A novel pretherapeutic gene expression-based risk score for treatment guidance in gastric cancer.

Background: Perioperative chemotherapy is an established treatment of advanced gastric cancer patients. Treatment selection is based on clinical staging (cT). We aimed to establish and validate a prognostic score including clinical and molecular factors, to optimize treatment decisions for these patients. Patients and methods: We analyzed 626 carcinomas of the stomach and of the gastro-esophageal junction from two academic centers including primarily resected and pre-/perioperatively treated patients. Patients were divided into a training (N = 269) and validation (N = 357) set. Expression of 11 target genes was measured by quantitative PCR in resected tumors. A risk score to predict overall survival (OS) was generated and validated. Intra-tumoral heterogeneity was assessed by analyzing 50 tumor areas from 10 patients. Results: A risk score including the expression of CCL5, CTNNB1, EXOSC3 and LZTR1 and the clinical parameters cT, tumor localization and histopathologic type suggested two groups with a significant difference in OS [hazard ratio (HR) 0.30; 95% confidence interval (CI) 0.17-0.52]. The risk score was successfully validated in an independent cohort (HR 0.32; 95% CI 0.21-0.51; P < 0.001) as well as in subgroups of primarily resected (HR 0.30; 95% CI 0.17-0.54; P < 0.001) and pre-/perioperatively treated patients (HR 0.37; 95% CI 0.17-0.81; P = 0.009). A significant difference in OS of high- and low-risk patients was also found in primarily resected patients with intestinal (HR 0.45; 95% CI 0.23-0.90; P = 0.020) and nonintestinal-type carcinomas (HR 0.1; 95% CI 0.02-0.42; P < 0.001). Intra-tumor heterogeneity analysis indicated a classification reliability of 95% for a supposed analysis of three biopsies. Conclusion: The identified risk score could substantially contribute to an improved management of gastric cancer patients in the context of perioperative chemotherapy.

Involuntary attentional capture by speech and non-speech deviations: a combined behavioral-event-related potential study.

This study applied an auditory distraction paradigm to investigate involuntary attention effects of unexpected deviations in speech and non-speech sounds on behavior (increase in response time and error rate) and event-related brain potentials (ΔN1/MMN and P3a). Our aim was to systematically compare identical speech sounds with physical vs. linguistic deviations and identical deviations (pitch) with speech vs. non-speech sounds in the same set of healthy volunteers. Sine tones and bi-syllabic pseudo-words were presented in a 2-alternative forced-choice paradigm with occasional phoneme deviants in pseudo-words, pitch deviants in pseudo-words, or pitch deviants in tones. Deviance-related ERP components were elicited in all conditions. Deviance-related negativities (ΔN1/MMN) differed in scalp distribution between phoneme and pitch deviants within phonemes, indicating that auditory deviance-detection partly operates in a deviance-specific manner. P3a as an indicator of attentional orienting was similar in all conditions, and was accompanied by behavioral indicators of distraction. Yet smaller behavioral effects and prolonged relative MMN-P3a latency were observed for pitch deviants within phonemes relative to the other two conditions. This suggests that the similarity and separability of task-relevant and task-irrelevant information is essential for the extent of attentional capture and distraction.

Nanoscale patterning induced strain redistribution in ultrathin strained Si layers on oxide.

We present a comparative study of the influence of the thickness on the strain behavior upon nanoscale patterning of ultrathin strained Si layers directly on oxide. The strained layers were grown on a SiGe virtual substrate and transferred onto a SiO(2)/Si substrate using wafer bonding and hydrogen ion induced exfoliation. The post-patterning strain was evaluated using UV micro-Raman spectroscopy for thin (20 nm) and thick (60 nm) nanostructures with lateral dimensions in the range of 80-400 nm. We found that about 40-50% of the initial strain is maintained in the 20 nm thick nanostructures, whereas this fraction drops significantly to approximately 2-20% for the 60 nm thick ones. This phenomenon of free surface induced relaxation is described using detailed three-dimensional finite element simulations. The simulated strain 3D maps confirm the limited relaxation in thin nanostructures. This result has direct implications for the fabrication and manipulation of strained Si nanodevices.

Serum levels of the adipokine lipocalin-2 are increased in preeclampsia.

BACKGROUND: Preeclampsia (PE) is a serious complication in pregnancy which increases the future risk for vascular and metabolic disease in both mother and newborn. Recently, lipocalin-2 has been introduced as a novel adipokine which contributes to obesity, insulin resistance, and vascular disease. AIM: In the current study, we investigated lipocalin-2 serum levels in PE patients as compared to healthy gestational age-matched controls. SUBJECTS AND METHODS: Lipocalin-2 serum concentrations were quantified by enzyme-linked immunosorbent assay in control (no.=22) and PE (no.=22) patients. Furthermore, lipocalin-2 levels were correlated to clinical and biochemical measures of renal function, glucose, and lipid metabolism, as well as inflammation. RESULTS: Median maternal lipocalin-2 concentrations were significantly increased in PE (121.3 µg/l) as compared to control subjects (99.8 µg/l) (p<0.05). Furthermore, circulating lipocalin 2 correlated positively with diastolic blood pressure, creatinine, and C reactive protein. In multivariate analyses, creatinine and C reactive protein remained independently associated with lipocalin-2 levels. CONCLUSIONS: We demonstrate that maternal lipocalin-2 concentrations are significantly increased in PE. Furthermore, markers of renal function and inflammation independently predict circulating lipocalin-2.

Fibroblast growth factor 19 serum levels: relation to renal function and metabolic parameters.

Fibroblast growth factor 19 (FGF19) was recently introduced as a novel metabolic regulator reversing diabetes mellitus, hepatic steatosis, hyperlipidemia, and adiposity. In the current study, we determined circulating FGF19 levels in patients on chronic hemodialysis (CD) as compared to controls with a glomerular filtration rate (GFR) above 50 ml/min. FGF19 was measured by ELISA in control (n=60) and CD (n=60) patients and correlated to clinical and biochemical measures of renal function, glucose, and lipid metabolism, as well as inflammation, in both groups. Median serum FGF19 levels were 1.5-fold higher in CD patients (266.7 microg/l) as compared to subjects with a GFR above 50 ml/min (178.1 microg/l) (p=0.001). Furthermore, fasting glucose negatively and independently predicted circulating FGF19 in controls (p<0.05). Moreover, adiponectin was a positive and C-reactive protein was a negative independent predictor of FGF19 serum concentrations in CD patients. Taken together, we have demonstrated that circulating FGF19 levels are significantly increased in end-stage renal disease. Furthermore, FGF19 is associated with a beneficial metabolic profile in both control and CD patients.

Regular dislocation networks in silicon as a tool for nanostructure devices used in optics, biology, and electronics.

Well-controlled fabrication of dislocation networks in Si using direct wafer bonding opens broad possibilities for nanotechnology applications. Concepts of dislocation-network-based light emitters, manipulators of biomolecules, gettering and insulating layers, and three-dimensional buried conductive channels are presented and discussed. A prototype of a Si-based light emitter working at a wavelength of about 1.5 microm with an efficiency potential estimated at 1% is demonstrated.

Nitride semiconductors free of electrostatic fields for efficient white light-emitting diodes

Compact solid-state lamps based on light-emitting diodes (LEDs) are of current technological interest as an alternative to conventional light bulbs. The brightest LEDs available so far emit red light and exhibit higher luminous efficiency than fluorescent lamps. If this luminous efficiency could be transferred to white LEDs, power consumption would be dramatically reduced, with great economic and ecological consequences. But the luminous efficiency of existing white LEDs is still very low, owing to the presence of electrostatic fields within the active layers. These fields are generated by the spontaneous and piezoelectric polarization along the [0001] axis of hexagonal group-III nitrides--the commonly used materials for light generation. Unfortunately, as this crystallographic orientation corresponds to the natural growth direction of these materials deposited on currently available substrates. Here we demonstrate that the epitaxial growth of GaN/(Al,Ga)N on tetragonal LiAlO2 in a non-polar direction allows the fabrication of structures free of electrostatic fields, resulting in an improved quantum efficiency. We expect that this approach will pave the way towards highly efficient white LEDs.

[Prenatal diagnosis and management of fetal arrhythmias]. / Pränatale Diagnostik und Management der fetalen Arrhythmien.

Reported in this paper are 25 cases of fetal arrhythmia handled at the Gynaecological Department of the Berlin School of Medicine (Charité) over a period of two years. They were subdivided by tachycardiac, bradycardiac, and simple forms, following ultrasound-assisted diagnosis (realtime, M-Mode, Doppler). This proved to be useful for better prenatal management and prognosis. The first and second forms were linked to higher rates of malformations or contributory and recordable causes, whereas the third form could be considered harmless, the more as spontaneous postnatal regression was to be expected. Successful experience is reported, as obtained from prenatal therapy either via the mother or by direct invasive treatment to the child (thigh, umbilical vein). Early referral to an adequately staffed and equipped centre and exclusion of cardiac defects are conditions for good success. Intrauterine deaths occurred in two cases due to cardiac malformations, and non-immunological fetal hydrops was established in four cases. Optimal management of the inhomogenous group of fetal arrhythmias should be undertaken in interdisciplinary teamwork at centres with experience in perinatal medicine.