INSTABILITY STUDIES WITH EBR-I, MARK III

The results of instability studies suggest that the operational characteristics of the fully ribbed and rigid Mark III loading are governed by feedback processes that guarantee safe and stable operation under normal operating condiiions. No evidence of positive reactivity effects was noted for the fully-ribbed rigid core. Logical extrapolations of full-power full-flow test data indicate that the reactor could be brought into a resonant condition for power levels exceeding 1000 Mw. Strong nonlinearities were observed in power coefficients and were considered to pose no serious operational problems above 200 kw in the power range associated with the tests. An application of the Nyquist stability criterion to the extrapolated fully sheared data results in the conclusion that the reactor would attain resonance instability at full flow at - 11 Mw. Logical extrapolations of test data for one-third flow results in resonance instability at -10 Mw, a power level -20 times that designed for onethird flow. Rib shearing was shown to result in an unexpected and unexplained increase in the magnitude of the delayed structural power coefficient component. An empirical fit of feedback data to a model describing the dynamic and static behavior of the partially sheared core resulted in ihe values for the respective prompt negative, rod-bowing, and delayed structural power coefficient components of -2.21 x 10/sup -6/ +0.543 x 10/sup -6/ and -0.873 x 10/sup -6/4 delta /k/kw. The over all behavior of the Mark III core, whether fully ribbed and rigid, fully ribbed and loose, or even partially or fully sheared, is one of extreme stability. The inclusion of stabilizing ribs and a system of tightening rods in the Mark lII design elimuinated, or at least reduced to a point beyond detection, the prompt positive rod-bowing component that existed in the Mark II. (B.O.G.

Categorical versus continuous circulating tumor cell enumeration as early surrogate marker for therapy response and prognosis during docetaxel therapy in metastatic prostate cancer patients

Background: Circulating tumor cell (CTCs) counts might serve as early surrogate marker for treatment efficacy in metastatic castration-resistant prostate cancer (mCRPC) patients. We prospectively assessed categorical and continuous CTC-counts for their utility in early prediction of radiographic response, progression-free (PFS) and overall survival (OS) in mCRPC patients treated with docetaxel. Methods: CTC-counts were assessed in 122 serial samples, as continuous or categorical (= 5 CTCs) variables, at baseline (q0) and after 1 (q1),4 (q4) and 10 (q10) cycles of docetaxel (3-weekly, 75 mg/m2) in 33 mCRPC patients. Treatment response (TR) was defined as non-progressive (non-PD) and progressive disease (PD),by morphologic RECIST or clinical criteria at q4 and q10. Binary logistic and Cox proportional hazards regression analyses were used as statistical methods. Results: Categorical CTC-count status predicted PD at q4 already after one cycle (q1) and after 4 cycles (q4) of chemotherapy with an odds ratio (OR) of 14.9 (p = 0.02) and 18.0 (p = 0.01). Continuous CTC-values predicted PD only at q4 (OR 1.04, p = 0.048). Regarding PFS, categorical CTC-counts at q1 were independent prognostic markers with a hazard ratio (HR) of 3.85 (95 % CI 1.1-13.8, p = 0.04) whereas early continuous CTC-values at q1 failed significance (HR 1.02, 95 % CI 0.99-1.05, p = 0.14). For OS early categorical and continuous CTC-counts were independent prognostic markers at q1 with a HR of 3.0 (95 % CI 1.6-15.7, p = 0.007) and 1.02 (95 % CI 1.0-1.040, p = 0.04). Conclusions: Categorical CTC-count status is an early independent predictor for TR, PFS and OS only 3 weeks following treatment initiation with docetaxel whereas continuous CTC-counts were an inconsistent surrogate marker in mCRPC patients. For clinical practice, categorical CTC-counts may provide complementary information towards individualized treatment strategies with early prediction of treatment efficacy and optimized sequential treatment

Imaging and quantification of the hepatic vasculature of mice using ultrafast Doppler ultrasound

Non-invasive in vivo imaging of the vasculature is a powerful tool for studying disease mechanisms in rodents. To achieve high sensitivity imaging of the microvasculature using Doppler ultrasound methods, imaging modalities employing the concept of ultrafast imaging are preferred. By increasing the frame rate of the ultrasound scanner to thousands of frames per second, it becomes possible to improve the sensitivity of the blood flow down to 2 mm/s and to obtain functional information about the microcirculation in comparison to a sensitivity of around 1 cm/s in conventional Doppler modes. While Ultrafast Doppler ultrasound (UFUS) imaging has become adopted in neuroscience, where it can capture brain activity through neurovascular coupling, it presents greater challenges when imaging the vasculature of abdominal organs due to larger motions linked to breathing. The liver, positioned anatomically under the diaphragm, is particularly susceptible to out-of-plane movement and oscillating respiratory motion. These artifacts not only adversely affect Doppler imaging but also complicate the anatomical analysis of vascular structures and the computation of vascular parameters. Here, we present a qualitative and quantitative imaging analysis of the hepatic vasculature in mice by UFUS. We identify major anatomical vascular structures and provide graphical illustrations of the hepatic macroscopical anatomy, comparing it to an in-depth anatomical assessment of the hepatic vasculature based on Doppler readouts. Additionally, we have developed a quantification protocol for robust measurements of hepatic blood volume of the microvasculature over time. To contemplate further research, qualitative vascular analysis provides a comprehensive overview and suggests a standardized terminology for researchers working with mouse models of liver disease. Furthermore, it offers the opportunity to apply ultrasound as a non-invasive complementary method to inspect hepatic vascular defects in vivo and measure functional microvascular alterations deep within the organ before unraveling blood vessel anomalies at the micron scale levels using ex vivo staining on tissue sections.</p

[Diagnostic imaging of urolithiais. Current recommendations and new developments].

Prevalence of urolithiasis is increasing in industrialized countries--in both adults and children, representing a unique diagnostic and therapeutic challenge. Risk-adapted diagnostic imaging currently means assessment with maximized sensitivity and specificity together with minimal radiation exposure. In clinical routine, imaging is performed by sonography, unenhanced computed tomography (NCCT) or intravenous urography (IVU) as well as plain kidney-ureter-bladder (KUB) radiographs.The aim of the present review is a critical guideline-based and therapy-aligned presentation of diagnostic imaging procedures for optimized treatment of urolithiasis considering the specifics in children and pregnant women

Detection of circulating tumor cells in different stages of prostate cancer.

To explore circulating tumor cell (CTCs) counts in different stages of prostate cancer (PC) in association with tumor burden, metastatic pattern and conventional serum biomarkers. Overall survival (OS) analyses were conducted with respect to optimized CTC cutoff levels.Circulating tumor cell counts were assessed in healthy controls (n = 15) as well as in locally advanced high risk (LAPC, n = 20), metastatic castration resistant (mCRPC, n = 40) and taxane-refractory (mTRPC, n = 15) PC patients. CTCs were detected using the CellSearch System.In metastatic PC (mPC), CTC counts were significantly increased compared to LAPC (p =3 CTCs compared to <3 CTCs (p = 0.001), a cutoff level applicable in mCRPC (p = 0.003) but not in mTRPC patients (p = 0.054).Circulating tumor cell counts are applicable as a prognostic molecular marker, especially in mCRPC patients harboring bone metastases with or without visceral metastases. For clinical practice, mPC patients with elevated CTC counts in combination with short PSA-DT, high alkaline phosphatase and lactate dehydrogenase levels as well as low hemoglobin levels are at high risk of disease progression and limited OS

[Detection of circulating tumor cells from peripheral blood in prostate cancer].

Circulating tumor cells (CTCs) can be detected with sensitive immunocytological and molecular methods and can potentially cause distant metastases. Consecutively the prognostic significance of CTC-counts for survival was demonstrated in metastatic prostate cancer (mPC) revealing CTCs as reliable surrogate marker during therapy. Comparatively the prognostic value of a CTC-threshold with = 5 CTCs was superior to the commonly used PSA-decrement algorithms. In contrast despite evidence of CTCs in localized PC, their clinical value in this stage is currently precarious. Furthermore, CTCs may serve as predictive markers with the ability to predict treatment sensitivity or resistance, since they may represent the heterogeneous molecular signature of primary as well as metastatic cancer lesions. Thus, the isolation of CTCs may serve not only as a prognostic tool but moreover as a liquid biopsy and a window towards personalized treatment. This review discusses the clinical impact of CTCs in the different stages of PC