This study investigated the influences of neighborhood factors (residential stability and neighborhood disadvantage) and variants of the serotonin transporter linked polymorphic region (5-HTTLPR) genotype on the development of substance use among African American children aged 10-24 years. To accomplish this, a harmonized data set of five longitudinal studies was created via pooling overlapping age cohorts to establish a database with 2,689 children and 12,474 data points to span ages 10-24 years. A description of steps used in the development of the harmonized data set is provided, including how issues such as the measurement equivalence of constructs were addressed. A sequence of multilevel models was specified to evaluate Gene × Environment effects on growth of substance use across time. Findings indicated that residential instability was associated with higher levels and a steeper gradient of growth in substance use across time. The inclusion of the 5-HTTLPR genotype provided greater precision to the relationships in that higher residential instability, in conjunction with the risk variant of 5-HTTLPR (i.e., the short allele), was associated with the highest level and steepest gradient of growth in substance use across ages 10-24 years. The findings demonstrated how the creation of a harmonized data set increased statistical power to test Gene × Environment interactions for an under studied sample.

Purpose: In the United States, stillbirths (fetal deaths ≥ 20 weeks' gestation) are now more common than infant deaths. Nationally available data are limited, and little is known about women's experiences around the time of a loss. The Pregnancy Risk Assessment Monitoring System (PRAMS), a state-based survey of women with a recent live birth, could be expanded to include women who experienced a stillbirth. We aimed to determine whether women with a recent stillbirth would be amenable to a PRAMS-like survey. Methods: Eligible women were Georgia residents aged ≥18 years with a reported stillbirth from December 1, 2012-February 28, 2013 identified through fetal death certificates. Women received a handwritten sympathy card, followed by a mailed questionnaire about their health and experiences around the time of the loss. Nonresponders received two additional mailings and up to three phone calls. Results: During the study period, 149 eligible women had a reported stillbirth. Forty-nine (33%) women responded. Excluding women with invalid contact information (n = 26) yields an adjusted response rate of 40%. Response differed by race and/or ethnicity, but not by fetal, delivery, or other maternal characteristics. Conclusions: Women appear willing to respond to a survey regarding a recent stillbirth. Further studies of the expansion of PRAMS to include stillbirth are warranted.

Collective cell responses to exogenous cues depend on cell-cell interactions. In principle, these can result in enhanced sensitivity to weak and noisy stimuli. However, this has not yet been shown experimentally, and little is known about how multicellular signal processing modulates single-cell sensitivity to extracellular signaling inputs, including those guiding complex changes in the tissue form and function. Here we explored whether cell-cell communication can enhance the ability of cell ensembles to sense and respond to weak gradients of chemotactic cues. Using a combination of experiments with mammary epithelial cells and mathematical modeling, we find that multicellular sensing enables detection of and response to shallow epidermal growth factor (EGF) gradients that are undetectable by single cells. However, the advantage of this type of gradient sensing is limited by the noisiness of the signaling relay, necessary to integrate spatially distributed ligand concentration information. We calculate the fundamental sensory limits imposed by this communication noise and combine them with the experimental data to estimate the effective size of multicellular sensory groups involved in gradient sensing. Functional experiments strongly implicated intercellular communication through gap junctions and calcium release from intracellular stores as mediators of collective gradient sensing. The resulting integrative analysis provides a framework for understanding the advantages and limitations of sensory information processing by relays of chemically coupled cells.

A webinar for ASERL members on the development and implementation of Emory’s Open Access Collection Development Policy. A video of the webinar is available at https://vimeo.com/169905536, or by clicking on Final Published Version above. Like other academic libraries, Emory University has been approached by a number of open access collection initiatives seeking funding. In this webinar, Lisa Macklin & Chris Palazzolo discuss that while all of these initiatives may have merit, how should Emory choose which to support, and why. Emory's Collection Management and Scholarly Communications Office drafted an Open Access Collections Policy which outlines basic principles and processes regarding the addition of open access content to the libraries collections. It defines the criteria for the library to provide financial support for emerging open access initiatives, as well as the process for the identification and selection of open access content for the collection. The speakers discuss the process of creating the policy, the questions they asked, and how this OA collections policy relates to other collection policies and library Open Access initiatives.

Background Few studies assess whether place characteristics are associated with social network characteristics that create vulnerability to substance use. Methods This longitudinal study analyzed 7 waves of data (2009-2014) from a predominantly substance-using cohort of 172 African-American adults relocated from public housing complexes in Atlanta, GA, to determine whether post-relocation changes in exposure to neighborhood conditions were associated with four network characteristics related to substance use: number of social network members who used illicit drugs or alcohol in excess in the past six months (“drug/alcohol network”), drug/alcohol network stability, and turnover into and out of drug/alcohol networks. Individual-and network-level characteristics were captured via survey and administrative data were used to describe census tracts where participants lived. Multilevel models were used to assess relationships of census tract-level characteristics to network outcomes over time. Results On average, participants relocated to census tracts that had less economic disadvantage, social disorder, and renter-occupied housing. Post-relocation reductions in exposure to economic disadvantage were associated with fewer drug/alcohol network members and less turnover into drug/alcohol networks. Post-relocation improvements in exposure to multiple census tract-level social conditions were associated with fewer drug/alcohol network members, less turnover into drug/alcohol networks, less drug/alcohol network stability, and more turnover out of drug/alcohol networks. Conclusion Relocating to neighborhoods with less economic disadvantage and better social conditions may weaken relationships with substance-using individuals.

Background: Identifying lung pathogens and acute spikes in lung counts remain a challenge in the treatment of patients with cystic fibrosis (CF). Bacteria from the deep lung may be sampled from aerosols produced during coughing. Methods: A new device was used to collect and measure bacteria levels from cough aerosols of patients with CF. Sputum and oral specimens were also collected and measured for comparison. Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae, and Streptococcus mitis were detected in specimens using Real-Time Polymerase Chain Reaction (RT-PCR) molecular assays. Results: Twenty adult patients with CF and 10 healthy controls participated. CF related bacteria (CFRB) were detected in 13/20 (65%) cough specimens versus 15/15 (100%) sputum specimens. Commensal S. mitis was present in 0/17 (0%, p=0.0002) cough specimens and 13/14 (93%) sputum samples. In normal controls, no bacteria were collected in cough specimens but 4/10 (40%) oral specimens were positive for CFRB. Conclusions: Non-invasive cough aerosol collection may detect lower respiratory pathogens in CF patients, with similar specificity and sensitivity to rates detected by BAL, without contamination by oral CFRB or commensal bacteria.

Two urea transporters, UT-A1 and UT-A3, are expressed in the kidney terminal inner medullary collecting duct (IMCD) and are important for the production of concentrated urine. UT-A1, as the largest isoform of all UT-A urea transporters, has gained much attention and been extensively studied; however, the role and the regulation of UT-A3 are less explored. In this study, we investigated UT-A3 regulation by glycosylation modification. A site-directed mutagenesis verified a single glycosylation site in UT-A3 at Asn279. Loss of the glycosylation reduced forskolin-stimulated UT-A3 cell membrane expression and urea transport activity. UT-A3 has two glycosylation forms, 45 and 65 kDa. Using sugar-specific binding lectins, the UT-A3 glycosylation profile was examined. The 45-kDa form was pulled down by lectin concanavalin A (Con A) and Galant husnivalis lectin (GNL), indicating an immature glycan with a high amount of mannose (Man), whereas the 65-kDa form is a mature glycan composed of acetylglucosamine (GlcNAc) and poly-N-acetyllactosame (poly-LacNAc) that was pulled down by wheat germ agglutinin (WGA) and tomato lectin, respectively. Interestingly, the mature form of UT-A3 glycan contains significant amounts of sialic acid. We explored the enzymes responsible for directing UT-A3 sialylation. Sialyltransferase ST6GalI, but not ST3GalIV, catabolizes UT-A3 α2,6-sialylation. Activation of protein kinase C (PKC) by PDB treatment promoted UT-A3 glycan sialylation and membrane surface expression. The PKC inhibitor chelerythrine blocks ST6GalI-induced UT-A3 sialylation. Increased sialylation by ST6GalI increased UT-A3 protein stability and urea transport activity. Collectively, our study reveals a novel mechanism of UT-A3 regulation by ST6GalI-mediated sialylation modification that may play an important role in kidney urea reabsorption and the urinary concentrating mechanism.

BACKGROUND: Urinary tract infection (UTI) in the United States is the most common bacterial infection, and urine cultures often make up the largest portion of workload for a hospital-based microbiology laboratory. Appropriately managing the factors affecting the preanalytic phase of urine culture contributes significantly to the generation of meaningful culture results that ultimately affect patient diagnosis and management. Urine culture contamination can be reduced with proper techniques for urine collection, preservation, storage, and transport, the major factors affecting the preanalytic phase of urine culture. OBJECTIVES: The purposes of this review were to identify and evaluate preanalytic practices associated with urine specimens and to assess their impact on the accuracy of urine culture microbiology. Specific practices included collection methods for men, women, and children; preservation of urine samples in boric acid solutions; and the effect of refrigeration on stored urine. Practice efficacy and effectiveness were measured by two parameters: reduction of urine culture contamination and increased accuracy of patient diagnosis. The CDC Laboratory Medicine Best Practices (LMBP) initiative's systematic review method for assessment of quality improvement (QI) practices was employed. Results were then translated into evidence-based practice guidelines. SEARCH STRATEGY: A search of three electronic bibliographic databases (PubMed, SCOPUS, and CINAHL), as well as hand searching of bibliographies from relevant information sources, for English-language articles published between 1965 and 2014 was conducted. SELECTION CRITERIA: The search contained the following medical subject headings and key text words: urinary tract infections, UTI, urine/analysis, urine/microbiology, urinalysis, specimen handling, preservation, biological, preservation, boric acid, boric acid/borate, refrigeration, storage, time factors, transportation, transport time, time delay, time factor, timing, urine specimen collection, catheters, indwelling, urinary reservoirs, continent, urinary catheterization, intermittent urethral catheterization, clean voided, midstream, Foley, suprapubic, bacteriological techniques, and microbiological techniques. MAIN RESULTS: Both boric acid and refrigeration adequately preserved urine specimens prior to their processing for up to 24 h. Urine held at room temperature for more than 4 h showed overgrowth of both clinically significant and contaminating microorganisms. The overall strength of this body of evidence, however, was rated as low. For urine specimens collected from women, there was no difference in rates of contamination for midstream urine specimens collected with or without cleansing. The overall strength of this evidence was rated as high. The levels of diagnostic accuracy of midstream urine collection with or without cleansing were similar, although the overall strength of this evidence was rated as low. For urine specimens collected from men, there was a reduction in contamination in favor of midstream clean-catch over first-void specimen collection. The strength of this evidence was rated as high. Only one study compared midstream collection with cleansing to midstream collection without cleansing. Results showed no difference in contamination between the two methods of collection. However, imprecision was due largely to the small event size. The diagnostic accuracy of midstream urine collection from men compared to straight catheterization or suprapubic aspiration was high. However, the overall strength of this body of evidence was rated as low. For urine specimens collected from children and infants, the evidence comparing contamination rates for midstream urine collection with cleansing, midstream collection without cleansing, sterile urine bag collection, and diaper collection pointed to larger reductions in the odds of contamination in favor of midstream collection with cleansing over the other methods of collection. This body of evidence was rated as high. The accuracy of diagnosis of urinary tract infection from midstream clean-catch urine specimens, sterile urine bag specimens, or diaper specimens compared to straight catheterization or suprapubic aspiration was varied. AUTHORS' CONCLUSIONS: No recommendation for or against is made for delayed processing of urine stored at room temperature, refrigerated, or preserved in boric acid. This does not preclude the use of refrigeration or chemical preservatives in clinical practice. It does indicate, however, that more systematic studies evaluating the utility of these measures are needed. If noninvasive collection is being considered for women, midstream collection with cleansing is recommended, but no recommendation for or against is made for midstream collection without cleansing. If noninvasive collection is being considered for men, midstream collection with cleansing is recommended and collection of first-void urine is not recommended. No recommendation for or against is made for collection of midstream urine without cleansing. If noninvasive collection is being considered for children, midstream collection with cleansing is recommended and collection in sterile urine bags, from diapers, or midstream without cleansing is not recommended. Whether midstream collection with cleansing can be routinely used in place of catheterization or suprapubic aspiration is unclear. The data suggest that midstream collection with cleansing is accurate for the diagnosis of urinary tract infections in infants and children and has higher average accuracy than sterile urine bag collection (data for diaper collection were lacking); however, the overall strength of evidence was low, as multivariate modeling could not be performed, and thus no recommendation for or against can be made.