Detecting genetic and nutritional lung cancer risk factors related to folate metabolism using Bayesian generalized linear models

Complex diseases, such as cancer, are caused by various genetic and environmental factors, and their interactions. Joint analysis of these factors and their interactions would increase the power to detect risk factors but is statistically. Bayesian generalized linear models using student-t prior distributions on coefficients, is a novel method to simultaneously analyze genetic factors, environmental factors, and interactions. I performed simulation studies using three different disease models and demonstrated that the variable selection performance of Bayesian generalized linear models is comparable to that of Bayesian stochastic search variable selection, an improved method for variable selection when compared to standard methods. I further evaluated the variable selection performance of Bayesian generalized linear models using different numbers of candidate covariates and different sample sizes, and provided a guideline for required sample size to achieve a high power of variable selection using Bayesian generalize linear models, considering different scales of number of candidate covariates. ^ Polymorphisms in folate metabolism genes and nutritional factors have been previously associated with lung cancer risk. In this study, I simultaneously analyzed 115 tag SNPs in folate metabolism genes, 14 nutritional factors, and all possible genetic-nutritional interactions from 1239 lung cancer cases and 1692 controls using Bayesian generalized linear models stratified by never, former, and current smoking status. SNPs in MTRR were significantly associated with lung cancer risk across never, former, and current smokers. In never smokers, three SNPs in TYMS and three gene-nutrient interactions, including an interaction between SHMT1 and vitamin B12, an interaction between MTRR and total fat intake, and an interaction between MTR and alcohol use, were also identified as associated with lung cancer risk. These lung cancer risk factors are worthy of further investigation.^

The relationship between hospital financial performance and information technology integration strategy selection

In light of the new healthcare regulations, hospitals are increasingly reevaluating their IT integration strategies to meet expanded healthcare information exchange requirements. Nevertheless, hospital executives do not have all the information they need to differentiate between the available strategies and recognize what may better fit their organizational needs. ^ In the interest of providing the desired information, this study explored the relationships between hospital financial performance, integration strategy selection, and strategy change. The integration strategies examined – applied as binary logistic regression dependent variables and in the order from most to least integrated – were Single-Vendor (SV), Best-of-Suite (BoS), and Best-of-Breed (BoB). In addition, the financial measurements adopted as independent variables for the models were two administrative labor efficiency and six industry standard financial ratios designed to provide a broad proxy of hospital financial performance. Furthermore, descriptive statistical analyses were carried out to evaluate recent trends in hospital integration strategy change. Overall six research questions were proposed for this study. ^ The first research question sought to answer if financial performance was related to the selection of integration strategies. The next questions, however, explored whether hospitals were more likely to change strategies or remain the same when there was no external stimulus to change, and if they did change, they would prefer strategies closer to the existing ones. These were followed by a question that inquired if financial performance was also related to strategy change. Nevertheless, rounding up the questions, the last two probed if the new Health Information Technology for Economic and Clinical Health (HITECH) Act had any impact on the frequency and direction of strategy change. ^ The results confirmed that financial performance is related to both IT integration strategy selection and strategy change, while concurred with prior studies that suggested hospital and environmental characteristics are associated factors as well. Specifically this study noted that the most integrated SV strategy is related to increased administrative labor efficiency and the hybrid BoS strategy is associated with improved financial health (based on operating margin and equity financing ratios). On the other hand, no financial indicators were found to be related to the least integrated BoB strategy, except for short-term liquidity (current ratio) when involving strategy change. ^ Ultimately, this study concluded that when making IT integration strategy decisions hospitals closely follow the resource dependence view of minimizing uncertainty. As each integration strategy may favor certain organizational characteristics, hospitals traditionally preferred not to make strategy changes and when they did, they selected strategies that were more closely related to the existing ones. However, as new regulations further heighten revenue uncertainty while require increased information integration, moving forward, as evidence already suggests a growing trend of organizations shifting towards more integrated strategies, hospitals may be more limited in their strategy selection choices.^

Geochemistry and oxygen and iron isotope ratios of mafic rocks

Recycling of oceanic crust into the deep mantle via subduction is a widely accepted mechanism for creating compositional heterogeneity in the upper mantle and for explaining the distinct geochemistry of mantle plumes. The oxygen isotope ratios (d18O) of some ocean island basalts (OIB) span values both above and below that of unmetasomatised upper mantle (5.5 ± 0.4 per mil) and provide support for this hypothesis, as it is widely assumed that most variations in d18O are produced by near-surface low-temperature processes. Here we show a significant linear relationship between d18O and stable iron isotope ratios (d57Fe) in a suite of pristine eclogite xenoliths. The d18O values of both bulk samples and garnets range from values within error of normal mantle to significantly lighter values. The observed range and correlation between d18O and d57Fe is unlikely to be inherited from oceanic crust, as d57Fe values determined for samples of hydrothermally altered oceanic crust do not differ significantly from the mantle value and show no correlation with d18O. It is proposed that the correlated d57Fe and d18O variations in this particular eclogite suite are predominantly related to isotopic fractionation by disequilibrium partial melting although modification by melt percolation processes cannot be ruled out. Fractionation of Fe and O isotopes by removal of partial melt enriched in isotopically heavy Fe and O is supported by negative correlations between bulk sample d57Fe and Cr content and bulk sample and garnet d18O and Sc contents, as Cr and Sc are elements that become enriched in garnet- and pyroxene-bearing melt residues. Melt extraction could take place either during subduction, where the eclogites represent the residues of melted oceanic lithosphere, or could take place during long-term residence within the lithospheric mantle, in which case the protoliths of the eclogites could be of either crustal or mantle origin. This modification of both d57Fe and d18O by melting processes and specifically the production of low-d18O signatures in mafic rocks implies that some of the isotopically light d18O values observed in OIB and eclogite xenoliths may not necessarily reflect near-surface processes or components.

Isotopic and trace element composition of basalts from DSDP Leg 82 Holes

Sr and Nd isotopic composition of 23 basalts from Sites 556-559 and 561-564. are reported. The 87Sr/86Sr ratios in fresh glasses and leached whole rocks range from 0.7025 to 0.7034 and are negatively correlated with the initial 143Nd/ 144Nd compositions, which range from 0.51315 to 0.51289. The Sr and Nd isotopic compositions (in glasses or leached samples) lie within the fields of mid-ocean ridge basalts (MORB) and ocean island basalts (OIB) from the Azores on the Nd-Sr mantle array/fan plot. In general, there is a correlation between the trace element characteristics and the 143Nd/144Nd composition (i.e., samples with Hf/Ta>7 and (Ce/Sm)N<1 [normal-MORB] have initial 143Nd/144Nd>0.51307, whereas samples with Hf/Ta<7 and (Ce/Sm)N>1 (enriched-MORB) have initial 143Nd/144Nd compositions <0.51300). A significant deviation from this general rule is found in Hole 558, where the N-MORB can have, within experimental limits, identical isotopic compositions to those found in associated E-MORB. The plume-depleted asthenosphere mixing hypothesis of Schilling (1975), White and Schilling (1978) and Schilling et al. (1977) provides a framework within which the present data can be evaluated. Given the distribution and possible origins of the chemical and isotopic heterogeneity observed in Leg 82 basalts, and some other basalts in the area, it would appear that the Schilling et al. model is not entirely satisfactory. In particular, it can be shown that trace element data may incorrectly estimate the plume component and more localized mantle heterogeneity (both chemical and isotopic) may be important.

Chemical composition of bottom sediments at DSDP Sites 91-595 and 91-596 and ODP Sites 114-701 and 129-801

Subducted sediments play an important role in arc magmatism and crust-mantle recycling. Models of continental growth, continental composition, convergent margin magmatism and mantle heterogeneity all require a better understanding of the mass and chemical fluxes associated with subducting sediments. We have evaluated subducting sediments on a global basis in order to better define their chemical systematics and to determine both regional and global average compositions. We then use these compositions to assess the importance of sediments to arc volcanism and crust-mantle recycling, and to re-evaluate the chemical composition of the continental crust. The large variations in the chemical composition of marine sediments are for the most part linked to the main lithological constituents. The alkali elements (K, Rb and Cs) and high field strength elements (Ti, Nb, Hf, Zr) are closely linked to the detrital phase in marine sediments; Th is largely detrital but may be enriched in the hydrogenous Fe-Mn component of sediments; REE patterns are largely continental, but abundances are closely linked to fish debris phosphate; U is mostly detrital, but also dependent on the supply and burial rate of organic matter; Ba is linked to both biogenic barite and hydrothermal components; Sr is linked to carbonate phases. Thus, the important geochemical tracers follow the lithology of the sediments. Sediment lithologies are controlled in turn by a small number of factors: proximity of detrital sources (volcanic and continental); biological productivity and preservation of carbonate and opal; and sedimentation rate. Because of the link with lithology and the wealth of lithological data routinely collected for ODP and DSDP drill cores, bulk geochemical averages can be calculated to better than 30% for most elements from fewer than ten chemical analyses for a typical drill core (100-1000 m). Combining the geochemical systematics with convergence rate and other parameters permits calculation of regional compositional fluxes for subducting sediment. These regional fluxes can be compared to the compositions of arc volcanics to asses the importance of sediment subduction to arc volcanism. For the 70% of the trenches worldwide where estimates can be made, the regional fluxes also provide the basis for a global subducting sediment (GLOSS) composition and flux. GLOSS is dominated by terrigenous material (76 wt% terrigenous, 7 wt% calcium carbonate, 10 wt% opal, 7 wt% mineral-bound H2O+), and therefore similar to upper continental crust (UCC) in composition. Exceptions include enrichment in Ba, Mn and the middle and heavy REE, and depletions in detrital elements diluted by biogenic material (alkalis, Th, Zr, Hf). Sr and Pb are identical in GLOSS and UCC as a result of a balance between dilution and enrichment by marine phases. GLOSS and the systematics of marine sediments provide an independent approach to the composition of the upper continental crust for detrital elements. Significant discrepancies of up to a factor of two exist between the marine sediment data and current upper crustal estimates for Cs, Nb, Ta and Ti. Suggested revisions to UCC include Cs (7.3 ppm), Nb (13.7 ppm), Ta (0.96 ppm) and TiO2 (0.76 wt%). These revisions affect recent bulk continental crust estimates for La/Nb and U/Nb, and lead to an even greater contrast between the continents and mantle for these important trace element ratios. GLOSS and the regional sediment data also provide new insights into the mantle sources of oceanic basalts. The classical geochemical distinction between 'pelagic' and 'terrigenous' sediment sources is not valid and needs to be replaced by a more comprehensive understanding of the compositional variations in complete sedimentary columns. In addition, isotopic arguments based on surface sediments alone can lead to erroneous conclusions. Specifically, the Nd/Hf ratio of GLOSS relaxes considerably the severe constraints on the amount of sediment recycling into the mantle based on earlier estimates from surface sediment compositions.

Morphology of Orbulina universa and Globorotalia scitula across local extinctions during Sapropel S5 (Eastern Mediterranean Sea, c.126-121 ka)

Extinction is a remarkably difficult phenomenon to study under natural conditions. This is because the outcome of stress exposure and associated fitness reduction is not known until the extinction occurs and it remains unclear whether there is any phenotypic reaction of the exposed population that can be used to predict its fate. Here we take advantage of the fossil record, where the ecological outcome of stress exposure is known. Specifically, we analyze shell morphology of planktonic Foraminifera in sediment samples from the Mediterranean, during an interval preceding local extinctions. In two species representing different plankton habitats, we observe shifts in trait state and decrease in variance in association with non-terminal stress, indicating stabilizing selection. At terminal stress levels, immediately before extinction, we observe increased growth asymmetry and trait variance, indicating disruptive selection and bet-hedging. The pre-extinction populations of both species show a combination of trait states and trait variance distinct from all populations exposed to non-terminal levels of stress. This finding indicates that the phenotypic history of a population may allow the detection of threshold levels of stress, likely to lead to extinction. It is thus an alternative to population dynamics in studying and monitoring natural population ecology.

Chemical and isotopic compositions of rocks and minerals from the Ashadze and Logachev hydrothermal fields, Mid-Atlantic Ridge

This study was aimed at reconstructing a sequence of events in the magmatic and metamorphic evolution of peridotites, gabbroids, and trondhjemites from internal oceanic complexes of the Ashadze and Logachev hydrothermal vent fields. Collections of plutonic rocks from Cruises 22 and 26 of R/V "Professor Logachev", Cruise 41 of R/V "Akademik Mstislav Keldysh", and from the Serpentine Russian-French expedition aboard R/V "Pourquoi pas?" were objects of this study. Data reported here suggest that the internal oceanic complexes of the Ashadze and Logachev fields formed via the same scenario in these two regions of the Mid-Atlantic Ridge. On the other hand, an analysis of petrological and geochemical characteristics of the rocks indicated that the internal oceanic complexes of the MAR axial zone between 12°58'N and 14°45'N show pronounced petrological and geochemical heterogeneity manifested in variations in degree of depletion of mantle residues and in Nd isotopic compositions of rocks from the gabbro-peridotite association. Trondhjemites from the Ashadze hydrothermal field can be considered as partial melting products of gabbroids under influence of hydrothermal fluids. It was supposed that presence of trondhjemites in internal oceanic complexes of MAR can be used as a marker for the highest temperature deep-rooted hydrothermal systems. Perhaps, the region of the MAR axial zone, in which petrologically and geochemically contrasting internal oceanic complexes are spatially superimposed, serves as an area for development of large hydrothermal clusters with considerable ore-forming potential.

Are trading partners complementary in international trade?

We use a unique dataset on trading transactions at the firm level to investigate a complementary effect in international transactions between sellers and buyers; trading transactions are more likely to be international when both sellers and buyers are large in size than when either sellers or buyers are large. Our econometric analysis provides evidence for the complementary effect between trading partners on the likelihood of international trade, which is most prominent for exports from North to South.

Simulating heterogeneous multinational firms

This paper develops a micro-simulation framework for multinational entry and sales activities across countries. The model is based on Eaton, Kortum, and Kramarz's (2010) quantitative trade model adapted towards multinational production. Using micro data on Japanese manufacturing firms, we first stylize the empirical regularities of multinational entry and sales activity and estimate the model's structural parameters with simulated method of moments. We then demonstrate that our adapted model is able to replicate important dimensions of the in-sample moments conditioned in our estimation strategy. Importantly, it is able to replicate activity under an economic period with a far different level of FDI barriers than was conditioned upon in our estimation sample. Overall, our research highlights the richness of the simulation framework for performing counterfactual analysis of various FDI policies.

Heterogeneous multinational firms and productivity gains from falling FDI barriers

During the past decade of declining FDI barriers, small domestic firms disproportionately contracted while large multinational firms experienced a substantial growth in Japan’s manufacturing sector. This paper quantitatively assesses the impact of FDI globalization on intra-industry reallocations and aggregate productivity. We calibrate the firm-heterogeneity model of Eaton, Kortum, and Kramarz (2011) to micro-level data on Japanese multinational firms. Estimating the structural parameters of the model, we demonstrate that the model can strongly replicate the entry and sales patterns of Japanese multinationals. Counterfactual simulations show that declining FDI barriers lead to a disproportionate expansion of foreign production by more efficient firms relative to less efficient firms. A hypothetical 20% reduction in FDI barriers is found to generate a 30.7% improvement in aggregate productivity through market-share reallocation.

FDI and investment barriers in developing economies

Does investment liberalization in developing economies affect FDI decisions differently across individual firms? To address this question, we simulate the response of individual firms to reductions in investment costs across developing economies. We explore two policy experiments: elimination of setup-procedure requirements for foreign investors and a reduction in corporate tax rates on foreign-owned multinationals. We find that a relaxing of discriminatory foreign investment procedures induces middle productive firms to increase their entry and production in developing economies substantially, but the most productive firms to expand moderately. Multinationals expand their entry and production in developing economies more substantially following a decline in entry barriers than following a decrease in corporate tax rates.

Why do oil importers diversify their import sources politically? : evidence from U.S. firm-level data

International politics affects oil trade. But why? We construct a firm-level dataset for all U.S. oil-importing companies over 1986-2008 to examine what kinds of firms are more responsive to change in "political distance" between the U.S. and her trading partners, measured by divergence in their UN General Assembly voting patterns. Consistent with previous macro evidence, we first show that individual firms diversify their oil imports politically, even after controlling for unobserved firm heterogeneity. We conjecture that the political pattern of oil imports from these individual firms is driven by hold-up risks, because oil trade is often associated with backward vertical FDI. To test this hold-up risk hypothesis, we investigate heterogeneity in responses by matching transaction-level import data with firm-level worldwide reserves. Our results show that long-run oil import decisions are indeed more elastic for firms with oil reserves overseas than those without, although the reverse is true in the short run. We interpret this empirical regularity as that while firms trade in the spot market can adjust their imports immediately, vertically-integrated firms with investment overseas tend to commit to term contracts in the short run even though they are more responsive to changes in international politics in the long run.

Political influence in commercial and financial oil trading : the evidence from US firms

International politics affects oil trade. But do financial and commercial traders who participate in spot oil trading also respond to changes in international politics? We construct a firm-level dataset for all U.S. oil-importing companies over 1986-2008 to examine how these firms respond to increases in "political distance" between the U.S. and her trading partners, measured by divergence in their UN General Assembly voting patterns. Consistent with previous macro evidence, we first show that individual firms diversify their oil imports politically, even after controlling for unobserved firm heterogeneity. However, the political pattern of oil imports is not entirely driven by the concerns of hold-up risks, which exist when oil transactions via term contracts are associated with backward vertical FDI that is subject to expropriation. In particular, our results indicate that even financial and commercial traders significantly reduce their oil imports from U.S. political enemies. Interestingly, while these traders diversify their oil imports politically immediately after changes in international politics, other oil companies reduce their oil imports with a significant time lag. Our findings suggest that in designing regulations to avoid harmful repercussions on commodity and financial assets, policymakers need to understand the nature of political risk.

Analysis of pattern recognition and dimensionality reduction techniques for odor biometrics

In this paper, we analyze the performance of several well-known pattern recognition and dimensionality reduction techniques when applied to mass-spectrometry data for odor biometric identification. Motivated by the successful results of previous works capturing the odor from other parts of the body, this work attempts to evaluate the feasibility of identifying people by the odor emanated from the hands. By formulating this task according to a machine learning scheme, the problem is identified with a small-sample-size supervised classification problem in which the input data is formed by mass spectrograms from the hand odor of 13 subjects captured in different sessions. The high dimensionality of the data makes it necessary to apply feature selection and extraction techniques together with a simple classifier in order to improve the generalization capabilities of the model. Our experimental results achieve recognition rates over 85% which reveals that there exists discriminatory information in the hand odor and points at body odor as a promising biometric identifier.