Beziehung zwischen IT-Erfolgsfaktoren und IT-Risikomanagement im eGovernment

Zusammenfassung: IT-Erfolgsfaktoren beschreiben Bedingungen, die maβgeblich zur erfolgreichen Umsetzung von IT-Projekten beitragen. Über das IT-Risikomanagement wird dabei präventiv versucht, kritischen Erfolgsfaktoren Rechnung zu tragen, was u.a. durch den Einsatz von IT-Governance-Methoden unterstützt und geprüft werden kann. Der vorliegende Beitrag setzt sich mit der Beziehung zwischen IT-Risikomanagement und IT-Erfolgsfaktoren im eGovernment und deren Zusammenhang auseinander. Dazu werden Erfolgsfaktoren aus acht Studien ausgewertet und konsolidiert. Es wird der Frage nachgegangen, inwieweit die identifizierten Erfolgsfaktoren in den in der schweizerischen Bundesverwaltung eingesetzten IT-Governance-Methoden im IT-Risikomanagement berücksichtigt werden. Aus der theoretischen Gegenüberstellung wird zusätzlicher Handlungsbedarf in der Methodenunterstützung für das Risikomanagement ersichtlich, um Risiken im eGovernment effektiv antizipieren zu könne

Improved identification of enriched peptide–RNA cross-links from ribonucleoprotein particles (RNPs) by mass spectrometry

Direct UV cross-linking combined with mass spectrometry (MS) is a powerful tool to identify hitherto non-characterized protein–RNA contact sites in native ribonucleoprotein particles (RNPs) such as the spliceosome. Identification of contact sites after cross-linking is restricted by: (i) the relatively low cross-linking yield and (ii) the amount of starting material available for cross-linking studies. Therefore, the most critical step in such analyses is the extensive purification of the cross-linked peptide–RNA heteroconjugates from the excess of non-crosslinked material before MS analysis. Here, we describe a strategy that combines small-scale reversed-phase liquid chromatography (RP-HPLC) of UV-irradiated and hydrolyzed RNPs, immobilized metal-ion affinity chromatography (IMAC) to enrich cross-linked species and their analysis by matrix-assisted laser desorption/ionisation (MALDI) MS(/MS). In cases where no MS/MS analysis can be performed, treatment of the enriched fractions with alkaline phosphatase leads to unambiguous identification of the cross-linked species

Long-Term Experience of Chemoradiotherapy Combined with Deep Regional Hyperthermia for Organ Preservation in High-Risk Bladder Cancer (Ta, Tis, T1, T2).

BackgroundThe aim of this study was to evaluate the efficacy and safety of chemoradiotherapy (RCT) combined with regional deep hyperthermia (RHT) of high-risk bladder cancer after transurethral resection of bladder tumor (TUR-BT).Materials and methodsBetween 1982 and 2016, 369 patients with pTa, pTis, pT1, and pT2 cN0-1 cM0 bladder cancer were treated with a multimodal treatment after TUR-BT. All patients received radiotherapy (RT) of the bladder and regional lymph nodes. RCT was administered to 215 patients, RCT + RHT was administered to 79 patients, and RT was used in 75 patients. Treatment response was evaluated 4-6 weeks after treatment with TUR-BT.ResultsComplete response (CR) overall was 83% (290/351), and in treatment groups was RT 68% (45/66), RCT 86% (178/208), and RCT + RHT 87% (67/77). CR was significantly improved by concurrent RCT compared with RT (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.05-5.12; p = .037), less influenced by hyperthermia (OR, 2.56; 95% CI, 0.88-8.00; p = .092). Overall survival (OS) after RCT was superior to RT (hazard ratio [HR], 0.7; 95% CI, 0.50-0.99; p = .045). Five-year OS from unadjusted Kaplan-Meier estimates was RCT 64% versus RT 45%. Additional RHT increased 5-year OS to 87% (HR, 0.32; 95% CI, 0.18-0.58; p = .0001). RCT + RHT compared with RCT showed a significantly better bladder-preservation rate (HR, 0.13; 95% CI, 0.03-0.56; p = .006). Median follow-up was 71 months. The median number of RHT sessions was five.ConclusionThe multimodal treatment consisted of a maximal TUR-BT followed by RT; concomitant platinum-based chemotherapy combined with RHT in patients with high-grade bladder cancer improves local control, bladder-preservation rate, and OS. It offers a promising alternative to surgical therapies like radical cystectomy.Implications for practiceRadical cystectomy with appropriate lymph node dissection has long represented the standard of care for muscle-invasive bladder cancer in medically fit patients, despite many centers reporting excellent long-term results for bladder preserving strategies. This retrospective analysis compares different therapeutic modalities in bladder-preservation therapy. The results of this study show that multimodal treatment consisting of maximal transurethral resection of bladder tumor followed by radiotherapy, concomitant platinum-based chemotherapy combined with regional deep hyperthermia in patients with Ta, Tis, T1-2 bladder carcinomas improves local control, bladder-preservation rate, and survival. More importantly, these findings offer a promising alternative to surgical therapies like radical cystectomy. The authors hope that, in the future, closer collaboration between urologists and radiotherapists will further improve treatments and therapies for the benefit of patients

Spontaneous Rupture of the Urinary Bladder 10 Years after Curative Radiotherapy

It has been reported that the rate of clinically relevant side effects following curative radiotherapy for primary carcinoma is about 3% for urologic complications. Such complications include hematuria, fibrosis, and cystitis. An extremely rare, but dangerous, medical complication following curative radiotherapy that can also be noted is spontaneous bladder perforation. We present such a case of a 27-year-old patient with spontaneous bladder perforation, who was initially misdiagnosed because of its rarity as well as unspecific clinical and laboratory findings

Anaplastic Sarcoma of the Kidney

We present a case of an extremely rare and relatively new tumor entity of the kidney, the anaplastic sarcoma. Although of unknown origin and pathogenesis, treating such a tumor as if it was anaplastic Wilms' tumor seems to be the only therapeutic solution at the present time. Newer immunohistochemical staining and molecular probes should be applied to this neoplasm in order for us to understand it nature and maximize therapy

Anaplastic Sarcoma of the Kidney

We present a case of an extremely rare and relatively new tumor entity of the kidney, the anaplastic sarcoma. Although of unknown origin and pathogenesis, treating such a tumor as if it was anaplastic Wilms' tumor seems to be the only therapeutic solution at the present time. Newer immunohistochemical staining and molecular probes should be applied to this neoplasm in order for us to understand it nature and maximize therapy

Vocational Education and Training and Transitions into the Labor Market

Stage 6 of the German National Educational Panel Study (NEPS) 6 is devoted to the transition of young people from school to work. Stage 6 focuses in particular on the transition from school to vocational education and training and then to work (for tertiary education, see Chap. 16). In all Western societies, vocational education and training (VET) systems face a number of challenges, including the need to adapt to increasing skill requirements across the economy and to handle the danger of producing an "underclass" of low-skilled youth. This chapter presents the life-course approach for investigating school-leavers' pathways from school into the labor market within NEPS. Several factors shape young people’s school-to-work transitions: their motivation and competence endowment, their decisions to apply for specific educational programs, the constraints they face regarding the opportunities for VET programs and the gatekeepers’ recruitment behavior, the information and support youths may or may not receive from social networks, and the learning environments they encounter in firms and schools. We outline the basic theories that guide our research concerning these influences and discuss how we take them into account within NEPS Stage 6. Thus, we provide an overview of the study’s research potential in the area of VET. For now, it is mainly the Scientific Use Files of Starting Cohort 4 (SC4) that provide ample opportunities for innovative interdisciplinary analyses - including analyses of students from special education schools. As the starting cohorts age, Starting Cohort 3 (SC3) has now also entered NEPS Stage 6 and its data on VET transitions will soon be available as well

Age-related glomerulosclerosis and interstitial fibrosis in Milan normotensive rats: A podocyte disease

Age-related glomerulosclerosis and interstitial fibrosis in Milan normotensive rats: A podocyte disease. In Milan normotensive (MNS) rats glomerulosclerosis and interstitial fibrosis develop spontaneously in the absence of hypertension. Renal changes were sequentially assessed in these rats between 2 and 10 months of age. At 10 months, rats were characterized by heavy proteinuria, increased serum creatinine, focal or global glomerulosclerosis in 51 ± 12% of the glomeruli as well as tubulointerstitial injury involving > 25% of the section area. Cell injury in podocytes (evidenced as increased expression of desmin and by electron microscopy) and interstitial fibroblasts (increased expression of α-smooth muscle actin) and mild glomerular hypertrophy were witnessed as early as three to four months of age and preceded glomerulosclerosis and interstitial fibrosis. Only minor evidence of mesangial cell activation (as assessed by glomerular de novo α-smooth muscle actin or type I collagen expression or increased cell proliferation) was noted throughout the observation period. Later stages of the disease were characterized by glomerular and/or tubulointerstitial macrophage influx and osteopontin expression (a chemoattractant), mild accumulation of lymphocytes, platelets, fibrinogen, as well as by a progressive accumulation of various matrix proteins. Progressive renal disease in MNS rats is thus noteworthy for the relative lack of mesangial cell activation. Rather, early podocyte damage, induced by yet unknown mechanisms, may underlie the development of glomerulosclerosis and subsequent interstitial fibrosis

A RAS-Independent Biomarker Panel to Reliably Predict Response to MEK Inhibition in Colorectal Cancer

Background: In colorectal cancer (CRC), mutations of genes associated with the TGF-β/BMP signaling pathway, particularly affecting SMAD4, are known to correlate with decreased overall survival and it is assumed that this signaling axis plays a key role in chemoresistance. Methods: Using CRISPR technology on syngeneic patient-derived organoids (PDOs), we investigated the role of a loss-of-function of SMAD4 in sensitivity to MEK-inhibitors. CRISPR-engineered SMAD4R361H PDOs were subjected to drug screening, RNA-Sequencing, and multiplex protein profiling (DigiWest®). Initial observations were validated on an additional set of 62 PDOs with known mutational status. Results: We show that loss-of-function of SMAD4 renders PDOs sensitive to MEK-inhibitors. Multiomics analyses indicate that disruption of the BMP branch within the TGF-β/BMP pathway is the pivotal mechanism of increased drug sensitivity. Further investigation led to the identification of the SFAB-signature (SMAD4, FBXW7, ARID1A, or BMPR2), coherently predicting sensitivity towards MEK-inhibitors, independent of both RAS and BRAF status. Conclusion: We identified a novel mutational signature that reliably predicts sensitivity towards MEK-inhibitors, regardless of the RAS and BRAF status. This finding poses a significant step towards better-tailored cancer therapies guided by the use of molecular biomarkers