scholarly journals Ozone-dependent increases in lung glucocorticoids and macrophage response: Effect modification by innate stress axis function

2021 ◽  
Vol 86 ◽  
pp. 103662
Author(s):  
Jith Thomas ◽  
Andrew Stalker ◽  
Dalibor Breznan ◽  
Errol M. Thomson
Author(s):  
J. R. Fekete ◽  
R. Gibala

The deformation behavior of metallic materials is modified by the presence of grain boundaries. When polycrystalline materials are deformed, additional stresses over and above those externally imposed on the material are induced. These stresses result from the constraint of the grain boundaries on the deformation of incompatible grains. This incompatibility can be elastic or plastic in nature. One of the mechanisms by which these stresses can be relieved is the activation of secondary slip systems. Secondary slip systems have been shown to relieve elastic and plastic compatibility stresses. The deformation of tungsten bicrystals is interesting, due to the elastic isotropy of the material, which implies that the entire compatibility stress field will exist due to plastic incompatibility. The work described here shows TEM observations of the activation of secondary slip in tungsten bicrystals with a [110] twist boundary oriented with the plane normal parallel to the stress axis.


2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
B. Herman ◽  
F. Mandel

Objective:There appears to be no dose-response effect for pregabalin at doses of 300-600 mg, and a modest dose-response effect in the range of 150-300 mg. The goal of the current investigation was to determine the effect of the starting dose on the speed of onset of anxiolytic efficacy.Methods:Data were analyzed from 7 trials of outpatients with DSM-IV GAD and a HAM-A total score ≥18. Starting doses of pregabalin ranged from 100 mg (N=301) or 150 mg (N=104), to 200 mg (N=167) and 300 mg (N=388). Assessment of early improvement included the HAM-A total score and CGI-Severity and Improvement scores.Results:The mean Week 1 HAM-A change score was similar for a starting dose of 200 mg/d with no titration (-8.24) when compared to patients who started on 200 mg/d and then titrated up to 400 mg/d on Day 4 (-8.64). The mean Week 1 HAM-A change score was somewhat higher for patients started on 300 mg/d, and then titrated to 450 mg/d on Day 4/5 (-8.84) when compared to patients started on a lower (100/150 mg/d) dose and titrated on Day 5 to 400/450 mg/d (-7.32). Starting on a dose of 300 mg/d with no titration resulted in an intermediate Week 1 change score (-7.87). The interaction of starting dose and titration schedule with baseline anxiety severity will be summarized in detail.Conclusion:The initial dose of pregabalin appears to have only a weak effect on the speed of onset of anxiolytic improvement.


Author(s):  
Leah H. Schinasi ◽  
Helen V. S. Cole ◽  
Jana A. Hirsch ◽  
Ghassan B. Hamra ◽  
Pedro Gullon ◽  
...  

Neighborhood greenspace may attract new residents and lead to sociodemographic or housing cost changes. We estimated relationships between greenspace and gentrification-related changes in the 43 largest metropolitan statistical areas (MSAs) of the United States (US). We used the US National Land Cover and Brown University Longitudinal Tracts databases, as well as spatial lag models, to estimate census tract-level associations between percentage greenspace (years 1990, 2000) and subsequent changes (1990–2000, 2000–2010) in percentage college-educated, percentage working professional jobs, race/ethnic composition, household income, percentage living in poverty, household rent, and home value. We also investigated effect modification by racial/ethnic composition. We ran models for each MSA and time period and used random-effects meta-analyses to derive summary estimates for each period. Estimates were modest in magnitude and heterogeneous across MSAs. After adjusting for census-tract level population density in 1990, compared to tracts with low percentage greenspace in 1992 (defined as ≤50th percentile of the MSA-specific distribution in 1992), those with high percentage greenspace (defined as >75th percentile of the MSA-specific distribution) experienced higher 1990–2000 increases in percentage of the employed civilian aged 16+ population working professional jobs (β: 0.18, 95% confidence interval (CI): 0.11, 0.26) and in median household income (β: 0.23, 95% CI: 0.15, 0.31). Adjusted estimates for the 2000–2010 period were near the null. We did not observe evidence of effect modification by race/ethnic composition. We observed evidence of modest associations between greenspace and gentrification trends. Further research is needed to explore reasons for heterogeneity and to quantify health implications.


2020 ◽  
Vol 8 (1) ◽  
pp. 54-69
Author(s):  
Peter B. Gilbert ◽  
Bryan S. Blette ◽  
Bryan E. Shepherd ◽  
Michael G. Hudgens

AbstractWhile the HVTN 505 trial showed no overall efficacy of the tested vaccine to prevent HIV infection over placebo, markers measuring immune response to vaccination were strongly correlated with infection. This finding generated the hypothesis that some marker-defined vaccinated subgroups were partially protected whereas others had their risk increased. This hypothesis can be assessed using the principal stratification framework (Frangakis and Rubin, 2002) for studying treatment effect modification by an intermediate response variable, using methods in the sub-field of principal surrogate (PS) analysis that studies multiple principal strata. Unfortunately, available methods for PS analysis require an augmented study design not available in HVTN 505, and make untestable structural risk assumptions, motivating a need for more robust PS methods. Fortunately, another sub-field of principal stratification, survivor average causal effect (SACE) analysis (Rubin, 2006) – which studies effects in a single principal stratum – provides many methods not requiring an augmented design and making fewer assumptions. We show how, for a binary intermediate response variable, methods developed for SACE analysis can be adapted to PS analysis, providing new and more robust PS methods. Application to HVTN 505 supports that the vaccine partially protected individuals with vaccine-induced T-cells expressing certain combinations of functions.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
C. J. MacDonald ◽  
A. L. Madika ◽  
G. Severi ◽  
A. Fournier ◽  
M. C. Boutron-Ruault

AbstractDyslipidaemia is a major risk factor for cardio-vascular disease, as it promotes atherosclerosis. While cross-sectional studies have identified higher serum cholesterol amongst individuals with the A blood group, there is less evidence from prospective studies whether this translates into a higher risk of dyslipidaemia that requires treatment, nor if this genetic factor interacts with smoking status. This study aimed to prospectively determine potential associations between smoking, ABO blood groups, and risk of incident dyslipidaemia requiring treatment, and to assess associations over strata of blood ABO group. We assessed associations between blood ABO group, smoking and dyslipidaemia in 74,206 women participating in the E3N cohort. We included women who did not have cardiovascular disease at baseline. Logistic regression was used to determine associations between ABO group, smoking and prevalent dyslipidaemia at baseline. Cox proportional hazard models were then used to determine if blood ABO group and smoking were associated with the risk of incident dyslipidaemia, amongst women free of dyslipidaemia at baseline. At baseline 28,281 women with prevalent dyslipidaemia were identified. Compared to the O-blood group, the non-O blood group was associated higher odds of with prevalent dyslipidaemia (ORnon-O = 1.09 [1.06: 1.13]). Amongst the women free of dyslipidaemia at baseline, 6041 incident cases of treated dyslipidaemia were identified during 454,951 person-years of follow-up. The non-O blood groups were associated with an increased risk of dyslipidaemia when compared to the O-group (HRnon-O = 1.16 [1.11: 1.22]), specifically the A blood-group (HRA = 1.18 [1.12: 1.25]). Current smokers were associated with an increased risk of incident dyslipidaemia (HR smokers = 1.27 [1.16: 1.37]), compared to never-smokers. No evidence for effect modification between smoking and ABO blood group was observed (p-effect modification = 0.45), although the highest risk was observed among AB blood group women who smoked (HR = 1.76 [1.22: 2.55]). In conclusion, the non-O blood groups, specifically the A group were associated with an increased risk of dyslipidaemia. Current smokers were associated with a 30% increased risk of dyslipidaemia. These results could aid in personalised approaches to the prevention of cardiovascular risk-factors.


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