Effects of dog ownership in early childhood on immune development and atopic diseases

Summary Background Exposure to pets in childhood has been associated with a reduced risk of wheezing and atopy. Objective Our objective was to determine whether the effects of pet exposure on immune development and atopy in early childhood can be explained by alterations in exposure to innate immune stimuli in settled dust. Methods Two hundred and seventy-five children at increased risk of developing allergic diseases were evaluated to age 3 years for pet ownership, blood cell cytokine responses, and atopy. Can f 1, Fel d 1, endotoxin, ergosterol, and muramic acid were measured in settled dust from 101 homes. Results Dog exposure at birth was associated with decreased atopic dermatitis (AD) (12% vs. 27%; P = 0.004) and wheezing (19% vs. 36%; P = 0.005) in year 3. The rates of AD (23%) and wheezing (42%) in year 3 were relatively high in children who acquired dogs after birth. The prevalence of dog sensitization (10-12%) did not vary according to dog exposure. Can f 1 levels in bedroom dust were positively associated with IL-10 (r = 0.26; P = 0.01), IL-5 (r = 0.34, P o 0.001), and IL-13 (r = 0.28; P = 0.004) responses at age 1, and IL-5 (r = 0.24; P = 0.022) and IL-13 (r = 0.25; P = 0.015) responses at age 3. In contrast, endotoxin was associated with IFN-g (r = 0.31; P = 0.002) and IL-13 (r = 0.27; P = 0.01) responses at age 3 but not at age 1, and similar relationships were present for muramic acid. Adjustment for levels of innate immune stimuli in house dust did not significantly affect the relationships between Can f 1 and cytokine responses. Conclusions Exposure to dogs in infancy, and especially around the time of birth, is associated with changes in immune development and reductions in wheezing and atopy. These findings are not explained by exposure to endotoxin, ergosterol, or muramic acid

Oblique decision trees for spatial pattern detection: optimal algorithm and application to malaria risk

BACKGROUND: In order to detect potential disease clusters where a putative source cannot be specified, classical procedures scan the geographical area with circular windows through a specified grid imposed to the map. However, the choice of the windows' shapes, sizes and centers is critical and different choices may not provide exactly the same results. The aim of our work was to use an Oblique Decision Tree model (ODT) which provides potential clusters without pre-specifying shapes, sizes or centers. For this purpose, we have developed an ODT-algorithm to find an oblique partition of the space defined by the geographic coordinates. METHODS: ODT is based on the classification and regression tree (CART). As CART finds out rectangular partitions of the covariate space, ODT provides oblique partitions maximizing the interclass variance of the independent variable. Since it is a NP-Hard problem in R(N), classical ODT-algorithms use evolutionary procedures or heuristics. We have developed an optimal ODT-algorithm in R(2), based on the directions defined by each couple of point locations. This partition provided potential clusters which can be tested with Monte-Carlo inference. We applied the ODT-model to a dataset in order to identify potential high risk clusters of malaria in a village in Western Africa during the dry season. The ODT results were compared with those of the Kulldorff' s SaTScan™. RESULTS: The ODT procedure provided four classes of risk of infection. In the first high risk class 60%, 95% confidence interval (CI95%) [52.22–67.55], of the children was infected. Monte-Carlo inference showed that the spatial pattern issued from the ODT-model was significant (p < 0.0001). Satscan results yielded one significant cluster where the risk of disease was high with an infectious rate of 54.21%, CI95% [47.51–60.75]. Obviously, his center was located within the first high risk ODT class. Both procedures provided similar results identifying a high risk cluster in the western part of the village where a mosquito breeding point was located. CONCLUSION: ODT-models improve the classical scanning procedures by detecting potential disease clusters independently of any specification of the shapes, sizes or centers of the clusters

Enhanced Neutralizing Antibody Responses to Rhinovirus C and Age-Dependent Patterns of Infection

Knowledge of prevalent RV types, antibody responses, and populations at risk based on age and genetics may guide the development of vaccines or other novel therapies against this important respiratory pathogen.Longitudinal data from the Childhood Origins of ASThma (COAST) birth cohort study were analyzed to determine relationships between age and RV-C infections. Neutralizing antibodies specific for rhinovirus A (RV-A) and RV-C (3 types each) were determined using a novel polymerase chain reaction-based assay. We pooled data from 14 study cohorts in the United States, Finland, and Australia and used mixed-effects logistic regression to identify factors related to the proportion of RV-C versus RV-A detection.In COAST, RV-A and RV-C infections were similarly common in infancy, while RV-C was detected much less often than RV-A during both respiratory illnesses and scheduled surveillance visits (pRhinovirus C (RV-C) can cause asymptomatic infection and respiratory illnesses ranging from the common cold to severe wheezing.To identify how age and other individual-level factors are associated with susceptibility to RV-C illnesses.</div

Resolving the tail instability in weighted log-rank statistics for clustered survival data

In this note, we consider weighted log-rank statistics applied to clustered survival data with variable cluster sizes and arbitrary treatment assignments within clusters. Specifically, we verify that the contribution over the time interval for which the risk set proportion is arbitrarily small (the so-called "tail instability") is asymptotically negligible. These results were claimed but not proven by Gangnon and Kosorok [2004. Sample-size formula for clustered survival data using weighted log-rank statistics. Biometrika 91, 263-275.] who developed sample size formulas in this context. The main difficulty is that standard martingale methods cannot be used on account of the dependencies within clusters, and new methods are required.Clustered data Local alternative Log-rank statistic Martingales Multivariate survival data Tail instability

Relationship of blood pressure and other factors to serial retinal arteriolar diameter measurements over time: The Beaver Dam Eye Study

10.1001/archophthalmol.2012.560Archives of Ophthalmology13081019-1027AROP

Developmental patterns in the nasopharyngeal microbiome during infancy are associated with asthma risk

BACKGROUND: Studies indicate that the nasal microbiome may correlate strongly with the presence or future risk of childhood asthma. OBJECTIVES: In this study, we tested whether developmental trajectories of the nasopharyngeal microbiome in early life and the composition of the microbiome during illnesses were related to risk of childhood asthma. METHODS: Children participating in the Childhood Origins of Asthma study (N = 285) provided nasopharyngeal mucus samples in the first 2 years of life, during routine healthy study visits (at 2, 4, 6, 9, 12, 18, and 24 months of age), and during episodes of respiratory illnesses, all of which were analyzed for respiratory viruses and bacteria. We identified developmental trajectories of early-life microbiome composition, as well as predominant bacteria during respiratory illnesses, and we correlated these with presence of asthma at 6, 8, 11, 13, and 18 years of age. RESULTS: Of the 4 microbiome trajectories identified, a Staphylococcus-dominant microbiome in the first 6 months of life was associated with increased risk of recurrent wheezing by age 3 years and asthma that persisted throughout childhood. In addition, this trajectory was associated with the early onset of allergic sensitization. During wheezing illnesses, detection of rhinoviruses and predominance of Moraxella were associated with asthma that persisted throughout later childhood. CONCLUSION: In infancy, the developmental composition of the microbiome during healthy periods and the predominant microbes during acute wheezing illnesses are both associated with the subsequent risk of developing persistent childhood asthma

A Severity Scale for Diabetic Macular Edema Developed from ETDRS Data

PURPOSE. To develop a severity scale for diabetic macular edema (DME) and to assess relationships between severity and duration of DME and visual acuity (VA). METHODS. From the Early Treatment Diabetic Retinopathy Study (ETDRS), mean baseline VA scores were tabulated for 7422 eyes cross-classified by (1) location of retinal thickening (RT) and its area within 1 disc diameter of the macular center, and (2) degree of RT at the center. Adjacent (row, column, and off-diagonal) cells with the greatest similarity in baseline VA (mean and SD) based on a Gaussian (normal) likelihood were merged. An initial eight-step scale was chosen using the Schwarz criterion (Bayesian information criterion; BIC) and was revised based on clinical judgment to nine steps. Relationships between baseline VA and other photographic and fluorescein angiographic characteristics were examined singly and in combination with the scale. RESULTS. Modeling baseline VA as a function of the nine-step scale yielded an R 2 of 38.0%, compared with 38.4% using the full cross-classification of these variables. Addition of each of the other baseline characteristics changed the adjusted R 2 for the combination very little. Between scale levels 1A and 5B mean (SD) VA decreased from 86.8 (5.8) letters to 59.8 (13.6) letters. In a model of change in VA as a function of time spent at each DME severity level, VA loss increased progressively from 1 letter per year at level 2 to 17 letters per year at level 5B. CONCLUSIONS. The scale facilitates documentation of the relationship of severity and duration of DME with VA. (Invest Ophthalmol Vis Sci. 2008;49:5041-5047) DOI:10.1167/iovs.08-2231 I n its initial report, the Early Treatment Diabetic Retinopathy Study (ETDRS) demonstrated that focal/grid photocoagulation treatment of diabetic macular edema (DME) reduces the 3-year risk of moderate visual loss (MVL, a decrease in visual acuity [VA] score of 15 or more letters, corresponding to a doubling of the visual angle) by approximately 50%, from 24% in untreated eyes to 12% in treated eyes. 1 In previous ETDRS reports, the principal measure of the morphologic severity of DME has been the presence or absence of &quot;clinically significant macular edema&quot; (CSME), which may be characterized as retinal thickening (RT) or adjacent hard exudate that involves or threatens the center of the macula. 1 CSME may be expanded to a three-step scale by subdividing the CSME-present category by the absence or presence of involvement of the macular center. On this scale, in untreated eyes with DME the 3-year risks of MVL were 17%, 22%, and 33%, respectively, in eyes with non-CSME, CSME without center involvement, and CSME with center involvement. 2 The ETDRS also reported several factors associated with baseline VA, the most notable of which were area of RT, degree of RT at the macular center, and severity of fluorescein leakage within 1 disc diameter (DD) of the macular center. In a subset of 741 eyes with mild to moderate nonproliferative retinopathy and macular edema questionably or definitely involving the macular center, VA score at baseline was Ն70 letters (corresponding to 20/40 or better) in 92.5% of eyes in which the area of RT within 1 DD of center was Ͻ0.5 disc area (DA) versus 43.4% of eyes in which this area was Ն2.0 DA. Corresponding proportions for eyes in the lowest and highest categories of fluorescein leakage were 85.2% and 50.0% and for degree of RT at the macular center, they were 91.3% and 63.4%. 3 The objectives of this report are to describe the development of a more detailed scale to categorize the severity of DME and to use the scale to assess the relationship between the duration of severe DME and VA. The scale is based on associations between baseline gradings of features characteristic of DME in stereoscopic color fundus photographs and best corrected baseline VA. 4,5 METHODS Baseline VA scores (mean and SD) were tabulated for eyes crossclassified by degree of RT at the macular center and by a combination of location of RT within a 30°photographic field centered on the macula (Field 2) and area of RT within 1 DD of the center. Relationships between baseline VA and other ocular characteristics included in the baseline gradings of fundus photographs and fluorescein angiograms were also examined singly and in combination with From the Departments o