Simultaneous confidence intervals for contrasts of quantiles.

Skewed distributions and inferences concerning quantiles are common in the health and social science researches. And most standard simultaneous inference procedures require the normality assumption. For example, few methods exist for comparing the medians of independent samples or quantiles of several distributions in general. To our knowledge, there is no easy-to-use method for constructing simultaneous confidence intervals for multiple contrasts of quantiles in a one-way layout. In this paper, we develop an asymptotic method for constructing such intervals both for differences and ratios of quantiles and extend the idea to that of right-censored time-to-event data in survival analysis. Small-sample performance of the proposed method and a bootstrap method were assessed in terms of coverage probabilities and average widths of the simultaneous confidence intervals. Good coverage probabilities were observed for most of the distributions considered in our simulations. The proposed methods have been implemented in an R package and are used to analyze two motivating datasets.

Type 2 Diabetes Self-Management Variables and Predictors.

Guided by the Self and Family-Management framework, relationships between diabetes distress, self-efficacy, resilience and outcomes of A1c, quality of life and health status were explored. A cross-sectional descriptive design was used. Seventy eight individuals were enrolled from US clinics. Data were analyzed to test for associations, main effects and interactions and predictors of self-management. Results indicated low diabetes distress (M = 20.53), high self-efficacy (M = 7.32), moderate resilience (M = 80.27), and mean A1c 7.35%/56.88 mmol/mol. Seventy six percent of participants scored above the mental health norm, and 46% scored above the physical health norm. The average weighted quality of life score was -1.74. Diabetes distress was negatively associated with self-efficacy, resilience, physical health, mental health, and quality of life. Self-efficacy was positively associated with resilience, physical health, and quality of life. Resilience was positively associated with physical health, mental health and quality of life. Positive associations were found between quality of life, and physical and mental health. No associations were found between A1c and variables in the study. Multiple significant interactions were found with A1c, mental health and quality of life outcomes. Terms in the model included treatment regimen, years since diagnosis, provider collaboration, and history of diabetes self-management education. Distress was a significant predictor of health status and quality of life. The results confirm self-management facilitators self-efficacy and resilience and barrier diabetes distress and their relationships with outcomes in the framework. This study contributes to the understanding of the emotional aspect of diabetes. Continuing this work will allow researchers to better understand self-management, support self-management efforts and better outcomes.

Using Electronic Medical Records and Health Claim Data to Develop a Patient Engagement Score for Patients With Multiple Chronic Conditions: An Exploratory Study.

The study objective was to (1) develop a statistical model that creates a novel patient engagement score (PES) from electronic medical records (EMR) and health claim data, and (2) validate this developed score using health-related outcomes and charges of patients with multiple chronic conditions (MCCs). This study used 2014-16 EMR and health claim data of patients with MCCs from Sanford Health. Patient engagement score was created based on selected patients' engagement behaviors using Gaussian finite mixture model. The PES was validated using multiple logistic and linear regression analyses to examine the associations between the PES and health-related outcomes, and hospital charges, respectively. Patient engagement score was generated from 5095 patient records and included low, medium, and high levels of patient engagement. The PES was a significant predictor for low-density lipoprotein, emergency department visit, hemoglobin A1c, estimated glomerular filtration rate, hospitalization, and hospital charge. The PES derived from patient behaviors recorded in EMR and health claim data can potentially serve as a patient engagement measure. Further study is needed to refine and validate the newly developed score.

Relationships between the age of 25,445 men attending infertility clinics and sperm chromatin structure assay (SCSA®) defined sperm DNA and chromatin integrity.

OBJECTIVE: To determine relationships between age of men with potential male factor infertility and sperm chromatin structure assay (SCSA) measures of sperm DNA fragmentation (SDF) and high DNA stainable sperm (HDS), and to compare these data with those obtained from healthy donor men without reproductive issues. DESIGN: Retrospective study. SETTING: Infertility clinics and diagnostic laboratory. PATIENTS: A total of 25,445 men attending infertility clinics. Donors were 87 men working at Lawrence Livermore National Laboratory. INTERVENTION: None. MAIN OUTCOME MEASURES: SCSA measures (% DNA fragmentation index (DFI), X DFI, SD DFI, and %HDS) of men aged 21-80 years. RESULTS: In the study population, advancing paternal age was associated with increased sperm DNA fragmentation (SDF) scored as increased percentage of sperm in semen ejaculates with measurable DNA strand breaks (%DFI). The slope of increase in %DFI prior to age 41.6 years was 0.39, which increased after age 41.6 to more than double at a slope of 0.86. These changes in DNA/chromatin in more than 25,000 aging men attending infertility clinics are similar to those seen over the same age span (20-80 years) in 87 nonpatient, healthy men without reproductive issues. For the age group 20-50 years, there was no major significant difference in %DFI between patients and donor men. According to a logistic regression model, the estimated probability is that, for example, a 40-year-old and a 50-year-old man have a 20% and 40% chance, respectively, to have a pathological DFI ≥25% by age factor alone. The condensation of sperm chromatin in patients increased with age in a linear fashion, from a mean of 12.2 %HDS at age 20-25 to a mean of 7.9 %HDS at age 60-65. Patients had a greater %HDS than donors across all ages. CONCLUSIONS: The great heterogeneity of both DFI and HDS values at a specific age prevents the automatic translation of age into an index of DNA fragmentation. However, it reinforces the idea that both DFI and HDS evaluation can play a role in detecting potential male infertility in cases that are not resolved by routine testing and in cases of multiple miscarriages. DFI and HDS data can help clinicians to predict a man's fertility potential, to consider corrective therapeutic approaches, as well as to assess the risk to the offspring's health.

Sporulating behavior of Bacillus licheniformis strains influences their population dynamics during raw milk holding.

To understand the role of strain variability, population dynamics of 2 strains of Bacillus licheniformis, ATCC 6634 and ATCC 14580, were modeled as a function of temperature (4.0-12.0°C) and duration (0-72 h) using regression analysis. Based on the initial spiking of vegetative cells (approximately 4.0 log cfu/mL) and spores (approximately 2.0 log cfu/mL), regression equations, elucidating B. licheniformis growth behavior during raw milk holding at low temperature, were obtained. Contour plots were developed to determine the time-temperature combinations, keeping the population changes to less than 1.0 log. In vegetative cell spiking study of B. licheniformis ATCC 6634 (S1), cell population changes remained below 1.0 log up to 72 h at 8°C. For B. licheniformis ATCC 14580 (S2), 1.0 log shift was not observed only after 80 h at 8°C, indicating higher multiplication potential of S1 as compared with S2. As S2 was a readily sporulating strain, the vegetative spiking study showed spore formation at different storage temperatures. Evidence of some parallel germination was observed for this strain at 8°C or higher, when raw milk samples were spiked with spores. The experimental values obtained for sporeformers and spore counts were validated with contour plot-generated values. Overall, for raw milk samples predominated by the low sporulating strain, the contour plots suggested holding at 8°C or below for up to 72 h. In the case of the readily sporulating strain (S2), raw milk could be held at 8°C for 80 h, where little or no sporulation is observed. Sporulation behavior, germination and multiplication ability, strain variability, and temperature and duration of holding raw milk influenced the population dynamics of Bacillus species. However, in the presence of equivalent numbers of both types of sporulating strains in raw milk, despite strain variability, holding milk at 8°C for not more than 72 h would keep any cell population changes below 1.0 log. In addition, under these storage conditions, the population would remain as vegetative cells that are likely to be inactivated by pasteurization. The contour plots, so generated, would help predict the population shifts and define optimum holding conditions for raw milk before further processing.

Listeria cross contamination levels in raw ice cream mix can serve as a predictor of their potential presence as heat-injured cells.

Listeriosis is a life-threatening infection caused by foods contaminated with Listeria monocytogenes. Some of the major ice cream recalls in recent years reaffirm the ability of this food-borne pathogen to survive in diverse dairy processing environments and cause cross contamination. Inspection reports revealed certain lapses in implementing adequate hygienic practices for Listeria persistence in the processing environment, leading to cross contamination of ice cream. The higher levels of cross contamination of raw ice cream mix might result in random heat-injured cells when exposed to minimum heat treatment (69°C for 30 min). These heat-injured cells could later recover under abusive storage and handling conditions and pose a health risk. Evidence about the presence of injured cells in ice cream mix may thus prove useful to establish the overall Listeria risk, which was the aim of this study. Challenge studies were conducted to evaluate the dose-dependent presence of heat-injured cells of Listeria. Ice cream mix formulations of 4 different types (36, 40, 42, and 45% total solids) were inoculated at 2.0, 3.0, and 4.0 log cfu/g levels of Listeria innocua (an established surrogate). The dose levels were selected based on a likely cross contamination on the raw side from environmental Listeria, especially due to their resident nature and growth in harborage sites. The samples were exposed to minimum heat treatment (69°C for 30 min) and the survivors, including heat-injured cells, were enumerated using standard protocols. A binary logistic regression model was fitted for evaluating the severity of risk. The influence of total solids, water activity, and pH variability were also studied on Listeria survival. The enrichment protocol, using buffered Listeria enrichment broth, followed by plating on modified oxford agar and Rapid L'mono medium, revealed the random presence of heat-injured cells in buffered Listeria enrichment broth, only at the highest dose level of 4+ logs. Any potential risk from heat-injured cells was thus limited only to the highest levels of cross contamination, irrespective of the type of the mix. Significantly, none of the pasteurized ice cream mix samples supported the recovery of any heat-injured cells of Listeria during 72 h holding at 7°C, even at the highest dose level of 4+ logs, under the conditions of experimentation. The level of cross contamination (dose) emerged as a predictor of the potential presence of heat-injured cells of Listeria exposed to minimum pasteurization treatment.

Perceptions of Equid Well Being Well-Being in South Dakota.

In South Dakota, the status of equid well being is relatively unknown. This study sought to (a) gain understanding about the current perceptions of nonhuman animal well being in South Dakota, with an emphasis on horses and other equids; (b) determine the level of care equids are reportedly receiving and the perceived challenges to equine well being in South Dakota, and (c) determine if people from diverse geographical locations (east or west of the Missouri River) have similar views on the well being of equids in South Dakota. Respondents indicated the current level of equid well being in South Dakota is sufficient, but there is room for improvement. Current challenges for the equid population of South Dakota were the high annual cost of horse care, poor horsemanship, dental problems, and whether caregivers understand basic equine care. Several significant associations arose between where a respondent lives (Western or Eastern South Dakota) and their level of agreement with various statements. The results provide a benchmark to gauge well being and help give direction for future educational needs that can continue to improve equid care.

Expression of estrus before fixed-time AI affects conception rates and factors that impact expression of estrus and the repeatability of expression of estrus in sequential breeding seasons.

Expression of estrus after PG and before fixed-time AI has been reported to change the uterine environment, increase accessory sperm numbers, fertilization rates, and overall embryo survival. Thus, expression of estrus can strongly impact overall pregnancy success. Because of variation in percentage of beef females detected in estrus and number of animals per study, it can be difficult to detect a significant effect of estrus on pregnancy success. Thus, a meta-analysis was conducted using data from 10,116 beef females in 22 studies that utilized variations of the 5 most common fixed-time AI protocols (CO-Synch, 7-day CO-Synch+CIDR, 5-day CIDR, PG 6-day CIDR, and the 14-day CIDR protocols) to examine the effect of detection in standing estrus on subsequent fixed-time AI pregnancy success. A random-effects model was used to combine the studies/herds. The overall model indicated a positive effect of estrus on conception rates with cows detected in estrus before fixed-time AI having a 27% greater (P<0.05; 95% CI=22-32%) conception rate compared with those not detected in estrus. Next we determined factors that influenced expression of estrus. Data were available on 547 cows synchronized with a CIDR based fixed-time AI protocols and observed for estrus before AI during 2-4 breeding seasons. Analysis of these cows indicated that days postpartum (P=0.22) did not impact estrous expression. In contrast, BCS influenced estrous expression (P=0.04) with cows in a BCS of ≤4 (51±5%) having decreased expression of estrus compared to cows with a BCS>4 (≥70±4%). Initiation of estrous cycles before the breeding season also influenced estrous expression (P=0.03), with anestrous cows having greater expression of estrus compared with estrus-cycling cows (78±5% vs. 70±5%, respectively). In conclusion, among all currently recommended fixed-time AI protocols, cows detected in estrus before fixed-time AI had improved conception rates, with BCS and estrus-cycling status having the greatest influence on expression of estrus.

Effect of Skin-to-Skin Holding on Stress in Mothers of Late-Preterm Infants: A Randomized Controlled Trial.

PURPOSE: To examine the effect of skin-to-skin care (SSC) on stress perception between mothers who provided SSC to their late-preterm born infants and mothers who provided blanket holding. DESIGN AND METHODS: This was a longitudinal 2-group randomized controlled trial of 40 infant-mother dyads recruited from a level 3 neonatal intensive care unit in the upper Midwest. OUTCOME MEASURE: Maternal stress was measured using the Parental Stressor: Neonatal Intensive Care Unit (PSS: NICU) scale pre- and post-SSC intervention. Demographic and other mother and infant covariates were extracted from medical records. Physiologic stability was measured by the Stability of the Cardiorespiratory System in Preterm Infants (SCRIP) score. Study personnel used daily logs to track frequency and duration of SSC and holding sessions. RESULTS: The intervention and the control groups had similar pre- (mean ± standard deviation, 2.34 ± 0.86 for SSC and 2.94 ± 0.87 for holding) and post-intervention (mean ± standard deviation, 2.55 ± 0.95 for SSC and 2.78 ± 0.90 for holding) overall stress scores. Hours of SSC holding positively correlated with the change in stress scores for the entire scale (r = 0.58; P = .001), and for infant appearance (r = 0.58; P = .001) and parent role alteration (r = 0.48; P = .02) subscales. This relationship remained significant after controlling for the infant's length of stay and SCRIP score. IMPLICATIONS FOR PRACTICE: Mothers who provide SSC may experience more stress related to a more facilitated progression in the mother and infant relationship. IMPLICATIONS FOR RESEARCH: The relationship between increased stress and the number of hours of SSC holding warrants further investigation.

Prevalence of thermoduric bacteria and spores in nonfat dry milk powders of Midwest origin.

Samples of nonfat dry milk powder were analyzed for the presence of heat-resistant bacteria. The samples were collected from Midwest manufacturing companies and were evaluated for the presence of spores, thermoduric bacteria, and the total bacterial count. Three companies were included in this study, and results showed differences between each of the companies in the heat-resistant microbial groups tested. Company 3 had the highest levels of total spores and thermoduric bacteria: 3.6±0.14 and 3.5±0.13 log cfu/g, respectively. Interestingly, this company did not have the highest total bacterial count but rather the second lowest total bacterial count for the group, perhaps because of the higher proportion of thermophiles present in the powders from this company. The average level of total bacterial counts was 2.57±0.07 log cfu/g. Isolates obtained from the samples were identified by mass spectrometry, and all of the companies showed Bacillus licheniformis as the most prevalent bacterial species identified.

Prevalence of thermoduric bacteria and spores on 10 Midwest dairy farms.

Thermoduric bacteria (TDB), including sporeformers and their spores, can be present in milk and dairy products even after pasteurization. They have the potential to adversely affect the quality and shelf life of products. The objectives of this study were to identify the origin and common species of heat-resistant bacteria occurring during summer and winter on Midwest dairy farms. Bulk tank milk samples were taken from 10 dairy farms located along the South Dakota section of Interstate 29, with herd sizes ranging from 650 to 3,500 lactating dairy cows. Milk samples were profiled for the prevalence of TDB and spore counts (SC). Corn silage samples and swabs of the milking clusters were also taken at the dairies to further profile the potential sources of TDB and SC. The samples were taken 3 times during 2 seasons [winter (January-March) and summer (June-August)] to track seasonal changes in the farm bacterial flora. During winter, the average TDB counts in bulk tank milk were 2.61 log compared with 2.76 log TDB counts in the summer. The SC was 1.08 log in the winter, which was half the 2.06 log SC present in the summer season. Corn silage sampled in winter contained a 7.57 log TDB count compared with an increased 10.77 log TDB count during summer sampling. Concentrations of SC in corn silage reached an average of 6.3 log in winter compared with 11.81 log for summer. The seasonal effect was evident with an increase in summer counts across the board for TDB and SC, both in the feed and bulk tank milk samples. Bacillus licheniformis was the predominant species identified in 62.4% of winter (85 total) and 49.4% of summer (83 total) samples. Bacillus subtilis made up 9.4% of the remaining winter isolates, followed by Bacillus sonorensis at 8.2%. Conversely, B. sonorensis made up 12% of the summer isolates followed by Bacillus pumilus at 10.8%. Bacillus licheniformis is a ubiquitous microbe and was isolated from both TDB and sporeformer categories in all 3 sample types. There were larger increases in SC than TDB, indicating that summer temperatures and conditions may favor proliferation of sporeforming bacteria over that of TDB. In conclusion, samples from bulk tank milk, milking cluster swabs, and corn silage samples at each of the 10 sites indicated that B. licheniformis was the major contaminant species, regardless of season. In this experiment, corn silage was the major environmental source of both TDB and SC with higher concentrations in summer when compared with winter.

Structural equation modeling for analyzing erythrocyte fatty acids in Framingham.

Research has shown that several types of erythrocyte fatty acids (i.e., omega-3, omega-6, and trans) are associated with risk for cardiovascular diseases. However, there are complex metabolic and dietary relations among fatty acids, which induce correlations that are typically ignored when using them as risk predictors. A latent variable approach could summarize these complex relations into a few latent variable scores for use in statistical models. Twenty-two red blood cell (RBC) fatty acids were measured in Framingham (N = 3196). The correlation matrix of the fatty acids was modeled using structural equation modeling; the model was tested for goodness-of-fit and gender invariance. Thirteen fatty acids were summarized by three latent variables, and gender invariance was rejected so separate models were developed for men and women. A score was developed for the polyunsaturated fatty acid (PUFA) latent variable, which explained about 30% of the variance in the data. The PUFA score included loadings in opposing directions among three omega-3 and three omega-6 fatty acids, and incorporated the biosynthetic and dietary relations among them. Whether the PUFA factor score can improve the performance of risk prediction in cardiovascular diseases remains to be tested.

Corrigendum to "Prevalence of thermoduric bacteria and spores on 10 Midwest dairy farms".

Thermoduric bacteria (TDB), including sporeformers and their spores, can be present in milk and dairy products even after pasteurization. They have the potential to adversely affect the quality and shelf life of products. The objectives of this study were to identify the origin and common species of heat-resistant bacteria occurring during summer and winter on Midwest dairy farms. Bulk tank milk samples were taken from 10 dairy farms located along the South Dakota section of Interstate 29, with herd sizes ranging from 650 to 3,500 lactating dairy cows. Milk samples were profiled for the prevalence of TDB and spore counts (SC). Corn silage samples and swabs of the milking clusters were also taken at the dairies to further profile the potential sources of TDB and SC. The samples were taken 3 times during 2 seasons [winter (January­March) and summer (June­August)] to track seasonal changes in the farm bacterial flora. During winter, the average TDB counts in bulk tank milk were 1.83 log compared with 1.89 log TDB counts in the summer. The SC was 0.85 log in the winter, which was about half the 1.37 log SC present in the summer season. Corn silage sampled in winter contained 4.09 log TDB count compared with an increased 5.85 log TDB count during summer sampling. Concentrations of SC in corn silage reached an average of 3.60 log in winter compared with 6.33 log for summer. The seasonal effect was evident with an increase in summer counts across the board for TDB and SC, both in the feed and bulk tank milk samples. Bacillus licheniformis was the predominant species identified in 62.4% of winter (85 total) and 49.4% of summer (83 total) samples. Bacillus subtilis made up 9.4% of the remaining winter isolates, followed by Bacillus sonorensis at 8.2%. Conversely, B. sonorensis made up 12% of the summer isolates followed by Bacillus pumilus at 10.8%. Bacillus licheniformis is a ubiquitous microbe and was isolated from both TDB and sporeformer categories in all 3 sample types. There were larger increases in SC than TDB, indicating that summer temperatures and conditions may favor proliferation of sporeforming bacteria over that of TDB. In conclusion, samples from bulk tank milk, milking cluster swabs, and corn silage samples at each of the 10 sites indicated that B. licheniformis was the major contaminant species, regardless of season. In this experiment, corn silage was the major environmental source of both TDB and SC with higher concentrations in summer when compared with winter.

Longitudinal effects of fat and lean mass on bone accrual in infants.

There are conflicting reports on the influence of lean and fat mass on bone accrual during childhood. No infant's studies have been reported that describe the influence of changes in body composition with changes in bone accrual during the first year of life. The objective of this research was to test the hypothesis that greater gains in lean mass will have a positive effect on bone mineral content (BMC) accrual, while greater gains in fat mass will have a negative effect on BMC accrual in infants. Longitudinal data from 3 previous infant studies were used. Linear mixed models, adjusting for age, sex, dietary calcium, and length were used to investigate longitudinal and cross-sectional associations between total body BMC and lean and fat mass in the individual studies and in a combined analysis. In both individual and combined analyses, we found that lean and fat mass were positively associated with whole body BMC accrual (all, P<0.001). The cross-sectional association of BMC and dietary calcium was negative in one study (P<0.05). No differences in BMC change between sexes were observed in three studies. Our results showed positive cross-sectional and longitudinal associations between total body BMC and lean mass in infants. In contradiction to our hypothesis for fat mass, we found a positive cross-sectional and longitudinal association between total body BMC and fat mass in infants.

Abiotic stresses modulate expression of major intrinsic proteins in barley (Hordeum vulgare).

In one of the most important crops, barley (Hordeum vulgare L.), gene expression and physiological roles of most major intrinsic proteins (MIPs) remained to be elucidated. Here we studied expression of five tonoplast intrinsic protein isoforms (HvTIP1;2, HvTIP2;1, HvTIP2;2, HvTIP2;3 and HvTIP4;1), a NOD26-like intrinsic protein (HvNIP2;1) and a plasma membrane intrinsic protein (HvPIP2;1) by using the quantitative real-time RT-PCR. Five-day-old seedlings were exposed to abiotic stresses (salt, heavy metals and nutrient deficiency), abscisic acid (ABA) and gibberellic acid (GA) for 24 h. Treatment with 100 mM NaCl, 0.1 mM ABA and 1 mM GA differentially regulated gene expression in roots and shoots. Nitrogen and prolonged P-deficiency downregulated expression of most MIP genes in roots. Intriguingly, gene expression was restored to the values in the control three days after nutrient supply was resumed. Heavy metals (0.2 mM each of Cd, Cu, Zn and Cr) downregulated the transcript levels by 60-80% in roots, whereas 0.2 mM Hg upregulated expressions of most genes in roots. This was accompanied by a 45% decrease in the rate of transpiration. In order to study the physiological role of the MIPs, cDNA of three genes (HvTIP2;1, HvTIP2;3 and HvNIP2;1) have been cloned and heterologous expression was performed in Xenopus laevis oocytes. Osmotic water permeability was determined by a swelling assay. However, no water uptake activity was observed for the three proteins. Hence, the possible physiological role of the proteins is discussed.

A ratio-to-control Williams-type test for trend.

Under certain conditions, many multiple contrast tests based on the difference of treatment means can also be conveniently expressed in terms of ratios. In this paper, a Williams test for trend is defined as ratios-to-control for ease of interpretation and to obtain directly comparable confidence intervals. Simultaneous confidence intervals for percentages are particularly helpful for interpretations in the case of multiple endpoints. Methods for constructing simultaneous confidence intervals are discussed under both homogeneous and heterogeneous error variances. This approach is available in the R extension package mratios. The proposed method is used to test for trend in an immunotoxicity study with several endpoints as an example.

Equivalence tests for shelf life and average drug content in stability studies.

Stability testing is a procedure frequently used in the pharmaceutical industry to estimate the shelf life of a drug. Hereby, a standard problem of interest is whether or not to pool a given number of batches to assign a single shelf life for the combined batches. In this paper, we propose two modified methods for the pooling process. One is based on the relative average drug contents of batches at a target shelf life, which basically involves specification of thresholds in relative terms, and the other is tests for the equivalence of shelf lives (using ratios of shelf lives) at a specified lower acceptance criteria of label claim. For both approaches, marginal and simultaneous confidence intervals are established. The methods will be illustrated using two different stability data. A simulation study is conducted to investigate the coverage probability of the proposed methods.