A previous study demonstrated generally small but often significant systematic differences among 4 algorithms widely used for automated ECG in the United States and that measurement differences could be related to the degree of abnormality of the underlying tracing. Since that publication, some algorithms have been adjusted, whereas other large manufacturers of automated ECGs have asked to participate in an extension of this comparison. Methods: Seven widely used automated algorithms for computer-based interpretation participated in this blinded study of 800 digitized ECGs provided by the Cardiac Safety Research Consortium. All tracings were different from the study of 4 algorithms reported in 2014, and the selected population was heavily weighted toward groups with known effects on the QT interval: included were 200 normal subjects, 200 normal subjects receiving moxifloxacin as part of an active control arm of thorough QT studies, 200 subjects with genetically proved long QT syndrome type 1 (LQT1), and 200 subjects with genetically proved long QT syndrome Type 2 (LQT2). Results: For the entire population of 800 subjects, pairwise differences between algorithms for each mean interval value were clinically small, even where statistically significant, ranging from 0.2 to 3.6 milliseconds for the PR interval, 0.1 to 8.1 milliseconds for QRS duration, and 0.1 to 9.3 milliseconds for QT interval. The mean value of all paired differences among algorithms was higher in the long QT groups than in normals for both QRS duration and QT intervals. Differences in mean QRS duration ranged from 0.2 to 13.3 milliseconds in the LQT1 subjects and from 0.2 to 11.0 milliseconds in the LQT2 subjects. Differences in measured QT duration (not corrected for heart rate) ranged from 0.2 to 10.5 milliseconds in the LQT1 subjects and from 0.9 to 12.8 milliseconds in the LQT2 subjects. Conclusions: Among current-generation computer-based electrocardiographs, clinically small but statistically significant differences exist between ECG interval measurements by individual algorithms. Measurement differences between algorithms for QRS duration and for QT interval are larger in long QT interval subjects than in normal subjects. Comparisons of population study norms should be aware of small systematic differences in interval measurements due to different algorithm methodologies, within-individual interval measurement comparisons should use comparable methods, and further attempts to harmonize interval measurement methodologies are warranted