Cadmium exposure and risk of kidney effects and bone fractures : population-based studies in England and Sweden

Cadmium (Cd) is a toxic metal with no beneficial biological function. The dissemination of cadmium to the surface environment, by industrial and agricultural practices, has led to increased human exposure. Food is the main source of exposure in the general non - smoking population however in areas close to industrial sources, contact with contaminated environmental media may also be important. Previous studies have shown toxic effects of cadmium on the kidneys and bone, however, considerable unce rtainty remains over the exposure levels at which these toxic effects may start to occur and the clinical relevance of the early effects observed following long - term, low - level cadmium exposure. The aims of this thesis were: 1) To assess cadmium body burde n and early signs of kidney dysfunction in a population exposed to industrial cadmium emissions and to develop and validate an air dispersion model of these emissions. 2) To identify urinary metabolites, associated with cadmium exposure, using metabolic pr ofiling techniques. 3) To prospectively assess the association between validated estimates of dietary cadmium exposure and chronic kidney disease (CKD) incidence, kidney stone incidence, and fracture incidence, in two large population - based cohorts of men and women. In a population - based sample of 180 subjects, living close to a zinc smelter in Avonmouth, Southwest England, urinary cadmium concentrations (median = 0.22 nmol Cd/mmol creatinine) were in the same range as those where associations with kidney a nd/or bone effects have been observed previously. Three percent had concentrations above 1nmol Cd/mmol creatinine (~1μg/g) – the point of departure for tubular proteinuria set by the European Food Safety Authority in 2009. Modelled air cadmium concentrat ions from the smelter were strongly correlated with those from air monitoring sites ( R 2 =0.84) and were a significant predictor of urinary cadmium (p=0.04). In a cross - sectional analysis, a significant dose - response relationship between urinary cadmium and one of the biomarkers of early tubular dysfunction (N - acetyl - β - d - glucosaminidase) was observed. Metabolic profiling identified six urinary metabolites, either related to mitochondrial metabolism or one carbon metabolism, associated with urinary cadmium. T wo large population - based cohorts of men and women from Central Sweden were used to investigate the association between dietary cadmium exposure and incidence of CKD, kidney stones and fractures. Median dietary cadmium exposure levels in our study populat ions were 19μg/day in men and 13μg/day women. During an average of 12 years of follow - up, we ascertained 599 incident cases of CKD among men (481,591 person - years) and 253 among women (415,432 person - years). We did not observe an association between diet ary Cd and rate of CKD in men, hazard ratio (HR) 0.97 (95% CI 0.77 - 1.21) or women HR 0.74 (95% CI 0.53 - 1.04), either before or after adjustment for potential confounders. During an average of 13 years of follow - up, we ascertained 707 incident cases of ki dney stone among men (421,611 person - years) and 290 among women (403,575 person - years). Likewise, we did not observe an association between dietary Cd and rate of kidney stones in men HR 0.97 (95% CI 0.77 - 1.23) or women HR 0.99 (95%CI 0.89 - 1.43), either b efore or after adjustment for potential confounders. We ascertained 2,183 cases of any fracture and 374 cases of hip fracture, during a 10 - year follow - up of 2 0 ,173 Swedish men. In the multivariable adjusted model, dietary cadmium was associated with a sta tistically significant 19% (HR: 1.19, 95%CI: 1.06 - 1.34) higher rate of any fracture, comparing highest tertile with lowest. Hip fracture rates were also higher in the highest tertile of cadmium exposure but only statistically significant among never smoke rs, with a 70% (HR: 1.70, 95%CI: 1.04 - 2.77) higher rate. This study provides the first data on hip fracture rates in relation to cadmium exposure and is the first to report an excess risk of any fracture associated with long - term low - level cadmium exposur e in men. The results of this thesis suggest that the adverse effects of cadmium exposure around the Avonmouth smelter may be detected in urinary biomarkers. In addition, the results of the prospective studies do not support a role of dietary cadmium expo sure, at the level seen in the general population, in the development of CKD or kidney stones. However, the results do provide further evidence of increase fracture risk in relation to cadmium exposure. In conjunction with recent findings, the results of this thesis suggest that bone may be a more sensitive target of cadmium toxicity than the kidney, in terms of clinically relevant outcomes

System-level investigation of multi-MW direct-drive wind power PM vernier generators

Surface mounted permanent magnet Vernier (SPM-V) machines are known for their high torque density but relatively poor power factor compared to conventional SPM machines. The high torque density feature of the SPM-V machines is desirable for direct-drive offshore wind power applications as it leads to reduced generator size, mass and cost. However, their poor power factor can negatively affect the converter cost and efficiency. This paper compares the system-level performance, including generator active and structural components and converter, between the SPM-V and the conventional SPM generator systems. Four different power ratings, i.e. 0.5MW, 3MW, 5MW and 10MW, have been considered to study the trend of system-level performance with increasing power rating. The study shows that the SPM-V generators can be lighter and cheaper than their conventional SPM counterparts. However, after the consideration of converter cost and efficiency, the conventional SPM generator exhibited slightly better overall performance. Nonetheless, with the development of novel Vernier topologies and reduction in converter costs in the future due to emerging technologies, the Vernier generators can still be competitive for direct-drive offshore wind power applications

Fusing Structural and Functional MRIs using Graph Convolutional Networks for Autism Classification

Geometric deep learning methods such as graph convolutional networks have recently proven to deliver generalized solutions in disease prediction using medical imaging. In this paper, we focus particularly on their use in autism classification. Most of the recent methods use graphs to leverage phenotypic information about subjects (patients or healthy controls) as additional contextual information. To do so, metadata such as age, gender and acquisition sites are utilized to define intricate relations (edges) between the subjects. We alleviate the use of such non-imaging metadata and propose a fully imaging-based approach where information from structural and functional Magnetic Resonance Imaging (MRI) data are fused to construct the edges and nodes of the graph. To characterize each subject, we employ brain summaries. These are 3D images obtained from the 4D spatiotemporal resting-state fMRI data through summarization of the temporal activity of each voxel using neuroscientifically informed temporal measures such as amplitude low frequency fluctuations and entropy. Further, to extract features from these 3D brain summaries, we propose a 3D CNN model. We perform analysis on the open dataset for autism research (full ABIDE I-II) and show that by using simple brain summary measures and incorporating sMRI information, there is a noticeable increase in the generalizability and performance values of the framework as compared to state-of-the-art graph-based models

Realistic Electron-Electron Interaction in a Quantum Wire

The form of an effective electron-electron interaction in a quantum wire with a large static dielectric constant is determined and the resulting properties of the electron liquid in such a one-dimensional system are described. The exchange and correlation energies are evaluated and a possibility of a paramagnetic-ferromagnetic phase transition in the ground state of such a system is discussed. Low-energy excitations are briefly described.Comment: 10 pages, 6 figure

Surface layering of liquids: The role of surface tension

Recent measurements show that the free surfaces of liquid metals and alloys are always layered, regardless of composition and surface tension; a result supported by three decades of simulations and theory. Recent theoretical work claims, however, that at low enough temperatures the free surfaces of all liquids should become layered, unless preempted by bulk freezing. Using x-ray reflectivity and diffuse scattering measurements we show that there is no observable surface-induced layering in water at T=298 K, thus highlighting a fundamental difference between dielectric and metallic liquids. The implications of this result for the question in the title are discussed.Comment: 5 pages, 4 figures, to appear in Phys. Rev. B. 69 (2004

Test of Sum Rules in Nucleon Transfer Reactions

The quantitative consistency of nucleon transfer reactions as a probe of the occupancy of valence orbits in nuclei is tested. Neutron-adding, neutron-removal, and proton-adding transfer reactions were measured on the four stable even Ni isotopes, with particular attention to the cross section determinations. The data were analyzed consistently in terms of the distorted wave Born approximation to yield spectroscopic factors. Valence-orbit occupancies were extracted, utilizing the Macfarlane-French sum rules. The deduced occupancies are consistent with the changing number of valence neutrons, as are the vacancies for protons, both at the level of <5%. While there has been some debate regarding the true “observability” of spectroscopic factors, the present results indicate that empirically they yield self-consistent results

Valence nucleon populations in the Ni isotopes

Measurements of neutron-adding, neutron-removing, and proton-adding reactions were carried out for the four stable even Ni isotopes. Particular attention was paid to obtaining precise values of the cross sections at the peaks of the angular distributions. Tests with sum rules for the neutron data indicate that the results are self-consistent at the level of a few tenths of a nucleon. Data on proton-adding reactions were also obtained and analyzed with a slightly different method—while these data are also consistent, the ambiguities are larger. The occupancies of the neutron orbits derived from the data, the proton vacancies, and the energy centroids of the neutron, neutron-hole, and proton single-particle excitations are obtained. The data also provide some estimate about the closure of the 0f7/2 shell. The results are compared to shell-model calculations and may serve as a reference point for future exploration