Variable selection when estimating effects in external target populations

External validity is an important part of epidemiologic research. To validly estimate effects in specific external target populations using a chosen effect measure (ie, "transport"), some methods require that one account for all effect measure modifiers (EMMs). However, little is known about how including other variables that are not EMMs (ie, non-EMMs) in adjustment sets affects estimates. Using simulations, we evaluated how inclusion of non-EMMs affected estimation of the transported risk difference (RD) by assessing the impacts of covariates that (1) differ (or not) between the trial and the target, (2) are associated with the outcome (or not), and (3) modify the RD (or not). We assessed variation and bias when covariates with each possible combination of these factors were used to transport RDs using outcome modeling or inverse odds weighting. Inclusion of variables that differed in distribution between the populations but were non-EMMs reduced precision, regardless of whether they were associated with the outcome. However, non-EMMs associated with selection did not amplify bias resulting from omission of necessary EMMs. Including all variables associated with the outcome may result in unnecessarily imprecise estimates when estimating treatment effects in external target populations

Proton-bound dimers of nitrogen heterocyclic molecules: Substituent effects on the structures and binding energies of homodimers of diazine, triazine, and fluoropyridine

The bonding energies of proton-bound homodimers BH+B were measured by ion mobilityequilibrium studies and calculated at the DFT B3LYP/6-311++G* * level, for a series of nitrogen heterocyclic molecules (B) with electron-withdrawing in-ring N and on-ring F substituents. The binding energies (ΔH°dissoc) of the proton-bound dimers (BH+B) vary significantly, from 29.7 to 18.1 kcal/mol, decreasing linearly with decreasing the proton affinity of the monomer (B). This trend differs significantly from the constant binding energies of most homodimers of other organic nitrogen and oxygen bases. The experimentally measured ΔH°dissoc for (1,3-diazine)2H+, i.e., (pyrimidine)2H+ and (3-F-pyridine)2H+ are 22.7 and 23.0 kcal/mol, respectively. The measured ΔH°dissoc for the pyrimidine ·+(3-F-pyridine) radical cation dimer (19.2 kcal/mol) is signifcantly lower than that of the proton-bound homodimers of pyrimidine and 3-F-pyridine, reflecting the stronger interaction in the ionic H-bond of the protonated dimers. The calculated binding energies for (1,2-diazine)2H+, (pyridine)2H+, (2-F-pyridine)2H+, (3-F-pyridine)2H+, (2,6-di-F-pyridine)2H+, (4-F-pyridine)2H+, (1,3-diazine)2H+, (1,4-diazine)2H+, (1,3,5-triazine)2H+, and (pentafluoropyridine)2H+ are 29.7, 24.9, 24.8, 23.3, 23.2, 23.0, 22.4, 21.9, 19.3, and 18.1 kcal/mol, respectively. The electron-withdrawing substituents form internal dipoles whose electrostatic interactions contribute to both the decreased proton affinities of (B) and the decreased binding energies of the protonated dimers BH+B. The bonding energies also vary with rotation about the hydrogen bond, and they decrease in rotamers where the internal dipoles of the components are aligned efficiently for inter-ring repulsion. For compounds substituted at the 3 or 4 (meta or para) positions, the lowest energy rotamers are T-shaped with the planes of the two rings rotated by 90° about the hydrogen bond, while the planar rotamers are weakened by repulsion between the ortho hydrogen atoms of the two rings. Conversely, inortho-substituted (1,2-diazine)2H+ and (2-F-pyridine)2H+, attractive interactions between the ortho (C–H) hydrogen atoms of one ring and the electronegative ortho atoms (N or F) of the other ring are stabilizing, and increase the protonated dimer binding energies by up to 4 kcal/mol. In all of the dimers, rotation about the hydrogen bond can involve a 2–4 kcal/mol barrier due to the relative energies of the rotamers

Simulated Anthrax Attacks and Syndromic Surveillance

Bioterrorism surveillance systems can be assessed using modeling to simulate real-world attacks

Social ageing can protect against infectious disease in a group-living primate

Funding: This work was supported by the following grants from the National Institute of Health (NIH): grant nos R01-AG060931, R00-AG051764, R01-MH096875, R37-MH109728, R01-MH108627, R01-MH118203, U01MH121260, R01-NS123054; and the Kaufman Foundation, grant no. KA2019−105548. The Cayo Santiago Field Station is supported by the Office of Research Infrastructure Programs of the NIH (2P40OD012217). M.J.S. is supported by a Royal Society University Research Fellowship URF\R1\2 21 800.The benefits of social living are well established, but sociality also comes with costs, including infectious disease risk. This cost–benefit ratio of sociality is expected to change across individuals’ lifespans, which may drive changes in social behaviour with age. To explore this idea, we combine data from a group-living primate for which social ageing has been described with epidemiological models to show that having lower social connectedness when older can protect against the costs of a hypothetical, directly transmitted endemic pathogen. Assuming no age differences in epidemiological characteristics (susceptibility to, severity and duration of infection), older individuals suffered lower infection costs, which was explained largely because they were less connected in their social networks than younger individuals. This benefit of ‘social ageing’ depended on epidemiological characteristics and was greatest when infection severity increased with age. When infection duration increased with age, social ageing was beneficial only when pathogen transmissibility was low. Older individuals benefited most from having a lower frequency of interactions (strength) and network embeddedness (closeness) and benefited less from having fewer social partners (degree). Our study provides a first examination of the epidemiology of social ageing, demonstrating the potential for pathogens to influence the evolutionary dynamics of social ageing in natural populations. This article is part of the discussion meeting issue ‘Understanding age and society using natural populations’.Peer reviewe

Using Automated Health Plan Data to Assess Infection Risk from Coronary Artery Bypass Surgery

We determined if infection indicators were sufficiently consistent across health plans to allow comparison of hospitals’ risks of infection after coronary artery bypass surgery. Three managed care organizations accounted for 90% of managed care in eastern Massachusetts, from October 1996 through March 1999. We searched automated inpatient and outpatient claims and outpatient pharmacy dispensing files for indicator codes suggestive of postoperative surgical site infection. We reviewed full text medical records of patients with indicator codes to confirm infection status. We compared the hospital-specific proportions of cases with an indicator code, adjusting for health plan, age, sex, and chronic disease score. A total of 536 (27%) of 1,953 patients had infection indicators. Infection was confirmed in 79 (53%) of 149 reviewed records with adequate documentation. The proportion of patients with an indicator of infection varied significantly (p<0.001) between hospitals (19% to 36%) and health plans (22% to 33%). The difference between hospitals persisted after adjustment for health plan and patients’ age and sex. Similar relationships were observed when postoperative antibiotic information was ignored. Automated claims and pharmacy data from different health plans can be used together to allow inexpensive, routine monitoring of indicators of postoperative infection, with the goal of identifying institutions that can be further evaluated to determine if risks for infection can be reduced

Computed tomographic enterography adds information to clinical management in small bowel Crohn's disease

Background: CT enterography yields striking findings in the bowel wall in Crohn's disease. These images may help to evaluate whether small bowel narrowing results from active disease requiring anti-inflammatory therapy. However, the clinical relevance of these images is unknown. It is also not known if these radiologic findings correlate with objective biomarkers of inflammation. Methods: In a blinded and independent evaluation, IBD subspecialty gastroenterologists reviewed clinical data, and CT radiologists reviewed CT enterography scans of 67 consecutive patients with Crohn's disease and suspicion of either small bowel inflammation or stricture. Comparisons were made between (1) clinical and radiologic assessments of inflammation and stricture, (2) clinical assessments before and after computed tomographic enterography (CTE) reports were revealed, and (3) radiologic findings and objective biomarkers of inflammation. Results: (1) Individual CTE findings correlated poorly (Spearman's rho < 0.30) with clinical assessment; (2) clinicians did not suspect 16% of radiologic strictures, and more than half the cases of clinically suspected strictures did not have them on CTE; (3) CTE data changed clinicians' perceptions of the likelihood of steroid benefit in 41 of 67 cases; (4) specific CTE findings correlated with CRP, and a distinct set of CTE findings correlated with ESR in the subset of patients who had these biomarkers measured. Conclusions: CTE seems to add unique information to clinical assessment, both in detecting additional strictures and in changing clinicians' perceptions of the likelihood of steroids benefiting patients. The biomarker correlations suggest that CTE is measuring real biologic phenomena that correlate with inflammation, providing information distinct from that in a standard clinical assessment. (Inflamm Bowel Dis 2006)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55965/1/20013_ftp.pd

Sociality predicts individual variation in the immunity of free-ranging rhesus macaques

This work was supported by CONICYT-Chilean scholarship [number 72190290], NIH grant [number R01AG060931] to N.S-M., L.J.N.B. and J.P.H., NIH grant [number R00AG051764] to N.S-M., NIH grant [number MH118203] to L.J.N.B.. and M.L.P, and NSF grant [number 1800558] to J.P.H. and Susan Anton. The CPRC is supported by the National Institutes of Health. An Animal and Biological Material Resource Center Grant [P40OD012217] was awarded to UPR from the Office of Research Infrastructure Programs (ORIP), and a Research Facilities Construction Grant [C06OD026690] was awarded for the renovation of CPRC facilities after Hurricane Maria.Social integration and social status can substantially affect an individual's health and survival. One route through which this occurs is by altering immune function, which can be highly sensitive to changes in the social environment. However, we currently have limited understanding of how sociality influences markers of immunity in naturalistic populations where social dynamics can be fully realized. To address this gap, we asked if social integration and social status in free-ranging rhesus macaques (Macaca mulatta) predict anatomical and physiological markers of immunity. We used data on agonistic interactions to determine social status, and social network analysis of grooming interactions to generate measures of individual variation in social integration. As measures of immunity, we included the size of two of the major organs involved in the immune response, the spleen and liver, and counts of three types of blood cells (red blood cells, platelets, and white blood cells). Controlling for body mass and age, we found that neither social status nor social integration predicted the size of anatomical markers of immunity. However, individuals that were more socially connected, i.e., with more grooming partners, had lower numbers of white blood cells than their socially isolated counterparts, indicating lower levels of inflammation with increasing levels of integration. These results build upon and extend our knowledge of the relationship between sociality and the immune system in humans and captive animals to free-ranging primates, demonstrating generalizability of the beneficial role of social integration on health.Publisher PDFPeer reviewe

Trade-offs between sociality and gastrointestinal parasite infection in the context of a natural disaster

This work was supported by ANID-Chilean scholarship [number 72190290], the National Institutes of Health Grants [R01AG060931] to N.S-M., L.J.N.B. and J.P.H., [R00AG051764] to N.S-M, [R01MH118203] to M.L.P., M.J.M, L.J.N.B. and N.S-M., [R01MH096875] to M.L.P., L.J.N.B. and M.J.M., [U01MH121260] to N.S-M., M.L.P. and M.J.M., a European Research Council Consolidator Grant to L.J.N.B. [Friend Origins - 864461].Parasites and infectious diseases constitute important challenges particularly for group-living animals. Social contact and shared space can both increase parasite transmission risk, while individual differences in social capital can help prevent infections. For example, high social status individuals and those with more or stronger affiliative partnerships may have better immunity and, thus, lower parasitic burden. To test for health trade-offs in the costs and benefits of sociality, we quantified how parasitic load varied with an individual's social status, as well as with their affiliative relationships with weakly and strongly bonded partners, in a free-ranging population of rhesus macaques, Macaca mulatta. We found that high status was associated with a lower risk of protozoa infection at older ages compared to younger and low-status animals. Social resources can also be protective against infection under environmentally challenging situations, such as natural disasters. Using cross-sectional data, we additionally examined the impact of a major hurricane on the sociality - parasite relationship in this system and found that the hurricane influenced the prevalence of specific parasites independent of sociality. Overall, our study adds to the growing evidence for social status as a strong predictor of infection risk and highlights how extreme environmental events could shape vulnerability and resistance to infection.Peer reviewe

Secondary organic aerosol formation from gasoline vehicle emissions in a new mobile environmental reaction chamber

We present a new mobile environmental reaction chamber for the simulation of the atmospheric aging of different emissions sources without limitation from the instruments or facilities available at any single site. Photochemistry is simulated using a set of 40 UV lights (total power 4 KW). Characterisation of the emission spectrum of these lights shows that atmospheric aging of emissions may be simulated over a range of temperatures (-7 to 25°C). A photolysis rate of NO2, JNO2, of (8.0±0.7)×10-3 s-1 was determined at 25°C. We demonstrate the utility of this new system by presenting results on the aging (OH=12×106 cm-3h) of emissions from a modern (Euro 5) gasoline car operated during a driving cycle (New European Driving Cycle, NEDC) on a chassis dynamometer in a vehicle test cell. Emissions from the entire NEDC were sampled and aged in the chamber. A thorough investigation of the composition of the gas phase emissions suggests that the observed SOA is from previously unconsidered precursors and processes. This large enhancement in PM mass from gasoline vehicle aerosol emissions due to SOA formation, if it occurs across a wider range of gasoline vehicles, would have significant implications for our understanding of the contribution of on-road gasoline vehicles to ambient aerosols.JRC.F.8-Sustainable Transpor