Ontogeny and regulation of interleukin-7 expressing thymic epithelial cells

T cell development is a multistage process of differentiation that depends on proper thymocyte-thymic epithelial cell (TEC) interactions. Epithelial cells in the thymus are organized in a three-dimensional network that provides support and signals for thymocyte maturation. Concurrently, proper TEC differentiation in the adult thymus relies on thymocyte-derived signals. TECs produce interleukin-7 (IL-7), a non-redundant cytokine that promotes the survival, differentiation, and proliferation of thymocytes. We have identified IL-7 expressing TECs throughout ontogeny and in the adult thymus by in situ hybridization analysis. IL-7 expression is initiated in the thymic fated domain of the thymic primordium by embryonic day 11.5, in a Foxn1 independent pathway. Marked changes occur in the localization and regulation of IL-7 expressing TECs during development. Whereas IL-7 expressing TECs are present throughout the early thymic rudiment, the majority of IL-7 producing TECs are concentrated in the adult thymic medulla. By analyzing mouse strains that sustain blocks at different stages of thymocyte development, we show that IL-7 expression is initiated independently of hematopoietic-derived signals during thymic organogenesis. However, thymocyte-derived signals play an essential role in regulating IL-7 expression in the adult TEC compartment. Furthermore, distinct thymocyte subsets regulate the expression of IL-7 and keratin 5 in adult cortical epithelium. Intraperitoneal injection of Recombination Activating Gene deficient mice (RAG-2−/−) with anti-CD3ϵ monoclonal antibody (mAb) induces CD4− 8− double negative thymocytes to undergo β-selection and differentiate into CD4+8+ cells. Analysis of the thymic stromal compartment reveals that progression through β-selection renders thymocytes competent to alter the pattern of IL-7 expression in the cortical TEC compartment. RAG-2−/− mice do not generate mature T cells and therefore the RAG-2−/− thymus is devoid of organized medullary regions. Histological examination of RAG-2−/− thymus following anti-CD3ϵ stimulation reveals the emergence of mature thymic medullary regions, as assessed by H & E staining and expression of thymic stromal medullary markers. Stromal medullary reorganization occurs in the absence of T cell receptor αβ expression, suggesting that activation of RAG-2−/− thymocytes by CD3ϵ ligation generates thymocyte-derived signals that induce thymic epithelial reorganization, generating a mature medullary compartment. This model provides a tool to assess the mechanisms underlying thymic medullary development. ^

A formative evaluation of the American Diabetes Association's Choosing Health and Sensible Exercise childhood obesity intervention

Background. The increasing prevalence of overweight among youth in the United States, and the parallel rise in related medical comorbidities has led to a growing need for efficient weight-management interventions. Purpose. The aim of this study was to evaluate the effects of the Choosing Health and Sensible Exercise (C.H.A.S.E.) childhood obesity prevention program on Body Mass Index (BMI), physical activity and dietary behaviors. Methods. This study utilized de-identified data collected during the fall 2006 session of the C.H.A.S.E. program. A total of 65 students at Woodview Elementary School and Deepwater Elementary School participated in this intervention. The C.H.A.S.E. program is a 10-week obesity prevention program that focuses on nutrition and physical activity education. Collection of height and weight data, and a health behavior survey was conducted during the first and last week of the intervention. Paired t-tests were used to determine statistically significant differences between pre- and post-intervention measurements. One-way analysis of variance was used to adjust for potential confounders, such as gender, age, BMI category ("normal weight", "at risk overweight", or "overweight"), and self-reported weight loss goals. Data were analyzed using STATA, v. 9.2. Results. A significant decrease in mean BMI (p< 0.05) was found after the 10-week intervention. While the results were statistically significant for the group as a whole, changes in BMI were not significant when stratified by age, sex, or ethnicity. The mean overall scores for the behavior survey did not change significantly pre- and post-intervention; however, significant differences were found in the dietary intention scale, indicating that students were more likely to intend to make healthier food choices (p<0.05). No statistically significant decreases in BMI were found when stratified for baseline BMI-for-age percentiles or baseline weight loss efforts (p>0.05). Conclusion. The results of this evaluation provide information that will be useful in planning and implementing an effective childhood obesity intervention in the future. Changes in the self-reported dietary intentions and BMI show that the C.H.A.S.E. program is capable of modifying food choice selection and decreasing BMI. Results from the behavior questionnaire indicate that students in the intervention program were making changes in a positive direction. Future implementation of the C.H.A.S.E. program, as well as other childhood obesity interventions, may want to consider incorporating additional strategies to increase knowledge and other behavioral constructs associated with decreased BMI. In addition, obesity prevention programs may want to increase parental involvement and increase the dose or intensity of the intervention. ^

Statistical and methodological challenges for disaster preparedness and medical needs assessment in Rio Grande Valley of Texas

In recent years, disaster preparedness through assessment of medical and special needs persons (MSNP) has taken a center place in public eye in effect of frequent natural disasters such as hurricanes, storm surge or tsunami due to climate change and increased human activity on our planet. Statistical methods complex survey design and analysis have equally gained significance as a consequence. However, there exist many challenges still, to infer such assessments over the target population for policy level advocacy and implementation. ^ Objective. This study discusses the use of some of the statistical methods for disaster preparedness and medical needs assessment to facilitate local and state governments for its policy level decision making and logistic support to avoid any loss of life and property in future calamities. ^ Methods. In order to obtain precise and unbiased estimates for Medical Special Needs Persons (MSNP) and disaster preparedness for evacuation in Rio Grande Valley (RGV) of Texas, a stratified and cluster-randomized multi-stage sampling design was implemented. US School of Public Health, Brownsville surveyed 3088 households in three counties namely Cameron, Hidalgo, and Willacy. Multiple statistical methods were implemented and estimates were obtained taking into count probability of selection and clustering effects. Statistical methods for data analysis discussed were Multivariate Linear Regression (MLR), Survey Linear Regression (Svy-Reg), Generalized Estimation Equation (GEE) and Multilevel Mixed Models (MLM) all with and without sampling weights. ^ Results. Estimated population for RGV was 1,146,796. There were 51.5% female, 90% Hispanic, 73% married, 56% unemployed and 37% with their personal transport. 40% people attained education up to elementary school, another 42% reaching high school and only 18% went to college. Median household income is less than $15,000/year. MSNP estimated to be 44,196 (3.98%) [95% CI: 39,029; 51,123]. All statistical models are in concordance with MSNP estimates ranging from 44,000 to 48,000. MSNP estimates for statistical methods are: MLR (47,707; 95% CI: 42,462; 52,999), MLR with weights (45,882; 95% CI: 39,792; 51,972), Bootstrap Regression (47,730; 95% CI: 41,629; 53,785), GEE (47,649; 95% CI: 41,629; 53,670), GEE with weights (45,076; 95% CI: 39,029; 51,123), Svy-Reg (44,196; 95% CI: 40,004; 48,390) and MLM (46,513; 95% CI: 39,869; 53,157). ^ Conclusion. RGV is a flood zone, most susceptible to hurricanes and other natural disasters. People in the region are mostly Hispanic, under-educated with least income levels in the U.S. In case of any disaster people in large are incapacitated with only 37% have their personal transport to take care of MSNP. Local and state government’s intervention in terms of planning, preparation and support for evacuation is necessary in any such disaster to avoid loss of precious human life. ^ Key words: Complex Surveys, statistical methods, multilevel models, cluster randomized, sampling weights, raking, survey regression, generalized estimation equations (GEE), random effects, Intracluster correlation coefficient (ICC).^

Development and evaluation of a nutrition education program designed to increase fruit and vegetable consumption in girls, ages 9--12

The purpose of this study is to evaluate the theory-based Eat 5 nutrition badge. It is designed to increase fruit and vegetable (F&V) intake in 4th-6th grade junior Girl Scouts. Twenty-two troops were recruited and randomized by grade level (4th, 5th, 6th, or mixed) into either the intervention or control conditions. The leaders in the intervention condition received a brief training and the materials and conducted the program with their troops during four meetings. The Girl Scouts in the intervention condition completed 1-day Food Frequency Questionnaires and Nutrition Questionnaires both before and after completing the Eat 5 badge, and a third measurement of F&V intake three months after the posttest. Girl Scouts in the control condition were only evaluated at the three time periods.^ The primary hypotheses were that the Girl Scouts in the intervention condition would increase their daily intake of fruits and vegetables at both the posttest and three months later, compared to the Girl Scouts in the control condition. Other study questions investigated the impact of the Eat 5 program on intervening variables such as knowledge, self-efficacy, barriers, norms, F&V preference, and F&V selection and preparation skills.^ A nested ANOVA, with troop as the unit of analysis nested within condition, was used to assess the effects of the program. Pretest F&V intake and grade level were used as covariates. Pretest mean F&V intake for the total sample of 210 girls was 2.50 servings per day; 3.0 for the intervention group (n = 101). Significant increases in F&V intake (to 3.4 servings per day), knowledge, and fruit and vegetable preference were found for the intervention condition troops compared to the troops in the control condition. Three months later, the mean F&V intake had returned to pretest levels.^ This study indicates that social groups such as Girl Scouts can provide a channel for nutrition education. Long term effects were not sustained by the intervention; a possible cause was the lack of change in self-efficacy. Therefore, additional interventions are recommended such as booster lessons to maintain increased F&V intake by Girl Scouts. ^

Network-based analysis of genome-wide scans of natural selection

The genomic era brought by recent advances in the next-generation sequencing technology makes the genome-wide scans of natural selection a reality. Currently, almost all the statistical tests and analytical methods for identifying genes under selection was performed on the individual gene basis. Although these methods have the power of identifying gene subject to strong selection, they have limited power in discovering genes targeted by moderate or weak selection forces, which are crucial for understanding the molecular mechanisms of complex phenotypes and diseases. Recent availability and rapid completeness of many gene network and protein-protein interaction databases accompanying the genomic era open the avenues of exploring the possibility of enhancing the power of discovering genes under natural selection. The aim of the thesis is to explore and develop normal mixture model based methods for leveraging gene network information to enhance the power of natural selection target gene discovery. The results show that the developed statistical method, which combines the posterior log odds of the standard normal mixture model and the Guilt-By-Association score of the gene network in a naïve Bayes framework, has the power to discover moderate/weak selection gene which bridges the genes under strong selection and it helps our understanding the biology under complex diseases and related natural selection phenotypes.^

Complications of misoprostol and other abortion induction methods in the developing world: A systematic review

OBJECTIVE: To systematically review published literature to examine the complications associated with the use of misoprostol and compare these complications to those associated with other forms of abortion induction. ^ DATA SOURCES: Studies were identified through searches of medical literature databases including Medline (Ovid), PubMed (NLM), LILACS, sciELO, and AIM (AFRO), and review of references of relevant articles. ^ STUDY SELECTION AND METHODS: A descriptive systematic review that included studies reported in English and published before December 2012. Eligibility criteria included: misoprostol (with or without other methods) and any other method of abortion in a developing country, as well as quantitative data on the complication of each method. The following is information extracted from each study: author/year, country/city, study design/study sample, age range, setting of data collection, sample size, the method of abortion induction, the number of cases for each method, and the percentage of complications with each method. RESULTS: A total of 4 studies were identified (all in Latin America) describing post-abortion complications of misoprostol and other methods in countries where abortion is generally considered unsafe and/or illegal. The four studies reported on a range of complications including: bleeding, infection, incomplete abortion, intense pelvic pain, uterine perforation, headache, diarrhea, nausea, mechanical lesions, and systemic collapse. The most prevalent complications of misoprostol-induced abortion reported were: bleeding (7-82%), incomplete abortion (33-70%), and infection (0.8-67%). The prevalence of these complications reported from other abortion methods include: bleeding (16-25%), incomplete abortion (15-82%), and infection (13-50%). ^ CONCLUSION: The literature identified by this systematic review is inadequate for determining the complications of misoprostol used in unsafe settings. Abortion is considered an illicit behavior in these countries, therefore making it difficult to investigate the details needed to conduct a study on abortion complications. Given the differences between the reviewed studies as well as a variety of study limitations, it is not possible to draw firm conclusions about the rates of specific-abortion related complications.^

The influence of antibacterial susceptibility and pharmacodynamics on the therapeutic response of infection

This prospective cohort study estimated how antibacterial resistance affected the time until clinical response. Relative rates of improvement and cure were estimated by proportional-hazards regression for 391 patients with culture-confirmed bacterial keratitis who had the ciprofloxacin minimal inhibitory concentration (MIC) measured of the principal corneal isolate and who were treated with ciprofloxacin 0.3% solution or ointment. After adjusting for age and hypopyon status and stratifying by ulcer size, clinic, and ciprofloxacin formulation, the summary rate of clinical improvement with ciprofloxacin therapy was reduced by 42% (95% confidence limits [CL], 3%, 65%) among patients whose corneal isolate's ciprofloxacin MIC exceeded 1.0 μg/mL compared to those with more sensitive isolates. The summary rate of resolution to improvement and cure was reduced by 36% (95% CL, 11%, 53%) among corneal infections having a higher ciprofloxacin MIC. Rate ratios were modified by the size of the presenting corneal ulceration; for ulcer diameters of 4 mm or less and of more than 4 mm, improvement rate ratios were 0.56 (95% CL, 0.31, 1.02) and 0.65 (95% CL, 0.23, 1.80), respectively; resolution rate ratios were 0.63 (95% CL, 0.44, 0.91) and 0.67 (95% CL, 0.32, 1.39), respectively. Sensitivity analysis showed that the summary improvement rate ratio could be maximally overestimated by 24% (95% CL, −29%, 114%) because of informative censoring or by 33% (95% CL, −21%, 126%) from loss to follow up. Based on reported corneal pharmacokinetics of topical ciprofloxacin, the probability of clinical improvement was 90% or more if the ratio of the achievable corneal ciprofloxacin concentration to the corneal isolate's ciprofloxacin MIC was above 8 or the ratio of the area under the 24-hour corneal concentration curve to the ciprofloxacin MIC was greater than 151. This study suggests that corneal infections by bacteria having a higher ciprofloxacin MIC respond more slowly to ciprofloxacin treatment than those with a lower MIC. While the rate of clinical resolution is affected by patient age and clinical severity, antimicrobial susceptibility testing of corneal cultures can indicate the relative effectiveness of antibacterial therapy. A pharmacodynamic approach to treating bacterial keratitis offers the prospect of optimal antimicrobial selection and modification. ^

Mean dynamic topography and oceanographic parameters estimated from an inverse model and satellite geodesy, with link to model result in one single NetCDF file (392 MB), including the inverse data error covariance

Geostrophic surface velocities can be derived from the gradients of the mean dynamic topography-the difference between the mean sea surface and the geoid. Therefore, independently observed mean dynamic topography data are valuable input parameters and constraints for ocean circulation models. For a successful fit to observational dynamic topography data, not only the mean dynamic topography on the particular ocean model grid is required, but also information about its inverse covariance matrix. The calculation of the mean dynamic topography from satellite-based gravity field models and altimetric sea surface height measurements, however, is not straightforward. For this purpose, we previously developed an integrated approach to combining these two different observation groups in a consistent way without using the common filter approaches (Becker et al. in J Geodyn 59(60):99-110, 2012, doi:10.1016/j.jog.2011.07.0069; Becker in Konsistente Kombination von Schwerefeld, Altimetrie und hydrographischen Daten zur Modellierung der dynamischen Ozeantopographie, 2012, http://nbn-resolving.de/nbn:de:hbz:5n-29199). Within this combination method, the full spectral range of the observations is considered. Further, it allows the direct determination of the normal equations (i.e., the inverse of the error covariance matrix) of the mean dynamic topography on arbitrary grids, which is one of the requirements for ocean data assimilation. In this paper, we report progress through selection and improved processing of altimetric data sets. We focus on the preprocessing steps of along-track altimetry data from Jason-1 and Envisat to obtain a mean sea surface profile. During this procedure, a rigorous variance propagation is accomplished, so that, for the first time, the full covariance matrix of the mean sea surface is available. The combination of the mean profile and a combined GRACE/GOCE gravity field model yields a mean dynamic topography model for the North Atlantic Ocean that is characterized by a defined set of assumptions. We show that including the geodetically derived mean dynamic topography with the full error structure in a 3D stationary inverse ocean model improves modeled oceanographic features over previous estimates.

Data base on heterotrophic dinoflagellates grazing and growth rate as a function of size, prey size and type compiled from the literature

Microzooplankton (the 20 to 200 µm size class of zooplankton) is recognised as an important part of marine pelagic ecosystems. In terms of biomass and abundance heterotrophic dinoflagellates are one of the important groups of organism in microzooplankton. However, their rates - grazing and growth - , feeding behaviour and prey preferences are poorly known and understood. A set of data was assembled in order to derive a better understanding of heterotrophic dinoflagellates rates, in response to parameters such as prey concentration, prey type (size and species), temperature and their own size. With these objectives, literature was searched for laboratory experiments with information on one or more of these parameters effect studied. The criteria for selection and inclusion in the database included: (i) controlled laboratory experiment with a known dinoflagellate feeding on a known prey; (ii) presence of ancillary information about experimental conditions, used organisms - cell volume, cell dimensions, and carbon content. Rates and ancillary information were measured in units that meet the experimenter need, creating a need to harmonize the data units after collection. In addition different units can link to different mechanisms (carbon to nutritive quality of the prey, volume to size limits). As a result, grazing rates are thus available as pg C dinoflagellate-1 h-1, µm3 dinoflagellate-1 h-1 and prey cell dinoflagellate-1 h-1; clearance rate was calculated if not given and growth rate is expressed as the growth rate per day.

Digital elevation model (DEM), surveyed stream network (SSN), mask and stream sampling points (SSP)

These data are provided to allow users for reproducibility of an open source tool entitled 'automated Accumulation Threshold computation and RIparian Corridor delineation (ATRIC)'

Morphology of Orbulina universa and Globorotalia scitula across local extinctions during Sapropel S5 (Eastern Mediterranean Sea, c.126-121 ka)

Extinction is a remarkably difficult phenomenon to study under natural conditions. This is because the outcome of stress exposure and associated fitness reduction is not known until the extinction occurs and it remains unclear whether there is any phenotypic reaction of the exposed population that can be used to predict its fate. Here we take advantage of the fossil record, where the ecological outcome of stress exposure is known. Specifically, we analyze shell morphology of planktonic Foraminifera in sediment samples from the Mediterranean, during an interval preceding local extinctions. In two species representing different plankton habitats, we observe shifts in trait state and decrease in variance in association with non-terminal stress, indicating stabilizing selection. At terminal stress levels, immediately before extinction, we observe increased growth asymmetry and trait variance, indicating disruptive selection and bet-hedging. The pre-extinction populations of both species show a combination of trait states and trait variance distinct from all populations exposed to non-terminal levels of stress. This finding indicates that the phenotypic history of a population may allow the detection of threshold levels of stress, likely to lead to extinction. It is thus an alternative to population dynamics in studying and monitoring natural population ecology.

Data base on pelagic ciliates grazing and growth rate as a function of size, prey size and type compiled from the literature

Microzooplankton (the 20 to 200 µm size class of zooplankton) is recognised as an important part of marine pelagic ecosystems. In terms of biomass and abundance pelagic ciliates are one of the important groups of organism in microzooplankton. However, their rates - grazing and growth - , feeding behaviour and prey preferences are poorly known and understood. A set of data was assembled in order to derive a better understanding of pelagic ciliates rates, in response to parameters such as prey concentration, prey type (size and species), temperature and their own size. With these objectives, literature was searched for laboratory experiments with information on one or more of these parameters effect studied. The criteria for selection and inclusion in the database included: (i) controlled laboratory experiment with a known ciliates feeding on a known prey; (ii) presence of ancillary information about experimental conditions, used organisms - cell volume, cell dimensions, and carbon content. Rates and ancillary information were measured in units that meet the experimenter need, creating a need to harmonize the data units after collection. In addition different units can link to different mechanisms (carbon to nutritive quality of the prey, volume to size limits). As a result, grazing rates are thus available as pg C/(ciliate*h), µm**3/(ciliate*h) and prey cell/(ciliate*h); clearance rate was calculated if not given and growth rate is expressed as the growth rate per day.