SymPy is an open source computer algebra system written in pure Python. It is built with a focus on extensibility and ease of use, through both interactive and programmatic applications. These ...characteristics have led SymPy to become a popular symbolic library for the scientific Python ecosystem. This paper presents the architecture of SymPy, a description of its features, and a discussion of select submodules. The supplementary material provide additional examples and further outline details of the architecture and features of SymPy.
The 2010
disaster led to the largest ever marine oil spill. Individuals who worked on the spill were exposed to toxicants and stressors that could lead to adverse effects.
The GuLF STUDY was designed ...to investigate relationships between oil spill exposures and multiple potential physical and mental health effects.
Participants were recruited by telephone from lists of individuals who worked on the oil spill response and clean-up or received safety training. Enrollment interviews between 2011 and 2013 collected information about spill-related activities, demographics, lifestyle, and health. Exposure measurements taken during the oil spill were used with questionnaire responses to characterize oil exposures of participants. Participants from Gulf states completed a home visit in which biological and environmental samples, anthropometric and clinical measurements, and additional health and lifestyle information were collected. Participants are being followed for changes in health status.
Thirty-two thousand six hundred eight individuals enrolled in the cohort, and 11,193 completed a home visit. Most were young (56.2% ≤ 45 years of age), male (80.8%), lived in a Gulf state (82.3%), and worked at least 1 day on the oil spill (76.5%). Workers were involved in response (18.0%), support operations (17.5%), clean-up on water (17.4%) or land (14.6%), decontamination (14.3%), and administrative support (18.3%). Using an ordinal job exposure matrix, 45% had maximum daily total hydrocarbon exposure levels ≥ 1.0 ppm.
The GuLF STUDY provides a unique opportunity to study potential adverse health effects from the
oil spill.
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CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Summary Background Preliminary evidence is equivocal about the role of exhaled nitric oxide (NO) in clinical asthma management. We aimed to assess whether measurement of exhaled NO, as a biomarker of ...airway inflammation, could increase the effectiveness of asthma treatment, when used as an adjunct to clinical care based on asthma guidelines for inner-city adolescents and young adults. Methods We did a randomised, double-blind, parallel-group trial at ten centres in the USA. We screened 780 inner-city patients, aged 12–20 years, who had persistent asthma. All patients completed a run-in period of 3 weeks on a regimen based on standard treatment. 546 eligible participants who adhered to treatment during this run-in period were then randomly assigned to 46 weeks of either standard treatment, based on the guidelines of the National Asthma Education and Prevention Program (NAEPP), or standard treatment modified on the basis of measurements of fraction of exhaled NO. The primary outcome was the number of days with asthma symptoms. We analysed patients on an intention-to-treat basis. This trial is registered with clinicaltrials.gov , number NCT00114413. Findings During the 46-week treatment period, the mean number of days with asthma symptoms did not differ between the treatment groups (1·93 95% CI 1·74 to 2·11 in the NO monitoring group vs 1·89 1·71 to 2·07 in the control group; difference 0·04 −0·22 to 0·29, p=0·780). Other symptoms, pulmonary function, and asthma exacerbations did not differ between groups. Patients in the NO monitoring group received higher doses of inhaled corticosteroids (difference 119 μg per day, 95% CI 49 to 189, p=0·001) than controls. Adverse events did not differ between treatment groups (p>0·1 for all adverse events). Interpretation Conventional asthma management resulted in good control of symptoms in most participants. The addition of fraction of exhaled NO as an indicator of control of asthma resulted in higher doses of inhaled corticosteroids, without clinically important improvements in symptomatic asthma control. Funding US National Institute of Allergy and Infectious Diseases, US National Institutes of Health.
The ability to control polyethylene branching density is of great interest as a means by which a polymer’s thermomechanical properties may be tailored. One particularly interesting way in which this ...can be achieved is by altering the electronic characteristics of Pd- and Ni-based α-diimine catalysts through the inclusion of electron-withdrawing or electron-donating substituents onto the ligand scaffold; however, a few critical fundamental studies are absent from the literature. These include a systematic examination of electronic perturbations of Ni-based α-diimine catalysts, as well as how placement of donating or withdrawing substituents on the backbone versus N-aryl moieties of the α-diimine ligand framework impact polymer topology. In addition, no method currently exists by which the polymer topology may be predicted based on an intrinsic characteristic of the (pre)catalyst or ligand without requiring extensive polymerization studies. Herein, we use both experimental and computational methods to understand how the placement of electron-donating or electron-withdrawing substituents on Ni α-diimine catalysts affects PE branching density, and compare those results to the analogous unsubstituted catalyst. We will show that inclusion of electron-withdrawing substituents decreases resultant PE branching density, whereas electron-donating substituents exhibit little to no change in PE branching density. Finally, we will show that as the placement and identity of donating or withdrawing substituents are varied, so too is the redox half-wave potential (E1/2) of the precatalysts, which can be used to generate a predictive curve by which PE branching density may be estimated for other substituted Ni-based α-diimine catalysts without the need for extensive polymerization studies.
The 2010 Deepwater Horizon (DWH) oil spill response and cleanup (OSRC) workers were exposed to airborne total hydrocarbons (THC), benzene, toluene, ethylbenzene, o-, m-, and p-xylenes and n-hexane ...(BTEX-H) from crude oil and PM2.5 from burning/flaring oil and natural gas. Little is known about asthma risk among oil spill cleanup workers. Objectives: We assessed the relationship between asthma and several oil spill-related exposures including job classes, THC, individual BTEX-H chemicals, the BTEX-H mixture, and PM2.5 using data from the Gulf Long-Term Follow-up (GuLF) Study, a prospective cohort of 24,937 cleanup workers and 7,671 nonworkers following the DWH disaster.
Our analysis largely focused on the 19,018 workers without asthma before the spill who had complete exposure, outcome, and covariate information. We defined incident asthma 1–3 years following exposure using both self-reported wheeze and self-reported physician diagnosis of asthma. THC and BTEX-H were assigned to participants based on measurement data and work histories, while PM2.5 used modeled estimates. We used modified Poisson regression to estimate risk ratios (RR) and 95% confidence intervals (CIs) for associations between spill-related exposures and asthma and a quantile-based g-computation approach to explore the joint effect of the BTEX-H mixture on asthma risk.
OSRC workers had greater asthma risk than nonworkers (RR: 1.60, 95% CI: 1.38, 1.85). Higher estimated THC exposure levels were associated with increased risk in an exposure-dependent manner (linear trend test p < 0.0001). Asthma risk also increased with increasing exposure to individual BTEX-H chemicals and the chemical mixture: A simultaneous quartile increase in the BTEX-H mixture was associated with an increased asthma risk of 1.45 (95% CI: 1.35,1.55). With fewer cases, associations were less apparent for physician-diagnosed asthma alone.
THC and BTEX-H were associated with increased asthma risk defined using wheeze symptoms as well as a physician diagnosis.
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•Proximity to concentrated animal feeding operation is associated with autoimmunity.•Proximity to CAFO is associated with rheumatoid arthritis.•Xenobiotic response gene ARNT SNPs are ...associated with rheumatoid arthritis.•AHR-ARNT pathway, vicinity to CAFO confer risk of some immune-mediated diseases.•ARNT SNPs, CAFO vicinity are associated with autoimmune disease, rheumatoid arthritis.
Concentrated animal feeding operations (CAFOs) are a source of environmental pollution and have been associated with a variety of health outcomes. Immune-mediated diseases (IMD) are characterized by dysregulation of the normal immune response and, while they may be affected by gene and environmental factors, their association with living in proximity to a CAFO is unknown.
We explored gene, environment, and gene-environment (GxE) relationships between IMD, CAFOs, and single nucleotide polymorphisms (SNPs) of prototypical xenobiotic response genes AHR, ARNT, and AHRR and prototypical immune response gene PTPN22.
The exposure analysis cohort consisted of 6,464 participants who completed the Personalized Environment and Genes Study Health and Exposure Survey and a subset of 1,541 participants who were genotyped. We assessed the association between participants’ residential proximity to a CAFO in gene, environment, and GxE models. We recombined individual associations in a transethnic model using METAL meta-analysis.
In White participants, ARNT SNP rs11204735 was associated with autoimmune diseases and rheumatoid arthritis (RA), and ARNT SNP rs1889740 was associated with RA. In a transethnic genetic analysis, ARNT SNPs rs11204735 and rs1889740 and PTPN22 SNP rs2476601 were associated with autoimmune diseases and RA. In participants living closer than one mile to a CAFO, the log-distance to a CAFO was associated with autoimmune diseases and RA. In a GxE interaction model, White participants with ARNT SNPs rs11204735 and rs1889740 living closer than eight miles to a CAFO had increased odds of RA and autoimmune diseases, respectively. The transethnic model revealed similar GxE interactions.
Our results suggest increased risk of autoimmune diseases and RA in those living in proximity to a CAFO and a potential role of the AHR-ARNT pathway in conferring risk. We also report the first association of ARNT SNPs rs11204735 and rs1889740 with RA. Our findings, if confirmed, could allow for novel genetically-targeted or other preventive approaches for certain IMD.
Analogues structurally related to anaplastic lymphoma kinase (ALK) inhibitor 1 were optimized for metabolic stability. The results from this endeavor not only led to improved metabolic stability, ...pharmacokinetic parameters, and in vitro activity against clinically derived resistance mutations but also led to the incorporation of activity for focal adhesion kinase (FAK). FAK activation, via amplification and/or overexpression, is characteristic of multiple invasive solid tumors and metastasis. The discovery of the clinical stage, dual FAK/ALK inhibitor 27b, including details surrounding SAR, in vitro/in vivo pharmacology, and pharmacokinetics, is reported herein.
Oil spill response and cleanup (OSRC) workers had potentially stressful experiences during mitigation efforts following the 2010 Deepwater Horizon disaster. Smelling chemicals; skin or clothing ...contact with oil; heat stress; handling oily plants/wildlife or dead animal recovery; and/or being out of regular work may have posed a risk to worker respiratory health through psychological stress mechanisms.
To evaluate the association between six potentially stressful oil spill experiences and lung function among OSRC workers 1–3 years following the Deepwater Horizon disaster, while controlling for primary oil spill inhalation hazards and other potential confounders.
Of 6811 GuLF STUDY participants who performed OSRC work and completed a quality spirometry test, 4806 provided information on all exposures and confounders. We carried out complete case analysis and used multiple imputation to assess risk among the larger sample. Potentially stressful work experiences were identified from an earlier study of these workers. The lung function parameters of interest include the forced expiratory volume in 1 s (FEV1, mL), the forced vital capacity (FVC, mL) and the ratio (FEV1/FVC, %).
On average, participants in the analytic sample completed spirometry tests 1.7 years after the spill. Among workers with at least 2 acceptable FEV1 and FVC curves, workers with jobs that involved oily plants/wildlife or dead animal recovery had lower values for FEV1 (Mean difference: −53 mL, 95% CI: −84, −22), FVC (Mean difference: −45 mL, 95% CI: −81, −9) and FEV1/FVC (Mean difference: −0.44%, 95% CI: −0.80, −0.07) compared to unexposed workers in analyses using multiple imputation.
Workers involved in handling oily plants/wildlife or dead animal recovery had lower lung function than unexposed workers after accounting for other OSRC inhalation hazards.
•Oil spill response and cleanup workers had unique experiences that may have adversely affected their respiratory health.•We examined the impact of these experiences on measured lung function 1-3 years after the Deepwater Horizon disaster.•Jobs that involved handling oily plants/wildlife or dead animal recovery were associated with lower lung function.•This large study is the first to examine lung function in relation to potentially stressful work experiences during the DWH disaster response and clean-up effort.
Studies of workers exposed to benzene at average air concentrations below one part per million suggest that benzene, a known hematotoxin, causes hematopoietic damage even at low exposure levels. ...However, evidence of such effects outside of occupational settings and for other volatile organic compounds (VOCs) is limited.
To investigate associations between ambient exposures to five VOCs, including benzene, and hematologic parameters among adult residents of the U.S. Gulf Coast.
Blood concentrations of selected VOCs were measured in a sample of adult participants in the Gulf Long-term Follow-up Study (GuLF STUDY) during 2012 and 2013. Complete blood counts with differentials were also performed on a subset of participants (n=406). We used these data together with detailed questionnaire data to estimate adjusted associations between blood BTEXS (benzene, toluene, ethylbenzene, o-xylene, m/p-xylene, and styrene) concentrations and hematologic parameters using generalized linear models.
We observed inverse associations between blood benzene concentrations and hemoglobin concentration and mean corpuscular hemoglobin concentration, and a positive association with red cell distribution width among tobacco smoke-unexposed participants (n=146). Among tobacco smoke-exposed participants (n=247), we observed positive associations between blood VOC concentrations and several hematologic parameters, including increased white blood cell and platelet counts, suggestive of hematopoietic stimulation typically associated with tobacco smoke exposure. Most associations were stronger for benzene than for the other VOCs.
Our results suggest that ambient exposure to BTEXS, particularly benzene, may be associated with hematologic effects, including decreased hemoglobin concentration, mean corpuscular hemoglobin concentration, and increased red cell distribution width.
•We evaluated associations between hematologic parameters and blood VOC levels.•We observed associations that differed by tobacco smoke exposure status.•Most associations with were stronger for benzene than for the other VOCs.
BACKGROUND:Various questionnaire-based definitions of chronic obstructive pulmonary disease (COPD) have been applied using the US representative National Health and Nutrition Examination Survey ...(NHANES), but few have been validated against objective lung function data. We validated two prior definitions that incorporated self-reported physician diagnosis, respiratory symptoms, and/or smoking. We also validated a new definition that we developed empirically using gradient boosting, an ensemble machine learning method.
METHODS:Data came from 7,996 individuals 40–79 years who participated in NHANES 2007–2012 and underwent spirometry. We considered participants “true” COPD cases if their ratio of postbronchodilator forced expiratory volume in 1 second to forced vital capacity was below 0.7 or the lower limit of normal. We stratified all analyses by smoking history. We developed a gradient boosting model for smokers only; predictors assessed (25 total) included sociodemographics, inhalant exposures, clinical variables, and respiratory symptoms.
RESULTS:The spirometry-based COPD prevalence was 26% for smokers and 8% for never smokers. Among smokers, using questionnaire-based definitions resulted in a COPD prevalence ranging from 11% to 16%, sensitivity ranging from 18% to 35%, and specificity ranging from 88% to 92%. The new definition classified participants based on age, bronchodilator use, body mass index (BMI), smoking pack-years, and occupational organic dust exposure, and resulted in the highest sensitivity (35%) and specificity (92%) among smokers. Among never smokers, the COPD prevalence ranged from 4% to 5%, and we attained good specificity (96%) at the expense of sensitivity (9-10%).
CONCLUSION:Our results can be used to parametrize misclassification assumptions for quantitative bias analysis when pulmonary function data are unavailable.
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