SNP and Haplotype Regional Heritability Mapping (SNHap-RHM): Joint Mapping of Common and Rare Variation Affecting Complex Traits

We describe a genome-wide analytical approach, SNP and Haplotype Regional Heritability Mapping (SNHap-RHM), that provides regional estimates of the heritability across locally defined regions in the genome. This approach utilises relationship matrices that are based on sharing of SNP and haplotype alleles at local haplotype blocks delimited by recombination boundaries in the genome. We implemented the approach on simulated data and show that the haplotype-based regional GRMs capture variation that is complementary to that captured by SNP-based regional GRMs, and thus justifying the fitting of the two GRMs jointly in a single analysis (SNHap-RHM). SNHap-RHM captures regions in the genome contributing to the phenotypic variation that existing genome-wide analysis methods may fail to capture. We further demonstrate that there are real benefits to be gained from this approach by applying it to real data from about 20,000 individuals from the Generation Scotland: Scottish Family Health Study. We analysed height and major depressive disorder (MDD). We identified seven genomic regions that are genome-wide significant for height, and three regions significant at a suggestive threshold (p-value < 1 × 10−5) for MDD. These significant regions have genes mapped to within 400 kb of them. The genes mapped for height have been reported to be associated with height in humans. Similarly, those mapped for MDD have been reported to be associated with major depressive disorder and other psychiatry phenotypes. The results show that SNHap-RHM presents an exciting new opportunity to analyse complex traits by allowing the joint mapping of novel genomic regions tagged by either SNPs or haplotypes, potentially leading to the recovery of some of the “missing” heritability.

Design and Performance Investigation of a Robot-Assisted Flexible Ureteroscopy System

Flexible ureteroscopy (FURS) has been developed and has become a preferred routine procedure for both diagnosis and treatment of kidney stones and other renal diseases inside the urinary tract. The traditional manual FURS procedure is highly skill-demanding and easily brings about physical fatigue and burnout for surgeons. The improper operational ergonomics and fragile instruments also hinder its further development and patient safety enhancement. A robotic system is presented in this paper to assist the FURS procedure. The system with a master-slave configuration is designed based on the requirement analysis in manual operation. A joint-to-joint mapping strategy and several control strategies are built to realize intuitive and safe operations. Both phantom and animal experiments validate that the robot has significant advantages over manual operations, including the easy-to-use manner, reduced intraoperative time, and improved surgical ergonomics. The proposed robotic system can solve the major drawbacks of manual FURS. The test results demonstrate that the robot has great potential for clinical applications.

Speckle-Based Sensing of Microscopic Dynamics in Expanding Polymer Foams: Application of the Stacked Speckle History Technique

Microscopic structural rearrangements in expanding polylactide foams were probed using multiple dynamic scattering of laser radiation in the foam volume. Formation and subsequent expansion of polylactide foams was provided by a rapid or slow depressurization of the “plasticized polylactide–supercritical carbon dioxide” system. Dynamic speckles induced by a multiple scattering of laser radiation in the expanding foam were analyzed using the stacked speckle history technique, which is based on a joint mapping of spatial–temporal dynamics of evolving speckle patterns. A significant decrease in the depressurization rate in the case of transition from a rapid to slow foaming (from 0.03 MPa/s to 0.006 MPa/s) causes dramatic changes in the texture of the synthesized stacked speckle history maps. These changes are associated with transition from the boiling dynamics of time-varying speckles to their pronounced translational motions and are manifested as significant slopes of individual speckle traces on the recovered stacked speckle history maps. This feature is interpreted in terms of the actual absence of a new cell nucleation effect in the expanding foam upon slow depressurization on the dynamic scattering of laser radiation.

Joint mapping of cardiovascular diseases: comparing the geographic patterns in incident acute myocardial infarction, stroke and atrial fibrillation, a Danish register-based cohort study 2014–15

Background Disease mapping aims at identifying geographic patterns in disease. This may provide a better understanding of disease aetiology and risk factors as well as enable targeted prevention and allocation of resources. Joint mapping of multiple diseases may lead to improved insights since e.g. similarities and differences between geographic patterns may reflect shared and disease-specific determinants of disease. The objective of this study was to compare the geographic patterns in incident acute myocardial infarction (AMI), stroke and atrial fibrillation (AF) using the unique, population-based Danish register data. Methods Incident AMI, stroke and AF was modelled by a multivariate Poisson model including a disease-specific random effect of municipality modelled by a multivariate conditionally autoregressive (MCAR) structure. Analyses were adjusted for age, sex and income. Results The study included 3.5 million adults contributing 6.8 million person-years. In total, 18,349 incident cases of AMI, 28,006 incident cases of stroke, and 39,040 incident cases of AF occurred. Estimated municipality-specific standardized incidence rates ranged from 0.76 to 1.35 for AMI, from 0.79 to 1.38 for stroke, and from 0.85 to 1.24 for AF. In all diseases, geographic variation with clusters of high or low risk of disease after adjustment was seen. The geographic patterns displayed overall similarities between the diseases, with stroke and AF having the strongest resemblances. The most notable difference was observed in Copenhagen (high risk of stroke and AF, low risk of AMI). AF showed the least geographic variation. Conclusion Using multiple-disease mapping, this study adds to the results of previous studies by enabling joint evaluation and comparison of the geographic patterns in AMI, stroke and AF. The simultaneous mapping of diseases displayed similarities and differences in occurrence that are non-assessable in traditional single-disease mapping studies. In addition to reflecting the fact that AF is a strong risk factor for stroke, the results suggested that AMI, stroke and AF share some, but not all environmental risk factors after accounting for age, sex and income (indicator of lifestyle and health behaviour).

SNP and Haplotype Regional Heritability Mapping (SNHap-RHM): joint mapping of common and rare variation affecting complex traits

We describe a genome-wide analytical approach, SNP and Haplotype Regional Heritability Mapping (SNHap-RHM), that provides regional estimates of the heritability across locally defined regions in the genome. This approach utilises relationship matrices that are based on sharing of SNP and haplotype alleles at local haplotype blocks delimited by recombination boundaries in the genome. We implemented the approach on simulated data and show that the haplotype-based regional GRMs capture variation that is complementary to that captured by SNP-based regional GRMs, and thus justifying the fitting of the two GRMs jointly in a single analysis (SNHap-RHM). SNHap-RHM captures regions in the genome contributing to the phenotypic variation that existing genome-wide analysis methods may fail to capture. We further demonstrate that there are real benefits to be gained from this approach by applying it to real data from about 20,000 individuals from the Generation Scotland: Scottish Family Health Study. We analysed height and major depressive disorder (MDD). We identified seven genomic regions that are genome-wide significant for height, and three regions significant at a suggestive threshold (p-value <1x10^(-5) ) for MDD. These significant regions have genes mapped to within 400kb of them. The genes mapped for height have been reported to be associated with height in humans, whiles those mapped for MDD have been reported to be associated with major depressive disorder and other psychiatry phenotypes. The results show that SNHap-RHM presents an exciting new opportunity to analyse complex traits by allowing the joint mapping of novel genomic regions tagged by either SNPs or haplotypes, potentially leading to the recovery of some of the "missing" heritability.

Fall of Ground Management Through Underground Joint Mapping: Shallow Chrome Mining Case Study

Joint properties and useful mapping techniques are key to the fall of ground management in underground mining. The study analysed the fall of ground management techniques at the mine with a view to identify the causal factors of the falls of ground. This paper practically demonstrates how two mapping techniques were used to obtain joint data. A brief description of geological discontinuities at the study area is given in the paper. Joint mapping was carried out in both the North and South sections of the mine. Procedures followed when collecting joint data are also provided. The collected joint data was used to evaluate rock fall probability. Rockfall probabilistic analysis carried out in the study indicates that about 80% of all key blocks formed are 1m3 in size. Results show that larger blocks are more likely to fail through the rotation. Furthermore, to prevent small blocks from falling between support units, areal coverage is suggested in heavily jointed rock masses. Probabilistic analysis can be used to evaluate the probability of rock falls, and support design for stability enhancement. The research noted that at the centre of effective falls of ground management are accurate and precise structural/joint mapping. This research is part of an MSc Engineering study.