Numerical algebraic geometry for model selection and its application to the life sciences

Researchers working with mathematical models are often confronted by the related problems of parameter estimation, model validation, and model selection. These are all optimization problems, well-known to be challenging due to non-linearity, non-convexity and multiple local optima. Furthermore, the challenges are compounded when only partial data is available. Here, we consider polynomial models (e.g., mass-action chemical reaction networks at steady state) and describe a framework for their analysis based on optimization using numerical algebraic geometry. Specifically, we use probability-one polynomial homotopy continuation methods to compute all critical points of the objective function, then filter to recover the global optima. Our approach exploits the geometric structures relating models and data, and we demonstrate its utility on examples from cell signaling, synthetic biology, and epidemiology.Comment: References added, additional clarification

Decomposing the Sources of Earnings Inequality: Assessing the Role of Reallocation

This paper exploits longitudinal employer-employee matched data from the U.S. Census Bureau to investigate the contribution of worker and firm reallocation to changes in earnings inequality within and across industries between 1992 and 2003. We find that factors that cannot be measured using standard cross-sectional data, including the entry and exit of firms and the sorting of workers across firms, are important sources of changes in earnings distributions over time. Our results also suggest that the dynamics driving changes in earnings inequality are heterogeneous across industries.inequality, linked employer-employee data, sorting

Decomposing the Sources of Earnings Inequality Assessing the Role of Reallocation

This paper uses matched employer-employee data from the Longitudinal Employer Household Dynamics database to investigate the contribution of worker and firm reallocation to within industry changes in wage inequality between 1992 and 2003. We find that the entry and exit of firms and the sorting of workers and firms based on underlying worker "skills" are important determinants of changes in industry earnings distributions over time. Our results suggest that the underlying dynamics of earnings inequality are complex and are due to factors that cannot be measured in standard crosssectional data.

Risk of second primary tumors in men diagnosed with prostate cancer: A population‐based cohort study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108272/1/cncr28769.pd

Global Performance Characterization of the Three Burn Trans-Earth Injection Maneuver Sequence over the Lunar Nodal Cycle

The Orion spacecraft will be required to perform a three-burn trans-Earth injection (TEI) maneuver sequence to return to Earth from low lunar orbit. The origin of this approach lies in the Constellation Program requirements for access to any lunar landing site location combined with anytime lunar departure. This paper documents the development of optimized databases used to rapidly model the performance requirements of the TEI three-burn sequence for an extremely large number of mission cases. It also discusses performance results for lunar departures covering a complete 18.6 year lunar nodal cycle as well as general characteristics of the optimized three-burn TEI sequence

Safety and efficacy of loteprednol etabonate ophthalmic ointment 0.5% for the treatment of inflammation and pain following cataract surgery

Timothy L Comstock1 Michael R Paterno1 Angele Singh1 Tara Erb1 Elizabeth Davis21Bausch and Lomb Inc., Rochester, NY, USA; 2Minnesota Eye Consultants, Bloomington, MN, USABackground: To compare the safety and efficacy of loteprednol etabonate ophthalmic ointment 0.5% (LE ointment), a new topical ointment formulation, with vehicle for the treatment of inflammation and pain following cataract surgery.Methods: Two randomized, multicenter, double-masked, parallel-group, vehicle-controlled studies were conducted. Patients aged ≥18 years with a combined postoperative anterior chamber cells and flare (ACI) ≥ Grade 3 following uncomplicated cataract surgery participated in seven study visits. Patients self-administered either topical LE ointment or vehicle four times daily for 14 days. Efficacy outcomes included the proportion of patients with complete resolution of ACI and the proportion of patients with no (Grade 0) pain at postoperative day 8. Safety outcomes included the incidence of adverse events, ocular symptoms, changes in intraocular pressure and visual acuity, and biomicroscopy and funduscopy findings.Results: Data from the two studies were combined. The integrated intent-to-treat population consisted of 805 patients (mean [standard deviation] age 69.0 [9.2] years; 58.0% female and 89.7% white). Significantly more LE ointment-treated patients than vehicle-treated patients had complete resolution of ACI (27.7% versus 12.5%) and no pain (75.5% versus 43.1%) at day 8 (P < 0.0001 for both). Fewer LE ointment-treated patients required rescue medication (27.7% versus 63.8%), and fewer had an ocular adverse event (47.2% versus 78.0%, P < 0.0001) while on study treatment. The most common ocular adverse events with LE ointment were anterior chamber inflammation, photophobia, corneal edema, conjunctival hyperemia, eye pain, and iritis. Mean intraocular pressure decreased in both treatment groups. Four patients had increased intraocular pressure ≥10 mmHg (three LE ointment and one vehicle) prior to rescue medication. Visual acuity and dilated funduscopy results were similar between the treatment groups, with the exception of visual acuity at visits 5 and 6, which favored LE ointment.Conclusion: LE ointment was efficacious and well tolerated in the treatment of ocular inflammation and pain following cataract surgery.Keywords: loteprednol etabonate, ophthalmic ointment, postoperative inflammation, postoperative pain, cataract surgery, intraocular pressur

Chimpanzees demonstrate individual differences in social information use

Studies of transmission biases in social learning have greatly informed our understanding of how behaviour patterns may diffuse through animal populations, yet within-species inter-individual variation in social information use has received little attention and remains poorly understood. We have addressed this question by examining individual performances across multiple experiments with the same population of primates. We compiled a dataset spanning 16 social learning studies (26 experimental conditions) carried out at the same study site over a 12-year period, incorporating a total of 167 chimpanzees. We applied a binary scoring system to code each participant’s performance in each study according to whether they demonstrated evidence of using social information from conspecifics to solve the experimental task or not (Social Information Score—‘SIS’). Bayesian binomial mixed effects models were then used to estimate the extent to which individual differences influenced SIS, together with any effects of sex, rearing history, age, prior involvement in research and task type on SIS. An estimate of repeatability found that approximately half of the variance in SIS was accounted for by individual identity, indicating that individual differences play a critical role in the social learning behaviour of chimpanzees. According to the model that best fit the data, females were, depending on their rearing history, 15–24% more likely to use social information to solve experimental tasks than males. However, there was no strong evidence of an effect of age or research experience, and pedigree records indicated that SIS was not a strongly heritable trait. Our study offers a novel, transferable method for the study of individual differences in social learning

Effects on L1 During Early Acquisition of L2: Speech Changes in Spanish at First English Contact

Spanish phonological development was examined in six sequential bilingual children at the point of contact with English and eight months later. We explored effects of the English vowel and consonant inventory on Spanish. Children showed a significant increase in consonant cluster accuracy and in vowel errors. These emerging sequential bilingual children showed effects of English on their first language, Spanish. Cross-linguistic transfer did not affect all properties of the phonology equally. Negative transfer may occur in specific areas where the second language is more complex, requiring reorganization of the existing system, as in the transition from the Spanish five-vowel to the English eleven-vowel system

Nonsuicidal Self-injury as a Risk Factor for Purging Onset: Negatively Reinforced Behaviours that Reduce Emotional Distress

Both nonsuicidal self-injury (NSSI) and purging behaviour are thought to involve harm to the self. The acquired capability for self-harm model holds that engaging in one self-harming behaviour increases the capability to tolerate harm to the self, thus increasing risk for engaging on other such behaviours. In addition, both behaviours are thought to serve the similar function of relief from distress. We thus tested whether engagement in one of these behaviours predicts the subsequent onset of the other. In a longitudinal design, 1158 first-year college women were assessed for purging and NSSI at two time points. Engagement in NSSI at time 1 predicted the college onset of purging behaviour 9 months later (OR = 2.20, p \u3c .04, CI = 1.07-4.19) beyond prediction from time 1 binge behaviour, and purging behaviour at time 1 predicted the subsequent onset of NSSI (OR = 6.54, p \u3c .01, CI = 1.71-25.04). These findings are consistent with the acquired capability for harm model and with the possibility that the two behaviours serve a similar function

Delirium, frailty and mortality:interactions in a prospective study of hospitalized older people

AbstractBackgroundIt is unknown if the association between delirium and mortality is consistent for individuals across the whole range of health states. A bimodal relationship has been proposed, where delirium is particularly adverse for those with underlying frailty, but may have a smaller effect (perhaps even protective) if it is an early indicator of acute illness in fitter people. We investigated the impact of delirium on mortality in a cohort simultaneously evaluated for frailty.MethodsWe undertook an exploratory analysis of a cohort of consecutive acute medical admissions aged ≥70. Delirium on admission was ascertained by psychiatrists. A Frailty Index (FI) was derived according to a standard approach. Deaths were notified from linked national mortality statistics. Cox regression was used to estimate associations between delirium, frailty and their interactions on mortality.ResultsThe sample consisted of 710 individuals. Both delirium and frailty were independently associated with increased mortality rates (delirium: HR 2.4, 95%CI 1.8-3.3, p&lt;0.01; frailty (per SD): HR 3.5, 95%CI 1.2-9.9, p=0.02). Estimating the effect of delirium in tertiles of FI, mortality was greatest in the lowest tertile: tertile 1 HR 3.4 (95%CI 2.1-5.6); tertile 2 HR 2.7 (95%CI 1.5-4.6); tertile 3 HR 1.9 (95% CI 1.2-3.0).ConclusionWhile delirium and frailty contribute to mortality, the overall impact of delirium on admission appears to be greater at lower levels of frailty. In contrast to the hypothesis that there is a bimodal distribution for mortality, delirium appears to be particularly adverse when precipitated in fitter individuals.</jats:sec