Fluorescence Correlation Spectroscopy Monitors the Fate of Degradable Nanocarriers in the Blood Stream

[Image: see text] The use of nanoparticles as carriers to deliver pharmacologically active compounds to specific parts of the body via the bloodstream is a promising therapeutic approach for the effective treatment of various diseases. To reach their target sites, nanocarriers (NCs) need to circulate in the bloodstream for prolonged periods without aggregation, degradation, or cargo loss. However, it is very difficult to identify and monitor small-sized NCs and their cargo in the dense and highly complex blood environment. Here, we present a new fluorescence correlation spectroscopy-based method that allows the precise characterization of fluorescently labeled NCs in samples of less than 50 μL of whole blood. The NC size, concentration, and loading efficiency can be measured to evaluate circulation times, stability, or premature drug release. We apply the new method to follow the fate of pH-degradable fluorescent cargo-loaded nanogels in the blood of live mice for periods of up to 72 h

An Instrument Design for the Accurate Determination of the Electron Beam Location in the Linac Coherent Light Source Undulator

The Linac Coherent Light Source (LCLS), currently under design, requires accurate alignment between the electron beam and each undulator's magnetic centerline. A beam finder wire (BFW) instrument has been developed to provide beam location information that is used to move the undulators to their appropriate positions. A BFW instrument is mounted at each of the 33 magnets in the undulator section. Beam detection is achieved by electrons impacting two carbon fiber wires and then sensing the downstream radiation. The wires are mounted vertically and horizontally on a wire card similar to that of a traditional wire scanner instrument. The development of the BFW presents several design challenges due to the need for high accuracy of the wires locations and the need for removal of the wires during actual operation of the LCLS (30 microns repeatability is required for the wire locations). In this paper, we present the technical specification, design criteria, mechanical design, and results from prototype tests for the BFW

Concomitant Carcinoma in situ in Cystectomy Specimens Is Not Associated with Clinical Outcomes after Surgery

Objective: The aim of this study was to externally validate the prognostic value of concomitant urothelial carcinoma in situ (CIS) in radical cystectomy (RC) specimens using a large international cohort of bladder cancer patients. Methods: The records of 3,973 patients treated with RC and bilateral lymphadenectomy for urothelial carcinoma of the bladder (UCB) at nine centers worldwide were reviewed. Surgical specimens were evaluated by a genitourinary pathologist at each center. Uni- and multivariable Cox regression models addressed time to recurrence and cancer-specific mortality after RC. Results: 1,741 (43.8%) patients had concomitant CIS in their RC specimens. Concomitant CIS was more common in organ-confined UCB and was associated with lymphovascular invasion (p < 0.001). Concomitant CIS was not associated with either disease recurrence or cancer-specific death regardless of pathologic stage. The presence of concomitant CIS did not improve the predictive accuracy of standard predictors for either disease recurrence or cancer-specific death in any of the subgroups. Conclusions: We could not confirm the prognostic value of concomitant CIS in RC specimens. This, together with the discrepancy between pathologists in determining the presence of concomitant CIS at the morphologic level, limits the clinical utility of concomitant CIS in RC specimens for clinical decision-making. Copyright (C) 2011 S. Karger AG, Base

Radiation Protection Studies for LCLS Tune Up Dump

The Linac Coherent Light Source (LCLS) at the Stanford Linear Accelerator Center is a pioneer fourth generation hard x-ray free electron laser that shall start to deliver laser pulses in 2009. Among other components of LCLS that present radiation protection concerns, the tune up dump (tdund) is of special interest because it also constitutes an issue for machine protection, as it is placed close to radiation sensitive components, like electronic devices and permanent magnets in the undulators. This paper first introduces the stopper of tdund looking at the heat load, and then it describes the shielding around the dump necessary to maintain the prompt and residual dose within design values. Next, preliminary comparisons of the magnetization loss in a dedicated on-site magnet irradiation experiment with FLUKA simulations serve to characterize the magnetic response to radiation of magnets like those of LCLS. The previous knowledge, together with the limit for the allowed demagnetization, are used to estimate the lifetime of the undulator. Further simulations provide guidelines on which lifetime can be expected for an electronic device placed at a given distance of tdund