IT-Management Gunnar Auth; Ulrike Baumöl; Wolfgang Bremer ...
06/2018
eBook
In den 15 Beiträgen dieses Buches erhalten Sie praktisches Fachwissen zu den bedeutendsten Themen des heutigen IT-Managements. Der Einsatz von Informationstechnologien (IT) entscheidet mehr denn je ...die Art und Weise, wie Unternehmen Geld verdienen. Dabei ergeben sich herausragende Geschäfts- und Innovationspotenziale für Unternehmen. Doch diese positiven Wirkungen ergeben sich nicht automatisch, sondern erfordern ein adäquates Management des IT-Einsatzes. Bei dieser Aufgabe stoßen jedoch viele der bisher eingesetzten Methoden und Vorgehensweisen des IT-Managements an ihre Grenzen. Denn die Rahmenbedingungen haben sich in den letzten Jahren signifi kant geändert: die Komplexität und Dynamik nehmen deutlich zu, gleichzeitig werden die Innovationszyklen in der IT immer kürzer. Für das Management der IT sind unter diesen veränderten Rahmenbedingungen neue Denkmuster und Lösungsansätze erforderlich. Erst damit können Chief Information Officer (CIO) die Herausforderungen der heutigen Zeit bewältigen und gleichzeitig die entscheidende Grundlage für eine differenzierende und wertschaffende Nutzung von IT schaffen. Bei den Autoren dieses Buches handelt es sich um 24 erfahrene Experten aus dem IT-Management. Dr. Michael Langist als Führungskraft bei einem der größten IT-Dienstleistungsunternehmen Europas tätig. Zudem ist er Lehrbeauftragter für Projekt- und IT-Management sowie Herausgeber von mehreren Fachbüchern.
Activating BRAF mutations, in particular V600E/K, drive many cancers and are considered mutually exclusive with mutant RAS, whereas inactivating BRAF mutations in the D(594)F(595)G(596) motif ...cooperate with RAS via paradoxical MEK/ERK activation. Due to the increasing use of comprehensive tumor genomic profiling, many non-V600 BRAF mutations are being detected whose functional consequences and therapeutic actionability are often unknown. We investigated an atypical BRAF mutation, F595L, which was identified along with mutant HRAS in histiocytic sarcoma and also occurs in epithelial cancers, melanoma and neuroblastoma, and determined its interaction with mutant RAS. Unlike other DFG motif mutants, BRAF(F595L) is a gain-of-function variant with intermediate activity that does not act paradoxically, but nevertheless cooperates with mutant RAS to promote oncogenic signaling, which is efficiently blocked by pan-RAF and MEK inhibitors. Mutation data from patients and cell lines show that BRAF(F595L), as well as other intermediate-activity BRAF mutations, frequently coincide with mutant RAS in various cancers. These data define a distinct class of activating BRAF mutations, extend the spectrum of patients with systemic histiocytoses and other malignancies who are candidates for therapeutic blockade of the RAF-MEK-ERK pathway and underscore the value of comprehensive genomic testing for uncovering the vulnerabilities of individual tumors.
The inclusion of less invasive surfactant administration (LISA) in the care of preterm infants has been found to be beneficial for respiratory outcomes. Recently, the OPTIMIST trial found higher ...mortality rates in the subgroup of infants born at 25 to 26 weeks' gestational age (GA) who received surfactant treatment while spontaneously breathing.
To analyze outcomes among LISA-exposed, highly vulnerable babies born at less than 27 weeks' GA within the large-scale observational cohort of the German Neonatal Network.
In this cohort study of data from 68 tertiary level neonatal intensive care units in Germany of infants born between 22 weeks 0 days to 26 weeks 6 days of gestation between April 1, 2009, and December 31, 2020, short-term outcomes among infants receiving LISA vs infants not receiving LISA were compared.
Use of LISA within the first 72 hours of life.
The main outcomes were rates of LISA use, use of mechanical ventilation within the first 72 hours (considered failure of LISA), and association of LISA with outcomes, including death from all causes, bronchopulmonary dysplasia (BPD), death and BPD combined, pneumothorax, retinopathy of prematurity, intracerebral hemorrhage, and periventricular leukomalacia. To address potential confounding factors, multivariate logistic regression models were used.
A total of 6542 infants (3030 46.3% female and 3512 53.7% male; mean SD GA, 25.3 (1.1) weeks; mean SD birth weight, 715 180 g) were analyzed; 2534 infants (38.7%) received LISA, which was most frequently given quasi-prophylactically during delivery room management. Among the infants who received LISA, 1357 (53.6%) did not require mechanical ventilation in the first 72 hours compared with 331 infants (8.3%) of 4008 who did not receive LISA. In a multivariate logistic regression model that adjusted for GA, small-for-GA status, sex, multiple birth, inborn status, antenatal steroid use, and maximum fraction of inspired oxygen in the first 12 hours of life, LISA was associated with reduced risks of all-cause death (odds ratio OR, 0.74; 95% CI, 0.61-0.90; P = .002), BPD (OR, 0.69; 95% CI, 0.62-0.78; P < .001), and BPD or death (OR, 0.64; 95% CI, 0.57-0.72; P < .001) compared with infants without LISA exposure.
The results of this long-term multicenter cohort study suggest that LISA may be associated with reduced risks of adverse outcomes in extremely preterm infants.
SummaryBackground: Skeletal muscle trauma leads to severe functional deficits, which cannot be addressed by current treatment options. Previous investigation could show the efficacy of a local ...transplantation (TX) of mesenchymal stroma cells (MSCs) for the therapy of muscle injury. Underlying mechanisms remain to be elucidated. The aim of the present work was to characterize the fiber composition changes following MSC-TX after open crush injury. Methods: 20 male SD rats received an open crush trauma of the left soleus muscle. 2.5 × 106 autologous MSCs were transplanted into the crushed soleus muscle of 10 animals 7 days after trauma (group 1, n = 10). Control animals received an injection of saline solution (group 2, n = 10). Histologic analysis of fibrosis, fiber type composition, and muscle force measurements were performed 28 days after trauma. Results: MSC-TX improved muscle force significantly (fast-twitch, treated: 0.76 (0.51-1.15), untreated: 0.45 (0.32-0.73); p = 0.01). Tetanic stimulation resulted in a significant increase of force development (treated: 0.63 (0.4-1.21), untreated: 0.34 (0.16-0.48); p = 0.04). Histological analyses showed no differences in the amount of fibrotic tissue (treated vs. untreated, p = 0.42). A shift towards fastMHC-positive fibers was observed following MSC-TX (treated vs. untreated; p = 0.01 (mm2) or 0.007 (%)). Conclusion: This study demonstrated an effect of locally administered MSCs in the treatment of skeletal muscle injuries on a structural level. For the first time a fiber type shift towards fastMHC following MSC-TX after crush injury could be demonstrated and related to MSC-TX. These results might open the discussion of an alternative mode of action of MSCs in tissue regeneration.
In order to assess the potential of sPLA
-X as a therapeutic target for atherosclerosis, novel sPLA
inhibitors with improved type X selectivity are required. To achieve the objective of identifying ...such compounds, we embarked on a lead generation effort that resulted in the identification of a novel series of indole-2-carboxamides as selective sPLA2-X inhibitors with excellent potential for further optimization.
Everolimus-eluting bioresorbable vascular scaffolds (BVS) represent an innovative treatment option for coronary artery disease. Clinical and angiographic results seem promising, however, data on its ...immediate procedural performance are still scarce. The aim of our study was to assess the mechanical properties of BVS by Optical Coherence Tomography (OCT) in clinical routine.
Post-implantation OCT images of 40 BVS were retrospectively compared to those of 40 metallic everolimus-eluting stents (EES). Post-procedural device related morphological features were assessed. This included incidences of gross underexpansion and the stent eccentricity index (SEI, minimum/maximum diameter) as a measure for focal radial strength.
Patients receiving BVS were younger than those with EES (54.0 ± 11.2 years versus 61.7 ± 11.4 years, p = 0.012), the remaining baseline, vessel and lesion characteristics were comparable between groups. Lesion pre-dilatation was more frequently performed and inflation time was longer in the BVS than in the EES group (n = 34 versus n = 23, p = 0.006 and 44.2 ± 12.8 versus 25.6 ± 8.4 seconds, p < 0.001, respectively). There were no significant differences in maximal inflation pressures and post-dilatation frequencies with non-compliant balloons between groups. Whereas gross device underexpansion was not significantly different, SEI was significantly lower in the BVS group (n = 12 (30 %) versus n = 14 (35 %), p = 0.812 and 0.69 ± 0.08 versus 0.76 ± 0.09, p < 0.001, respectively). There was no difference in major adverse cardiac event-rate at six months.
Our data show that focal radial expansion was significantly reduced in BVS compared to EES in a clinical routine setting using no routine post-dilatation protocol. Whether these findings have impact on scaffold mid-term results as well as on clinical outcome has to be investigated in larger, randomized trials.
The International Pharmaco-EEG Society (IPEG) presents guidelines summarising the requirements for the recording and computerised evaluation of pharmaco-sleep data in man. Over the past years, ...technical and data-processing methods have advanced steadily, thus enhancing data quality and expanding the palette of sleep assessment tools that can be used to investigate the activity of drugs on the central nervous system (CNS), determine the time course of effects and pharmacodynamic properties of novel therapeutics, hence enabling the study of the pharmacokinetic/pharmacodynamic relationship, and evaluate the CNS penetration or toxicity of compounds. However, despite the presence of robust guidelines on the scoring of polysomnography -recordings, a review of the literature reveals inconsistent -aspects in the operating procedures from one study to another. While this fact does not invalidate results, the lack of standardisation constitutes a regrettable shortcoming, especially in the context of drug development programmes. The present guidelines are intended to assist investigators, who are using pharmaco-sleep measures in clinical research, in an effort to provide clear and concise recommendations and thereby to standardise methodology and facilitate comparability of data across laboratories.
Staphylococcus aureus can induce platelet aggregation. The rapidity and degree of this correlates with the severity of disseminated intravascular coagulation, and depends on platelet peptidoglycans. ...Surface-located thiol isomerases play an important role in platelet activation. The staphylococcal extracellular adherence protein (Eap) functions as an adhesin for host plasma proteins. Therefore we tested the effect of Eap on platelets.
We found a strong stimulation of the platelet-surface thiol isomerases protein disulfide isomerase and endoplasmic reticulum stress proteins 57 and 72 by Eap. Eap induced thiol isomerase-dependent glycoprotein IIb/IIIa activation, granule secretion, and platelet aggregation. Treatment of platelets with thiol blockers, bacitracin, and anti-protein disulfide isomerase antibody inhibited Eap-induced platelet activation. The effect of Eap on platelets and protein disulfide isomerase activity was completely blocked by glycosaminoglycans. Inhibition by the hydrophobic probe bis(1-anilinonaphthalene 8-sulfonate) suggested the involvement of hydrophobic sites in protein disulfide isomerase and platelet activation by Eap.
In the present study, we found an additional and yet unknown mechanism of platelet activation by a bacterial adhesin, involving stimulation of thiol isomerases. The thiol isomerase stimulatory and prothrombotic features of a microbial secreted protein are probably not restricted to S aureus and Eap. Because many microorganisms are coated with amyloidogenic proteins, it is likely that the observed mechanism is a more general one.
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