Background
Allergy can be diagnosed using basophil tests. Several methods measuring basophil activation are available. This study aimed at comparing basophil activation test (BAT), histamine release ...assay (HR), and passive sensitization histamine release assay (passive HR) in the diagnosis of peanut allergy.
Methods
BAT, HR, and passive HR were performed on 11 peanut‐allergic and 14 nonallergic subjects. Blood was incubated with peanut extract or anti‐IgE and tests were performed as follows: BAT—CD63 upregulation was assessed by flow cytometry; HR—released histamine was quantified by a glass fiber‐based fluorometric method; passive HR—IgE‐stripped donor basophils were incubated with participants' serum and histamine release was quantified as HR.
Results
CDsens, a measure of basophil allergen sensitivity, was significantly higher for BAT (80.1±17.4) compared to HR (23.4±10.31) and passive HR (11.1±2.0). BAT, HR, and passive HR had a clinical sensitivity of 100%, 100%, and 82% and specificity of 100%, 100%, and 100%, respectively, when excluding inconclusive results. BAT identified 11 of 11 allergic patients, HR 10, and passive HR 9. Likewise, BAT recognized 12 of 14 nonallergic subjects, HR 10, and passive HR 13. However, the tests' diagnostic performances were not statistically different. Interestingly, nonreleasers in HR but not in BAT had lower basophil count compared to releasers (249 vs 630 counts/min).
Conclusion
BAT displayed a significantly higher CDsens compared to HR and passive HR. The basophil tests' diagnostic performances were not significantly different. Still, BAT could diagnose subjects with low basophil number in contrast to HR.
An Aerodyne high resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS) was deployed during the Carbonaceous Aerosols and Radiative Effects Study (CARES) that took place in northern ...California in June 2010. We present results obtained at Cool (denoted as the T1 site of the project) in the foothills of the Sierra Nevada Mountains, where intense biogenic emissions are periodically mixed with urban outflow transported by daytime southwesterly winds from the Sacramento metropolitan area. During this study, the average mass loading of submicrometer particles (PM1) was 3.0 μg m−3, dominated by organics (80%) and sulfate (9.9%). The organic aerosol (OA) had a nominal formula of C1H1.38N0.004OM0.44, thus an average organic mass-to-carbon (OM/OC) ratio of 1.70. Two distinct oxygenated OA factors were identified via Positive matrix factorization (PMF) of the high-resolution mass spectra of organics. The more oxidized MO-OOA (O/C = 0.54) was interpreted as a surrogate for secondary OA (SOA) influenced by biogenic emissions whereas the less oxidized LO-OOA (O/C = 0.42) was found to represent SOA formed in photochemically processed urban emissions. LO-OOA correlated strongly with ozone and MO-OOA correlated well with two 1st generation isoprene oxidation products (methacrolein and methyl vinyl ketone), indicating that both SOAs were relatively fresh. A hydrocarbon like OA (HOA) factor was also identified, representing primary emissions mainly due to local traffic. On average, SOA (= MO-OOA + LO-OOA) accounted for 91% of the total OA mass and 72% of the PM1 mass observed at Cool. Twenty three periods of urban plumes from T0 (Sacramento) to T1 (Cool) were identified using the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem). The average PM1 mass loading was considerably higher in urban plumes than in air masses dominated by biogenic SOA. The change in OA mass relative to CO (ΔOA/ΔCO) varied in the range of 5-196 μg m−3 ppm−1, reflecting large variability in SOA production. The highest ΔOA/ΔCO was reached when air masses were dominated by anthropogenic emissions in the presence of a high concentration of biogenic volatile organic compounds (BVOCs). This ratio, which was 97 μg m−3 ppm−1 on average, was much higher than when urban plumes arrived in a low BVOC environment (~36 μg m−3 ppm−1) or during other periods dominated by biogenic SOA (35 μg m−3 ppm−1). These results demonstrate that SOA formation is enhanced when anthropogenic emissions interact with biogenic precursors.
Background
Treatment for pancreatic cancer with pharmacological ascorbate (ascorbic acid, vitamin C) decreases tumor progression in preclinical models. A phase I clinical trial was performed to ...establish safety and tolerability of pharmacological ascorbate combined with gemcitabine in patients with biopsy-proven stage IV pancreatic adenocarcinoma.
Design
Nine subjects received twice-weekly intravenous ascorbate (15–125 g) employing Simon’s accelerated titration design to achieve a targeted post-infusion plasma level of ≥350 mg/dL (≥20 mM). Subjects received concurrent gemcitabine. Disease burden, weight, performance status, hematologic and metabolic laboratories, time to progression and overall survival were monitored.
Results
Mean plasma ascorbate trough levels were significantly higher than baseline (1.46 ± 0.02 vs. 0.78 ± 0.09 mg/dL, i.e., 83 vs. 44 μM,
p
< 0.001). Adverse events attributable to the drug combination were rare and included diarrhea (
n
= 4) and dry mouth (
n
= 6). Dose-limiting criteria were not met for this study. Mean survival of subjects completing at least two cycles (8 weeks) of therapy was 13 ± 2 months.
Conclusions
Data suggest pharmacologic ascorbate administered concurrently with gemcitabine is well tolerated. Initial data from this small sampling suggest some efficacy. Further studies powered to determine efficacy should be conducted.
Graphical abstract Highlights ► NMDA glutamate receptor subunits are located in mossy fibres. ► Most of the NMDA receptor subunits are present in the postsynaptic membrane. ► GluN1, GluN2B, GluN2D ...and GluN3B have a presynaptic localization.
Objective
To assess the separate and combined associations of maternal pre‐pregnancy body mass index (BMI) and gestational weight gain with the risks of pregnancy complications and their population ...impact.
Design
Individual participant data meta‐analysis of 39 cohorts.
Setting
Europe, North America, and Oceania.
Population
265 270 births.
Methods
Information on maternal pre‐pregnancy BMI, gestational weight gain, and pregnancy complications was obtained. Multilevel binary logistic regression models were used.
Main outcome measures
Gestational hypertension, pre‐eclampsia, gestational diabetes, preterm birth, small and large for gestational age at birth.
Results
Higher maternal pre‐pregnancy BMI and gestational weight gain were, across their full ranges, associated with higher risks of gestational hypertensive disorders, gestational diabetes, and large for gestational age at birth. Preterm birth risk was higher at lower and higher BMI and weight gain. Compared with normal weight mothers with medium gestational weight gain, obese mothers with high gestational weight gain had the highest risk of any pregnancy complication (odds ratio 2.51, 95% CI 2.31– 2.74). We estimated that 23.9% of any pregnancy complication was attributable to maternal overweight/obesity and 31.6% of large for gestational age infants was attributable to excessive gestational weight gain.
Conclusions
Maternal pre‐pregnancy BMI and gestational weight gain are, across their full ranges, associated with risks of pregnancy complications. Obese mothers with high gestational weight gain are at the highest risk of pregnancy complications. Promoting a healthy pre‐pregnancy BMI and gestational weight gain may reduce the burden of pregnancy complications and ultimately the risk of maternal and neonatal morbidity.
Tweetable
Promoting a healthy body mass index and gestational weight gain might reduce the population burden of pregnancy complications.
Tweetable
Promoting a healthy body mass index and gestational weight gain might reduce the population burden of pregnancy complications.
The structure of GP-zones in an industrial, 7xxx-series Al–Zn–Mg alloy has been investigated by transmission electron microscopy methods: selected area diffraction, conventional and high-resolution ...imaging. Two types of GP-zones, GP(I) and (II) are characterized by their electron diffraction patterns. GP(I)-zones are formed over a wide temperature range, from room temperature to 140–150°C, independently of quenching temperature. The GP(I)-zones are coherent with the aluminum matrix, with internal ordering of Zn and Al/Mg on the matrix lattice, suggested to be based on AuCu(I)-type sub-unit, and anti-phase boundaries. GP(II) are formed after quenching from temperatures above 450°C, by aging at temperatures above 70°C. The GP(II)-zones are described as zinc-rich layers on {111}-planes, with internal order in the form of elongated domains. The structural relation to the η′-precipitate is discussed.
Currently available test methods are not well-suited for the identification of chemicals that disturb hormonal processes involved in female reproductive development and function. This renders women's ...reproductive health at increasing risk globally, which, coupled with increasing incidence rates of reproductive disorders, is of great concern. A woman's reproductive health is largely established during embryonic and fetal development and subsequently matures during puberty. The endocrine system influences development, maturation, and function of the female reproductive system, thereby making appropriate hormone levels imperative for correct functioning of reproductive processes. It is concerning that the effects of human-made chemicals on the endocrine system and female reproductive health are poorly addressed in regulatory chemical safety assessment, partly because adequate test methods are lacking. Our EU-funded project FREIA aims to address this need by increasing understanding of how endocrine disrupting chemicals (EDCs) can impact female reproductive health. We will use this information to provide better test methods that enable fit-for-purpose chemical regulation and then share our knowledge, promote a sustainable society, and improve the reproductive health of women globally.
The California Research at the Nexus of Air Quality and Climate Change (CalNex) and Carbonaceous Aerosol and Radiative Effects Study (CARES) field campaigns during May and June 2010 provided a data ...set appropriate for studying the structure of the atmospheric boundary layer (BL). The NASA Langley Research Center (LaRC) airborne high spectral resolution lidar (HSRL) was deployed to California onboard the NASA LaRC B-200 aircraft to aid in characterizing aerosol properties during these two field campaigns. Measurements of aerosol extinction (532 nm), backscatter (532 and 1064 nm), and depolarization (532 and 1064 nm) profiles during 31 flights, many in coordination with other research aircraft and ground sites, constitute a diverse data set for use in characterizing the spatial and temporal distribution of aerosols, as well as the depth and variability of the daytime mixed layer (ML) height. The paper describes the modified Haar wavelet covariance transform method used to derive the ML heights from HSRL backscatter profiles. HSRL ML heights are validated using ML heights derived from two radiosonde profile sites during CARES. Comparisons between ML heights from HSRL and a Vaisala ceilometer operated during CalNex were used to evaluate the representativeness of a fixed measurement over a larger region. In the Los Angeles basin, comparisons of ML heights derived from HSRL measurements and ML heights derived from the ceilometer result in a very good agreement (mean bias difference of 10 m and correlation coefficient of 0.89) up to 30 km away from the ceilometer site, but are essentially uncorrelated for larger distances, indicating that the spatial variability of the ML height is significant over these distances and not necessarily well captured by limited ground stations. The HSRL ML heights are also used to evaluate the performance in simulating the temporal and spatial variability of ML heights from the Weather Research and Forecasting Chemistry (WRF-Chem) community model. When compared to aerosol ML heights from HSRL, thermodynamic ML heights from WRF-Chem were underpredicted in the CalNex and CARES regions, shown by a bias difference value of -157 m and -29 m, respectively. Better agreement over the Central Valley than in mountainous regions suggests that some variability in the ML height is not well captured at the 4 km grid resolution of the model. A small but significant number of cases have poor agreement when WRF-Chem consistently overestimates the ML height in the late afternoon. Additional comparisons with WRF-Chem aerosol mixed layer heights show no significant improvement over thermodynamic ML heights, confirming that any differences between measurement and model are not due to the methodology of ML height determination.
Background
The pathology of allergic diseases involves type 2 immune cells, such as Th2, ILC2, and basophils exerting their effect by production of IL‐4, IL‐5, and IL‐13. However, surface receptors ...that are specifically expressed on type 2 immune cells are less well documented. The aim of this investigation was to identify surface markers associated with type 2 inflammation.
Methods
Naïve human CD4+ T cells were short‐term activated in the presence or absence of IL‐4 and analyzed for expression of >300 cell‐surface proteins. Ex vivo‐isolated peripheral blood mononuclear cells (PBMCs) from peanut‐allergic (PA) and nonallergic subjects were stimulated (14–16 h) with peanut extract to detect peanut‐specific CD4+CD154+ T cells. Biopsies were obtained for transcriptomic analysis from healthy controls and patients with extrinsic or intrinsic atopic dermatitis (AD) and psoriasis.
Results
Expression analysis of >300 surface proteins enabled identification of IL‐4‐upregulated surface proteins, such as CD90, CD108, CD109, and CD200R (CD200R1). Additional analysis of in vitro‐differentiated Th0, Th1, and Th2 cultures identified CD200R as upregulated on Th2 cells. From ex vivo‐isolated PBMCs, we found high expression of CD200R on Th2 and ILC2 cells and basophils. In PA subjects, the peanut‐specific Th2 (CD154+CRTh2+) cells expressed more CD200R than the non‐allergen‐specific Th2 (CD154−CRTh2+) cells. Moreover, costaining of CD161 and CD200R identified peanut‐specific highly differentiated IL‐4+IL‐5+ Th2 cells. Finally, transcriptomic analysis revealed upregulation of CD200R in lesional skin from subjects with an extrinsic AD phenotype compared to healthy skin.
Conclusion
These results indicate that CD200R expression strongly correlates with Th2 pathology; though, the mechanism is as yet elusive.
Background The National Lung Screening Trial (NLST), a randomized study conducted at 33 US sites, is comparing lung cancer mortality among persons screened with reduced dose helical computerized ...tomography and among persons screened with chest radiograph. In this article, we present characteristics of the study population. Methods Eligible participants were aged 55–74 years and were current or former smokers with a cigarette smoking history of at least 30 pack-years. Randomization was stratified by site, sex, and age. To assess representativeness of the study population, demographic characteristics of individuals from the general population who met NLST age and smoking history inclusion criteria were obtained from the Tobacco Use Supplement of the US Census Bureau Current Population Surveys. Results The NLST enrolled 53 456 persons, with 26 733 randomly assigned to chest radiograph screening and 26 723 to computerized tomography screening. Characteristics of the participants were as follows: 31 533 (59%) were men, 39 234 (73%) were younger than 65 years, 25 779 (48%) were current smokers, and 16 839 (32%) had a college or higher degree. Median cigarette exposure was 48 pack-years. Among Tobacco Use Supplement respondents who met NLST age and smoking history criteria, 59% were men, 65% were younger than 65 years, and 57% were current smokers. Median cigarette exposure among this group was 47 pack-years, and 14% had a college degree or higher. Conclusion The NLST cohort has a distribution of sex and pack-year history that is similar to the component of the general US population that meets the major NLST eligibility criteria; however, NLST participants are younger, better educated, and less likely to be current smokers.
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