External validation of the Prostate Cancer Prevention Trial and the European Randomized Study of Screening for Prostate Cancer risk calculators in a Chinese cohort

Several prediction models have been developed to estimate the outcomes of prostate biopsies. Most of these tools were designed for use with Western populations and have not been validated across different ethnic groups. Therefore, we evaluated the predictive value of the Prostate Cancer Prevention Trial （PCPT） and the European Randomized Study of Screening for Prostate Cancer （ERSPC） risk calculators in a Chinese cohort. Clinicopathological information was obtained from 495 Chinese men who had undergone extended prostate biopsies between January 2009 and March 2011. The estimated probabilities of prostate cancer and high-grade disease （Gleason 〉6） were calculated using the PCPT and ERSPC risk calculators. Overall measures, discrimination, calibration and clinical usefulness were assessed for the model evaluation. Of these patients, 28.7% were diagnosed with prostate cancer and 19.4% had high-grade disease. Compared to the PCPT model and the prostate-specific antigen （PSA） threshold of 4 ng m1-1, the ERSPC risk calculator exhibited better discriminative ability for predicting positive biopsies and high-grade disease （the area under the curve was 0.831 and 0.852, respectively, P〈O.01 for both）. Decision curve analysis also suggested the favourable clinical utility of the ERSPC calculator in the validation dataset. Both prediction models demonstrated miscalibration： the risk of prostate cancer and high-grade disease was overestimated by approximately 20% for a wide range of predicted probabilities. In conclusion, the ERSPC risk calculator outperformed both the PCPT model and the PSA threshold of 4 ng ml- z in predicting prostate cancer and high-grade disease in Chinese patients. However, the prediction tools derived from Western men significantly overestimated the probability of prostate cancer and high-grade disease compared to the outcomes of biopsies in a Chinese cohort.

Random phase screen influence of the inhomogeneous tissue layer on the generation of acoustic vortices

The influence of the inhomogeneous tissue layer on the generation of acoustic vortices （AV） is studied theoretically and experimentally based on the phase screen model. By considering the time-shift of a random phase screen, the formula of acoustic pressure for the AV beam generated by a circular array of eight planar piston sources is derived. With the actual correlation length of the abdominal wall, numerical simulations before and after the insertion of the inhomogeneous tissue layer are conducted, and also demonstrated by experimental measurements. It is proved that, when the thickness variation of the phase screen is less than one wavelength, no significant influence on the generation of AVs can be produced. The variations of vortex nodes and antinodes in terms of the location, shape, and size of AVs are not obvious. Although the circular pressure distribution might be deformed by the phase interference with a larger thickness variation, AVs can still be generated around the center axis with perfect phase spirals in a reduced effective radius. The favorable results provide the feasibility of AV generation inside the human body and suggest the application potential of AVs in object manipulation for biomedical engineering.

Tissue-targeting lead generation and optimization from random and directed screening of technetium-99m labeled tripeptide complex libraries in vivo

Background Screening libraries against a molecular target in vitro are idealized models that cannot reflect the real state in vivo where biomolecules coexist and interact. C-terminal amide tripeptides labelled with Technetium-99m can provide a unique noninvasive approach to trace a large number of compounds in vivo. Methods The C-terminal amide tripeptide libraries were synthesized on Rink Amide-MBHA resin using iterative and pooling protocol. Technetium （V） oxo core [TcO^3＋] was bound to each tripeptide via 4 deprotonated nitrogen atoms to form a library of 8000 ^99mTc tripeptoid complexes. The radiocombinatorial screening （RCS） in vivo was carried out on SD rats and A549 tumour bearing mice. Results Signals of tissue distribution and metabolism of libraries were recorded by counting or imaging and tissue targeting leads identified by both random and directed RCS. Among them, ^99mTc RPA, ^99mTc VIG and ^99mTC RES had specific tissue targeting in kidney, liver and tumour respectively. The percent injected dose per gram tissue of ^99mTc labelled leads in their target tissue was highly structure dependent. Because the nontarget tissue binding and the metabolism of ^99mTc tripeptoid sublibraries were simultaneously monitored successfully by RCS, the interference of background activity was limited to the lowest level. Optimization of renal function agent from the labelled libraries was carried out by directed screening. ^99mTc DSG was finally identified the most promising agent for renal function studies. Conclusions RCS in vivo is a powerful tool for the discovery of tissue targeting drugs. The potential screening bias is probably the major limitation of labelled libraries.