P-N junctions in intermetallic semiconductors

Imperial Users onl

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

A computer for determining human cardiac output

In the last twenty years many methods of cardiac output determination have been developed such as the Ballistocardiograph by Henderson and later by Cournand, pulse and blood pressure techniques employed by Bazett and associates, magnetic procedures and lately ferromagnetic resonance techniques have been tried. Most of these methods, however, either have severe operational disadvantages or are still in experimental states. Of course, efforts to determine cardiac output would be fruitless if its determinations were of no practical importance. However, much valuable information is given by a knowledge of cardiac output and blood transit time through the heart and lungs. At present a surgeon or physician can have the blood pressure, pulse and electrocardiogram continuously available to him during surgery or diagnostic work. If at the same time the cardiac output were available, its correlation with the above information would give a much clearer picture of the condition and reactions of the cardiovascular system. It is therefore obvious that the determination of cardiac output is not only of general interest but is of considerable importance in medical practice. To date, the most clinically adaptable method appears to be that using the indicator dilution technique. This method depends upon two important considerations. The indicator that is used must be non-toxic, even in large doses. The unit used for the detection of the dilution must be sensitive only to that indicator. The indicator may be either a chemical dye and the recording apparatus a densitometer, or an isotope with the detecting unit being a radiation monitor. Indicator dilution curves depend for their validity upon satisfactory and complete mixing of the dye with the blood. In addition, it is assumed that the densitometer samples a representative portion of that blood. Recent work (17) has shown that the indicator dilution technique for cardiac output determination has many advantages over the other methods mentioned above. This method allows the determination of cardiac output on severely ill patients. It is also possible to make repeated measurements, and in addition this method allows the determination of other important cardiovascular indices. However, a technician must spend between 30 and 60 minutes analysing each curve before all the answers are available. Thus, while this technique has many advantages, this time factor is one criticism. It was therefore thought desirable to design a computer which would allow the rapid determination of these important cardiopulmonary variables. Such a computer should be technically and operationally as simple as possible and should have an accuracy consistent with the accuracy of the method of determination. Numbers in brackets refer to bibliography