Enhanced Economic Evaluation – Approach for a Holistic Evaluation of Factory Planning Variants

The building of a factory can be a strategic investment owing to its long service life. An evaluation that only focuses, for example, on payments for the building, the technical equipment of the factory, and the personnel for the enterprise is – considering the complexity of the system factory – not sufficient for this long-term view. The success of an investment is secured, among other things, by the attainment of nonmonetary goals, too, like transformability. Such aspects are not considered in traditional investment calculations like the net present value method. This paper closes this gap with the enhanced economic evaluation (EWR) for factory planning. The procedure and the first results of an application in a project are presented

Variability in Blood Pressure Assessment in Patients Supported with the HeartMate 3TM

Targeted blood pressure (BP) control is a goal of left ventricular assist device medical management, but the interpretation of values obtained from noninvasive instruments is challenging. In the MOMENTUM 3 Continued Access Protocol, paired BP values in HeartMate 3 (HM3) patients were compared from arterial (A)-line and Doppler opening pressure (DOP) (319 readings in 261 patients) and A-line and automated cuff (281 readings in 247 patients). Pearson (R) correlations between A-line mean arterial (MAP) and systolic blood pressures (SBP) were compared with DOP and cuff measures according to the presence (\u3e1 pulse in 5 seconds) or absence of a palpable radial pulse. There were only moderate correlations between A-line and noninvasive measurements of SBP (DOP R = 0.58; cuff R = 0.47) and MAP (DOP R = 0.48; cuff R = 0.37). DOP accuracy for MAP estimation, defined as the % of readings within ± 10 mmHg of A-line MAP, decreased from 80% to 33% for DOP ≤ 90 vs. \u3e90 mmHg, and precision also diminished (mean absolute difference [MAD] increased from 6.3 ± 5.6 to 16.1 ± 11.4 mmHg). Across pulse pressures, cuff MAPs were within ±10 mmHg of A-line 62.9%-68.8% of measures and MADs were negligible. The presence of a palpable pulse reduced the accuracy and precision of the DOP-MAP estimation but did not impact cuff-MAP accuracy or precision. In summary, DOP may overestimate MAP in some patients on HM3 support. Simultaneous use of DOP and automated cuff and radial pulse may be needed to guide antihypertensive medication titration in outpatients on HM3 support

The Thioesterase Domain in Glycopeptide Antibiotic Biosynthesis Is Selective for Cross-Linked Aglycones

The biosynthesis of the glycopeptide antibiotics (GPAs)which include teicoplanin and vancomycinis a complex enzymatic process relying on the interplay of nonribosomal peptide synthesis and a cytochrome P450-mediated cyclization cascade. This unique cyclization cascade generates the highly cross-linked state of these nonribosomal peptides, which is crucial for their antimicrobial activity. Given that these essential oxidative transformations occur while the peptide remains bound to the terminal module of the nonribosomal peptide synthetase (NRPS) machinery, it is important to assess the selectivity of the terminal thioesterase (TE) domain and how this domain contributes to the maintenance of an efficient biosynthetic pathway while at the same time ensuring GPA maturation is completed. In this study, we report the <i>in vitro</i> characterization of the thioesterase domain from teicoplanin biosynthesis, the first GPA thioesterase to be characterized. Our results show that the activity of this TE domain relies on the presence of an unusual extended N-terminal linker region that appears to be unique to the NRPS machineries found in GPA biosynthesis. In addition, we show that the activity of this domain against carrier protein bound substrates is dramatically enhanced for mature GPA aglycones as opposed to linear peptides and partially cyclized intermediates. These results demonstrate how the interplay between NRPS and P450s during late stage GPA biosynthesis is not only maintained but also leads to the efficient production of mature GPA aglycones. Thus, GPA TE domains represent another impressive example of the ability of TE domains to act as logic gates during NRPS biosynthesis, ensuring that essential late-stage peptide modifications are completed before catalyzing the release of the mature, bioactive peptide product

Changeable manufacturing - classification, design and operation

Flexibility and changeability are key enablers for meeting the challenges of a global market. The paper first describes the main change drivers and takes then a deeper look at how changeability in a previous manufacturing enterprise can be classified and operationalized. The next sections are devoted to changeability in reconfigurable previous manufacturing systems, assembly systems and factories including buildings and infrastructure. New challenges, perspectives and approaches for process plan reconfiguration as well as for Production Planning and Control are discussed. Finally, the evaluation and economic justification of changeability are addressed and a control loop of changeability is presented

Influence of donor cocaine use on outcome after cardiac transplantation: analysis of the United Network for Organ Sharing Thoracic Registry

Heart transplantation from donors with a history of cocaine abuse remains controversial. Therefore, we examined the consequence of donor cocaine-use history on all-cause mortality and the development of coronary artery disease after heart transplantation. Using the United Network for Organ Sharing Thoracic Registry we identified 9,217 first-time heart-only adult transplant recipients between January 1999 and December 2003, and then divided this cohort into sub-groups based on the reported history of donor cocaine use. Multivariate analysis revealed no difference in mortality or development of coronary artery disease at 1 and 5 years between transplant recipients who received an organ from donors with a history of cocaine use when compared with donors having no history of cocaine use