Profiling studies of mRNA and microRNA, particularly microarray-based studies, have been extensively used to create compendia of genes that are preferentially expressed in the immune system. In some ...instances, functional studies have been subsequently pursued. Recent efforts such as the Encyclopedia of DNA Elements have demonstrated the benefit of coupling RNA sequencing analysis with information from expressed sequence tags (ESTs) for transcriptomic analysis. However, the full characterization and identification of transcripts that function as modulators of human immune responses remains incomplete. In this study, we demonstrate that an integrated analysis of human ESTs provides a robust platform to identify the immune transcriptome. Beyond recovering a reference set of immune-enriched genes and providing large-scale cross-validation of previous microarray studies, we discovered hundreds of novel genes preferentially expressed in the immune system, including noncoding RNAs. As a result, we have established the Immunogene database, representing an integrated EST road map of gene expression in human immune cells, which can be used to further investigate the function of coding and noncoding genes in the immune system. Using this approach, we have uncovered a unique metabolic gene signature of human macrophages and identified PRDM15 as a novel overexpressed gene in human lymphomas. Thus, we demonstrate the utility of EST profiling as a basis for further deconstruction of physiologic and pathologic immune processes.
IntroductionA motor vehicle collision (MVC) is one of the most common life-threatening events experienced by individuals living in the USA. While most individuals recover following MVC, a significant ...proportion of individuals develop adverse post-traumatic sequelae such as post-traumatic stress disorder or persistent musculoskeletal pain. Adverse post-traumatic sequelae are common, morbid and costly public health problems in the USA and other industrialised countries. The pathogenesis of these disorders following MVC remains poorly understood. In the USA, available data suggest that African-Americans experience an increased burden of adverse post-traumatic sequelae after MVC compared to European Americans, but to date no studies examining the pathogenesis of these disorders among African-Americans experiencing MVC have been performed.Methods and analysisThe African-American CRASH (AA CRASH) study is an NIH-funded, multicentre, prospective study that enrols African-Americans (n=900) who present to the emergency department (ED) within 24 hours of MVC. Participants are enrolled at 13 ED sites in the USA. Individuals who are admitted to the hospital or who report a fracture or tissue injury are excluded. Participants complete a detailed ED interview that includes an assessment of crash history, current post-traumatic symptoms and health status prior to the MVC. Blood samples are also collected in the ED using PAXgene DNA and PAXgene RNA tubes. Serial mixed-mode assessments 6 weeks, 6 months and 1 year after MVC include an assessment of adverse sequelae, general health status and health service utilisation. The results from this study will provide insights into the incidence and pathogenesis of persistent pain and other post-traumatic sequelae in African-Americans experiencing MVC.Ethics and disseminationAA CRASH has ethics approval in the USA, and the results will be published in a peer-reviewed journal.
Background
Automated radiosynthesizers are vital for routine production of positron-emission tomography tracers to minimize radiation exposure to operators and to ensure reproducible synthesis ...yields. The recent trend in the synthesizer industry towards the use of disposable kits aims to simplify setup and operation for the user, but often introduces several limitations related to temperature and chemical compatibility, thus requiring reoptimization of protocols developed on non-cassette-based systems. Radiochemists would benefit from a single hybrid system that provides tremendous flexibility for development and optimization of reaction conditions while also providing a pathway to simple, cassette-based production of diverse tracers.
Methods
We have designed, built, and tested an automated three-reactor radiosynthesizer (ELIXYS) to provide a flexible radiosynthesis platform suitable for both tracer development and routine production. The synthesizer is capable of performing high-pressure and high-temperature reactions by eliminating permanent tubing and valve connections to the reaction vessel. Each of the three movable reactors can seal against different locations on disposable cassettes to carry out different functions such as sealed reactions, evaporations, and reagent addition. A reagent and gas handling robot moves sealed reagent vials from storage locations in the cassette to addition positions and also dynamically provides vacuum and inert gas to ports on the cassette. The software integrates these automated features into chemistry unit operations (e.g., React, Evaporate, Add) to intuitively create synthesis protocols. 2-Deoxy-2-
18
Ffluoro-5-methyl-β-
l
-arabinofuranosyluracil (
l
-
18
FFMAU) and 2-deoxy-2-
18
Ffluoro-β-
d
-arabinofuranosylcytosine (
d
-
18
FFAC) were synthesized to validate the system.
Results
l
-
18
FFMAU and
d
-
18
FFAC were successfully synthesized in 165 and 170 min, respectively, with decay-corrected radiochemical yields of 46% ± 1% (
n
= 6) and 31% ± 5% (
n
= 6), respectively. The yield, repeatability, and synthesis time are comparable to, or better than, other reports.
d
-
18
FFAC produced by ELIXYS and another manually operated apparatus exhibited similar biodistribution in wild-type mice.
Conclusion
The ELIXYS automated radiosynthesizer is capable of performing radiosyntheses requiring demanding conditions: up to three reaction vessels, high temperatures, high pressures, and sensitive reagents. Such flexibility facilitates tracer development and the ability to synthesize multiple tracers on the same system without customization or replumbing. The disposable cassette approach simplifies the transition from development to production.
The ability to accurately validate high–spectral resolution infrared radiance measurements from space using comparisons with a high‐altitude aircraft spectrometer has been successfully demonstrated. ...The demonstration is based on a 21 November 2002 underflight of the AIRS on the NASA Aqua spacecraft by the Scanning‐HIS on the NASA ER‐2 high‐altitude aircraft. A comparison technique which accounts for the different viewing geometries and spectral characteristics of the two sensors is introduced, and accurate comparisons are made for AIRS channels throughout the infrared spectrum. Resulting brightness temperature differences are found to be 0.2 K or less for most channels. Both the AIRS and the Scanning‐HIS calibrations are expected to be very accurate (formal 3‐sigma estimates are better than 1 K absolute brightness temperature for a wide range of scene temperatures), because high spectral resolution offers inherent advantages for absolute calibration and because they make use of high‐emissivity cavity blackbodies as onboard radiometric references. AIRS also has the added advantage of a cold space view, and the Scanning‐HIS calibration has recently benefited from the availability of a zenith view from high‐altitude flights. Aircraft comparisons of this type provide a mechanism for periodically testing the absolute calibration of spacecraft instruments with instrumentation for which the calibration can be carefully maintained on the ground. This capability is especially valuable for assuring the long‐term consistency and accuracy of climate observations, including those from the NASA EOS spacecraft (Terra, Aqua and Aura) and the new complement of NPOESS operational instruments. The validation role for accurately calibrated aircraft spectrometers also includes application to broadband instruments and linking the calibrations of similar instruments on different spacecraft. It is expected that aircraft flights of the Scanning‐HIS and its close cousin the NPOESS Airborne Sounder Test Bed (NAST) will be used to check the long‐term stability of AIRS and the NPOESS operational follow‐on sounder, the Cross‐track Infrared Sounder (CrIS), over the life of the missions.
The fundamental measurement of the Tropospheric Emission Spectrometer (TES) on board the Aura spacecraft is upwelling infrared spectral radiances. Accurate TES retrievals of surface and atmospheric ...parameters such as trace gas amounts critically depend on well‐calibrated radiance spectra. On‐orbit TES nadir observations were evaluated using carefully selected, nearly coincident spectral radiance measurements from Atmospheric Infrared Sounder (AIRS) on Aqua and special scanning high‐resolution interferometer sounder (SHIS) underflights. Modifications to the L1B calibration algorithms for TES version 2 data resulted in significant improvements for the TES‐AIRS comparisons. The comparison of TES with SHIS (adjusted for geometric differences) show mean and standard deviation differences of less than 0.3 K at warmer brightness temperatures of 290–295 K. The TES/SHIS differences are less than 0.4 K at brightness temperatures of 265–270 K. There are larger TES/SHIS comparison differences for higher‐frequency TES 1A1 filter, which has less upwelling radiance signal. The TES/AIRS comparisons show mean differences of less than 0.3 K at 290–295 K and less than 0.5 K at 265–270 K with standard deviation less than 0.6 K for the majority of the spectral regions and brightness temperature range. A procedure to warm up the optical bench for better alignment in December 2005 gave a fourfold increase in the signal‐to‐noise ratio at higher frequency ranges. Recent results from a long‐term comparison of TES sea surface temperature (SST) observations with the Reynolds optimally interpolated (ROI) SST product demonstrates TES radiometric stability.
Rheumatoid arthritis patients are at increased risk for periprosthetic joint infection after arthroplasty. The reason is multifactorial. Nasal colonization with Staphylococcus aureus is a modifiable ...risk factor; carriage rates in RA patients are unknown. The goal of this study is to determine the S aureus nasal carriage rates of RA patients on biologics, RA patients on traditional disease-modifying anti-rheumatic drugs (DMARDs), and osteoarthritis.
Consecutive patients with RA on biologics (±DMARDs), RA on non-biologic DMARDs, or OA were prospectively enrolled from April 2017 to May 2018. One hundred twenty-three patients were determined necessary per group to show a difference in carriage rates. Patients underwent a nasal swab and answered questions to identify additional risk factors. S aureus positive swabs were further categorized using spa typing. Logistic regression evaluated the association with S aureus colonization between the groups after controlling for known risk factors.
RA patients on biologics, 70% of whom were on DMARDs, had statistically significant increase in S aureus colonization (37%) compared to RA on DMARDs alone (24%), or OA (20%) (P = .01 overall). After controlling for glucocorticoids, antibiotic use, recent hospitalization, and diabetes, RA on biologics had a significant increased risk of S aureus nasal colonization (Odds ratio 1.80, 95% confidence interval 1.00-3.22, P = .047).
S aureus colonization risk was increased for RA on biologics compared to RA not on biologics and OA. Nasal S aureus carriage increases the risk of surgical site infection; this modifiable risk factor should be addressed prior to total joint arthroplasty for this higher risk patient group.
Purpose
Breast terminal duct lobular units (TDLUs) are the main source of breast cancer (BC) precursors. Higher serum concentrations of hormones and growth factors have been linked to increased TDLU ...numbers and to elevated BC risk, with variable effects by menopausal status. We assessed associations of circulating factors with breast histology among premenopausal women using artificial intelligence (AI) and preliminarily tested whether parity modifies associations.
Methods
Pathology AI analysis was performed on 316 digital images of H&E-stained sections of normal breast tissues from Komen Tissue Bank donors ages ≤ 45 years to assess 11 quantitative metrics. Associations of circulating factors with AI metrics were assessed using regression analyses, with inclusion of interaction terms to assess effect modification.
Results
Higher prolactin levels were related to larger TDLU area (
p
< 0.001) and increased presence of adipose tissue proximate to TDLUs (
p
< 0.001), with less significant positive associations for acini counts (
p
= 0.012), dilated acini (
p
= 0.043), capillary area (
p
= 0.014), epithelial area (
p
= 0.007), and mononuclear cell counts (
p
= 0.017). Testosterone levels were associated with increased TDLU counts (
p
< 0.001), irrespective of parity, but associations differed by adipose tissue content. AI data for TDLU counts generally agreed with prior visual assessments.
Conclusion
Among premenopausal women, serum hormone levels linked to BC risk were also associated with quantitative features of normal breast tissue. These relationships were suggestively modified by parity status and tissue composition. We conclude that the microanatomic features of normal breast tissue may represent a marker of BC risk.
The effects of elevated CO2 and temperature on principal carbon constituents (PCC) and C and N allocation between needle, woody (stem and branches) and root tissue of Pseudotsuga menziesii Mirb. ...Franco seedlings were determined. The seedlings were grown in sun‐lit controlled‐environment chambers that contained a native soil. Chambers were controlled to reproduce ambient or ambient +180 ppm CO2 and either ambient temperature or ambient +3.5 °C for 4 years. There were no significant CO2 × temperature interactions; consequently the data are presented for the CO2 and temperature effects. At the final harvest, elevated CO2 decreased the nonpolar fraction of the PCC and increased the polar fraction and amount of sugars in the needles. In contrast, elevated temperature increased the nonpolar fraction of the PCC and decreased sugars in needles. There were no CO2 or temperature effects on the PCC fractions in the woody tissue or root tissue. Elevated CO2 and temperature had no significant effects on the C content of any of the plant tissues or fractions. In contrast, the foliar N content declined under elevated CO2 and increased under elevated temperature; there were no significant effects in other tissues. The changes in the foliar N concentrations were in the cellulose and lignin fractions, the fractions, which contain protein, and are the consequences of changes in N allocation under the treatments. These results indicate reallocation of N among plant organs to optimize C assimilation, which is mediated via changes in the selectivity of Rubisco and carbohydrate modulation of gene expression.
OBJECTIVE: This study tested whether a relationship exists between concentration and response following discontinuation of selective serotonin reuptake inhibitors. METHOD: Eight patients with ...remitted major depression who were taking 20 mg day of either fluoxetine or paroxetine underwent placebo substitution for 3 days. Serum drug and brain fluorine levels were obtained before and after placebo substitution. RESULTS: With placebo substitution, a mean of 88% (SD=13%) of brain fluorine signal from fluoxetine (plus fluorinated metabolites) remained, compared with a mean of 38% (SD=17%) of the brain fluorine signal from paroxetine (plus fluorinated metabolites). Among patients taking paroxetine, adverse events during placebo substitution correlated highly with steady-state brain drug levels. CONCLUSIONS: The correlation of clinical effects with brain drug levels in the paroxetine group suggests that relationships between drug response and brain drug concentrations merit further investigation.
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