Biomarkers in Wave III of the Add Health Study

One of the many unique features of Wave III of the Add Health Study was the collection of biological samples. These biological samples permitted the identification of individuals with sexually transmitted infections [STI] (including HIV), and genotype ascertainment for pairs of full-siblings or twins who resided in the same households. The STI testing allows for analyses of individual, household, family, and environmental risk factors for laboratory-confirmed sexually transmitted infections (versus self-report), and the genetic sample facilitates analyses that differentiate between parental, social, and genetic influence, as well as the extent to which genetic differences in neurotransmitter function are associated with a wide range of behaviors. The inclusion of these biomarker data requires special considerations in the analysis of Wave III Add Health data. Thus, the purpose of this monograph is to outline relevant procedures, design, and sampling schemes used in the collection of biomarker data, and to serve as a user’s guide for its analysis and interpretation. The monograph is intended to supplement existing descriptions of the Add Health study, rather than to replace them. Therefore, please refer to the web pages describing the Add Health Study design for more extensive detail on the study (www.cpc.unc.edu/addhealth) and the sampling weights necessary to work with the data (www.cpc.unc.edu/addhealth/codebooks/wave3). Issues that require special consideration include sample design (e.g., who was selected for each type of biomarker test), specimen collection, laboratory methods, and laboratory test performance. Each of these themes is described in separate chapters to this monograph, but should be viewed as complementary to each other

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS). Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response

Reevaluation of Air-Water Exchange Fluxes of PCBs in Green Bay and Southern Lake Michigan.

Abstract not availableJRC.H-Institute for environment and sustainability (Ispra

Low-frequency stimulation enhances ensemble co-firing and dexterity after stroke

Electrical stimulation is a promising tool for modulating brain networks. However, it is unclear how stimulation interacts with neural patterns underlying behavior. Specifically, how might external stimulation that is not sensitive to the state of ongoing neural dynamics reliably augment neural processing and improve function? Here, we tested how low-frequency epidural alternating current stimulation (ACS) in non-human primates recovering from stroke interacted with task-related activity in perilesional cortex and affected grasping. We found that ACS increased co-firing within task-related ensembles and improved dexterity. Using a neural network model, we found that simulated ACS drove ensemble co-firing and enhanced propagation of neural activity through parts of the network with impaired connectivity, suggesting a mechanism to link increased co-firing to enhanced dexterity. Together, our results demonstrate that ACS restores neural processing in impaired networks and improves dexterity following stroke. More broadly, these results demonstrate approaches to optimize stimulation to target neural dynamics

Atmospheric Concentrations and Deposition or Organochlorine Pesticides in US Mid-Atlantic Region

Organochlorine pesticides (OCPs) were measured in the atmosphere over the period January 2000- May 2001 at six locations as part of New Jersey Atmospheric Deposition Network (NJADN). Gas phase, particle phase and precipitation con centrations of 22 OCP species, including chloranes, DDTs, HCHs, endosulfan I and II, aldrin and diedrin, were measured. OCPs are found predominantly in the gas phase in all seasons, representing over 95% of the total air concentrations.JRC.H.5-Rural, water and ecosystem resource

Comparison of Transcription-Mediated Amplification and PCR Assay Results for Various Genital Specimen Types for Detection of Mycoplasma genitalium

Mycoplasma genitalium is now recognized as a possible cause of several idiopathic sexually transmitted disease (STD) syndromes. However, due to the difficulty of culture of this fastidious bacterium, nucleic acid amplification tests (NAATs) are necessary for its detection in patient specimens. In the current study we compared a newly developed research-only transcription-mediated amplification (TMA) assay (Gen-Probe Incorporated) to our in-house DNA-based PCR assay for detection of M. genitalium. The relative performance characteristics of these two NAATs were assessed with genital specimens from 284 women and 352 men reporting to an STD clinic in Seattle, WA. Among the women, M. genitalium was detected by the TMA and PCR assays in 36 (13%) and 39 (14%) vaginal swab specimens, respectively (κ = 0.923); 26 (9%) and 23 (8%) cervical swab specimens, respectively (κ = 0.843); and 25 (9%) and 28 (10%) urine specimens, respectively (κ = 0.687). Among the M. genitalium-positive women, the relative sensitivities of detection for the TMA and PCR assays were 84% and 91%, respectively, for vaginal swab specimens; 60% and 53%, respectively, for cervical swab specimens; and 58% and 65%, respectively, for urine specimens. By using an infected patient (a woman positive at any site by TMA assay and at any site by PCR) as a proxy for a “gold standard,” the specificities of detection were >99.5% for both the TMA and the PCR assays. Among the men, M. genitalium was detected in 24 urine specimens (6.8%) by the TMA assay, 26 (7.4%) urine specimens by PCR assay, and 32 urine specimens (9%) by either test (κ = 0.791). We conclude that the M. genitalium TMA and PCR assays are highly specific and that vaginal swab specimens are the most sensitive specimen type for the detection of M. genitalium in women

Wet Deposition of Polychlorinated Biphenyls in Urban and Background Areas of the Mid-Atlantic States.

Abstract not availableJRC.H-Institute for environment and sustainability (Ispra

Mycoplasma genitalium Among Young Adults in the United States: An Emerging Sexually Transmitted Infection

Objectives. We sought to determine the prevalence of and risk factors associated with Mycoplasma genitalium infection in a nationally representative sample of young adults in the United States