Extracapsular extension but not the tumour burden of lymph node metastases is an independent adverse risk factor in lymph node-positive bladder cancer

To evaluate risk factors in lymph node-positive bladder cancer.

The double-stranded RNA-activated protein kinase mediates radiation resistance in mouse embryo fibroblasts through nuclear factor kappaB and Akt activation

PURPOSE: Activation of the double-stranded RNA-activated protein kinase (PKR) leads to the induction of various pathways including the down-regulation of translation through phosphorylation of the eukaryotic translation initiation factor 2alpha (eIF-2alpha). There have been no reports to date about the role of PKR in radiation sensitivity. EXPERIMENTAL DESIGN: A clonogenic survival assay was used to investigate the sensitivity of PKR mouse embryo fibroblasts (MEF) to radiation therapy. 2-Aminopurine (2-AP), a chemical inhibitor of PKR, was used to inhibit PKR activation. Nuclear factor-kappaB (NF-kappaB) activation was assessed by electrophoretic mobility shift assay (EMSA). Expression of PKR and downstream targets was examined by Western blot analysis and immunofluorescence. RESULTS: Ionizing radiation leads to dose- and time-dependent increases in PKR expression and function that contributes to increased cellular radiation resistance as shown by clonogenic survival and terminal nucleotidyl transferase-mediated nick end labeling (TUNEL) apoptosis assays. Specific inhibition of PKR with the chemical inhibitor 2-AP restores radiation sensitivity. Plasmid transfection of the PKR wild-type (wt) gene into PKR(-/-) MEFs leads to increased radiation resistance. The protective effect of PKR to radiation may be mediated in part through NF-kappaB and Akt because both NF-kappaB and Akt are activated after ionizing radiation in PKR+/+ but not PKR-/- cells. CONCLUSIONS: We suggest a novel role for PKR as a mediator of radiation resistance modulated in part through the protective effects of NF-kappaB and Akt activation. The modification of PKR activity may be a novel strategy in the future to overcome radiation resistance.

Preclinical disability as a risk factor for falls in community-dwelling older adults

BACKGROUND: Falls are common and serious problems in older adults. The goal of this study was to examine whether preclinical disability predicts incident falls in a European population of community-dwelling older adults. METHODS: Secondary data analysis was performed on a population-based longitudinal study of 1644 community-dwelling older adults living in London, U.K.; Hamburg, Germany; Solothurn, Switzerland. Data were collected at baseline and 1-year follow-up using a self-administered multidimensional health risk appraisal questionnaire, including validated questions on falls, mobility disability status (high function, preclinical disability, task difficulty), and demographic and health-related characteristics. Associations were evaluated using bivariate and multivariate logistic regression analyses. RESULTS: Overall incidence of falls was 24%, and increased by worsening mobility disability status: high function (17%), preclinical disability (32%), task difficulty (40%), test-of-trend p <.003. In multivariate analysis adjusting for other fall risk factors, preclinical disability (odds ratio [OR] = 1.7, 95% confidence interval [CI], 1.1-2.5), task difficulty (OR = 1.7, 95% CI, 1.1-2.6) and history of falls (OR = 4.7, 95% CI, 3.5-6.3) were the strongest significant predictors of falls. In stratified multivariate analyses, preclinical disability equally predicted falls in participants with (OR = 1.7, 95% CI, 1.0-3.0) and without history of falls (OR = 1.8, 95% CI, 1.1-3.0). CONCLUSIONS: This study provides longitudinal evidence that self-reported preclinical disability predicts incident falls at 1-year follow-up independent of other self-reported fall risk factors. Multidimensional geriatric assessment that includes preclinical disability may provide a unique early warning system as well as potential targets for intervention.

Effects of aspirin and propranolol on the acute psychological stress response in factor VIII coagulant activity: a randomized, double-blind, placebo-controlled experimental study

Activity of clotting factor VIII has been shown to acutely increase with sympathetic nervous system stimulation. We investigated whether aspirin and propranolol affect the responsiveness of plasma clotting factor VIII activity levels to acute psychosocial stress. We randomized 54 healthy subjects double-blind to 5-day treatment with a single daily oral dosage of either 100 mg aspirin plus 80 mg propranolol combined, 100 mg of aspirin, 80 mg of propranolol, or placebo medication. Thereafter, subjects underwent a 13-min standardized psychosocial stressor. Plasma levels of clotting factor VIII activity were determined immediately before, immediately after, 45 min and 105 min after stress. Controlling for demographic, metabolic, and life style factors repeated measures analysis of covariance showed that the change in clotting factor VIII activity from prestress to 105 min poststress differed between medication groups (P = 0.023; partial eta = 0.132). The clotting factor VIII activity level decreased from prestress to immediately poststress in the aspirin/propranolol group relative to the placebo group (P = 0.048) and the aspirin group (P < 0.06). Between 45 min and 105 min poststress, clotting factor VIII levels increased in the aspirin/propranolol group relative to the placebo group (P = 0.007) and the aspirin group (P = 0.039). The stress response in clotting factor VIII activity levels was not significantly different between the aspirin/propranolol group and the propranolol group. Propranolol in combination with aspirin diminished the acute response in clotting factor VIII activity to psychosocial stress compared with placebo medication and aspirin alone. The effect of single aspirin on the acute clotting factor VIII stress response was indistinguishable from a placebo effect.

Relationship between heart rate variability, interleukin-6, and soluble tissue factor in healthy subjects

Decreased heart rate variability (HRV) has been associated with an increased risk of atherosclerosis. We hypothesized that a decrease in frequency domains of resting HRV would be associated with elevated plasma levels of interleukin (IL)-6 and soluble tissue factor (sTF) both previously shown to prospectively predict atherothrombotic events in healthy subjects. Subjects were 102 healthy and unmedicated black and white middle-aged men and women. We determined IL-6 and sTF antigen in plasma and HRV measures from surface electrocardiogram data using spectral analysis. All statistical analyses controlled for age, gender, ethnicity, smoking status, blood pressure, and body mass index. Low amounts of low frequency (LF) power (beta=-0.31, p=0.007) and high frequency (HF) power (beta=-0.36, p=0.002) were associated with increased amounts of IL-6, explaining 7% and 9% of the variance, respectively. Interactions between LF power and IL-6 (p=0.002) and between HF power and IL-6 (p=0.012) explained 8% and 5%, respectively, of the variance in sTF. Post hoc analyses showed associations between IL-6 and sTF when LF power (beta=0.51, p<0.001) and HF power (beta=0.48, p<0.001) were low but not when LF power and high HF power were high. The findings suggest that systemic low-grade inflammatory activity is associated with a decrease in HRV. Furthermore, there was a positive relationship between plasma levels of IL-6 and sTF antigen when HRV was low. Inflammation and related hypercoagulability might particularly contribute to atherothrombotic events in a setting of decreased HRV.

Is a change in patient-reported dysphagia after induction chemotherapy in locally advanced esophageal cancer a predictive factor for pathological response to neoadjuvant chemoradiation?

GOALS OF WORK: In patients with locally advanced esophageal cancer, only those responding to the treatment ultimately benefit from preoperative chemoradiation. We investigated whether changes in subjective dysphagia or eating restrictions after two cycles of induction chemotherapy can predict histopathological tumor response observed after chemoradiation. In addition, we examined general long-term quality of life (QoL) and, in particular, eating restrictions after esophagectomy. MATERIALS AND METHODS: Patients with resectable, locally advanced squamous cell- or adenocarcinoma of the esophagus were treated with two cycles of chemotherapy followed by chemoradiation and surgery. They were asked to complete the EORTC oesophageal-specific QoL module (EORTC QLQ-OES24), and linear analogue self-assessment QoL indicators, before and during neoadjuvant therapy and quarterly until 1 year postoperatively. A median change of at least eight points was considered as clinically meaningful. MAIN RESULTS: Clinically meaningful improvements in the median scores for dysphagia and eating restrictions were found during induction chemotherapy. These improvements were not associated with a histopathological response observed after chemoradiation, but enhanced treatment compliance. Postoperatively, dysphagia scores remained low at 1 year, while eating restrictions persisted more frequently in patients with extended transthoracic resection compared to those with limited transhiatal resection. CONCLUSIONS: The improvement of dysphagia and eating restrictions after induction chemotherapy did not predict tumor response observed after chemoradiation. One year after esophagectomy, dysphagia was a minor problem, and global QoL was rather good. Eating restrictions persisted depending on the surgical technique used.

Simulationsgestützte Untersuchung der Spurtreue von Routenzügen

Für den innerbetrieblichen Transport und besonders für die Materialversorgung in der Produktion werden zunehmend Routenzüge eingesetzt, die aus einem Schleppfahrzeug und bis zu fünf Anhängern bestehen. Um gute Manövrierbarkeit und einen geringen Platzbedarf zu gewährleisten, sollten Routenzuganhänger möglichst spurtreu sein. In diesem Beitrag wird die Spurtreue exemplarisch für zwei am Markt verfügbare Anhänger für Routenzüge mit zwei ungelenkten und vier gelenkten Rädern untersucht. Hierfür wird zunächst ein Gütekriterium definiert, das die maximale Abweichung von der Spurtreue quantitativ erfasst. Außerdem werden Testszenarien vorgeschlagen, um die verschiedenen Fahrwerks- und Lenkkonzepte vergleichen zu können. Mit Hilfe eines entwickelten analytischen Modells werden die Abweichungen in der Spurtreue bei stationärer Kreisfahrt für die zwei gewählten Konzepte berechnet und dargestellt. Zusätzlich wird eine Mehrkörper-Simulation, die eine tiefere physikalische Modellierung und die Untersuchung komplexerer Fahrmanöver erlaubt, durchgeführt und mit den analytischen Ergebnissen verglichen. Es kann gezeigt werden, dass neben der Lenkkinematik weitere Parameter wie das Schräglaufverhalten der Reifen Einfluss auf die Spurtreue haben.

Beitrag einer nutzungsabhängigen Instandhaltung zur Planung von Leistungsverfügbarkeit

Stets darauf bedacht, die Anlagen- und Maschinenverfügbarkeit bei möglichst geringem Ressourceneinsatz zu gewährleisten, wird die Rolle der Instandhaltung als unternehmerischer Wertschöpfungsfaktor immer bedeutsamer. Voraussetzung für eine Nutzbarmachung bestehender Potentiale sind neue Werkzeuge und Ansätze, deren Umsetzung eine effiziente Sicherstellung von Verfügbarkeit ermöglicht. Vor diesem Hintergrund wurde im Teilprojekt C3 des DFG Paketantrags 672 ein Konzept zur nutzungsabhängigen Instandhaltung entwickelt. Auf Grundlage des bestehenden Zusammenhangs von Nutzung und Abnutzung risikobehafteter Bauteile intralogistischer Systeme können damit die durch zukünftige Systemlasten hervorgerufenen Beanspruchungen antizipiert werden. Instandhaltungsmaßnahmen und technische Verfügbarkeiten werden dadurch anforderungsgerecht und ressourcen-optimal planbar.

Konstruktion und erste Validierung eines Fragebogens zur umfassenden Erfassung von Achtsamkeit: Das Comprehensive Inventory of Mindfulness Experiences

In der vorliegenden Arbeit werden Entwicklung und Validierung eines Fragebogens zur umfassenden Erfassung der Achtsamkeit, des Comprehensive Inventory of Mindfulness Experiences (CHIME), beschrieben. An einer Allgemeinbevölkerungs-Stichprobe (N = 298) und einer Stichprobe von TeilnehmerInnen an MBSR-Kursen (N = 161) wurde die Faktorenstruktur des CHIME ermittelt und seine Reliabilität und Validität geprüft. Faktorenanalytische Verfahren ergaben eine achtfaktorielle Struktur. Die Struktur wurde in einer zusätzlichen konfirmatorischen Stichprobe (N = 202) überprüft. Der Fragebogen sowie seine Unterskalen weisen gute Reliabilitätswerte auf (interne Konsistenz und Retest-Reliabilität). Analysen zur Messinvarianz der einzelnen Items über Gruppen, die sich bezüglich Meditationserfahrung, Alter, Geschlecht und Symptombelastung unterschieden, zeigten keine systematischen Unterschiede im Verständnis der Items. Die Kennwerte zur Konstrukt-, Kriterium-, und inkrementellen Validität sowie zur Veränderungssensitivität waren alle mindestens zufriedenstellend. Mit dem CHIME steht somit ein Fragebogen mit guten psychometrischen Eigenschaften zur Selbsteinschätzung der Achtsamkeit zur Verfügung. Der CHIME basiert auf allen in den aktuellen Instrumenten enthaltenen Aspekten des Achtsamkeitskonstrukts.

Darwin, Deutschland und die Juden oder der Juda-Jesuitismus : 33 Thesen nebst einer Nachschrift über einen vergessenen Factor der Volkswirthschaft

von O. Beta