CD11cHi monocyte-derived macrophages are a major cellular compartment infected by Mycobacterium tuberculosis

During tuberculosis, lung myeloid cells have two opposing roles: they are an intracellular niche occupied by Mycobacterium tuberculosis, and they restrict bacterial replication. Lung myeloid cells from mice infected with yellow-fluorescent protein expressing M. tuberculosis were analyzed by flow cytometry and transcriptional profiling to identify the cell types infected and their response to infection. CD14, CD38, and Abca1 were expressed more highly by infected alveolar macrophages and CD11cHi monocyte-derived cells compared to uninfected cells. CD14, CD38, and Abca1 triple positive (TP) cells had not only the highest infection rates and bacterial loads, but also a strong interferon-gamma signature and nitric oxide synthetase-2 production indicating recognition by T cells. Despite evidence of T cell recognition and appropriate activation, these TP macrophages are a cellular compartment occupied by M. tuberculosis long-term. Defining the niche where M. tuberculosis resists elimination promises to provide insight into why inducing sterilizing immunity is a formidable challenge

Repeat Human Immunodeficiency Virus Testing by Transmission Risk Group and Rurality of Residence in North Carolina

Background Understanding of repeat human immunodeficiency virus (HIV) testing (RHT) is limited and the impact of rural residence as a potential barrier to RHT is unknown. Rural populations are of particular interest in the Southeastern United States because of their disproportionate HIV burden. Methods We used HIV surveillance data from publicly funded HIV testing sites in North Carolina to assess repeat testing by transmission risk group and residential rurality in a retrospective cohort study. Linear binomial regression models were used to estimate adjusted, 1-year cumulative incidences and cumulative incidence differences comparing RHT within transmission risk populations by level of rurality. Results In our total study population of 600,613 persons, 19,275 (3.2%) and 9567 (1.6%) self-identified as men who have sex with men (MSM) and persons who inject drugs (PWID), respectively. A small minority, 13,723 (2.3%) resided in rural ZIP codes. Men who have sex with men were most likely to repeat test (unadjusted, 1-year cumulative incidence after an initial negative test, 16.4%) compared with PWID (13.2%) and persons who did not identify as either MSM or PWID (13.6%). The greatest effect of rurality was within PWID; the adjusted, 1-year cumulative incidence of RHT was 6.4 (95% confidence interval, 1.4-11.4) percentage points higher among metropolitan versus rural PWID. Conclusions One-year cumulative incidence of RHT was low among all clients of publicly funded HIV testing sites in North Carolina, including MSM and PWID for whom annual testing is recommended. Our findings suggest a need for public health efforts to increase access to and support for RHT, particularly among rural PWID

Head Impact Exposure in Youth Football: Elementary School Ages 9–12 Years and the Effect of Practice Structure

Head impact exposure in youth football has not been well-documented, despite children under the age of 14 accounting for 70% of all football players in the United States. The objective of this study was to quantify the head impact exposure of youth football players, age 9–12, for all practices and games over the course of single season. A total of 50 players (age = 11.0 ± 1.1 years) on three teams were equipped with helmet mounted accelerometer arrays, which monitored each impact players sustained during practices and games. During the season, 11,978 impacts were recorded for this age group. Players averaged 240 ± 147 impacts for the season with linear and rotational 95th percentile magnitudes of 43 ± 7 g and 2034 ± 361 rad/s(2). Overall, practice and game sessions involved similar impact frequencies and magnitudes. One of the three teams however, had substantially fewer impacts per practice and lower 95th percentile magnitudes in practices due to a concerted effort to limit contact in practices. The same team also participated in fewer practices, further reducing the number of impacts each player experienced in practice. Head impact exposures in games showed no statistical difference. While the acceleration magnitudes among 9–12 year old players tended to be lower than those reported for older players, some recorded high magnitude impacts were similar to those seen at the high school and college level. Head impact exposure in youth football may be appreciably reduced by limiting contact in practices. Further research is required to assess whether such a reduction in head impact exposure will result in a reduction in concussion incidence

Development and Use of Engineering Standards for Computational Fluid Dynamics for Complex Aerospace Systems

Computational fluid dynamics (CFD) and other advanced modeling and simulation (M&S) methods are increasingly relied on for predictive performance, reliability and safety of engineering systems. Analysts, designers, decision makers, and project managers, who must depend on simulation, need practical techniques and methods for assessing simulation credibility. The AIAA Guide for Verification and Validation of Computational Fluid Dynamics Simulations (AIAA G-077-1998 (2002)), originally published in 1998, was the first engineering standards document available to the engineering community for verification and validation (V&V) of simulations. Much progress has been made in these areas since 1998. The AIAA Committee on Standards for CFD is currently updating this Guide to incorporate in it the important developments that have taken place in V&V concepts, methods, and practices, particularly with regard to the broader context of predictive capability and uncertainty quantification (UQ) methods and approaches. This paper will provide an overview of the changes and extensions currently underway to update the AIAA Guide. Specifically, a framework for predictive capability will be described for incorporating a wide range of error and uncertainty sources identified during the modeling, verification, and validation processes, with the goal of estimating the total prediction uncertainty of the simulation. The Guide's goal is to provide a foundation for understanding and addressing major issues and concepts in predictive CFD. However, this Guide will not recommend specific approaches in these areas as the field is rapidly evolving. It is hoped that the guidelines provided in this paper, and explained in more detail in the Guide, will aid in the research, development, and use of CFD in engineering decision-making

Relationship between foot pronation and rotation of the tibia and femur during walking

ABSTRACT The purpose of this study was to test the hypothesis that the magnitude and timing of peak foot pronation would be predictive of the magnitude and timing of peak rotation of tibia and femur. Thirty subjects who demonstrated a wide range of pronation participated. Threedimensional kinematics of the foot, tibia, and femur segments were recorded during self-selected free walking trials using a six-camera VICON motion analysis system. Regression analysis demonstrated that the magnitude and timing of peak pronation was not predictive of the magnitude and timing of tibial and femoral rotation. The lack of a relationship between peak foot pronation and the rotation of the tibia and femur is contrary to the clinical hypothesis that increased pronation results in greater lower extremity rotation. It would seem, therefore, that the relationship between foot pronation and rotation of the lower extremity segments should be assessed on a patient-by-patient basis

Associations of CDH1 germline variant location and cancer phenotype in families with hereditary diffuse gastric cancer (HDGC)

INTRODUCTION: Hereditary diffuse gastric cancer (HDGC) is a cancer syndrome associated with variants in E-cadherin (CDH1), diffuse gastric cancer and lobular breast cancer. There is considerable heterogeneity in its clinical manifestations. This study aimed to determine associations between CDH1 germline variant status and clinical phenotypes of HDGC. METHODS: One hundred and fifty-two HDGC families, including six previously unreported families, were identified. CDH1 gene-specific guidelines released by the Clinical Genome Resource (ClinGen) CDH1 Variant Curation Expert Panel were applied for pathogenicity classification of truncating, missense and splice site CDH1 germline variants. We evaluated ORs between location of truncating variants of CDH1 and incidence of colorectal cancer, breast cancer and cancer at young age (gastric cancer at \u3c40 or breast cancer \u3c50 years of age). RESULTS: Frequency of truncating germline CDH1 variants varied across functional domains of the E-cadherin receptor gene and was highest in linker (0.05785 counts/base pair; p=0.0111) and PRE regions (0.10000; p=0.0059). Families with truncating CDH1 germline variants located in the PRE-PRO region were six times more likely to have family members affected by colorectal cancer (OR 6.20, 95% CI 1.79 to 21.48; p=0.004) compared with germline variants in other regions. Variants in the intracellular E-cadherin region were protective for cancer at young age (OR 0.2, 95% CI 0.06 to 0.64; p=0.0071) and in the linker regions for breast cancer (OR 0.35, 95% CI 0.12 to 0.99; p=0.0493). Different CDH1 genotypes were associated with different intracellular signalling activation levels including different p-ERK, p-mTOR and β-catenin levels in early submucosal T1a lesions of HDGC families with different CDH1 variants. CONCLUSION: Type and location of CDH1 germline variants may help to identify families at increased risk for concomitant cancers that might benefit from individualised surveillance and intervention strategies

Dyadic Interaction: Greater than the Sum of its Parts?

The study of dyadic interaction plays a major role in infancy research. To advance conceptually-informed measurement of dyadic interaction and integration across studies, we examined factor structure of individual parents’ and infants’ measures and dyadic measures from face-to-face interactions in two samples of 6-mo-old infants and their parents: mothers from a demographically heterogeneous sample (N = 164) and mothers and fathers (N = 156) from a Caucasian middle-class sample. Results suggested: a) individual and dyadic measures, and parents’ and infants’ behaviors contribute independent information, b) measures of both valence and process are needed, c) there are context-general and context-specific qualities, and d) structure of dyadic interaction is more similar among mother-infant dyads from independent samples than between mother- and father-infant dyads within the same sample. Future research should use multiple measures incorporating valence, temporal processes, contextual influences, and behaviors of individual partners along with dyadic measures to adequately assess the quality of dyadic interaction

Derivation of Pre-X Inactivation Human Embryonic Stem Cells under Physiological Oxygen Concentrations

The presence of two active X chromosomes (XaXa) is a hallmark of the ground state of pluripotency specific to murine embryonic stem cells (ESCs). Human ESCs (hESCs) invariably exhibit signs of X chromosome inactivation (XCI) and are considered developmentally more advanced than their murine counterparts. We describe the establishment of XaXa hESCs derived under physiological oxygen concentrations. Using these cell lines, we demonstrate that (1) differentiation of hESCs induces random XCI in a manner similar to murine ESCs, (2) chronic exposure to atmospheric oxygen is sufficient to induce irreversible XCI with minor changes of the transcriptome, (3) the Xa exhibits heavy methylation of the XIST promoter region, and (4) XCI is associated with demethylation and transcriptional activation of XIST along with H3K27-me3 deposition across the Xi. These findings indicate that the human blastocyst contains pre-X-inactivation cells and that this state is preserved in vitro through culture under physiological oxygen.Susan WhiteheadHillel and Liliana Bachrac

HIV Treatment as Prevention: Debate and Commentary-Will Early Infection Compromise Treatment-as-Prevention Strategies?

Universal HIV testing and immediate antiretroviral therapy for infected individuals has been proposed as a way of reducing the transmission of HIV and thereby bringing the HIV epidemic under control. It is unclear whether transmission during early HIV infection—before individuals are likely to have been diagnosed with HIV and started on antiretroviral therapy—will compromise the effectiveness of treatment as prevention. This article presents two opposing viewpoints by Powers, Miller, and Cohen, and Williams and Dye, followed by a commentary by Fraser

Interactions between white-tailed deer density and the composition of forest understories in the northern United States

Forest understories across the northern United States (US) are a complex of tree seedlings, endemic forbs, herbs, shrubs, and introduced plant species within a forest structure defined by tree and forest floor attributes. The substantial increase in white-tailed deer (Odocoileus virginianus Zimmerman) populations over the past decades has resulted in heavy browse pressure in many of these forests. To gain an objective assessment of the role of deer in forested ecosystems, a region-wide forest inventory across the northern US was examined in concert with white-tailed deer density information compiled at broad scales. Results indicate that deer density may be an additional driver of tree seedling abundance when analyzed along with stand attributes such as above ground biomass, relative density, and stand age. Tree seedling abundance generally decreased as deer density increased above 5.8 deer km2 for all forest type groups with the exception of oak-dominated forests. Findings indicate that introduced plant species, of which 393 were recorded in this study, increased in areas with higher deer density. The abundance of white-tailed deer is just as important as forest stand and site attributes in the development of forest understories. Given the complexity of forest and land use dynamics across the northern US, this study provides directions for future research as more data linking forest-dependent wildlife and forest dynamics at regional and national scales become available