Decomposing the age effect on risk tolerance

Postprint.The importance of investment portfolio allocation has become more apparent since the onset of the late 2000s Great Recession. Individual willingness to take financial risks affects portfolio decisions and investment returns among other factors. Previous research found that people of different ages have dissimilar levels of risk tolerance but the effects of generation, period, and aging were confounded. Using the 1998 to 2007 Survey of Consumer Finances cross-sectional datasets, this study uses an analytical method to separate such effects on financial risk tolerance. Aging and period effects on financial risk tolerance were statistically significant. Implications for researchers and financial planning practitioners and educators are provided.Includes bibliographical references

Population Effect Model Identifies Gene Expression Predictors of Survival Outcomes in Lung Adenocarcinoma for Both Caucasian and Asian Patients

Background: We analyzed and integrated transcriptome data from two large studies of lung adenocarcinomas on distinct populations. Our goal was to investigate the variable gene expression alterations between paired tumor-normal tissues and prospectively identify those alterations that can reliably predict lung disease related outcomes across populations. Methods: We developed a mixed model that combined the paired tumor-normal RNA-seq from two populations. Alterations in gene expression common to both populations were detected and validated in two independent DNA microarray datasets. A 10-gene prognosis signature was developed through a l1 penalized regression approach and its prognostic value was evaluated in a third independent microarray cohort. Results: Deregulation of apoptosis pathways and increased expression of cell cycle pathways were identified in tumors of both Caucasian and Asian lung adenocarcinoma patients. We demonstrate that a 10-gene biomarker panel can predict prognosis of lung adenocarcinoma in both Caucasians and Asians. Compared to low risk groups, high risk groups showed significantly shorter overall survival time (Caucasian patients data: HR = 3.63, p-value = 0.007; Asian patients data: HR = 3.25, p-value = 0.001). Conclusions: This study uses a statistical framework to detect DEGs between paired tumor and normal tissues that considers variances among patients and ethnicities, which will aid in understanding the common genes and signalling pathways with the largest effect sizes in ethnically diverse cohorts. We propose multifunctional markers for distinguishing tumor from normal tissue and prognosis for both populations studied

Effects of Paroxetine and Sertraline on Low-Density Lipoprotein Cholesterol: An Observational Cohort Study

Background: Antidepressant use in US adults increased 3-fold from 2.5% in 1988–94 to 8.1% in 1999–2002, based on National Health and Nutrition Examination Surveys. As the use of antidepressants increases, a comprehensive understanding of the potential health risks that may be associated with their use becomes increasingly important. Objective: This study evaluated the effects of paroxetine and sertraline on low-density lipoprotein cholesterol (LDL-C). Study Design: An observational cohort study (1997–2004) of adults who had taken paroxetine or sertraline for at least 60 continuous days and had ≥2 LDL-C values measured during the study period, one while taking and one while not taking paroxetine or sertraline. A total of 13 634 LDL-C values clustered within 2682 patients were studied. Methods: We conducted mixed model regression analyses to quantify the relationship between antidepressant use and LDL-C values. Results: The number of days taking paroxetine (β = 0.0045; 95% CI 0.0018, 0.0073) and sertraline (β = 0.0074; 95% CI 0.0054, 0.0093) prior to the LDL-C test were related to higher LDL-C values, after accounting for age, sex, year LDL-C was tested, co-morbidity, depression and lipid medication. The number of days that had passed since exposure to paroxetine (β =−0.0013; 95% CI −0.0020, −0.00061) or sertraline (β = −0.00093; 95% CI −0.016, −0.00022) were related to lower LDL-C values. The significant interaction between exposure to an antidepressant and taking a lipid medication demonstrates that the increase in LDL-C values associated with antidepressant use is ameliorated among patients who were taking a lipid medication when LDL-C was measured. Conclusion: Our study showed that long-term use of paroxetine or sertraline may have a measurable adverse impact on cardiovascular risk in adults. Clinical strategies should be used to address cardiovascular risk while maintaining effective treatment of major depression. In light of these findings, attention to LDL-C values should accompany antidepressant use

Potential misinterpretations caused by collapsing upper categories of comorbidity indices: An illustration from a cohort of older breast cancer survivors

BACKGROUND: Comorbidity indices summarize complex medical histories into concise ordinal scales, facilitating stratification and regression in epidemiologic analyses. Low subject prevalence in the highest strata of a comorbidity index often prompts combination of upper categories into a single stratum (\u27collapsing\u27). OBJECTIVE: We use data from a breast cancer cohort to illustrate potential inferential errors resulting from collapsing a comorbidity index. METHODS: Starting from a full index (0, 1, 2, 3, and \u3e/=4 comorbidities), we sequentially collapsed upper categories to yield three collapsed categorizations. The full and collapsed categorizations were applied to analyses of (1) the association between comorbidity and all-cause mortality, wherein comorbidity was the exposure; (2) the association between older age and all-cause mortality, wherein comorbidity was a candidate confounder or effect modifier. RESULTS: Collapsing the index attenuated the association between comorbidity and mortality (risk ratio, full versus dichotomized categorization: 4.6 vs 2.1), reduced the apparent magnitude of confounding by comorbidity of the age/mortality association (relative risk due to confounding, full versus dichotomized categorization: 1.14 vs 1.09), and obscured modification of the association between age and mortality on both the absolute and relative scales. CONCLUSIONS: Collapsing categories of a comorbidity index can alter inferences concerning comorbidity as an exposure, confounder and effect modifier

In Helicobacter pylori auto-inducer-2, but not LuxS/MccAB catalysed reverse transsulphuration, regulates motility through modulation of flagellar gene transcription.

BACKGROUND: LuxS may function as a metabolic enzyme or as the synthase of a quorum sensing signalling molecule, auto-inducer-2 (AI-2); hence, the mechanism underlying phenotypic changes upon luxS inactivation is not always clear. In Helicobacter pylori, we have recently shown that, rather than functioning in recycling methionine as in most bacteria, LuxS (along with newly-characterised MccA and MccB), synthesises cysteine via reverse transsulphuration. In this study, we investigated whether and how LuxS controls motility of H. pylori, specifically if it has its effects via luxS-required cysteine metabolism or via AI-2 synthesis only. RESULTS: We report that disruption of luxS renders H. pylori non-motile in soft agar and by microscopy, whereas disruption of mccAHp or mccBHp (other genes in the cysteine provision pathway) does not, implying that the lost phenotype is not due to disrupted cysteine provision. The motility defect of the DeltaluxSHp mutant was complemented genetically by luxSHp and also by addition of in vitro synthesised AI-2 or 4, 5-dihydroxy-2, 3-pentanedione (DPD, the precursor of AI-2). In contrast, exogenously added cysteine could not restore motility to the DeltaluxSHp mutant, confirming that AI-2 synthesis, but not the metabolic effect of LuxS was important. Microscopy showed reduced number and length of flagella in the DeltaluxSHp mutant. Immunoblotting identified decreased levels of FlaA and FlgE but not FlaB in the DeltaluxSHp mutant, and RT-PCR showed that the expression of flaA, flgE, motA, motB, flhA and fliI but not flaB was reduced. Addition of DPD but not cysteine to the DeltaluxSHp mutant restored flagellar gene transcription, and the number and length of flagella. CONCLUSIONS: Our data show that as well as being a metabolic enzyme, H. pylori LuxS has an alternative role in regulation of motility by modulating flagellar transcripts and flagellar biosynthesis through production of the signalling molecule AI-2

230 Th normalization: new insights on an essential tool for quantifying sedimentary fluxes in the modern and quaternary ocean

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Costa, K. M., Hayes, C. T., Anderson, R. F., Pavia, F. J., Bausch, A., Deng, F., Dutay, J., Geibert, W., Heinze, C., Henderson, G., Hillaire-Marcel, C., Hoffmann, S., Jaccard, S. L., Jacobel, A. W., Kienast, S. S., Kipp, L., Lerner, P., Lippold, J., Lund, D., Marcantonio, F., McGee, D., McManus, J. F., Mekik, F., Middleton, J. L., Missiaen, L., Not, C., Pichat, S., Robinson, L. F., Rowland, G. H., Roy-Barman, M., Alessandro, Torfstein, A., Winckler, G., & Zhou, Y. 230 Th normalization: new insights on an essential tool for quantifying sedimentary fluxes in the modern and quaternary ocean. Paleoceanography and Paleoclimatology, 35(2), (2020): e2019PA003820, doi:10.1029/2019PA003820.230Th normalization is a valuable paleoceanographic tool for reconstructing high‐resolution sediment fluxes during the late Pleistocene (last ~500,000 years). As its application has expanded to ever more diverse marine environments, the nuances of 230Th systematics, with regard to particle type, particle size, lateral advective/diffusive redistribution, and other processes, have emerged. We synthesized over 1000 sedimentary records of 230Th from across the global ocean at two time slices, the late Holocene (0–5,000 years ago, or 0–5 ka) and the Last Glacial Maximum (18.5–23.5 ka), and investigated the spatial structure of 230Th‐normalized mass fluxes. On a global scale, sedimentary mass fluxes were significantly higher during the Last Glacial Maximum (1.79–2.17 g/cm2kyr, 95% confidence) relative to the Holocene (1.48–1.68 g/cm2kyr, 95% confidence). We then examined the potential confounding influences of boundary scavenging, nepheloid layers, hydrothermal scavenging, size‐dependent sediment fractionation, and carbonate dissolution on the efficacy of 230Th as a constant flux proxy. Anomalous 230Th behavior is sometimes observed proximal to hydrothermal ridges and in continental margins where high particle fluxes and steep continental slopes can lead to the combined effects of boundary scavenging and nepheloid interference. Notwithstanding these limitations, we found that 230Th normalization is a robust tool for determining sediment mass accumulation rates in the majority of pelagic marine settings (>1,000 m water depth).We thank Zanna Chase and one anonymous reviewer for valuable feedback. K. M. C. was supported by a Postdoctoral Scholarship at WHOI. L. M. acknowledges funding from the Australian Research Council grant DP180100048. The contribution of C. T. H., J. F. M., and R. F. A. were supported in part by the U.S. National Science Foundation (US‐NSF). G. H. R. was supported by the Natural Environment Research Council (grant NE/L002434/1). S. L. J. acknowledges support from the Swiss National Science Foundation (grants PP002P2_144811 and PP00P2_172915). This study was supported by the Past Global Changes (PAGES) project, which in turn received support from the Swiss Academy of Sciences and the US‐NSF. This work grew out of a 2018 workshop in Aix‐Marseille, France, funded by PAGES, GEOTRACES, SCOR, US‐NSF, Aix‐Marseille Université, and John Cantle Scientific. All data are publicly available as supporting information to this document and on the National Center for Environmental Information (NCEI) at https://www.ncdc.noaa.gov/paleo/study/28791

Noncrossover dither creeping mutation-based genetic algorithm for pipe network optimization

A non-crossover dither creeping mutation-based genetic algorithm (CMBGA) for pipe network optimization has been developed and is analyzed. This CMBGA differs from the classic GA optimization in that it does not utilize the crossover operator, but instead it only uses selection and a proposed dither creeping mutation operator. The creeping mutation rate in the proposed dither creeping mutation operator is randomly generated in a range throughout a GA run rather than being set to a fixed value. In addition, the dither mutation rate is applied at an individual chromosome level rather than at the generation level. The dither creeping mutation probability is set to take values from a small range that is centered about 1/ND (where ND=number of decision variables of the optimization problem being considered). This is motivated by the fact that a mutation probability of approximately 1/ND has been previously demonstrated to be an effective value and is commonly used for the GA. Two case studies are used to investigate the effectiveness of the proposed CMBGA. An objective of this paper is to compare the performance of the proposed CMBGA with four other GA variants, and other published results. The results show that the proposed CMBGA exhibits considerable improvement over the considered GA variants, and comparable performance with respect to other previously published results. A big advantage of CMBGA is its simplicity and that it requires the tuning of fewer parameters compared with other GA variants.Feifei Zheng, Aaron C. Zecchin, Angus R. Simpson and Martin F. Lamber