Replication study of genome-wide associated SNPs with late-onset Alzheimer's disease.

Late-onset Alzheimer's disease (LOAD) is a multifactorial disease with the potential involvement of multiple genes. Four recent genome-wide association studies (GWAS) have found variants showing significant association with LOAD on chromosomes 6, 10, 11, 12, 14, 18, 19, and on the X chromosome. We examined a total of 12 significant SNPs from these studies to determine if the results could be replicated in an independent large case-control sample. We genotyped these 12 SNPs as well the E2/E3/E4 APOE polymorphisms in up to 993 Caucasian Americans with LOAD and up to 976 age-matched healthy Caucasian Americans. We found no statistically significant associations between the 12 SNPs and the risk of AD. Stratification by APOE*4 carrier status also failed to reveal statistically significant associations. Additional analyses were performed to examine potential associations between the 12 SNPs and age-at-onset (AAO) and disease duration among AD cases. Significant associations were observed between AAO and ZNF224/rs3746319 (P = 0.002) and KCNMA1/rs16934131 (P = 0.0066). KCNMA1/rs16934131 also demonstrated statistically significant association with disease duration (P = 0.0002). Although we have been unable to replicate the reported GWAS association with AD risk in our sample, we have identified two new associations with AAO and disease duration that need to be confirmed in additional studies.

Monte Carlo simulations: a useful tool to extend in vivo calibrations and explore alternative approaches.

Designing and testing new equipment can be an expensive and time consuming process or the desired performance characteristics may preclude its construction due to technological shortcomings. Cost may also prevent other types of scenario being tested. An alternative is to use Monte Carlo simulations to make the investigations. This paper exemplifies how Monte Carlo code calculations can be used to fill the gap by describing two investigations: (1) the possible self-attenuation of homogeneously distributed natural uranium in a lung phantom; and (2) the effect of activity deposited in the ribs on the activity estimate from a lung count.

The uncertainty in the activity estimate from a lung count due to the variability in chest wall thickness profile.

Calibration of a lung counter requires the use of a realistic torso phantom. The depth profile of both torso phantoms' (LLNL and JAERI) chest plate covers is fixed and assumed to be equivalent to a person's chest wall; however, ultrasound measurements of humans have shown this to be an approximation. When the depth profile of a calibration phantom is different from that of a subject, then a systematic uncertainty will be introduced into the activity estimate. Monte Carlo simulation has shown that changes in the depth profile of the chest wall thickness affect the counting efficiency. Ultrasound measurements have suggested that the coefficient of variation in the depth profile of the chest wall thickness lies between 13% and 26% for male workers; therefore, the added uncertainty to an activity estimate will be an over or underestimate of about a factor of 1.07 resulting from the different depth profile. The factor will be somewhat higher for females, probably about 1.2 at the extreme. These additional uncertainties resulting from depth profile differences are small compared with other uncertainties commonly encountered in lung counting: detector positioning, deposition patterns of the activity, measurement of the chest wall thickness, etc.

Chest wall thickness measurements: the alternative approach extended for 241Am.

The Human Monitoring Laboratory has extended the technique of determining the chest wall thickness of an individual using information from the spectrum produced by internally deposited radionuclides. The technique has been investigated both theoretically and practically using germanium detectors and the Lawrence Livermore Torso Phantom. The phantom was used with a lung set containing homogeneously distributed 241Am. Chest wall thicknesses were varied by using a series of muscle equivalent overlay plates that gave a range of 1.6 cm to 3.9 cm thickness. It was found that a 3-cm chest wall thickness can be estimated to within 18%. Using a spectral addition technique 1 kBq was estimated to be the "practical" lower limit of activity for this method.

The Canadian National Calibration Reference Centre for In-Vivo Monitoring: thyroid monitoring. Part I: The national inter-comparison programme.

This article is the first part of a five-part series covering various aspects of occupational thyroid monitoring. The Canadian National Calibration Reference Centre for In-Vivo Monitoring conducts a thyroid inter-comparison programme that now includes more than 100 facilities. The scope of the programme, begun in 1988, has greatly expanded in the last two years following a considerable effort to locate and inform facilities. This article presents the details of the programme, its results, and the lessons learned. Subsequent articles will discuss sources of errors, methodology, instrumental configuration, and counting geometry optimization.